This article summarizes the domestic and international research progress of recombinant human follicle stimulating hormone(rFSH).According to relevant guidelines and application cases,the general requirements and common problems for non-clinical evaluation of rFSH are summarized.The clinical development prospects of long-acting rFSH products which is a hot research topic in recent years are analyzed and corresponding suggestions are given in order to provide reference for related work.

Objective This study aimed to investigate the potential relationship between urinary metals copper (Cu), arsenic (As), strontium (Sr), barium (Ba), iron (Fe), lead (Pb) and manganese (Mn) and grip strength. Methods We used linear regression models, quantile g-computation and Bayesian kernel machine regression (BKMR) to assess the relationship between metals and grip strength.Results In the multimetal linear regression, Cu (β=-2.119), As (β=-1.318), Sr (β=-2.480), Ba (β=0.781), Fe (β= 1.130) and Mn (β=-0.404) were significantly correlated with grip strength (P < 0.05). The results of the quantile g-computation showed that the risk of occurrence of grip strength reduction was -1.007 (95％ confidence interval:-1.362, -0.652; P < 0.001) when each quartile of the mixture of the seven metals was increased. Bayesian kernel function regression model analysis showed that mixtures of the seven metals had a negative overall effect on grip strength, with Cu, As and Sr being negatively associated with grip strength levels. In the total population, potential interactions were observed between As and Mn and between Cu and Mn (Pinteractions of 0.003 and 0.018, respectively).Conclusion In summary, this study suggests that combined exposure to metal mixtures is negatively associated with grip strength. Cu, Sr and As were negatively correlated with grip strength levels, and there were potential interactions between As and Mn and between Cu and Mn.

Objective To observe the clinical effect of Dongjing Tiaoshen Comprehensive Therapy combined with computerized cognitive behavioral therapy for insomnia(CCBT-I)in the treatment of chronic insomnia patients with liver depression and spleen deficiency syndrome.Methods A total of 60 patients with chronic insomnia of liver depression and spleen deficiency type were randomly divided into observation group and control group,30 cases in each group.Both groups of patients were treated with CCBT-I as the basic treatment,the observation group was additionally treated with Dongjing Tiaoshen Comprehensive Therapy,i.e.,mind-regulating acupuncture therapy combined with regular aerobic exercises and Dantian Qigong exercises,and the control group was additionally treated with cranial electrotherapy stimulation.The course of treatment for the two groups covered 4 weeks.The changes of Pittsburgh Sleep Quality Index(PSQI)score,Self-rating Anxiety Scale(SAS)score and Self-rating Depression Scale(SDS)score in the two groups were observed before and after treatment,and the clinical efficacy of the two groups was evaluated after treatment.Results(1)After 4 weeks of treatment,the total effective rate of the observation group was 86.67%(26/30),and that of the control group was 70.00%(21/30).The intergroup comparison(tested by rank sum test)showed that the curative effect of the observation group was significantly superior to that of the control group,and the difference was statistically significant(P＜0.05).(2)After treatment,the PSQI scores of the two groups were significantly lower than those before treatment(P＜0.05),and the decrease of PSQI scores in the observation group was significantly superior to that in the control group,the difference being statistically significant(P＜0.05).(3)After treatment,the SAS and SDS scores of the two groups were significantly lower than those before treatment(P＜0.05),and the decrease of SAS and SDS scores in the observation group tended to be superior to that in the control group,but there was no significant difference between the two groups(P＞0.05).Conclusion For the treatment of chronic insomnia of liver depression and spleen deficiency type,the combination of Dongjing Tiaoshen Comprehensive Therapy with CCBT-I can significantly improve the sleep quality,relieve anxiety and depression,and improve the quality of life of the patients,which exerts significant efficacy.

Objective:To develop a risk prediction model for identifying bronchopulmonary dysplasia (BPD) associated pulmonary hypertension (PH) in very premature infants.Methods:This was a retrospective cohort study. The clinical data of 626 very premature infants whose gestational age <32 weeks and who suffered from BPD were collected from October 1 st, 2015 to December 31 st, 2021 of the Seventh Medical Center of the People′s Liberation Army General Hospital as a modeling set. The clinical data of 229 very premature infants with BPD of Hunan Children′s Hospital from January 1 st, 2020 to December 31 st, 2021 were collected as a validation set for external verification. The very premature infants with BPD were divided into PH group and non PH group based on the echocardiogram after 36 weeks′ corrected age in the modeling set and validation set, respectively. Univariate analysis was used to compare the basic clinical characteristics between groups, and collinearity exclusion was carried out between variables. The risk factors of BPD associated PH were further screened out by multivariate Logistic regression, and the risk assessment model was established based on these variables. The receiver operating characteristic (ROC) area under curve (AUC) and Hosmer-Lemeshow goodness-of-fit test were used to evaluate the model′s discrimination and calibration power, respectively. And the calibration curve was used to evaluate the accuracy of the model and draw the nomogram. The bootstrap repeated sampling method was used for internal verification. Finally, decision curve analysis (DCA) to evaluate the clinical practicability of the model was used. Results:A total of 626 very premature infants with BPD were included for modeling set, including 85 very premature infants in the PH group and 541 very premature infants in the non PH group. A total of 229 very premature infants with BPD were included for validation set, including 24 very premature infants in the PH group and 205 very premature infants in the non PH group. Univariate analysis of the modeling set found that 22 variables, such as artificial conception, fetal distress, gestational age, birth weight, small for gestational age, 1 minute Apgar score ≤7, antenatal corticosteroids, placental abruption, oligohydramnios, multiple pulmonary surfactant, neonatal respiratory distress syndrome (NRDS)>stage Ⅱ, early pulmonary hypertension, moderate-severe BPD, and hemodynamically significant patent ductus arteriosus (hsPDA) all had statistically significant influence between the PH group and the non PH group (all P<0.05). Antenatal corticosteroids, fetal distress, NRDS >stage Ⅱ, hsPDA, pneumonia and days of invasive mechanical ventilation were identified as predictive variables and finally included to establish the Logistic regression model. The AUC of this model was 0.86 (95% CI 0.82-0.90), the cut-off value was 0.17, the sensitivity was 0.77, and the specificity was 0.84. Hosmer-Lemeshow goodness-of-fit test showed that P>0.05. The AUC for external validation was 0.88, and the Hosmer-Lemeshow goodness-of-fit test suggested P>0.05. Conclusions:A high sensitivity and specificity risk prediction model of PBD associated PH in very premature infants was established. This predictive model is useful for early clinical identification of infants at high risk of BPD associated PH.

Objective:To evaluate the efficiency of the four domestic language models,ERNIE Bot,ChatGLM2,Spark Desk and Qwen-14B-Chat,all with a massive user base and significant social attention,in response to consultations about PCa-related perio-perative nursing and health education.Methods:We designed a questionnaire that includes 15 questions commonly concerned by patients undergoing radical prostatectomy and 2 common nursing cases,and inputted the questions into each of the four language models for simulation consultation.Three nursing experts assessed the model responses based on a pre-designed Likert 5-point scale in terms of accuracy,comprehensiveness,understandability,humanistic care,and case analysis.We evaluated and compared the performance of the four models using visualization tools and statistical analyses.Results:All the models generated high-quality texts with no mis-leading information and exhibited satisfactory performance.Qwen-14B-Chat scored the highest in all aspects and showed relatively sta-ble outputs in multiple tests compared with ChatGLM2.Spark Desk performed well in terms of understandability but lacked comprehen-siveness and humanistic care.Both Qwen-14B-Chat and ChatGLM2 demonstrated excellent performance in case analysis.The overall performance of ERNIE Bot was slightly inferior.All things considered,Qwen-14B-Chat was superior to the other three models in con-sultations about PCa-related perioperative nursing and health education.Conclusion:In PCa-related perioperative nursing,large language models represented by Qwen-14B-Chat are expected to become powerful auxiliary tools to provide patients with more medical expertise and information support,so as to improve the patient compliance and the quality of clinical treatment and nursing.

The methanol extract of Huperzia serrata was separated and purified by ODS, AB-8 macroporous adsorption resin, dextran gel Sephadex LH-20 and silica gel column chromatography combined with the semi-pre HPLC. The chemical structures of the isolated compounds were identified by MS, IR, NMR, etc. Four compounds were isolated from Huperzia serrata and identified, named as serratinine C (1), lycobeline C (2), diphaladin A (3) and crenatine (4). Compound 1 is a new alkaloid, compounds 2-4 were isolated for the first time. In vitro biological activity experiments showed that compound 1 could significantly reduce the levels of nitric oxide and reactive oxygen species in glial cells induced by lipopolysaccharide and had significant antioxidant biological activity.

In order to investigate the effects of asiaticoside (Ass) on H9C2 cardiomyocytes, the present study examined the potential intervention of Ass on the proliferation and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/Bcl-2 homology domain protein (Beclin-1) signaling pathway in H9C2 cardiomyocytes following oxygen and glucose deprivation/reperfusion (OGD/R) injury. H9C2 cardiomyocytes were selected as the research objects, and the activity of H9C2 was detected by cell counting kit-8 (CCK-8). H9C2 cells were divided into control group, OGD/R group, Ass low concentration group (10 μmol·L^-1), Ass high concentration group (80 μmol·L^-1) and Ass high concentration + chloroquine group (80 μmol·L^-1 + 50 μmol·L^-1). The control group was cultured under normal conditions, and the other groups were treated with oxygen and glucose deprivation for 4 h and reperfusion for 2 h. The activity and content of aspartic aminotransferase (AST), lactate dehydrogenase (LDH) and creatine kinase (CK) in the supernatant of H9C2 cardiomyocytes were detected by enzyme-linked immunosorbent assay. Autophagy staining assay kit with monodansylcadaverine (MDC) method to observe cellular autophagy; molecular docking technique to identify the molecular targets of Ass. Immunofluorescence was used to observe the effect of the drug on cell number. The expression levels of PI3K, Akt, selective autophagy adaptor protein (P62) and Beclin-1 were detected by Western blot. Compared with OGD/R group, Ass group had a protective effect from 10-80 μmol·L^-1, and the activities and contents of AST, LDH and CK were decreased. The protein expression levels of PI3K, Akt, P62 and Beclin-1 were decreased. Compared with the administration group, the activities and contents of AST, LDH and CK in Ass high-concentration + chloroquine group were significantly decreased, and the protein expression levels of PI3K, Akt, Beclin-1 and P62 were significantly decreased. Immunofluorescence showed that the inhibitor group and each administration group had different degrees of protective effect compared with the model group. Asiaticoside can reduce the injury of H9C2 cardiomyocyte induced by OGD/R, reduce the content of AST, LDH and CK, reduce the expression level of P62 protein, and reduce autophagy, which may be closely related to the inhibition of PI3K/Akt/Beclin-1 signaling pathway activation.

Objective: This cross-sectional investigation aimed to determine the incidence, clinical characteristics, prognosis, and related risk factors of olfactory and gustatory dysfunctions related to infection with the SARS-CoV-2 Omicron strain in mainland China. Methods: Data of patients with SARS-CoV-2 from December 28, 2022, to February 21, 2023, were collected through online and offline questionnaires from 45 tertiary hospitals and one center for disease control and prevention in mainland China. The questionnaire included demographic information, previous health history, smoking and alcohol drinking, SARS-CoV-2 vaccination, olfactory and gustatory function before and after infection, other symptoms after infection, as well as the duration and improvement of olfactory and gustatory dysfunction. The self-reported olfactory and gustatory functions of patients were evaluated using the Olfactory VAS scale and Gustatory VAS scale. Results: A total of 35 566 valid questionnaires were obtained, revealing a high incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain (67.75%). Females(χ2=367.013, P<0.001) and young people(χ2=120.210, P<0.001) were more likely to develop these dysfunctions. Gender(OR=1.564, 95%CI: 1.487-1.645), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), oral health status (OR=0.881, 95%CI: 0.839-0.926), smoking history (OR=1.152, 95%CI=1.080-1.229), and drinking history (OR=0.854, 95%CI: 0.785-0.928) were correlated with the occurrence of olfactory and taste dysfunctions related to SARS-CoV-2(above P<0.001). 44.62% (4 391/9 840) of the patients who had not recovered their sense of smell and taste also suffered from nasal congestion, runny nose, and 32.62% (3 210/9 840) suffered from dry mouth and sore throat. The improvement of olfactory and taste functions was correlated with the persistence of accompanying symptoms(χ2=10.873, P=0.001). The average score of olfactory and taste VAS scale was 8.41 and 8.51 respectively before SARS-CoV-2 infection, but decreased to3.69 and 4.29 respectively after SARS-CoV-2 infection, and recovered to 5.83and 6.55 respectively at the time of the survey. The median duration of olfactory and gustatory dysfunctions was 15 days and 12 days, respectively, with 0.5% (121/24 096) of patients experiencing these dysfunctions for more than 28 days. The overall self-reported improvement rate of smell and taste dysfunctions was 59.16% (14 256/24 096). Gender(OR=0.893, 95%CI: 0.839-0.951), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), history of head and facial trauma(OR=1.180, 95%CI: 1.036-1.344, P=0.013), nose (OR=1.104, 95%CI: 1.042-1.171, P=0.001) and oral (OR=1.162, 95%CI: 1.096-1.233) health status, smoking history(OR=0.765, 95%CI: 0.709-0.825), and the persistence of accompanying symptoms (OR=0.359, 95%CI: 0.332-0.388) were correlated with the recovery of olfactory and taste dysfunctions related to SARS-CoV-2 (above P<0.001 except for the indicated values). Conclusion: The incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain is high in mainland China, with females and young people more likely to develop these dysfunctions. Active and effective intervention measures may be required for cases that persist for a long time. The recovery of olfactory and taste functions is influenced by several factors, including gender, SARS-CoV-2 vaccination status, history of head and facial trauma, nasal and oral health status, smoking history, and persistence of accompanying symptoms.
Female ; Humans ; Adolescent ; SARS-CoV-2 ; Smell ; COVID-19/complications* ; Cross-Sectional Studies ; COVID-19 Vaccines ; Incidence ; Olfaction Disorders/etiology* ; Taste Disorders/etiology* ; Prognosis

Background and Objectives: Osteoblasts are derived from bone marrow mesenchymal stem cells (BMMSCs) and playimportant role in bone remodeling. While our previous studies have investigated the cell subtypes and heterogeneity in osteoblasts and BMMSCs separately, cell-to-cell communications between osteoblasts and BMMSCs in vivo in humans have not been characterized. The aim of this study was to investigate the cellular communication between human primary osteoblasts and bone marrow mesenchymal stem cells. Methods: and Results: To investigate the cell-to-cell communications between osteoblasts and BMMSCs and identifynew cell subtypes, we performed a systematic integration analysis with our single-cell RNA sequencing (scRNA-seq) transcriptomes data from BMMSCs and osteoblasts. We successfully identified a novel preosteoblasts subtype which highly expressed ATF3, CCL2, CXCL2 and IRF1. Biological functional annotations of the transcriptomes suggested that the novel preosteoblasts subtype may inhibit osteoblasts differentiation, maintain cells to a less differentiated status and recruit osteoclasts. Ligand-receptor interaction analysis showed strong interaction between mature osteoblasts and BMMSCs. Meanwhile, we found FZD1 was highly expressed in BMMSCs of osteogenic differentiation direction. WIF1 and SFRP4, which were highly expressed in mature osteoblasts were reported to inhibit osteogenic differentiation. We speculated that WIF1 and sFRP4 expressed in mature osteoblasts inhibited the binding of FZD1 to Wnt ligand in BMMSCs, thereby further inhibiting osteogenic differentiation of BMMSCs. Conclusions Our study provided a more systematic and comprehensive understanding of the heterogeneity of osteogenic cells. At the single cell level, this study provided insights into the cell-to-cell communications between BMMSCs and osteoblasts and mature osteoblasts may mediate negative feedback regulation of osteogenesis process.

AIM: To investigate the effects of curcumin on the proliferation and apoptosis and migration of human pterygium fibroblasts(HPF)in vitro.METHODS: A total of 7 cases of pterygium tissue removed at our hospital from November 24, 2021 to December 16, 2021 were collected. Then, primary fibroblasts were cultured in vitro and identified by immunofluorescence staining. HPF were treated with 0, 10, 20, 40, 80 and 160μmol/L curcumin containing equal amount of dimethyl sulfoxide for 24h, then the cell proliferation was detected by CCK8 assay. According to the results of CCK8, the cells were divided into control group, 20μmol/L curcumin group and 40μmol/L curcumin group, and the cells were treated with corresponding concentration of curcumin for 24h in each group. Flow cytometry was used to detect apoptosis, Transwell migration assay was used to detect cell migration, and real-time fluorescence quantitative polymerase chain reaction and Western blot were used to detect the expression of mRNA and protein of B-cell lymphoma-2 associated X protein(Bax), B-cell lymphoma-2(Bcl-2), Cyclin D1 and matrix metalloproteinase 2(MMP2).RESULTS: Compared with the control group, both 20μmol/L curcumin group and 40μmol/L curcumin group can inhibit the proliferation and migration of HPF and induce its apoptosis(all P<0.05). Compared with the control group, 20μmol/L curcumin group can down-regulate the mRNA expression of Cyclin D1 and MMP2, up-regulate the mRNA expression of Bax, and down-regulate the protein expression of Bcl-2(all P<0.05). Compared with the control group, 40μmol/L curcumin group can down-regulate the expression of mRNA and protein of Bcl-2, Cyclin D1 and MMP2, and up-regulate the expression of mRNA and protein of Bax(all P<0.05). Compared with 20 μmol/L curcumin group, the 40 μmol/L curcumin group can down-regulate the mRNA expression of MMP2, down-regulate the protein expression of Bcl-2, and up-regulate the mRNA and protein expression of Bax(all P<0.05).CONCLUSION: Curcumin can inhibit the proliferation of HPF by inhibiting the expression of Cyclin D1, induce the apoptosis of HPF by down-regulating Bcl-2 and up-regulating the expression of Bax, and inhibit the migration of HPF by down-regulating the expression of MMP2.