Umbilical cord mesenchymal stem cells (UC-MSCs) have been widely used in regenerative medicine, but there is limited research on the stability of UC-MSCs formulation during production. This study aims to assess the stability of the cell stock solution and intermediate product throughout the production process, as well as the final product following reconstitution, in order to offer guidance for the manufacturing process and serve as a reference for formulation reconstitution methods. Three batches of cell formulation were produced and stored under low temperature (2-8 ℃) and room temperature (20-26 ℃) during cell stock solution and intermediate product stages. The storage time intervals for cell stock solution were 0, 2, 4, and 6 h, while for intermediate products, the intervals were 0, 1, 2, and 3 h. The evaluation items included visual inspection, viable cell concentration, cell viability, cell surface markers, lymphocyte proliferation inhibition rate, and sterility. Additionally, dilution and culture stability studies were performed after reconstitution of the cell product. The reconstitution diluents included 0.9% sodium chloride injection, 0.9% sodium chloride injection + 1% human serum albumin, and 0.9% sodium chloride injection + 2% human serum albumin, with dilution ratios of 10-fold and 40-fold. The storage time intervals after dilution were 0, 1, 2, 3, and 4 h. The reconstitution culture media included DMEM medium, DMEM + 2% platelet lysate, 0.9% sodium chloride injection, and 0.9% sodium chloride injection + 1% human serum albumin, and the culture duration was 24 h. The evaluation items were viable cell concentration and cell viability. The results showed that the cell stock solution remained stable for up to 6 h under both low temperature (2-8 ℃) and room temperature (20-26 ℃) conditions, while the intermediate product remained stable for up to 3 h under the same conditions. After formulation reconstitution, using sodium chloride injection diluted with 1% or 2% human serum albumin maintained a viability of over 80% within 4 h. It was observed that different dilution factors had an impact on cell viability. After formulation reconstitution, cultivation in medium with 2% platelet lysate resulted in a cell viability of over 80% after 24 h. In conclusion, the stability of cell stock solution within 6 h and intermediate product within 3 h meets the requirements. The addition of 1% or 2% human serum albumin in the reconstitution diluent can better protect the post-reconstitution cell viability.

Objective To evaluate the bioequivalence of oral sidenafil citrate tablets manufactured(100 mg)test preparations and reference preparations in healthy subjects under fasting and fed conditions.Methods Using a single-dose,randomized,open-lable,two-period,two-way crossover design,36 healthy subjects respectively for fasting and fed study were enrolled,and randomized into two groups to receive a single dose of test 100 mg with 7-day washout period.Plasma concentration of sidenafil and N-demethylsildenafil was determined by liquid chromatography-tandem mass spectrometry(LC-MS/MS)method.The pharmacokinetic parameters were calculated by Analyst 1.6.3(AB Scie)using non-compartmental model,and bioequivalence evaluation was performed for the two preparations.Relevant safety evaluations were performed during the trial.Results The main pharmacokinetic parameters of sidenafil after a single oral dose of sidenafil citrate tablets under fasting condition for test and reference were as follows:Cmax were(494.69±230.94)and(558.78±289.83)ng·mL-1,AUC0-t were(1 336.21±509.78)and(1 410.82±625.99)h·ng·mL-1,AUC0-were(1 366.49±512.16)and(1 441.84±628.04)h·ng·mL-1,respectively.The main pharmacokinetic parameters of sidenafil under fed condition for T and R were as follows:Cmax were(381.89±126.53)and(432.47±175.91)ng·mL-1,AUC0-t were(1 366.34±366.99)and(1 412.76±420.37)h·ng·mL-1,AUC0-were(1 403.28±375.32)and(1 454.13±429.87)h·ng·mL-1,respectively.The results demonstrated the bioequivalence of sidenafil citrate tablets between T and R.The incidence of adverse events in fasting and fed tests were 33.33％and 25.00％,respectively.No serious adverse event was reported.Conclusion The test and reference formulation of sidenafil citrate tablets were equivalent and was safe.

Objective To observe the efficacy and safety of Morinda officinalis oligosaccharides in the continuation treatment of mild and moderate depression.Methods An open,single-arm,multi-center design was adopted in our study.Adult patients with mild and moderate depression who had received acute treatment of Morinda officinalis oligosaccharides were enrolled and continue to receive Morinda officinalis oligosaccharides capsules for 24 weeks,the dose remained unchanged during continuation treatment.The remission rate,recurrence rate,recurrence time,and the change from baseline to endpoint of Hamilton Depression Scale(HAMD),Hamilton Anxiety Scale(HAMA),Clinical Global Impression-Severity(CGI-S)and Arizona Sexual Experience Scale(ASEX)were evaluated.The incidence of treatment-related adverse events was reported.Results The scores of HAMD-17 at baseline and after treatment were 6.60±1.87 and 5.85±4.18,scores of HAMA were 6.36±3.02 and 4.93±3.09,scores of CGI-S were 1.49±0.56 and 1.29±0.81,scores of ASEX were 15.92±4.72 and 15.57±5.26,with significant difference(P＜0.05).After continuation treatment,the remission rate was 54.59％(202 cases/370 cases),and the recurrence rate was 6.49％(24 cases/370 cases),the recurrence time was(64.67±42.47)days.The incidence of treatment-related adverse events was 15.35％(64 cases/417 cases).Conclusion Morinda officinalis oligosaccharides capsules can be effectively used for the continuation treatment of mild and moderate depression,and are well tolerated and safe.

Background/Aims: Cholestatic liver diseases including primary biliary cholangitis (PBC) are associated with active hepatic fibrogenesis, which ultimately progresses to cirrhosis. Activated hepatic stellate cells (HSCs) are the main fibrogenic effectors in response to cholangiocyte damage. JCAD regulates cell proliferation and malignant transformation in nonalcoholic steatoheaptitis-associated hepatocellular carcinoma (NASH-HCC). However, its participation in cholestatic fibrosis has not been explored yet. Methods: Serial sections of liver tissue of PBC patients were stained with immunofluorescence. Hepatic fibrosis was induced by bile duct ligation (BDL) in wild-type (WT), global JCAD knockout mice (JCAD-KO) and HSC-specific JCAD knockout mice (HSC-JCAD-KO), and evaluated by histopathology and biochemical tests. In situ-activated HSCs isolated from BDL mice were used to determine effects of JCAD on HSC activation. Results: In consistence with staining of liver sections from PBC patients, immunofluorescent staining revealed that JCAD expression was identified in smooth muscle α-actin (α-SMA)-positive fibroblast-like cells and was significantly up-regulated in WT mice with BDL. JCAD deficiency remarkably ameliorated BDL-induced hepatic injury and fibrosis, as documented by liver hydroxyproline content, when compared to WT mice with BDL. Histopathologically, collagen deposition was dramatically reduced in both JCAD-KO and HSC-JCAD-KO mice compared to WT mice, as visualized by Trichrome staining and semi-quantitative scores. Moreover, JCAD deprivation significantly attenuated in situ HSC activation and reduced expression of fibrotic genes after BDL. Conclusions JCAD deficiency effectively suppressed hepatic fibrosis induced by BDL in mice, and the underlying mechanisms are largely through suppressed Hippo-YAP signaling activity in HSCs.

OBJECTIVE: To explore the underlying mechanism of inhibition by Jinkui Shenqi Pills (JKSQP) on glucocorticoid-enhanced axial length elongation in experimental lens-induced myopia (LIM) guinea pigs. METHODS: Sixty 2-week old male guinea pigs were randomly divided into 4 groups with 15 guinea pigs in each group, according to the random numbers generated by SPSS software: control, LIM, saline and JKSQP groups. The control group includes animals with no treatment, while the guinea pigs in the other 3 groups received lens-induced myopization on the right eyes throughout the experiment (for 8 weeks). The saline and JKSQP groups were given daily intraperitoneal injections of 10 mg/kg hydrocortisone for 2 consecutive weeks at the same time, and then orally administered either saline or JKSQP [13.5 g/(kg•d) for 6 consecutive weeks. Body weight, anal temperature and animal appearance were observed and recorded to evaluate the GC-associated symptoms. The ocular parameters, including refraction and axial length, were measured by streak retinoscopy and A-scan ultrasonography, respectively. The levels of plasma hormones associated with the hypothalamic-pituitary-adrenal axis (HPAA), including free triiodothyronine, free thyroxine, estradiol and testosterone, were measured by radioimmunoassay, and cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate were measured by enzyme-linked immunosorbent assay. In addition, the mRNA and protein expressions of retinal amphiregulin (AREG) was measured by quantitative real-time polymerase chain reaction and Western blotting, respectively. RESULTS: JKSQP effectively increased body weight and anal temperature, improved animal appearance and suppressed axial length elongation in glucocorticoid-enhanced myopic guinea pigs with normalization of 4 HPAA-associated plasma hormones (all P<0.05). The plasma level of cAMP was significantly increased, whereas the plasma level of cGMP and the mRNA and protein expressions of retinal AREG were decreased after treatment with JKSQP (all P<0.05). CONCLUSION JKSQP exhibited a significant inhibitory effect on axial length elongation with decreased expression of AREG in the retina, and normalized 4 HPAA-associated plasma hormones and the expression of cAMP and cGMP in GC-enhanced myopic guinea pigs.
Guinea Pigs ; Male ; Animals ; Glucocorticoids ; Hypothalamo-Hypophyseal System ; Pituitary-Adrenal System ; Myopia/metabolism* ; Body Weight ; RNA, Messenger ; Disease Models, Animal

Humans ; Child ; Metabolic Diseases/therapy*

Objective: To explore the clinical and chest computed tomography (CT) features and the outcome of immune checkpoint inhibitor-related pneumonitis (CIP). Methods: Clinical and chest CT data of 38 CIP patients with malignant tumors from the Cancer Hospital, Chinese Academy of Medical Sciences between August 2017 and April 2021 were retrospectively reviewed, and the outcomes of pneumonitis were followed up. Results: The median time from the administration of immune checkpoint inhibitors (ICIs) to the onset of CIP was 72.5 days in 38 patients with CIP, and 22 patients developed CIP within 3 months after the administration of ICIs. The median occurrence time of CIP in 24 lung cancer patients was 54.5 days, earlier than 119.0 days of non-lung cancer patients (P=0.138), with no significant statistical difference. 34 patients (89.5%) were accompanied by symptoms when CIP occurred. The common clinical symptoms were cough (29 cases) and dyspnea (27 cases). The distribution of CIP on chest CT was asymmetric in 31 cases and symmetrical in 7 cases. Among the 24 lung cancer patients, inflammation was mainly distributed ipsilateral to the primary lung cancer site in 16 cases and diffusely distributed throughout the lung in 8 cases. Ground glass opacities (37 cases) and consolidation (30 cases) were the common imaging manifestations, and organizing pneumonia (OP) pattern (15 cases) was the most common pattern. In 30 CIP patients who were followed up for longer than one month, 17 cases had complete absorption (complete absorption group), and 13 cases had partial absorption or kept stable (incomplete absorption group). The median occurrence time of CIP in the complete absorption group was 55 days, shorter than 128 days of the incomplete absorption group (P=0.022). Compared with the incomplete absorption group, there were less consolidation(P=0.010) and CIP were all classified as hypersensitivity pneumonitis (HP) pattern (P=0.004) in the complete absorption group. Conclusions: CIP often occurs within 3 months after ICIs treatment, and the clinical and CT findings are lack of specificity. Radiologic features may have a profound value in predicting the outcome of CIP.
Humans ; Immune Checkpoint Inhibitors/adverse effects* ; Retrospective Studies ; Pneumonia/drug therapy* ; Lung Neoplasms/drug therapy* ; Tomography, X-Ray Computed/methods*

OBJECTIVE: To investigate humanistic practice ability of nurses in a general hospital in Hunan Province and analyze the factors affecting their practices to provide evidence for interventions to improve humanistic practice ability of the nurses. METHODS: A total of 1196 nurses were surveyed using a self-designed questionnaire and a nurse humanistic practice ability assessment scale questionnaire for assessment of their abilities for humanistic care practice, psychological adjustment, interpersonal communication, self-management, ethics and legal practice. Univariate and multivariate analyses were performed for analysis of the factors affecting the practice abilities of the nurses. RESULTS: The total score of humanistic practice ability of the 1196 nurses was 105.69±16.45 (the full score of the scale was 130), and the scores of humanistic care practice ability, psychological adjustment ability, interpersonal communication ability, self-management ability, ethics and legal practice ability were 40.95±6.46, 16.41±2.66, 16.41±2.66, 11.32±2.05 and 12.43±2.00, respectively. Univariate analysis and multiple linear regression analysis showed that gender (P=0.033), age (P < 0.001), department (P=0.015), working years (P < 0.001), professional title (P < 0.001), first academic degree (P < 0.001), highest academic degree (P < 0.001), family location (P=0.010), marital status (P=0.023), number of patients to care for (P=0.022), number of children (P=0.001), previous humanities related training (P < 0.001), training times (P < 0.001), and care received from family members (P < 0.001) and colleagues (P < 0.001) were all the factors affecting humanistic practice ability of the nurses. Among these factors, age, working in department of obstetrics and gynecology and emergency department, professional title, humanities training, and care from family and colleagues explained 20.7% of the variance. CONCLUSION The humanistic practice ability of nurses in this general hospital is above the average level, but their self-management ability needs to be improved. Intervention measures should be implemented to improve the nurses' humanistic practice ability including more attentions to the key groups and departments, strengthening the training of humanistic practice ability, and improving the promotion assessment system.
Child ; Female ; Pregnancy ; Humans ; Hospitals, General ; Emergency Service, Hospital ; Multivariate Analysis ; Research Design

Abstract: Objective　To predict the potential distribution of talaromycosis marneffei (TSM) and analyze its driving factors, so as to provide evidence for the surveillance and prevention of this disease. Methods　The data of all laboratory-confirmed, non-duplicating TSM published in the English and Chinese literature from the first case in January 1964 to December 2018 was collected. A Maxent ecology model using environmental variables, Rhizomys distribution and HIV/AIDS epidemic was developed to forecast ecological niche of TSM worldwide, as well as identify the driving factors. Results　A total of 705 articles (477 in Chinese and 228 in English) were obtained during the study period. After excluding imported cases, a total of 100 foci information were included in the model. The area under the receiver operating characteristic (ROC) curve (AUC) of the model was 0.997 for the training set and 0.991 for the test set. Maxent model revealed that Rhizomys distribution, mean temperature of warmest quarter, precipitation of wettest month, HIV/AIDS epidemic and mean temperature of driest quarter were the top 5 important variables affecting TSM distribution. In addition to identifying traditional TSM endemic areas (South of the Yangtze River in China, Southeast Asian, North and Northeast India), other potential endemic areas were also identified, including parts of the North of the Yangtze River, Central America, West Coast of Africa, East Coast of South America, the Korean Peninsula and Japan. Conclusion　Our finding has discovered hidden high-risk areas and provided insights about driving factors of TSM distribution, which will help inform surveillance strategies and improve the effectiveness of public health interventions against TM infections.

Objective: To identify the clinically relevant factors of steroid-resistant nephrotic syndrome (SSNS) in children and establish a predictive model followed by verifying its feasibility. Methods: A retrospective analysis was performed in a total of 111 children with nephrotic syndrome admitted to Children's Hospital of ShanXi from January 2016 to December 2021. The clinical data of general conditions, manifestations, laboratory tests, treatment, and prognosis were collected. According to the steroid response, patients were divided into SSNS and steroid resistant nephrotic syndrome (SRNS) group. Single factor Logistic regression analysis was used for comparison between the 2 groups, and variables with statistically significant differences were included in multivariate Logistic regression analysis. The multivariate Logistic regression analysis was used to identify the related variables of children with SRNS. The area under the receiver operating characteristic curve (ROC), the calibration curve and the clinical decision curve were used to evaluate its effectiveness of the variables. Results: Totally 111 children with nephrotic syndrome was composed of 66 boys and 45 girls, aged 3.2 (2.0, 6.6) years. There were 65 patients in the SSNS group and 46 in the SRNS group.Univariate Logistic regression analysis showed that the 6 variables, including erythrocyte sedimentation rate, 25-hydroxyvitamin D, suppressor T cells, D-dimer, fibrin degradation products, β2-microglobulin, had statistically significant differences between SSNS and SRNS groups (85 (52, 104) vs. 105 (85, 120) mm/1 h, 18 (12, 39) vs. 16 (12, 25) nmol/L, 0.23 (0.19, 0.27) vs. 0.25 (0.20, 0.31), 0.7 (0.6, 1.1) vs. 1.1 (0.9, 1.7) g/L, 3.1 (2.3, 4.1) vs. 3.3 (2.7, 5.8) g/L, 2.3 (1.9,2.8) vs. 3.0 (2.5, 3.7) g/L, χ²=3.73, -2.42, 2.24, 3.38, 2.24,3.93,all P<0.05), were included in the multivariate Logistic regression analysis. Finally, we found that 4 variables including erythrocyte sedimentation rate, suppressor T cells, D-dimer and β2-microglobulin (OR=1.02, 1.12, 25.61, 3.38, 95%CI 1.00-1.04, 1.03-1.22, 1.92-341.04, 1.65-6.94, all P<0.05) had significant correlation with SRNS. The optimal prediction model was selected. The ROC curve cut-off=0.38, with the sensitivity of 0.83, the specificity of 0.77 and area under curve of 0.87. The calibration curve showed that the predicted probability of SRNS group occurrence was in good agreement with the actual occurrence probability, χ²=9.12, P=0.426. The clinical decision curve showed good clinical applicability. The net benefit is up to 0.2. Make the nomogram. Conclusions: The prediction model based on the 4 identified risk factors including erythrocyte sedimentation rate, suppressor T cells, D-dimer and β2-microglobulin was suitable for the early diagnosis and prediction of SRNS in children. The prediction effect was promising in clinical application.
Male ; Female ; Humans ; Child ; Nephrotic Syndrome/diagnosis* ; Retrospective Studies ; Models, Statistical ; Prognosis ; Steroids/therapeutic use*