ObjectiveTo investigate the mechanism of the modified of Bazhentang combined with Guishentang in improving pregnancy outcomes in mouse models of embryo implantation dysfunction by regulating T helper 1/T helper 2 （Th1/Th2） immune balance. MethodsEighty ICR female mice were randomly divided into four groups （n=20 per group） on gestational day 1 （GD1）： control， model， western medicine， and traditional Chinese medicine （TCM） groups. Except for the control group， all mice received mifepristone solution （0.2 mg/mouse） via oral gavage on GD4 to induce embryo implantation dysfunction. The TCM group received a water decoction of the modified of Bazhentang combined with Guishentang （20.8 g·kg^-1）， with the western medicine group administered dydrogesterone （3.9 mg·kg^-1）， and the control/model groups given equal volumes of saline. All treatments were administered once daily from GD1 until one day before sample collection. Outcomes included implantation site counts （macroscopic observation）， pregnancy rates， body weight， endometrial histopathology （hematoxylin-eosin staining）， uterine expression of T-box expressed in T cells （T-bet）， GATA-binding protein 3 （GATA3）， interferon gamma （IFN-γ）， and interleukin-4 （IL-4） at protein （Western blot） and mRNA （real-time polymerase chain reaction， Real-time PCR） levels， serum IFN-γ and IL-4 levels （enzyme-linked immunosorbent assay， ELISA）， and Th1/Th2 immune balance evaluated by calculating T-bet/GATA3 and IFN-γ/IL-4 ratios. ResultsCompared to the control group， the model group showed no significant change in pregnancy rate but exhibited a marked reduction in average implantation sites and body weight （P<0.01）. Histopathological analysis revealed endometrial abnormalities， including decreased glandular density， stromal compaction， and absence of nucleolar vacuoles. At the molecular level， uterine tissue in the model group demonstrated significantly upregulated expression of T-bet and IFN-γ （P<0.05， P<0.01）， alongside markedly downregulated GATA3 and IL-4 expression （P<0.05， P<0.01）. Serum analysis confirmed markedly elevated IFN-γ （P<0.01） and reduced IL-4 levels （P<0.01）， resulting in significantly increased T-bet/GATA3 and IFN-γ/IL-4 ratios （P<0.01）. Compared to the model group， pregnancy rates in all treatment groups showed no significant change. Implantation sites and body weight increased substantially （P<0.01）， with restored endometrial morphology characterized by enhanced glandular density， stromal edema， and reappearance of nucleolar vacuoles. Significant downregulation of T-bet and IFN-γ （P<0.01） and upregulation of GATA3 and IL-4 （P<0.05， P<0.01） in uterine tissue were observed. Serum IFN-γ levels were significantly reduced （P<0.05， P<0.01）， while IL-4 levels were significantly elevated （P<0.05）. The Th1/Th2 ratios were significantly decreased （P<0.01）. ConclusionThe modified of Bazhentang combined with Guishentang significantly enhances the number of embryo implantation sites in mice with embryo implantation dysfunction， potentially through modulating T-bet/GATA3 expression， restoring Th1/Th2 immune balance， and improving endometrial receptivity.

Objective: To investigate the therapeutic efficacy and potential mechanisms of fecal microbiota transplantation (FMT) in patients with type 2 diabetes mellitus (T2DM), and to preliminarily identify the traditional Chinese medicine (TCM) syndrome element characteristics of FMT in the treatment of T2DM. Methods: Between March 25, 2023 and September 30, 2024, T2DM patients who met the inclusion and exclusion criteria were enrolled at the Department of Rheumatology and Endocrinology of the Second Affiliated Hospital of Fujian University of Traditional Chinese Medicine. Participants received oral microbiota capsules as an adjunct to metformin therapy. Information obtained by four diagnostic methods of TCM, along with clinical and laboratory parameters, was collected before and after the intervention. Metagenomic sequencing was employed to analyze the gut microbiota, and Spearman correlation analysis was used to explore the relationship between laboratory indicators and differential bacterial genera. According to the post-treatment reduction in glycosylated hemoglobin (HbA1c), patients were categorized into a response (R) group and a non-response (NR) group. Treatment outcomes, safety indicators, gut microbiota changes, and TCM syndrome element features were compared between the two groups. Results: A total of 53 T2DM patients were included in the final analysis, and 30 patients were assigned to R group and 23 to NR group. After treatment, the R group exhibited significant reductions in HbA1c, fasting plasma glucose (FPG), and 2-hour postprandial glucose (2hPG) (P < 0.05 or P < 0.01). The NR group also showed significant decreases in HbA1c and FPG levels P < 0.01 or P < 0.05. Compared with the NR group, after treatment, FPG level in the R group demonstrated significant reductions (P < 0.01). As compared with before treatment, pancreatic islet function demonstrated enhancement in the R group, a significant increase in the 2-hour pastprandial C-peptide (2hC-P) levels in R group (P < 0.05), whereas no marked change was observed in the NR group. Regarding body composition indicators, the R group showed significantly lower waist-hip ratio (WHR), visceral fat (VF), and subcutaneous fat (SF) levels compared with the NR group (P < 0.01). After treatment, the NR group exhibited a significant elevation in aspartate aminotransferase (AST) levels (P < 0.05). Other safety-related indicators fluctuated within normal reference ranges, and no other adverse events, such as diarrhea, fever, or nausea, were reported. Metagenomic sequencing showed that FMT improved the diversity and richness of the gut microbiota, remodeling its overall structure. At the phylum level, the abundance of p_Firmicutes decreased significantly (P < 0.01), while the abundances of p_Bacteroidota and p_Proteobacteria increased significantly (P < 0.01). At the family level, among the 125 identified taxa, the abundances of f_Bacteroidaceae, f_Lactobacillaceae, and f_Sutterellaceae were significantly elevated, whereas six families, including f_Lachnospiraceae, f_Ruminococcaceae, and f_Coriobacteriaceae, were significantly decreased (all P < 0.05). Among the 367 taxa at the genus level, the top 10 differential genera showed significantly increased abundances of g_Bacteroides and g_Sutterella, and significantly decreased abundances in eight genera, including g_Faecalibacterium, g_Ruminococcus, g_Blautia, and g_Collinsella (all P < 0.05). Correlation analysis suggested that the phylum p_Bacillota was positively correlated with improvements in T2DM laboratory parameters, g_norank_f_Prevotellaceae was significantly positively correlated with fasting C-peptide (FC-P) and 2hC-P (P < 0.05). HbA1c demonstrated a significantly positive correlation with g_Blautia and g_Gemmiger (P < 0.05) and a significantly negative correlation with g_Bacteroides and g_Collinsella (P > 0.05). Analysis of syndrome element characteristics revealed that the R group was primarily characterized by pathological patterns of dampness, phlegm, and Yang deficiency. Before treatment, statistically significant reductions in syndrome element scores were observed for dampness, Yang deficiency, spleen, phlegm, Qi deficiency, Qi stagnation, and Yin deficiency (P < 0.01), as well as for heat and liver (P < 0.05). The NR group was mainly featured with Qi deficiency and Yin deficiency. Statistically significant changes in their syndrome element scores after treatment were noted for Qi deficiency (P < 0.01), and for spleen, Qi stagnation, liver, and blood deficiency (P < 0.05). In this group, the score changes for Yang deficiency, Yin deficiency, heat, and dampness were not statistically significant (P > 0.05). Conclusion The principles of syndrome element differentiation can be effectively applied to predict treatment efficacy and facilitate patient selection for FMT in the treatment of T2DM. Patients with T2DM presented with specific TCM syndrome element characteristics, notably dampness, phlegm, and Yang deficiency, represent a highly responsive population to FMT therapy.

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 determine the blood physiological and biochemical indexes in the inbred SHANXI MU strain of spontaneous type 2 diabetes(T2DM)Chinese hamsters.Methods Chinese hamsters with spontaneously developed T2DM and normal hamsters(n=10 hamsters per group),aged 12 months,were selected for the study.Fasting blood samples were collected and 15 physiological parameters and 16 biochemical indicators were analyzed using a Sysmex XT automated hematology analyzer and Hitachi fully automatic biochemical analyzer.Results The white cell count,red cell count,platelet count,hemoglobin level,alanine transaminase,aspartate transaminase,glutamate,total cholesterol,triglycerides,and uric acid all differed significantly between the diabetic and control groups(P＜0.05).Conclusions The change of blood physiological and biochemical indexes in the Chinese hamster spontaneous T2DM model were in line with the trend in human T2DM incidence,thus providing basic data for the application of this model.

Objective:To investigate the accuracy of magnetic resonance imaging (MRI) cine sequences in determining the range of tumor motion in radiotherapy, providing a basis for the precise delineation of the target volume in motion for radiation therapy.Methods:A modified chest motion phantom was placed in a MRI scanner, and a water-filled sphere was used to simulate a tumor. True fast imaging with steady precession (TrueFISP) MRI cine sequences from Siemens were used to capture the two-dimensional motion images of the simulated tumor. The phantom experiments were divided into three modes: head-foot motion mode, rotation motion mode, and actual respiratory waveform mode. In the head-foot motion mode, respiratory motion period (3, 4, 5, 6, 7 and 8 s), amplitude (5, 10 and 15 mm), and respiratory waveform of the simulated tumor (sin and cos4) were set, resulting in a total of 36 motion combinations. In the rotation motion mode, a cos4 waveform was used for respiration, with respiratory periods of 3, 4, 5, 6, 7 and 8 s, head-foot motion set amplitudes of 5, 10 and 15 mm, and anterior-posterior (AP) and left-right (LR) motion set amplitudes in three combinations ([2.5, 2.5] mm, [2.5, 5.0] mm, [5.0, 5.0] mm), resulting in a total of 54 motion combinations. In the actual respiratory waveform mode, respiratory waveforms of 5 randomly selected patients from Affiliated Cancer Hospital of Zhengzhou University were obtained. Under each motion combination, TrueFISP cine images (30 frames, with an acquisition time of 11 s per frame) were obtained. The code was used to automatically identify the two-dimensional coordinates of the center of the simulated tumor in each image, and sin and cos4 functions were separately employed to fit the tumor position in the motion direction, thereby obtaining the fitted motion period and amplitude. The difference between the maximum and minimum values of the tumor's center coordinates in the head-to-foot direction is taken as the range of movement, referred to as the calculated amplitude. For the actual respiratory waveform, the distance between the measured maximum and minimum positions is used to calculate the amplitude.Results:In the head-foot motion mode, the fitted amplitudes of both sin and cos4 waveforms deviated from the set amplitudes by 0-0.51 mm, with relative deviations of 0%-4.2%. The deviation range between the calculated amplitudes and the set amplitudes of the two waveforms were 0.08-0.94 mm, with relative deviations of 1.1%-6.3%. In the rotation motion mode, the fitted amplitudes deviated from the set amplitudes by 0-0.61 mm, with relative deviations of 0%-6.2%. And the deviation range between the calculated amplitudes and the set amplitudes were 0.16-0.94 mm, with relative deviations of 0%-6.3%. In the actual respiratory waveform motion mode, the deviation range between the calculated amplitudes and the set amplitudes were 0.10-0.48 mm, with relative deviations of 2.2%-8.6%.Conclusion:TrueFISP cine sequences show minimal deviations in determining the range of tumor head-foot motion and effectively captures the tumor's movement state, thereby providing important support for the precise definition of the tumor movement target area during radiotherapy .

Objective:To analyze the dose-response relationship of 99Tc m-dimercaptosuccinic acid (DMSA) in pediatric renal static imaging. Methods:A retrospective analysis of children (model group: n=199, 81 males, 118 females; validation group: n=30, 13 males, 17 females; all age: 1 month-14 years) who underwent 99Tc m-DMSA renal static imaging from January 2022 to November 2023 in Wuhan Children′s Hospital, Tongji Medical College, Huazhong University of Science and Technology were conducted. Post-administration radiation counts and related clinical data were collected. Imaging quality was evaluated using visual analogue scoring (VAS). ROC curve analysis was used to assess the relationship between radiation count intensity (RCI) and imaging quality. A nonlinear mixed-effects modeling method was employed to establish the dose-response relationship for 99Tc m-DMSA in pediatric renal static imaging. Internal and external validations of the model were performed. Final model was utilized to evaluate patient dosing protocols. Results:Body weight was considered as a significant determinant of the dose-response relationship in 99Tc m-DMSA renal static imaging( χ2 values: 120.79, 116.36, both P<0.05). ROC curve analysis showed that the quality of diagnostic images was acceptable when the anterior renal RCI was ≥32.61 (cut-point) and the posterior renal RCI was ≥35.46 (cut-point). Both internal and external validation results demonstrated that the dose-response model established exhibited good prediction performance. Based on the final model graph, the image quality could meet the requirements for clinical diagnosis. Conclusions:The 99Tc m-DMSA dose-response model for pediatric renal static imaging is successfully established. Individualized dosage based on the model can provide a reference for clinical individualized dosing decision-making.

Objective To investigate the effects of long-term exposure to three new types of light emitting diode (LED) sources on the behavior, learning, and memory of rats. Methods A total of 160 specific pathogen-free SD rats were divided into eight groups as followed, trichromatic fluorescent lamps color temperature control group, violet-chip full-spectrum white LED group, blue-chip white LED group, and blue-chip full-spectrum white LED group based on the light sources types, with color temperature of 4 000 K and 6 500 K groups in each group using the 4×2 factorial design. There were 20 rats in each group, with half of the rats were males and half females. Rats were exposed to artificial lighting, and the illumination was set at 750 lx. The rats in each group were exposed to different lighting environments for 12 hours per day for 24 weeks. The open-field and step-down tests were conducted in rats after 24 weeks exposure, followed by sacrifice of rats and measurement of organ coefficients. Differences in body weight, organ coefficients, and neurobehavioral indexes of rats in different groups were compared. Results The spleen coefficient of female rats decreased in blue-chip white LED of 6 500 K color temperature group, and the liver coefficient of male rats decreased in the violet-chip full-spectrum white LED of 4 000 K color temperature, blue-chip full-spectrum white LED of 4 000 K color temperature, and blue-chip full-spectrum white LED of 6 500 K color temperature groups, compared with the same-sex rats in trichromatic fluorescent lamps with same-color temperature control group (all P<0.05). The result of different types of light sources compared in the open-field test showed that the index of total distance and movement speed of female rats in the blue-chip full-spectrum white LED group were lower than those in the other three groups, and the time cost to the central area was longer than that in the blue-chip white LED group and the violet-chip full-spectrum white LED group (all P<0.05). The total distance and movement speed of male rats in the blue-chip full-spectrum white LED group were longer or higher than those in the violet-chip full-spectrum white LED group (all P<0.05). Based on the comparison of color temperature, the time and total distance of male rats in 6 500 K color temperature group were lower than that in the 4 000 K color temperature group (both P<0.05). In the step-down test, both male and female rats in the blue-chip full-spectrum white LED group made more errors compared with other three groups with the same gender (all P<0.05). Conclusion Based on the experimental conditions of this study, the blue-chip full-spectrum white light LED affects behavior, learning and memory of the rats, and trichromatic fluorescent lamp has the lowest effect on neurobehavior. The color temperature also affects behavior of the rats, and high color temperature has higher risk.

OBJECTIVE: To design and construct a graphene oxide (GO)/silver nitrate (Ag₃PO₄)/chitosan (CS) composite coating for rapidly killing bacteria and preventing postoperative infection in implant surgery. METHODS: GO/Ag₃PO₄ composites were prepared by ion exchange method, and CS and GO/Ag₃PO₄ composites were deposited on medical titanium (Ti) sheets successively. The morphology, physical image, photothermal and photocatalytic ability, antibacterial ability, and adhesion to the matrix of the materials were characterized. RESULTS: The GO/Ag₃PO₄ composites were successfully prepared by ion exchange method and the heterogeneous structure of GO/Ag₃PO₄ was proved by morphology phase test. The heterogeneous structure formed by Ag₃PO₄ and GO reduced the band gap from 1.79 eV to 1.39 eV which could be excited by 808 nm near-infrared light. The photothermal and photocatalytic experiments proved that the GO/Ag₃PO₄/CS coating had excellent photothermal and photodynamic properties. In vitro antibacterial experiments showed that the antibacterial rate of the GO/Ag₃PO₄/CS composite coating against Staphylococcus aureus reached 99.81% after 20 minutes irradiation with 808 nm near-infrared light. At the same time, the composite coating had excellent light stability, which could provide stable and sustained antibacterial effect. CONCLUSION GO/Ag₃PO₄/CS coating can be excited by 808 nm near infrared light to produce reactive oxygen species, which has excellent antibacterial activity under light.
Chitosan ; Silver Nitrate ; Titanium ; Anti-Bacterial Agents/pharmacology* ; Coloring Agents

Objective:To compare the efficacy and safety of programmed death-1(PD-1)inhibitors in combination with chemotherapy versus chemotherapy alone in patients with metastatic bladder cancer.Methods:A retrospective analysis was performed on the clinical data of 77 cases of metastatic bladder cancer who were admitted to the First Affiliated Hospital of Zhengzhou University from January 2014 to October 2022. According to the different clinical treatment regimens, they were divided into two groups. Patients treated with PD-1 inhibitors combined with gemcitabine and cisplatin (GC) regimen were referred to as IGC group, and patients who received GC chemotherapy alone were referred to as GC group. There were 24 cases in IGC group, including 18 males and 6 females, with a median age of 60 (56, 67) years old. Seventeen cases had a history of smoking. Fifteen cases had an Eastern Cooperative Oncology Group (ECOG) score of 0 and 9 cases had a score of 1. Twenty-three cases suffered distant metastasis (stage M 1). Two cases suffered lymph node metastasis only, 6 cases with liver metastasis, 8 cases with lung metastasis, and 8 cases with bone metastasis. There were 53 cases in GC group, including 45 males and 8 females, with a median age of 63 (55, 69) years old. Thirty-one cases had a history of smoking. Thirty cases had an ECOG score of 0 and 23 cases had a score of 1, 48 cases suffered stage M 1, 2 cases suffered lymph node metastasis only. Nineteen cases suffered liver metastasis. Twenty-seven cases suffered lung metastasis. And 23 cases suffered bone metastasis. There was no statistically significant difference in the above general information between the two groups ( P>0.05). Kaplan-Meier method was used to plot the survival curves, and the difference of median progression-free survival (mPFS) and median overall survival (mOS) between the two groups was compared by log-rank test. Finally, the difference in adverse reactions between the two groups was compared. Results:The objective response rate (ORR) was 41.7% and the disease control rate (DCR) was 87.5% in the IGC group.As a comparison, the ORR was 43.4% and the DCR was 83.0% in the GC group. The differences in ORR ( P=0.887) and DCR ( P=0.871) between the two groups were not statistically significant. All patients were followed up for 3 to 45 months, with a median follow-up time of 24 (14, 43) months. The mPFS was 7.0 (95% CI 5.7-8.3) months in the GC group and 8.0 (95% CI 3.0-13.1) months in the IGC group, and the difference was statistically significant between the two groups ( P=0.026). The mOS of patients in the GC group was 16.0 (95% CI 14.4-17.6) months, the mOS was not yet reached in the IGC group, and patients in the IGC group had longer mOS with a statistically significant difference ( P=0.022). All patients experienced treatment-related adverse reactions. Grade 3-4 adverse reactions occurred in 8 cases (33.3%) in the IGC group and in 16 cases (30.2%) in the GC group, and no adverse reaction-related deaths were observed( P=0.992). The most common adverse reactions in both groups were anemia, including 18 cases (75.0%) in IGC group and 38 cases (71.7%) in GC group. There were 4 cases (16.7%) of grade 1-2 hypothyroidism in the IGC group but no patients with hypothyroidism were found in the GC group, and the difference was statistically significant ( P=0.012). There were 8 cases (33.3%) and 4 cases (7.5%) of grade 1-2 skin adverse reactions in the IGC and GC groups, respectively, and the difference was statistically significant ( P=0.011). The immune-related adverse reactions of PD-1 inhibitors in IGC group were 1 case of hyperthyroidism (4.2%), 4 cases of hypothyroidism (16.7%), 1 case of adrenal insufficiency (4.2%), and 1 case of immune colitis (4.2%). Conclusions:Compared with chemotherapy alone, PD-1 inhibitors combined with chemotherapy for metastatic bladder cancer can effectively prolong the mPFS and median mOS. The adverse reactions of the two groups were tolerable, and there was no significant difference in the incidence of grade 3-4 adverse reactions. In general, PD-1 inhibitors combined with chemotherapy in the treatment of metastatic bladder cancer is safe and feasible, but attention should be paid to the immune-related adverse reactions of PD-1 inhibitors.

Hypertensive disorder of pregnancy (HDP) involves two major public health issues: mother-infant safety and prevention and controlling major chronic disease. HDP poses a serious threat to maternal and neonatal safety, and it is one of the leading causes of maternal and perinatal morbidity and mortality worldwide, as well as an important risk factor for long-term cardiovascular disease (CVD). In order to explore effective strategies to prevent and control the source of CVD and reduce its risk, we have established a cohort of HDPs in Shenzhen for the primordial prevention of CVD. The construction of the HDP cohort has already achieved preliminary progress till now. A total of 2 239 HDP women have been recruited in the HDP cohort. We have established a cohort data management platform and Biobank. The follow-up and assessment of postpartum cardiovascular metabolic risk in this cohort has also been launched. Our efforts will help explore the pathophysiological mechanism of HDP, especially the pathogenesis and precision phenotyping, prediction, and prevention of pre-eclampsia, which, therefore, may reduce the risk of adverse pregnancy outcomes, and provide a bridge to linking HDP and maternal-neonatal cardiovascular, metabolic risk to promote the cardiovascular health of mothers and their infants.