Objective To investigate the effects of Xiaozheng Yiai decoction on the proliferation and migration of ovarian cancer SKOV3 cells and to explore the underlying mechanism. Methods The key active components and core targets of the decoction against ovarian cancer were analyzed with network pharmacology, and the related biological processes and pathways were screened with gene ontology(GO)and Kyoto Encyclopedia of genes and genomes(KEGG)enrichment analysis. Serum containing Xiaozheng Yiai decoction was prepared and SKOV3 cells were treated with it. Its effects on the proliferation of SKOV3 cells was detected with CCK-8 and EdU staining; its effects on the migration of SKOV3 cells was determined with wound healing assay and Transwell migration assay; its effects on the autophagy protein(P62), autophagy-related protein 3(ATG3), microtubule-associated protein 1 light chain 3 Beta(LC3B)and adenosine 5-monophosphate-activated protein kinase(AMPK)/ protein kinase B(AKT)/ mammalian target of rapamycin(mTOR)pathway related proteins in SKOV3 cells were assessed with Western blotting. Results Network pharmacology studies showed that the key active components of Xiaozheng Yiai decoction against ovarian cancer were quercetin, kaempferol, luteolin, wogonin, naringenin, and the core targets were MAPK3, AKT1, SRC, MAPK1, TP53, and so on. KEGG enrichment analysis identified 171 pathways(P<0.01). The pathways with the highest Degree ranking and associated with ovarian cancer mainly involved the cancer pathway, PI3K-AKT pathway, MAPK pathway, AMPK pathway, autophagy, and mTOR pathway. The results of in vitro experiments showed that compared with the control group, the 10% and 20% drug-containing serum groups had decreased cell viability, EdU positive cell rate, cell migration, and number of migrating cells(all P<0.001). The results of Western blotting showed that the protein expression levels of P62, ATG3 and LC3B-II were up-regulated after treatment with 10% and 20% drug-containing serum(all P<0.05), the p-AMPK/AMPK ratio was up-regulated(P<0.001), and the expression levels of p-AKT/AKT and p-mTOR/mTOR decreased (P<0.05 or P<0.01). Conclusion Xiaozheng Yiai decoction can inhibit the proliferation and migration of ovarian cancer SKOV3 cells, possibly via the regulation of AMPK/AKT/mTOR pathway and the blocking of autophagic flux.

Objective To explore the effects of interferon-γ(IFN-γ)on the proliferation of non-Hodgkin lymphoma(NHL)by regulating the expression of programmed cell death ligand 1(PD-L1)and the mechanism. Methods The expression of PD-L1 in various NHL cell lines was detected with flow cytometry. After NHL cell lines U937 and Jeko-1 were treated with IFN-γ, the expression of PD-L1 was detected with flow cytometry and quantitative real-time PCR(qRT-PCR). After NHL cells were co-cultured with INF-γ and phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin(PI3K/Akt/mTOR)signaling pathway inhibitor, change in the expression of PD-L1 was detected with Western blotting and flow cytometry. Cell proliferation was detected with cytotoxicity detection kit(CCK-8)and carboxyfluorescein diacetate succinimidyl ester(CFSE)staining incorporation method. Cell proliferation rate was detected with Edu labeling method. Cell cycle was detected with flow cytometry. Results The qRT-PCR results showed that PD-L1 was expressed on the surface of various NHL cell lines. After IFN-γ treatment, the mRNA and protein expressions of PD-L1 in U937 and Jeko-1 cells were increased. After U937 and Jeko-1 cells were co-treated with IFN-γ and signaling pathway inhibitors, the PI3K/Akt/mTOR signaling pathway inhibitor inhibited the up-regulation of PD-L1 expression by IFN-γ, and cell proliferation was inhibited. Conclusion IFN-γ can up-regulate the expression of PD-L1 in NHL cells through the PI3K/Akt/mTOR signaling pathway; IFN-γ promotes NHL cell proliferation by up-regulating the expression of PD-L1.

Objective To investigate the frequency of muscle cramp and analyze the risk factors in patients with type 2 diabetes mellitus(T2DM). Methods A total of 136 T2DM patients were involved and assessed with the Muscle Spasm Scale. According to the results of the scale, they were divided into muscle cramp group(n=65)and non muscle cramp group(n=71). Patients age, gender, body mass index(BMI), smoking history, alcohol consumption, mean arterial pressure(MAP), duration of diabetes, plasma glucose, glycosylated hemoglobin A1c(HbA1c), fasting C-peptide, serum albumin(ALB), serum creatinine(Scr), magnesium(Mg), total calcium(Ca)and vitamin D(VIT-D)were assessed. Risk factors of muscle cramp were screened with multivariate binary Logistic regression. Results The study revealed that47.8%(65/136)patients suffered from various degrees of muscle cramp. The ALB level of the muscle cramp group was significantly lower than that of the non muscle spasm group(P=0.023). The duration of diabetes was also significantly prolonged(P=0.045). There were no significant differences in other parameters between the two groups(P>0.05). Multivariate Logistic regression showed that increased duration of diabetes(OR=1.068, 95%CI: 1.008-1.131)and reduced ALB level(OR=1.159, 95%CI: 1.015-1.323)were independent risk factors of muscle cramp. Conclusion Decreased ALB level and extended diabetes duration may be independent risk factors for the occurrence of muscle cramp in patients with T2DM.

Objective To explore the etiology, clinical manifestations, treatment and outcomes of acquired coagulation factor deficiency. Methods Clinical data of 31 patients with acquired coagulation factor deficiency during Jul. 2011 and Oct. 2021 were retrospectively analyzed. Patients with acquired hemophilia A(AHA)were grouped according to FⅧ inhibitor levels and intergroup correlation analysis was conducted. Results Of the 31 cases, 29 were AHA and 2 were acquired coagulation factor V deficiency(AFVD). The most common clinical symptoms of AHA were subcutaneous bleeding(62.07%)and muscle and soft tissue hematoma(34.48%). The AFVD patients had symptoms of hematuria and skin hemorrhagic spots. Patients with higher FⅧ inhibitor titer had longer activated partial thromboplastin time and lower level of FⅧ: C(P<0.05), but there was no correlation between the level of FⅧ inhibitor titer and severity of bleeding. Conclusion Screening the etiology of patients, combined with the comprehensive evaluation of the etiology, age, underlying diseases, levels of coagulation factors and other indicators to formulate an individualized treatment plan, has an important guiding significance for the clinical management of acquired coagulation factor deficiency.

Objective To analyze the effects of different preoperative model for end-stage liver disease(MELD)scores on the early death and postoperative complications in patients with acute Stanford type A aortic dissection(ATAAD)undergoing surgical treatment, and to explore the risk factors of early postoperative death. Methods The clinical data of 304 ATAAD patients who received surgery during Jan. 2018 and Dec. 2021 were retrospectively analyzed. According to the preoperative MELD score, the patients were divided into three groups: low MELD group(n=204, MELD <10), medium MELD group(n=72, 10≤MELD<15)and high MELD group(n=28, MELD≥15). The general data and perioperative clinical data were compared among the groups. Effects of preoperative MELD scores and other factors on the survival were determined with Cox regression analysis. Results Of the 304 patients enrolled, 63(20.7%)died in the early postoperative period. Patients with higher preoperative MELD score had significantly higher rate of mortality(P<0.001)and major adverse clinical events(MACEs)(P=0.007). Multivariate Cox regression showed that preoperative MELD ≥15 was independently associated with in-hospital mortality. Conclusion Increased preoperative MELD score and decreased liver function significantly increase early postoperative mortality and MACEs in patients with ATAAD. Preoperative MELD score is helpful for risk stratification of patients, and early prevention and intervention of high-risk patients can help improve the prognosis.

Objective To analyze the influencing factors of disease transformation in 47 patients with single demyelinating lesion of spinal cord. Methods The clinical data of 92 patients with single demyelinating lesion of spinal cord were retrospectively analyzed. According to the presence of neuromyelitis optica spectrum disorders(NMOSD), multiple sclerosis(MS), and myelin oligodendrocytes glycoprotein associated disorders(MOG-AD)during the follow-up, the patients were divided into transformed group(n=47)and non-transformed group(n=45). Independent-samples t test, χ2 test, Fishers exact test or Mann-Whitney U test were used to compare the clinical data of the two groups. The independent risk factors of disease transformation were analyzed with binary Logistic regression. Results There were significant association between disease transformation and patients age, visual impairment during follow-up, segments of spinal cord ≥3, abnormality of rheumatic series, positive central nervous system demyelinating antibody and recurrence(P<0.05). Binary Logistic regression analysis showed that recurrence(OR=6.850, 95%CI: 2.206-21.270, P=0.001), segments of spinal cord ≥3(OR=3.968, 95%CI: 1.230-12.805, P=0.021), and positive central nervous system demyelinating antibody(OR=19.983, 95%CI: 2.258-176.816, P=0.007)were independent risk factors of disease transformation. Conclusion The transformation of a single demyelinating lesion of spinal cord is associated with age, visual impairment during follow-up, segments of spinal cord ≥3, positive central nervous system demyelinating antibody, abnormality of rheumatism series and recurrence.

Objective To investigate the effects of progesterone elevation on the day of human chorionic gonadotropin(hCG)administration on in vitro fertilization(IVF)pregnancy outcomes, and to explore the relationship between the number of retrieved oocytes and IVF outcomes correlated with elevated progesterone. Methods A total of 2,437 patients who underwent IVF/intracytoplasmic sperm injection(ICSI)treatment cycles during Jan. 2019 and Dec. 2020 were retrospectively enrolled. The effects of progesterone elevation on IVF pregnancy outcomes were determined with univariate regression analysis, multivariate Logistic regression analysis, smoothed curve fitting and threshold effects, and whether the effects were related to the number of retrieved oocytes was assessed with stratified analysis. Results After confounding factors were adjusted, analysis of threshold effects showed when the progesterone level was ≥1.5 ng/mL on hCG day, with a 1 ng/mL increase in the progesterone level, the clinical pregnancy rate decreased by 60%(95%CI: 0.2-0.7, P=0.004), the intrauterine pregnancy rate decreased by 70%(95%CI: 0.2-0.7, P=0.003), and the live birth rate decreased by 70%(95%CI: 0.1-0.7, P=0.004). After grouping according to the number of retrieved oocytes, when the number of retrieved oocytes was 5-10 and the progesterone level was ≥1.8 ng/mL on hCG day, with a 1 ng/mL increase in the progesterone level, the clinical pregnancy rate decreased by 100%(95%CI: 0.0-0.1, P=0.002), and the intrauterine pregnancy rate decreased by 100%(95%CI: 0.0-0.010, P<0.001). When the progesterone level was ≥1.6 ng/mL on hCG day, with a 1 ng/mL increase in the progesterone level, the live birth rate decreased by 90%(95%CI: 0.0-1.0, P=0.049). When the number of retrieved oocytes was 10-15 and the progesterone level was ≥1.1 ng/mL on hCG day, with a 1 ng/mL increase in the progesterone level, the clinical pregnancy rate decreased by 70%(95%CI: 0.1-0.7, P=0.006), the intrauterine pregnancy rate decreased by 70%(95%CI: 0.1-0.6, P=0.003), and the live birth rate decreased by 70%(95%CI: 0.1-0.6, P=0.003). Conclusion Elevated progesterone level on hCG day is an independent risk factor affecting the IVF pregnancy outcomes. There is a remarkable effect on patients with the number of oocytes 5-15 with elevated progesterone. So the pregnancy outcomes of normal ovarian response patients can be improved by freezing all embryos when the progesterone level is more than 1.5 ng/mL.

Objective To explore the effects of exosomal miR-100 derived from human umbilical cord mesenchymal stem cells(hUC-MSCs)on the inflammation of granulosa cells(GCs)in polycystic ovary syndrome(PCOS). Methods A total of 70 PCOS patients treated during Mar. 2021 and Dec. 2021 were enrolled as the PCOS group, and another 70 patients treated due to tubal factors were selected as the control group. The clinical characteristics and in vitro fertilization(IVF)outcomes were compared between the two groups. The expressions of pro-inflammatory cytokines TNF-α and IFN-γ in patients’ GCs were detected with real-time quantitative PCR(RT-qPCR). The risk factors influencing the occurrence of PCOS were analyzed with binary Logistic regression analysis. The expression of miR-100 in hUC-MSCs exosomes(exos)was verified with RT-qPCR. After the miR-100 mimics and miR-NC were synthesized and transfected into human ovarian granulosa cells(KGN), the expression of miR-100 was determined with RT-qPCR. After the miR-100 mimics and miR-NC were transfected into lipopolysaccharide(LPS)-induced KGN cells, the mRNA expressions of TNF-α and IFN-γ were detected with RT-qPCR. The target gene of miR-100 was verified with dual-luciferase reporter gene assay. After miR-100 was overexpressed in LPS-induced KGN cells, the effector molecular of Toll-like receptor-4/nuclear factor kappa B(TLR4/NF-κB)signaling pathways, including TLR4, p-IκBa, IκBa, p-p65 and p65, were detected with Western blotting. Results PCOS group had higher body mass index(BMI), luteinizing hormone(LH), estradiol(E₂), testosterone(T), homeostasis model assessment for insulin resistance index(HOMA-IR), antral follicle count(AFC), and number of retrieved oocytes than the control group, whereas lower MII oocyte rate and 2PN fertilization rate(P<0.001, P<0.001, P=0.020, P<0.001, P<0.001, P<0.001, P<0.001, P<0.001, P<0.001). The PCOS group had significantly higher expressions of TNF-α and IFN-γ than the control group(P<0.001). Binary Logistic regression analysis revealed that LH, HOMA-IR, TNF-α and IFN-γ were risk factors influencing the occurrence of PCOS(P=0.031, 0.001, 0.030, 0.005). RT-qPCR showed that miR-100 was enriched in hUC-MSCs-exos. Overexpression of miR-100 significantly inhibited LPS-induced increase of the mRNA expressions of TNF-α and IFN-γ(P=0.041, P<0.001). Dual-luciferase reporter gene assay showed that miR-100 directly targeted TLR4 mRNA 3’UTR and inhibited its expression(P<0.001). Western blotting showed that miR-100 efficiently inhibited LPS-induced elevation of the protein expressions of TLR4, p-IκB and p-p65(P<0.001, P<0.001, P=0.049), but the protein expression of IκB significantly increased(P<0.001). Conclusion The increased expressions of TNF-α and IFN-γ are risk factors influencing the occurrence of PCOS. Exosomal miR-100 derived from hUC-MSCs inhibits the inflammation of granulosa cells via TLR4/NF-κB signaling pathway in PCOS.

Objective To investigate the value of a radiomic nomogram model based on initial CT scan to predict the 90-day functional outcomes of supratentorial spontaneous intracerebral hemorrhage(sICH). Methods Clinical data of 376 patients with supratentorial sICH were retrospectively analyzed. According to the 90-day modified Rankin Scale(mRS), the patients were divided into poor outcome group(n=121, mRS score 4-6)and good outcome group(n=255, mRS score 0-3). Radiomic features were extracted from the initial CT scan, radiomic score(Rad-score)was calculated and a radiomic model was constructed. The clinical risk factors of poor outcome were selected to construct a clinical model, and then combined with Rad-score to construct a nomogram model. The diagnostic values of the three models were compared. Results Altogether 20 features were selected to establish the radiomic model. The clinical model was composed of age(OR=1.045, 95%CI: 1.023-1.066), Glasgow Coma Scale(GCS)≤8(OR=4.128, 95%CI: 2.161-7.887), hematoma breaking into ventricle(OR=3.071, 95%CI: 1.744-5.408)and hematoma volume >30 mL(OR=5.802, 95%CI: 3.327-10.117). In the training set, the area under the curve(AUC)of the nomogram model was 0.892, which was higher than that of the clinical model(0.814)and the radiomics model(0.862), and the difference was statistically significant(Z=3.356, 2.231, P=0.000 8, 0.025 7). Conclusion The nomogram model can effectively predict the 90-day outcomes for supratentorial sICH patients, which is helpful for clinical decision-making.

Objective To investigate the immediate efficacy and long-term prognosis of patients with repeated bleeding after interventional therapy. Methods The clinical data of three patients with repeated bleeding after hemorrhoidal surgery were retrospectively analyzed at the follow-up of 114, 110 and 78 months, respectively. The bleeding sites were the end of the left superior rectal artery, the end of the superior rectal artery branch and the end of the left internal iliac artery. Two cases had successful first-stage embolization, and one case had re-bleeding after first-stage embolization and successfully stopped bleeding after a second interventional treatment. No patients had bleeding after interventional treatment. Results All three patients had accurate hemostasis, and there were no serious complications such as intestinal necrosis and death. All patients had falling and painful symptoms; One patient developed scrotal edema and erectile dysfunction, and recovered after long-term follow-up. Conclusion Interventional embolization is effective in the treatment of persistent bleeding after refractory hemorrhoids, but the safety requires long-term follow-up and observation of multi-center and large samples.

Objective To explore the clinical characteristics of oligomeganephronia with paired box2(PAX2)gene mutation. Methods Clinical data of a child diagnosed with oligomeganephronia by renal biopsy and PAX2 gene missense mutation by genetic testing were retrospectively analyzed, and relevant literature was reviewed. Results A boy aged 9 years and 8 months presented with non-nephrotic proteinuria and renal insufficiency. Pathological diagnosis of renal biopsy showed oligomeganephronia and focal segmental glomerulosclerosis. Genetic testing showed a heterozygous mutation of c.94C>T(p.P32S)in PAX2 gene, and Sanger sequencing verified that the mutation was from the father. Conclusion The heterozygous mutation of PAX2 gene from the father may cause the disease, leading to renal dysplasia. The onset of oligomeganephronia is insidious. In clinical practice, solitary proteinuria with renal insufficiency should be warned of this disease, and timely renal biopsy should be performed.

Objective To evaluate the efficacy of Terminal Patient Condition Assessment Form in predicting the survival time of terminal patients. Methods Clinical data of 26 terminal patients admitted to the geriatric ward of Shandong Electric Power Central Hospital during Apr. 2020 and Feb. 2022 were retrospectively analyzed. The match rate between predicted and actual survival time was calculated, and the rationality of score threshold for predicting survival time less than 30 d was determined. The survival curve was drawn and the influence of each predicting factor on survival time was investigated. The vital signs and other indicators were scored with the Terminal Patient Condition Assessment Form, the total scores were obtained, and the correlation between the scores and survival time was analyzed. Results The match rate of assessment at admission was 65.38%. Some predicting items included warning indicators. The match rate of warning indicators in predicting survival time less than 3 d was 100%. The most common warning indicators were the changes of consciousness(76.92%), systolic blood pressure <80 mmHg(38.46%), and respiratory rate>30/min(26.92%). The sensitivity and specificity of 50 points as score threshold for predicting survival time less than 30 d were 77.78% and 83.33%, respectively; the positive and negative predictive value were 93.33% and 55.55%, respectively; the Youden index was 0.61. There was significant difference in survival time between the group with score ≤50 points and group with score >50 points(P=0.021). Cox analysis showed scores of respiratory(HR=0.609, 95%CI:0.381-0.973), pulse(HR=0.615, 95%CI:0.426-0.889)and organ status(HR=0.362, 95%CI:0.170-0.773)had significant effects on survival time(P<0.05). Conclusion Terminal Patient Condition Assessment Form can accurately predict the survival time of terminal patients with advanced cancer, chronic organ failures, dementia and so on.

Objective To analyze the situation, disease burden and risk factors of human immunodeficiency virus/acquired immunodeficiency syndrome(HIV/AIDS)in China from 1990 to 2019 and to forecast the incidence and mortality from 2020 to 2030. Methods The situation of HIV/AIDS in China from 1990 to 2019 was explored and its temporal trend of incidence and disease burden were analyzed with Joinpoint regression. The trend of incidence and mortality from 2020 to 2030 were predicted with Bayesian age-period-cohort(BAPC)model integrated with nested Laplace approximations. Results The age-standardized incidence and mortality rate of HIV/AIDS in China in males were higher than those in females. The age-standardized incidence showed an increasing trend in people aged 15 to 19 years and 20 to 24 years, and showed the largest variation in people aged 75 to 79 years. The age-standardized incidence and disability-adjusted life years(DALYs)rate of HIV/AIDS in China increased from 1990 to 2019 and there were statistically significant differences(P<0.001); the age-standardized DALYs rate of HIV/AIDS attributable to unsafe sex was the highest. The BAPC predicted that the age-standardized mortality rate of HIV/AIDS in China in males would increase from 2020 to 2030. Conclusion The risk of HIV/AIDS incidence in adolescents continues to increase in China and the risk of mortality in elderly should not be ignored. The disease burden of HIV/AIDS shows an increasing trend and unsafe sex is the primary risk factor. In the future, prevention and control measures should be taken for the key population.

Objective To analyze the epidemic and whole genome characteristics of coxsackievirus A16(CV-A16)in Jining in 2021. Methods A total of 513 stool samples were collected from patients with hand, foot and mouth disease(HFMD), which were then underwent nucleic acid detection of CV-A16 and virus isolation. Whole genome sequencing and bioinformatics analysis were performed on 4 CV-A16 strains. Results Altogether 36 cases were positive for CV-A16, with a positive rate of 7.02%(36/513). The positive rate was the highest from July to September. The 4 strains were distributed in B1a and B1b branches. Compared with prototype strain G-10(CAU05876), the 4 strains had homology of nucleotide and amino acid of 77.5%-78.0% and 94.7%-94.9%, respectively. There were multiple amino acid changes in the encoded proteins of the 4 strains. Conclusion CV-A16 was one of the main pathogens of HFMD in Jining in 2021, including B1a and B1b subtypes. The surveillance of the disease should be strengthened.

Objective To analyze the epidemic characteristics of influenza in Shenzhen and Jinan from April 2016 to March 2022, so as to explore the differences between the north and south of China. Methods Data of influenza-like illness(ILI)and virologic surveillance of national sentinel hospitals of Shenzhen and Jinan were analyzed to determine the epidemic trend and characteristics of influenza during 2016 and 2022. Results The average percentage of ILI(ILI%)were 2.25% and 3.45% in Shenzhen and Jinan, and the years with the highest ILI% in both cities were from 2021 to 2022. Children aged 0 to 4 years were the most vulnerable group, accounting for 40% and 46% of all cases in Shenzhen and Jinan, respectively. The monthly ILI% and influenza virus were positively correlated in Shenzhen and Jinan(r=0.238, P<0.05; r=0.425, P<0.001). The dominant influenza virus subtypes varied in the different influenza seasons, while the subtypes of prevalent strains in each year and the dominant strains in epidemic peak were basically the same in both cities. Conclusion At the beginning of the novel coronavirus pneumonia epidemic(2020-2021), the influenza activity was significantly lower than the average level in previous years and the circulating virus type was single in Shenzhen and Jinan. The epidemic characteristics of influenza in the other monitoring years were basically consistent with the influenza epidemic characteristics in the south and north of China.

Objective To investigate the bidirectional causal association between amino acids and type 2 diabetes(T2D). Methods Data of genome-wide association study on amino acids and T2D were collected. Inverse variance weighted method, weighted median method, MR-Egger regression method, MR robust adjusted profile score method and MR pleiotropy residual sum and outlier method(MR-PRESSO)were adopted for two-sample bidirectional mendelian randomization(MR)analysis. Cochrans Q test, MR-Egger intercept test, and MR-PRESSO global test were used to evaluate the heterogeneity and pleiotropy of the results. Results The results of inverse variance weighted method showed that leucine(OR=1.239, 95%CI: 1.078-1.424, P=0.002 5)and valine(OR=1.222, 95%CI: 1.071-1.394, P=0.002 9)increased the risk of T2D, while glycine(OR=0.885, 95%CI: 0.831-0.942, P=0.000 1)decreased the risk. The results of reverse MR analysis showed that the risk of T2D was causally associated with increased leucine, isoleucine, valine, alanine, phenylalanine and tyrosine, and decreased glycine. The results of multiple MR methods suggested robustness of causal associations and no potential pleiotropy was found in the sensitivity analysis. Conclusion Higher levels of leucine and valine and lower level of glycine have bidirectional causal associations with T2D risk. T2D has positive causal effects on isoleucine, alanine, phenylalanine and tyrosine.