ObjectiveWith the development of society and the increasing demand for pregnancy at an advanced age， diminished ovarian reserve （DOR） has attracted wider attention. This disease affects the normal menstruation of women and poses a threat to their mental health. Current research on DOR is still in the initial stage， and advancing research progress in DOR necessitates the construction of effective and clinically relevant animal models. Building on existing literature and integrating the diagnosis criteria of DOR in traditional Chinese medicine （TCM） and Western medicine， this study summarized， analyzed， and evaluated existing models， providing a reference for optimizing DOR animal models. MethodsA retrospective analysis of literature on DOR-related animal models was conducted， and the diagnostic criteria of DOR in TCM and Western medicine were sorted out. By means of evaluation methods of animal models， the clinical relevance of each model to TCM and Western medicine was assessed. ResultsDOR animal models included those based on natural factors， iatrogenic factors， immune factors， metabolic factors， and environmental factors. Among them， the model based on iatrogenic factors， especially models induced by Tripterygium wilfordii preparations， cyclophosphamide， and cisplatin， had a high degree of relevance to both Western medical diseases and TCM syndromes and was confirmed as the optimal modeling method for studying DOR at present. ConclusionThe existing DOR modeling methods mostly have a high degree of clinical relevance to Western medical diseases， while the number of DOR animal models with clear TCM syndromes is very limited. TCM plays an indispensable role in exploring DOR treatment methods. Therefore， the development of DOR animal models related to TCM syndromes should be strengthened， further exploring the potential of TCM and providing strong theoretical support for the application of TCM in DOR treatment.

Objective To retrospectively analyze the epidemiological trend of children with lower gastrointestinal bleeding in recent 10 years,and investigate the change of their disease burden,so as to provide a theoretical basis for the accurate prevention and control of children's lower gastrointestinal bleeding. Methods A total of 671 children with "lower gastrointestinal bleeding" who were diagnosed in our hospital from 2012 to 2021 were collected as research subjects. To analyze the microscopic examination rate and common etiology of lower gastrointestinal bleeding in children in the past 10 years,as well as the epidemiological characteristics of different age groups, different regions and different basic diseases; Calculate and compare the rate of disability life lost (YLD), early death life lost (YLL) and disability adjusted life year (DALY) of children with lower gastrointestinal bleeding within 10 years, and calculate the annual change percentage (AAPC) to analyze the change trend of disease burden. Results The microscopic examination rate of children with lower gastrointestinal bleeding showed a trend of increasing in the past 10 years (P<0.001). Among them, the most common causes are Crohn's disease, ulcerative colitis and chronic colitis. The proportion of children with lower gastrointestinal bleeding was higher in boys, >18 years old, hypertension and gastroenteritis. The DALY rate, YLL rate and YLD rate caused by lower gastrointestinal bleeding in the past 10 years showed an upward trend (P<0.05). Conclusion The microscopic examination rate of lower gastrointestinal bleeding in children was graduallyincreasing,and the prevalence rate of basic diseases such as boys,hypertension and gastroenteritis was increasing;in addition,the disease burden caused by children's lower gastrointestinal bleeding was also increasing year by year and should be protected.

At present, the late diagnosis of HIV-infected patients is not optimistic, which has a significant impact on the efficacy, cost, and prognosis of HIV antiretroviral therapy and HIV transmission. Late diagnosis is an important indicator for evaluating HIV testing. This article reviews the influencing factors of late diagnosis of HIV-infected patients and provides a reference for formulating and improving HIV testing strategies and measures in China.

Objective To investigate the correlation between serum C1q/tumor necrosis factor related protein 9(CTRP9)and soluble CD146(sCD146)levels and coronary artery lesions(CAL)in children with Kawasaki disease(KD).Methods A total of 116 children with KD admitted to the People's Hospital of Kaizhou District,CQ from October 2020 to February 2023 were selected as the study subjects(KD group).According to the ultrasound diagnosis results,children with KD were grouped into CAL group(n=40)and non CAL group(n=76).According to the severity of CAL,children with KD in the CAL group were separated into mild group(n=14),moderate group(n=18)and severe group(n=8).Enzyme linked immunosorbent assay(ELISA)was applied to measure serum levels of CTRP9 and sCD146.The differences in serum levels of CTRP9 and sCD146 in control group,CAL group,non CAL,and children with different severity of CAL were compared.Multiple Logistic regression was applied to analyze the factors affecting the occurrence of CAL in children with KD.Receiver operating characteristic(ROC)curve was applied to analyze the predictive value of serum CTRP9 and sCD146 levels for the occurrence of CAL in KD children.Results Compared with the control group,the serum CTRP9 level in the KD group was decreased(3.27±0.27ng/ml vs 3.79±0.91ng/ml),while the sCD146 level was increased(191.28±50.39 ng/ml vs 143.97±38.29 ng/ml),with significant differences(t=5.900,8.051,all P＜0.05).The serum CTRP9 level in the CAL group was lower than that in the non CAL group(3.01±0.23ng/ml vs 3.41±0.29 ng/ml),but the sCD146 level was higher than that in the non CAL group(232.18±59.37 ng/ml vs 169.76±45.66 ng/ml),with significant differences(t=7.557,6.294,all P＜0.05).Compared with the mild group,the serum CTRP9 level in the moderate and severe groups was decreased(q=3.277,6.281),with sCD146 level increased(q=3.154,5.551),the serum CTRP9 level in the severe group was lower than that in the moderate group(q=3.845),with sCD146 level was higher than that in the moderate group(q=3.145),and the differences were statistically significant(all P＜0.05).The results of multivariate logistic regression analysis showed that white blood cell count(WBC),erythrocyte sedimentation rate(ESR),C reactive protein(CRP),CTRP9 and sCD146 were all influencing factors for the occurrence of CAL in children with KD(all P＜0.05).The results of ROC curve showed that the AUCs of CTRP9 and sCD146 separately predicted the occurrence of CAL in KD children were 0.781 and 0.782,with sensitivity of 82.5％and 67.5％,and specificity of 52.2％and 55.7％,respectively.The AUC for the combined diagnosis of CAL in children with KD was 0.889,with sensitivity and specificity of 97.5％and 65.9％,respectively.Conclusion Serum CTRP9 and sCD146 were influencing factors for the occurrence of CAL in children with KD,and the level of CTRP9 was decreased,while sCD146 was increased in the serum of children with CAL.The combination of the two can effectively predict the occurrence of CAL in children with KD.

Objective To explored the correlation between diabetic kidney disease(DKD)and MRI of cerebral small vessel disease(CSVD).Methods 476 type 2 diabetes mellitus(T2DM)patients who were hospitalized in Chengdu University of Traditional Chinese Medicine Affiliated Hospital from January to August 2022 were selected and divided into simple T2DM group(UACR＜30 mg/g,n=330)and DKD group(UACR≥30 mg/g,n=146).General data,biochemical indicators and head MRI images of the two groups were compared.The correlation between DKD and CSVD and the influencing factors of white matter hyperintensities(WMHs)severity were analyzed.Results Age,DM duration,TG,Scr,HbA1c,SUA,cystatin C(Cys C),fibrinogen(Fib)and the incidence of hypertension were higher(P<0.05),while the ALT was lower in DKD group than in T2DM group(P<0.05).Spearman correlation analysis showed tha the presence of DKD was positively correlated with WMHs,lacunar infarction(LI)and brain atrophy(P<0.05).eGFR was negatively correlated with WMHs,LI and brain atrophy(P<0.05).Logistic regression analysis showed that age and HbA1c were the influencing factors for the severity of WMHs.Conclusion Patients with DKD have a higher incidence of CSVD,which may be related to worsening renal function.HbA1c may have predictive value for the severity of WMHs.

Somatostatin (SST) is an inhibitory polypeptide hormone that plays an important role in a variety of biological processes. Somatostatin receptor 2 (SSTR2) is the most widely expressed somatostatin receptor. However, the specific cell types expressing Sstr2 in the tissues have not been investigated. In this study, we detected the expression pattern of SSTR2 protein in mouse at different development stages, including the embryonic 15.5 days and the postnatal 1, 7, 15 days as well as 3 and 6 months, by multicolour immunofluorescence analyses. We found that Sstr2 was expressed in some specific cells types of several tissues, including the neuronal cells and astrocytes in the brain, the mesenchymal cells, the hematopoietic cells, the early hematopoietic stem cells, and the B cells in the bone marrow, the macrophages, the type Ⅱ alveolar epithelial cells, and the airway ciliated cells in the lung, the epithelial cells and the neuronal cells in the intestine, the hair follicle cells, the gastric epithelial cells, the hematopoietic stem cells and the nerve fibre in the spleen, and the tubular epithelial cells in the kidney. This study identified the specific cell types expressing Sstr2 in mouse at different developmental stages, providing new insights into the physiological function of SST and SSTR2 in several cell types.
Mice ; Animals ; Receptors, Somatostatin/metabolism* ; Hematopoietic Stem Cells/metabolism* ; Epithelial Cells

The global COVID-19 coronavirus pandemic has infected over 109 million people, leading to over 2 million deaths up to date and still lacking of effective drugs for patient treatment. Here, we screened about 1.8 million small molecules against the main protease (M^pro) and papain like protease (PL^pro), two major proteases in severe acute respiratory syndrome-coronavirus 2 genome, and identified 1851M^pro inhibitors and 205 PL^pro inhibitors with low nmol/l activity of the best hits. Among these inhibitors, eight small molecules showed dual inhibition effects on both M^pro and PL^pro, exhibiting potential as better candidates for COVID-19 treatment. The best inhibitors of each protease were tested in antiviral assay, with over 40% of M^pro inhibitors and over 20% of PL^pro inhibitors showing high potency in viral inhibition with low cytotoxicity. The X-ray crystal structure of SARS-CoV-2 M^pro in complex with its potent inhibitor 4a was determined at 1.8 Å resolution. Together with docking assays, our results provide a comprehensive resource for future research on anti-SARS-CoV-2 drug development.
Humans ; Antiviral Agents/chemistry* ; COVID-19 ; COVID-19 Drug Treatment ; High-Throughput Screening Assays ; Molecular Docking Simulation ; Protease Inhibitors/chemistry* ; SARS-CoV-2/enzymology* ; Viral Nonstructural Proteins

Objective:To observe any effect of using the International Classification of Functioning, Disability and Health (ICF) rehabilitation set in rehabilitating the physical ability of hemiplegic stroke survivors.Methods:Ninety stroke survivors with hemiplegia were selected and randomly divided into an observation group ( n=45) and a control group ( n=45). The observation group was first assessed using the ICF and then given 60 minutes of individualized rehabilitation, 5 or 6 times a week for 4 weeks in addition to a weekly one-hour rehabilitation course. The control group were evaluated and treated traditionally. Before and after the intervention, both groups were evaluated using the Fugl-Meyer exercise assessment (FM) and functional independence assessment (FIM). Results:After the treatment the average upper and lower limb scores as well as the total FM scores had improved significantly. Those of the observation group were then significantly different from the control group′s averages.Conclusion:Basing rehabilitation on the ICF can more effectively improve the physical functioning of hemiplegic stroke survivors.

Objective:To analyze the basic characteristics and change trend of mortality in HIV-infected patients aged ≥60 years in China from 2013 to 2021.Methods:The data of HIV-infected patients aged ≥60 years at diagnosis were collected from China Information System for Disease Control and Prevention to calculate the mortality density. The trajectory model was fitted using the Proc traj process in software SAS 9.4 to explore trajectory of AIDS-related mortality density and non-AIDS-related mortality density under different combinations of region, gender and age.Results:Between 2013 and 2021, a total of 244 770 HIV-infected patients were reported with 40 079 AIDS-related deaths and 50 245 non-AIDS-related deaths. The AIDS-related mortality density was 6.32 per 100 person-years, and the non-AIDS-related mortality density was 7.92 per 100 person-years, both of which showed decreasing trends over the years, and the mortality density in men was higher than that in women. Two developmental trajectories could be categorized for different trends of AIDS-related mortality density: the lower mortality density group accounted for 80.95% and showed a slow decreasing trend; the higher mortality density group accounted for 19.05% and showed a three-curve developmental trend. There were three developmental trajectories of non-AIDS-related mortality density trends: the lower mortality density group accounted for 59.52% and the medium mortality density group accounted for 28.57%, with a flat overall trend in these two groups; the higher mortality density group accounted for 11.91% with a three-curve trend.Conclusions:The mortality in HIV-infected patients aged ≥60 years in China is still high. Further attention should be paid to the early detection, diagnosis and treatment of HIV infection to effectively reduce the density of AIDS-related deaths. At the same time, attention should be paid to non-AIDS-related deaths in the elderly, and comprehensive interventions should be taken. It is necessary to conduct targeted HIV/AIDS prevention and control based on actual situation in different areas and populations

Objective:To explore the clinical efficacy and safety of the camrelizumab combined with apatinib and chemotherapy as second-line or later therapy in human epidermal growth factor receptor-2 (HER-2) negative advanced gastric cancer.Methods:A total of 66 patients with HER-2 negative advanced gastric cancer and first-line treatment failure in Shandong Cancer Hospital Affiliated to Shandong First Medical University from March 2018 to September 2021 were selected. They were divided into study group ( n=22) and control group ( n=44) according to the different treatment regimens. The patients in the study group were treated with camrelizumab combined with apatinib and chemotherapy, and the patients in the control group were treated with chemotherapy alone. The short-term efficacy, progression-free survival (PFS) , overall survival (OS) and the occurrence of adverse reactions were compared, and Cox regression analysis was used to analyze the influencing factors of prognosis. Results:After at least 2-4 cycles of treatment, the ORR in the study group and the control group were 9.1% (2/22) and 0 (0/44) respectively, with no statistically significant difference ( P=0.108) . DCR in the two groups were 77.3% (17/22) and 45.5% (20/44) respectively, with a statistically significant difference ( χ2=6.03, P=0.014) . The study group didn’t reach median OS and the median OS in the control group was 11.7 months, with no statistically significant difference ( χ2=1.59, P=0.207) . The study group didn’t reach median PFS and the median PFS in the control group was 3.2 months, with a statistically significant difference ( χ2=10.13, P=0.001) . Multivariate Cox regression analysis showed that treatment method was an independent influencing factor for PFS in patients with HER-2 negative advanced gastric cancer ( HR=0.33, 95% CI: 0.15-0.75, P=0.008) . In terms of adverse reactions, there was a statistically significant difference in the incidence of elevated alanine aminotransferase between the study group and the control group [31.8% (7/22) vs. 6.8% (3/44) , χ2=5.32, P=0.021]. There were no adverse-related deaths in both groups. Conclusion:Compared with chemotherapy alone, camrelizumab combined with apatinib and chemotherapy as a second-line or later therapy in HER-2 negative advanced gastric cancer can prolong PFS and improve DCR, but the incidence of elevated alanine aminotransferase increases significantly.