Objective To construct reference ranges of cardiac size and morphologic parameters in low-risk fetuses at 28-39 gestational weeks using two-dimensional speckle tracking technique.Methods A prospective collection of 453 low-risk singleton pregnancies with echocardiography at Obstetrics and Gynecology Hospital,Fudan University was used to assess the size(length,width,and area)and morphology(sphericity index,i.e.,the ratio of length to width)of the fetal four-chamber view and two ventricles using two-dimensional speckle tracking technique.Repeated inter-and intra-observer agreement of measurements was assessed using the intraclass correlation coefficients(ICCs).Statistical analysis of cardiac measurement parameters was performed to establish reference ranges of values for cardiac size and morphology in low-risk fetuses.Results The inter-and intra-group ICCs for reproducibility tests of fetal cardiac parameters measurements were 0.691 to 0.980.Fetal four-chamber view and ventricular size increased with gestational week(all P<0.001),the end-diastolic length of the left ventricle was larger than that of the right ventricle,and the end-diastolic diameter was smaller than that of the right ventricle(both P<0.001),while there was no significant difference in the end-diastolic area of the two ventricles(P= 0.050).The spherical index of four-chamber view did not correlate with gestational week(P=0.811).The sphericity index of the basal and intermediate segments of the left ventricle was greater than that of the right ventricle,and the sphericity index of the apical segment was less than that of the right ventricle,the differences were statistically significant(all P<0.01).Conclusion The two-dimensional speckle tracking technique for measuring fetal cardiac parameters has good reproducibility.The reference ranges for cardiac size and morphology in low-risk fetuses developed in this study will be useful for prenatal evaluation of cardiac remodeling.

Objective:To analyse the clinical significance of selective single embryo transfer by time-lapse mo-nitoring(TLM)or conventional morphology assessment(CMA)in vitro fertilization/intracytoplasmic sperm in-jection and embryo transfer(IVF/ICSI-ET),and to initially explore the predictive value of Raman spectral analy-sis of embryo culture medium for clinical pregnancy rate.Methods:The study is a prospective randomized con-trolled clinical trial.We assigned 139 patients treated with IVF/ICSI-ET in Reproductive and Genetics Center of Suzhou Municipal Hospital from April 2019 to July 2020,which were randomly assigned to either the CMA or the TLM group.We performed selective single-embryo transfer(fresh cycle and FET)after selecting the optimal em-bryos with TLM or CMA respectively.If the patient's first embryo transfer was unsuccessful,a second one would be performed to compare the differences in the cumulative live birth rate of embryo transfer and other pregnancy outcomes between the two groups.Meanwhile,we collected 15 μl of embryo culture medium at day 3 after IVF/ISCI fertilization for Raman spectroscopy analysis.Results:There were no differences in cumulative live birth,cu-mulative clinical pregnancy,cumulative premature birth,cumulative early spontaneous abortion,cumulative ectopic pregnancy and LGA or SGA between TLM and CMA groups(P＞0.05).The Neonatal sex ratio in the TLM group was lower than that in the CMA group,but the difference was not significant(P＞0.05).Raman spectros-copy analysis of embryo culture medium predicted the clinical pregnancy rate with 67.21％accuracy.Conclu-sions:In young women with a good ovarian reserve,the advantage of using TLM to evaluate embryos is not obvi-ous,so we should remain vigilant that embryo selection based on morphokinetic parameters may affect the sex ratio.Raman spectroscopic analysis of embryo culture medium is not yet able to effectively predict the planting ability of embryos.

Objective To investigate the effects of microsurgical varicocelectomy on testicular function and sexual function in patients with varicocele.Methods The clinical data of 90 patients with varicocele admitted to our hospital were retrospectively analyzed,and the patients were divided into the laparoscopic group(received laparoscopic varicocelectomy)and the microscopic group(received microsurgical varicocelectomy)according to different surgical methods,with 45 cases in each group.The testicular function and sexual function related indexes including sperm density,normal sperm ratio,rate of sperm motility(grades a+b),forward motility sperm rate,international index of erectile function-5(IIEF-5)score,and the levels of testosterone,follicle-stimulating hormone,luteinizing hormone,and androgen levels before and 6 months after surgery in the two groups were compared.The incidence of complications and recurrence 6 months after surgery in the two groups were counted.Results Compared with those before surgery,the sperm density,forward motility sperm rate,rate of sperm motility(grades a+b),normal sperm ratio,IIEF-5 score,testosterone level,and androgen level 6 months after surgery of patients in the two groups were significantly increased(P<0.05),and the levels of luteinizing hormone and follicle-stimulating hormone were decreased(P<0.05).Compared with the laparoscopic group,the levels of follicle-stimulating hormone and luteinizing hormone,and incidence of complications 6 months after surgery of patients in the microscopic group were decreased(P<0.05),and the levels of testosterone and androgens,and IIEF-5 score 6 months after surgery were increased(P<0.05).There was no significant difference in the recurrence rate between the two groups(P>0.05).Conclusion Microsurgical varicocelectomy can improve the testicular function and sexual function of patients with varicocele,with a low incidence of complications.

Objective:To investigate the value of antioxidant-associated long non-coding RNAs(lncRNAs)risk score model in prognosis and the association with immune microenvironment of the gastric cancer patients.Methods:Gastric cancer transcriptome data and clinical information were downloaded from TCGA database.Antioxidant-associated lncRNAs were obtained by co-ex-pression analysis of lncRNAs and antioxidant genes.Risk score was constructed using univariate cox regression analysis and lasso regression analysis.Log-Rank test was used to compare the survival differences between two groups.Receiver operating characteristic curve(ROC)was used to assess the specificity and sensitivity of the prognostic risk score model.Nomogram was constructed com-bining risk score and clinical parameters.Immune cell infiltration was assessed by TIMER 2.0.Im-munotherapy sensitivity of each sample was analyzed at TIDE website.Results:A risk score in-cluding 12 IncRNAs was constructed by univariate cox regression analysis and lasso regression anal-ysis.The risk score was an independent factor influencing patient prognosis[HR=5.406(3.131～9.335),P＜0.001].Risk score was positively correlated with multiple suppressive immune cells infil-tration(M2 macrophage,tumor-associated fibroblast).Meanwhile,multiple aberrant expression of immune checkpoint genes and higher TIDE score were found in high-risk group,suggesting that high-risk groups may be more sensitive to immunotherapy.Conclusion:The antioxidant-associ-ated IncRNAs risk score is a good prognostic predictor and can act as a reference in individualized immunotherapy for gastric cancer patients.

AIM To study the extraction process,enzymatic properties and practical application of glucuronic hydrolase in Scutellaria baicalensis stems and leaves(sbsl GUS).METHODS With granularity,water consumption,extraction time and extraction frequency as influencing factors,enzymatic activity as an evaluation index,the extraction process was optimized by orthogonal test on the basis of single factor test.The relationship between substrate(baicalin)concentration and enzymolysis rate,after which Vmax and Km were calculated,the effects of pH value,temperature and metal ion on enzymatic activity were investigated,pH stability and heat stability were evaluated.sbsl GUS was adotped in the enzymolysis of baicalin to prepare baicalein,then the effects of pH value,temperature,reaction time,initial substrate concentration and enzyme addition on transfer rate were investigated.RESULTS The optimal extraction process was determined to be 40 mesh for granularity,10 times for water consumption,15 min for extraction time,and 3 times for extraction frequency.The enzymolysis accorded with the kinetics of enzymatic reaction,Km was 0.006 3 mol/L,Vmax was 70.42 μmol/h,the strongest enzymatic activity was found at the pH value of 6.0,temperature of 45℃and metal ion of 100 mmol/L Cu2+,sbsl GUS demonstrated good stability at the ranges of 4.0-7.0 for pH value and 4-30℃for temperature.The optimal preparation process was determined to be 6.0 for pH value,45℃for temperature,more than 12 h for reaction time,67.2 mmol/L for initial substrate concentration,and 1 mL/0.269 mmol baicalin for enzyme addition,the transfer rate was 97.83%.CONCLUSION sbsl GUS enzymolysis exhibits high efficiency and mild condition,which can provide a simple preparation method for obtaining baicalein,and expand the application path of Scutellaria baicalensis stems and leaves.

Objective To investigate the effects of Shenqi Tiaoshen Formula(SQTSF)for alleviating airway inflammation in rats with both chronic obstructive pulmonary disease(COPD)and lung-kidney qi deficiency syndrome and explore its therapeutic mechanism.Methods Forty-eight SD rats were randomly divided into control group,model group,low-,medium-,and high-dose SQTSF groups,and aminophylline(APL)group.In all but the control group,rat models of COPD with lung-kidney qi deficiency syndrome were established and treated with saline,SQTSF or APL via daily gavage as indicated(starting from day 30).The rats were observed for changes in body weight,grip strength,lung function,lung pathology,inflammatory cytokines in bronchoalveolar lavage fluid(BALF),oxidative stress levels,iron ion metabolism,cellular and mitochondrial ultrastructural changes in the lung tissue,and expressions of Nrf2/SLC7A11/GPX4 signaling pathway and ferroptosis-related proteins.Results The rats in the model group exhibited obvious symptoms of lung-kidney qi deficiency syndrome with significantly decreased body weight,grip strength,and lung function parameters.Examination of the lung tissue revealed showed significant inflammatory cell infiltration and emphysema with obvious bronchial,perivascular,and alveolar inflammation and alveolar destruction,significantly increased IL-1β,TNF-α,IL-6,and IL-13 levels in BALF,and elevated pulmonary oxidative stress levels and Fe2+and total iron ion concentrations.The rat models also showed characteristic ultrastructural changes of ferroptosis in the lung tissue cells under transmission electron microscope and significantly decreased Nrf2,GPX4,and SLC7A11 and increased ACSL4 expressions in the lung tissue.Treatment with SQTSF significantly improved these pathological changes in the rat models with a better effect than APL.Conclusion SQTSF can effectively improve airway inflammation and oxidative stress in COPD rats with lung-kidney qi deficiency possibly by inhibiting ferroptosis via regulating the Nrf2/SLC7A11/GPX4 signaling pathway.

ObjectiveTo investigate the protective mechanism of Qianyang Yuyin granules （QYYY） on aldosterone-induced podocyte injury. MethodA total of 30 C57BL/6J mice were randomly divided into five groups： control group， model group， QYYY low dose （QYYY-L） group， QYYY high dose （QYYY-H） group， and spironolactone （SPL） group， with six mice in each group. Except for the control group， mice were implanted with osmotic minipumps and injected continuously with aldosterone （300 μg·kg^-1·d^-1） to induce renal injury. The drug administration group was given low and high doses （2.6， 5.2 g·kg^-1·d^-1） of QYYY and SPL （18 mg·kg^-1·d^-1） for 28 days. The renal pathological changes of mice were observed by hematoxylin-eosin （HE） staining and Masson staining. The expression levels of Nephrin， Desmin， B-cell lymphoma-2 （Bcl-2）， Bcl-2-associated X （Bax）， cleaved Caspase-3， nuclear receptor subfamily 3 group C member 2 （NR3C2）， extracellular regulated protein kinases （ERK）， and phospho-ERK （p-ERK） in kidney tissue were detected by Western blot. The apoptosis levels of kidney tissue were detected by TdT-mediated dUTP nick and labeling （TUNEL） staining， and the superoxide dismutase （SOD） levels were detected. In vitro， the mice were divided into five groups： Control group， model group （aldosterone concentration of 200 nmol·L^-1）， QYYY-L group， QYYY medium dose （QYYY-M） group， and QYYY-H group （25， 50， and 100 mg·L^-1）. The effect of different concentrations of QYYY on the relative viability of aldosterone-induced podocytes was detected by cell proliferation and viability assay （CCK-8）. The expressions of Nephrin， Desmin， Bax， Bcl-2， cleaved Caspase-3， NR3C2， and p-ERK/ERK were detected by Western blot. AnnexinV-FITC/PI flow cytometry was used to detect the apoptosis levels of podocytes. Reactive oxygen species （ROS） in podocytes were observed by DCFH-DA. ResultCompared with the control group， the model group showed structural pathological changes and fibrotic conditions in the kidney， increased apoptosis levels （P<0.01）， and decreased SOD levels （P<0.01）. Aldosterone concentration at 200 nmol·L^-1 showed a significant decrease in podocyte activity （P<0.05）. Podocytes in the model group showed structural pathological changes， disordered arrangement of intercellular microfilaments， increased apoptosis levels （P<0.01）， and increased intracellular ROS levels （P<0.01）. The protein expressions of Nephrin， Bcl-2， and p-ERK/ERK in kidney tissue and podocytes were decreased （P<0.05， P<0.01）. The protein expressions of Desmin， Bax， cleaved Caspase-3， and NR3C2 were increased （P<0.05， P<0.01）. Compared with the model group， QYYY alleviated the structural damage and fibrosis of the kidney， decreased the apoptosis levels （P<0.05， P<0.01）， and enhanced the SOD content of the kidney （P<0.05， P<0.01）. QYYY improved the activity of podocytes （P<0.05， P<0.01）， restored the foot process structure of podocytes， and decreased apoptosis levels （P<0.01） and ROS levels of podocytes （P<0.01）. The protein expressions of Nephrin， Bcl-2， and p-ERK/ERK in kidney tissue and podocytes were increased （P<0.05， P<0.01）， and the protein expressions of Desmin， Bax， cleaved Caspase-3， and NR3C2 were down-regulated （P<0.05， P<0.01）. ConclusionQYYY improves aldosterone-induced podocyte injury by regulating the NR3C2/ROS/ERK pathway.

Objective To investigate the efficacy and safety of camrelizumab monoclonal antibody combined with molecular-targeted therapy in elderly patients with unresectable or advanced hepatocellular carcinoma(HCC).Methods A retrospective analysis was performed for the patients with unresectable/advanced HCC who attended six hospitals from January 1,2019 to March 31,2021,and all patients received camrelizumab monoclonal antibody treatment,among whom 84.8%also received targeted therapy.According to the age of the patients,they were divided into elderly group(≥65 years)and non-elderly group(＜65 years).The two groups were assessed in terms of overall survival(OS),progression-free survival(PFS),objective response rate(ORR),disease control rate(DCR),and immune-related adverse events(irAE).The chi-square test or the Fisher's exact test was used for comparison of categorical data between groups;the independent samples t-test was used for comparison of normally distributed continuous data,and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups.The Kaplan-Meier method was used for survival analysis,and the log-rank test was used for comparison of survival curves.Univariate and multivariate Cox proportional hazards regression analyses were used to determine the independent influencing factors for PFS and DCR at 6 months.Results A total of 99 HCC patients were enrolled,with 27 in the elderly group and 72 in the non-elderly group.The elderly group had an OS rate of 67.8%,an ORR of 44.4%,and a DCR of 74.1%at 12 months and a median PFS of 6.4(95%confidence interval[CI]:3.0-12.4)months,with no significant differences compared with the non-elderly group(all P＞0.05).The median OS was unavailable for the elderly group,while the non-elderly group had an OS of 18.9(95%CI:13.0-24.8)months;there was no significant difference between the two groups(P=0.485).The univariate and multivariate Cox regression analyses showed that major vascular invasion(MVI)was an independent risk factor for PFS(hazard ratio[HR]=2.603,95%CI:1.136-5.964,P=0.024)and DCR(HR=3.963,95%CI:1.671-9.397,P=0.002)at 6 months,while age,sex,etiology of HBV infection,presence of extrahepatic metastasis,Child-Pugh class B,and alpha-fetoprotein＞400 ng/mL were not associated with PFS or DCR at 6 months.For the elderly group,the incidence rates of any irAE and grade 3/4 irAE were 51.9%and 25.9%,respectively,with no significant differences compared with the non-elderly group(P＞0.05),and skin disease was the most common irAE in both groups(39.4%).Conclusion Camrelizumab monoclonal antibody combined with molecular-targeted therapy has similar efficacy and safety in patients with unresectable/advanced HCC aged≥65 years and those aged＜65 years.MVI is associated with suboptimal response to immunotherapy and poor prognosis.

Objective: To analyze the epidemiological and etiological characteristics of foodborne diseases in Karamay City, Xinjiang Uygur Autonomous Region from 2018 to 2022, so as to provide insights into formulation of foodborne disease control measures. Methods: Active surveillance data of foodborne disease cases in Karamay City from 2018 to 2022 were collected from Foodborne Disease Monitoring and Reporting System. Population distribution, temporal distribution, spatial distribution, etiological characteristics and history of suspicious food exposure of foodborne diseases were descriptively analyzed. Results: A total of 715 cases with foodborne diseases were reported in Karamay City from 2018 to 2022, and 672 samples were detected, with a sampling rate of 93.99% and a positive rate of 4.17%. Positive rates of detected pathogens showed an increasing trend from 2018 to 2022 (P<0.05). There were 352 men (49.23%) and 363 women (50.77%), 272 cases (38.04%) were at ages of 20 to 39 years, and 225 cases (31.47%) were workers. The detection of foodborne diseases was concentrated during the period between November and December (312 cases, 43.64%), followed by the period between July and August (209 cases, 29.23%). The main clinical symptoms were digestive system symptoms (700 cases, 97.90%). Norovirus were detected (28 cases), while Salmonella, Shigella, Vibrio parahaemolyticus and diarrheagenic Escherichia coli were not detected. The suspicious food exposure was predominantly meat and meat products (211 cases, 29.51%), and the suspicious food exposure place was predominantly at food service establishments (350 cases, 48.95%). Conclusions Foodborne diseases were highly prevalent during the period between November and December and between July and August in Karamay City from 2018 to 2022. Residents at ages of 20 to 39 years and workers are high-risk populations. Meat and meat products are the main suspicious food products and dining places are the main exposed places.

The pathogenesis of depression is complex, and some existing monoamine antidepressants have problems such as drug resistance or off-target failure. Traditional Chinese medicine has the characteristics of "multi-component and multi-target", and has been used in the treatment of depression in clinical practice. Yueju pill is effective in the treatment of depression. Geniposide and ligustrazine, the active ingredients of Gardeniae fructus and Ligusticum sinense 'Chuanxiong', play a key role in the treatment of depression. In this study, based on the neuroprotective activity of genipin and the rapid antidepressant activity of tetramethylpyrazine, a series of novel genipin derivatives were designed and synthesized through pharmacophore assembly principle, and their neuroprotective activity and antidepressant effect were investigated. The results showed that the novel genipin derivatives had well neuroprotective activity on the glutamate-induced HT-22 cell model, with compounds W-1 and W-3 showing better protective activity. In behavioral despair depression (BDD) model mice, compound W-3 was found to have better antidepressant activity than W-1 in tail suspension test and forced swimming test. Further study on the behavior of chronic unpredictable mild stress (CUMS) model mice showed that W-3 could significantly improve the depression-like behavior of model mice. All animal experiments were approved by the Experimental Animal Ethics Committee of Anhui University of Chinese Medicine (approval number: AHUCM-mouse-2022027). The effects of the preferred compound W-3 on protein kinase A (PKA), cAMP response element binding protein (CREB), brain-derived neurotrophic factor (BDNF), 5-hydroxytryptamine 1A (5-HT_1A) receptor, N-methyl-D-aspartate ionic glutamate receptor 2A (GluN2A) and N-methyl-D-aspartate ionic glutamate receptor 2B (GluN2B) were analyzed by Western blot. W-3 treatment significantly up-regulated the protein expression of PKA, CREB, BDNF and 5-HT_1A, and down-regulated the protein expression of GluN2A and GluN2B. The results of qRT-PCR were consistent with those of Western blot. According to the above results, compound W-3 has a potential antidepressant effect, and its mechanism may be related to the activation of PKA-CREB-BDNF signaling pathway by regulating the expression of GluN2A, GluN2B and 5-HT_1A receptor proteins.