ObjectiveTo evaluate the clinical efficacy of Fuzheng Huaji Formula （扶正化积方） for chronic hepatitis B to reduce the incidence of liver cirrhosis and hepatocellular carcinoma. MethodsA retrospective cohort study was conducted， collecting medical records of 118 patients with chronic hepatitis B and 234 patients with hepatitis B-related cirrhosis who visited the hospital between January 1， 2014， and December 31， 2018. The use of Fuzheng Huaji Formula was designated as the exposure factor. Patients receiving antiviral treatment for hepatitis B without concurrent Fuzheng Huaji Formula therapy were included in the western medicine group， while those receiving antiviral treatment combined with Fuzheng Huaji Formula for a cumulative treatment lasting longer than 3 months were included in the combined treatment group. The follow-up observation period was five years. Kaplan-Meier survival analysis was used to assess the cumulative incidence of cirrhosis in patients with chronic hepatitis B and the cumulative incidence of hepatocellular carcinoma in patients with hepatitis B-related cirrhosis. Univariate and multivariate Cox regression analyses were employed to examine the factors influencing the occurrence of cirrhosis and hepatocellular carcinoma. ResultsAmong patients with chronic hepatitis B， there were 55 cases in the combined treatment group and 63 cases in the western medicine group； among patients with hepatitis B-related cirrhosis， there were 110 cases in the combined treatment group and 124 cases in the western medicine group. Five-year follow-up outcomes for chronic hepatitis B patients showed that the cumulative incidence of cirrhosis was 5.45% （3/55） in the combined treatment group and 17.46% （11/63） in the western medicine group， with a statistically significant difference between groups （Z = 2.003， P = 0.045）. Five-year follow-up outcomes for hepatitis B-related cirrhosis patients showed that the cumulative incidence of hepatocellular carcinoma was 8.18% （9/110） in the combined treatment group and 22.58% （28/124） in the western medicine group， also showing a statistically significant difference （Z = 3.007， P = 0.003）. Univariate and multivariate Cox regression analyses indicated that treatment with Fuzheng Huaji Formula is an independent protective factor in preventing the progression of chronic hepatitis B to cirrhosis and the progression of hepatitis B-related cirrhosis to hepatocellular carcinoma （P＜0.05）. ConclusionCombining Fuzheng Huaji Formula with antiviral therapy for hepatitis B can effectively intervene in the disease progression of chronic hepatitis B， reducing the incidence of cirrhosis and hepatocellular carcinoma.

ObjectiveTo investigate the influence of entecavir （ETV） versus tenofovir alafenamide fumarate （TAF） on renal function in previously untreated patients with chronic hepatitis B （CHB）. MethodsA retrospective analysis was performed for the clinical data of 167 previously untreated CHB patients who received ETV or TAF treatment for at least 48 weeks at the outpatient service of Department of Infectious Diseases in The First Affiliated Hospital of Nanchang University from September 2019 to November 2023， and according to the antiviral drug used， they were divided into ETV group with 117 patients and TAF group with 50 patients. In order to balance baseline clinical data， propensity score matching （PSM） was used for matching and analysis at a ratio of 2∶1， and the two groups were compared in terms of estimated glomerular filtration rate （eGFR） and the incidence rate of abnormal renal function at week 48. According to eGFR at week 48， the patients were divided into normal renal function group and abnormal renal function group. The independent-samples t test or the Mann-Whitney U test was used for comparison of continuous data between two groups， and the chi-square test or the Fisher’s exact test was used for comparison of categorical data between two groups. The multivariate Logistic regression analysis was used to investigate the influencing factors for abnormal renal function， and the receiver operating characteristic （ROC） curve was used to assess the performance of each indicator in predicting abnormal renal function. The Kaplan-Meier method was used to analyze the cumulative incidence rate of abnormal renal function， and the log-rank test was used for comparison. The analysis of variance with repeated measures was used to compare the dynamic changes of eGFR during antiviral therapy in CHB patients. ResultsAfter PSM matching， there were 100 patients in the ETV group and 50 patients in the TAF group. There were no significant differences in baseline clinical data between the ETV group and the TAF group （all P>0.05）， with an eGFR level of 112.29±9.92 mL/min/1.73 m² in the ETV group and 114.72±12.15 mL/min/1.73 m² in the TAF group. There was a reduction in eGFR from baseline to week 48 in both groups， and compared with the TAF group at week 48， the ETV group had a significantly lower eGFR （106.42±14.12 mL/min/1.73 m² vs 112.25±13.44 mL/min/1.73 m²， t=-2.422， P=0.017） and a significantly higher incidence rate of abnormal renal function （17.00% vs 4.00%， χ²=5.092， P=0.024）. After the patients were divided into normal renal function group with 131 patients and abnormal renal function group with 19 patients， the univariate analysis showed that there were significant differences between the two groups in age （Z=-2.039， P=0.041）， treatment drug （ETV/TAF） （χ²=5.092， P=0.024）， and baseline eGFR level （t=4.023， P<0.001）， and the multivariate Logistic regression analysis showed that baseline eGFR （odds ratio ［OR］=0.896， 95% confidence interval ［CI］： 0.841 — 0.955， P<0.001） and treatment drug （OR=5.589， 95%CI： 1.136 — 27.492， P=0.034） were independent influencing factors for abnormal renal function. Baseline eGFR had an area under the ROC curve of 0.781 in predicting abnormal renal function in CHB patients， with a cut-off value of 105.24 mL/min/1.73 m²， a sensitivity of 73.68%， and a specificity of 82.44%. The Kaplan-Meier curve analysis showed that the patients with baseline eGFR≤105.24 mL/min/1.73 m² had a significantly higher cumulative incidence rate of abnormal renal function than those with baseline eGFR>105.24 mL/min/1.73 m² （χ²=22.330， P<0.001）， and the ETV group had a significantly higher cumulative incidence rate of abnormal renal function than the TAF group （χ²=4.961， P=0.026）. With the initiation of antiviral therapy， both the ETV group and the TAF group had a significant reduction in eGFR （F=5.259， P<0.001）， but the ETV group only had a significant lower level of eGFR than the TAF group at week 48 （t=-2.422， P=0.017）； both the baseline eGFR≤105.24 mL/min/1.73 m² group and the baseline eGFR>105.24 mL/min/1.73 m² group had a significant reduction in eGFR （F=5.712， P<0.001）， and there was a significant difference in eGFR between the two groups at baseline and weeks 12， 24， 36， and 48 （t=-13.927， -9.780， -8.835， -9.489， and -8.953， all P<0.001）. ConclusionFor CHB patients initially treated with ETV or TAF， ETV antiviral therapy has a higher risk of renal injury than TAF therapy at week 48.

ObjectiveTo analyze the metabolomic characteristics of platelets in fibrinogen（FIB） overexpression rats of coronary heart disease with blood stasis syndrome（CHD-BSS）， explore potential biomarkers， and investigate the mechanism of FIB overexpression on CHD-BSS. MethodsSD rats were randomly divided into BSS group and BSS+FIB overexpression group（BSS+FIB group）， with 10 rats in each group. Both the BSS+FIB group and the BSS group were fed a high-fat diet combined with oral administration of vitamin D₃ and subcutaneous injection of isoproterenol， but rats in the BSS+FIB group were overexpressed with FIB during the initial modeling stage by transfection with adeno-associated virus（AAV）. The overexpression level of FIB in rat liver and plasma samples was detected by enzyme-linked immunosorbent assay（ELISA） and real-time fluorescence quantitative polymerase chain reaction（Real time PCR）， as well as the expression level of liver FIB A（FGA） mRNA. The characteristics of metabolites in rat platelet samples were analyzed by ultra-high performance liquid chromatography-quadrupole-electrostatic field orbital trap high-resolution mass spectrometry（UPLC-Q-Exactive Orbitrap-MS）， and the differential metabolites between groups were screened by principal component analysis（PCA） and orthogonal partial least squares-discriminant analysis（OPLS-DA）， and the enriched pathways were analyzed. The accuracy of potential biomarkers in the diagnosis of CHD-BSS was evaluated by receiver operating characteristic（ROC） curve. The expression of autophagy related proteins phosphorylated adenosine monophosphate（AMP） activated protein kinase（p-AMPK）/AMPK， phosphorylated mammalian target of rapamycin（p-mTOR）/mTOR， microtubule-associated protein 1 light chain 3（LC3） Ⅱ/Ⅰ and p62 in platelets were detected by Western blot. ResultsCompared with the BSS group， the expression levels of FIB in liver and plasma samples of the BSS+FIB group were significantly increased（P<0.05， P<0.01）， and the expression level of FIB mRNA in the liver was remarkably increased（P<0.01）， indicating successful overexpression of FIB. Platelet metabolomics results showed significant differences in metabolic profiles between the BSS+FIB group and the BSS group， and a total of 25 significantly enriched metabolic pathways and 8 metabolites involved in these metabolic pathways， among which uric acid， guanosine and ribose 1-phosphate levels were up-regulated， while adenosine diphosphate（ADP）， AMP， guanosine diphosphate（GDP）， adenylosuccinate and norepinephrine levels were down-regulated. The diagnostic ability analysis of differential metabolites showed that all 8 differential metabolites had good diagnostic ability， with an area under the curve（AUC）>0.85. Western blot results showed that compared with the BSS group， the expression levels of p-mTOR/mTOR and p62 proteins in platelets of the BSS+FIB group was significantly reduced（P<0.01）， while the expression levels of p-AMPK/AMPK and LC3Ⅱ/Ⅰ proteins were increased， but the difference was not statistically significant. ConclusionOverexpression of FIB can change the metabolic characteristics of CHD-BSS rat model， involving multiple aspects such as vascular endothelial injury， platelet activation and myocardial function damage. Among them， overexpression of FIB may enhance the occurrence of platelet autophagy， thereby inducing platelet activation and promoting thrombus formation.

Based on the implementation of GMP, comprehensive improvement of quality control measures, and consideration of the 3Rs principle for experimental animals, Several years ago, WHO, the European Pharmacopoeia and the FDA gradually abolished the testing for abnormal toxicity of biological products, and the Chinese Pharmacopoeia 2025 Edition(Volume Ⅲ)also revised the testing for abnormal toxicity of biological products. In order to help users of the Chinese Pharmacopoeia(Volume Ⅲ) better understand and implement this pharmacopoeia, this article provides a detailed review of the changes in regulatory concepts for abnormal toxicity test in various countries and the process of gradually phasing out abnormal toxicity test, as well as the actual situation of China’s pharmaceutical industry. It also interprets the ideas and considerations for revising the Chinese Pharmacopoeia 2025 Edition(Volume Ⅲ) on abnormal toxicity test for biological products.

BACKGROUND:The micro/nanostructured gradient biomimetic surface of implant materials can simulate the structure of the extracellular environment in human bone tissue,thereby achieving perfect bone integration function.However,further research is needed on the mechanisms by which the surface microstructure of bone implant materials regulates cell function and promotes osteogenesis. OBJECTIVE:To analyze the effect of titanium sheet microstructure surface on osteogenic differentiation of MC3T3-E1 osteoblasts. METHODS:(1)At a constant voltage of 5 V or 20 V,nanotube arrays of different diameters were prepared on the surface of titanium sheets by acid etching and anodic oxidation techniques,and were recorded as group R5 and group R20,respectively.The surface morphology,roughness,and hydrophilicity of pure titanium sheet(without acid etching or anodizing treatment)were measured in group R5 and group R20.(2)MC3T3-E1 osteoblasts of logarithmic growth stage were inoculated on the surface of pure titanium sheets,R5 group and R20 group respectively.After 24 hours of osteogenic induction culture,the expression of mechanical sensitive channel protein 1 was analyzed by RT-PCR and immunofluorescence staining.Osteoblast inducible base with or without the mechanosensitive channel protein 1 activator Yada1 was added,and alkaline phosphatase staining was performed after 7 days of culture.Alizarin red staining was performed after 14 days of culture. RESULTS AND CONCLUSION:(1)The surface of pure titanium sheets was smooth under scanning electron microscope.Relatively uniform and orderly nanotube arrays with average diameters of about 30 nm and 100 nm were observed on the surface of titanium sheets of groups R5 and R20,respectively.The results of scanning electron microscope were further verified by atomic force microscopy.The surface roughness of titanium sheet of group R5 was higher than that of pure titanium(P<0.05),and the water contact angle was lower than that of pure titanium(P<0.05).The surface roughness of titanium sheet in group R20 was higher than that in group R5(P<0.05),and the water contact angle was lower than that in group R5(P<0.05).(2)RT-PCR and immunofluorescence staining showed that the expression of mechanosensitive channel protein 1 in group R5 was higher than that in pure titanium group(P<0.05),and the expression of mechanosensitive channel protein 1 in group R20 was higher than that in group R5(P<0.05).Under the osteogenic induction,compared with the condition without Yada1,there were no significant changes in the activity of alkaline phosphatase and the deposition of calcified nodules in pure titanium group after Yada1 addition,while the activity of alkaline phosphatase and the deposition of calcified nodules in groups R5 and R20 after Yada1 addition were significantly increased(P<0.05).With or without Yada1,the alkaline phosphatase activity and calcified nodule deposition in group R5 were higher than those in pure titanium group(P<0.05),and the alkaline phosphatase activity and calcified nodule deposition in group R20 were higher than those in group R5(P<0.05).(3)The results show that the surface microstructure of titanium sheet can promote the osteogenic differentiation of osteoblast MC3T3-E1 by activating mechanosensitive channel protein 1.

Chimeric antigen receptor T (CAR-T) cells have reshaped the treatment landscape of hematological malignancies, offering a potentially curative option for patients. Despite these major milestones in the field of immuno-oncology, growing experience with CAR-T cells has also highlighted several limitations of this strategy. The production process of CAR-T cells is complex, time-consuming, and costly, thus leading to poor drug accessibility. The potential carcinogenic risk of viral transfection systems remains a matter of controversy. Treatment-related side effects, such as cytokine release syndrome, can be life-threatening. And the biggest challenge is the inadequate efficacy related to poor infiltration and retention of CAR-T cells in tumor tissues and impaired T cell activation caused by the immunosuppressive tumor microenvironment (TME). Innovative strategies are urgently needed to address these problems, and nanomedicine offers good solutions to these challenges. In this review, we provide a comprehensive summary of recent advancements in the application of nanomaterials to enhance CAR-T cell therapy. We examine the role of innovative nanoparticle-based delivery systems in the production of CAR-T cells, with a particular focus on polymeric delivery systems and lipid nanoparticles (LNPs). Furthermore, we explore various strategies for delivering immune stimulators, which significantly enhance the efficacy of CAR-T cells by modulating T cell viability and functionality or by reprogramming the immunosuppressive TME. In addition, we discuss several novel therapeutic approaches aimed at mitigating the adverse effects associated with CAR-T therapies. Finally, we offer an integrated perspective on the future challenges and opportunities facing CAR-T therapies.
Humans ; Nanomedicine/methods* ; Receptors, Chimeric Antigen/metabolism* ; Immunotherapy, Adoptive/methods* ; T-Lymphocytes/immunology* ; Nanoparticles/chemistry* ; Animals

OBJECTIVES: Near vision loss (NVL) is one of the leading causes of visual impairment worldwide, exerting a profound impact on individual quality of life and socio-economic development. This study aims to analyze the burden of NVL in China by sex and age groups from 1990 to 2021 and to project trends over the next 15 years. METHODS: Using data from the Global Burden of Disease (GBD) 2021 database, we conducted descriptive analyses of NVL prevalence in China, calculated age-standardized prevalence rates (ASPR) and age-standardized disability-adjusted life years rates (ASDR) to compare burden differences between sexes and age groups, and applied an autoregressive integrated moving average (ARIMA) model to predict NVL trends for the next 15 years. The model selection was based on best-fit criteria to ensure reliable projections. RESULTS: From 1990 to 2021, China's ASPR of NVL rose from 10 096.24/100 000 to 15 624.54/100 000, and ASDR increased from 101.75/100 000 to 158.75/100 000. In 2021, ASPR (16 551.70/100 000) and ASDR (167.69/100 000) were higher among females than males (14 686.21/100 000 and 149.76/100 000, respectively). China ranked highest globally in both NVL cases and disability-adjusted life years (DALYs), with female burden significantly exceeding male burden. Projections indicated this trend and sex gap will persist until 2036. Compared with 1990, the prevalence cases and DALYs increased by 239.20% and 238.82%, respectively in 2021, with the highest burden among females and the 55-59 age group. The ARIMA model predicted continued increases in prevalence and DALYs by 2036, with females maintaining a higher burden than males. CONCLUSIONS This study reveals a marked increase in the NVL burden in China and predicts continued growth in the coming years. Public health policies should prioritize NVL prevention and control, with special attention to women and middle-aged populations to mitigate long-term societal and health impacts.
Humans ; China/epidemiology* ; Male ; Female ; Prevalence ; Middle Aged ; Disability-Adjusted Life Years ; Adult ; Global Burden of Disease ; Adolescent ; Quality-Adjusted Life Years ; Aged ; Sex Factors ; Child ; Young Adult ; Child, Preschool ; Cost of Illness ; Infant ; Aged, 80 and over ; Vision Disorders/epidemiology*

Objective To establish a method for determination of pyriclobenzuron (PBU) residues in rice and paddy environments, and to determine the residual amounts and observe the degradation dynamics of PBU. Methods In July 2022, the paddies of Zhejiang Academy of Agricultural Sciences were selected as experimental fields, and were divided into the blank control group (no pesticide application), the 1-fold-concentration pesticide group (1 kg/667 m²), and the 5-fold-concentration pesticide group (5 kg/667 m²), with a 100 m² area in each group. At the early tillering stage of rice, 20% suspension of PBU sulfate was sprayed once in the 1-fold-concentration and 5-fold-concentration pesticide groups, and rice plants, paddy water and soil samples were collected 2 h, and 1, 2, 3, 5, 7, 11, 14, 21, 28, 35, 49 d and 63 d following spraying PBU, while rice straw, field soil, brown rice and rice husk samples were collected 98 d following spraying. PBU was extracted and purified in samples using a quick, easy, cheap, effective, rugged, and safe (QuEChERS) pretreatment technique, and the PBU contents were determined in samples using ultrahigh performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). The solvent standard working solution and matrix standard working solution were prepared. A linear regression equation was fitted between PBU concentration (x-axis) and peak area (y-axis), and the ratio of the slope (k) of the matrix standard curve to the slope (K) of the solvent standard curve was calculated to evaluate the matrix effect of PBU in samples. According to the Guidelines for Pesticide Residue Testing in Crops (NY/T 788—2018), the addition levels of PBU were set at 0.005, 0.050, 5.000, 1 000.000 mg/kg in rice plants, 0.005, 0.050, 2.000, 10.000 mg/kg in paddy water, 0.005, 0.050, 2.000 mg/kg in soil, and 0.005, 0.050, 5.000 mg/kg in brown rice and rice husks. The recovery and relative standard deviation (RSD) of PBU addition were calculated to evaluate the effectiveness of UPLC-MS/MS for determination of PBU contents. The first-order kinetic equation of PBU concentration was fitted in samples at different sampling time points to analyze the trends in PBU degradation in rice plants, paddy water, and soil, and the half-life of PBU was calculated in different samples. Results There was a good linear relationship between the mass concentration and peak area of PBU at concentrations of 0.000 1 to 0.020 0 mg/kg under solvent and matrix conditions (R² = 0.985 8 to 0.999 7, t = -0.47 to 1.62, all P values < 0.01). The matrix effects of PBU were 70.26%, 65.42% and 65.12% in rice plants, brown rice and rice husks, indicating a matrix-inhibitory effect, and the matrix effect was 87.06% in soils, indicating a weak matrix effect. The recovery of PBU addition was 77.61% to 100.12% in different samples, with RSD of 1.43% to 6.74%, and a limit of quantification (LOQ) of 0.005 mg/kg, and the addition recovery and RSD met the requirements of the Guidelines for Pesticide Residue Testing in Crops (NY/T 788—2018), validating the effectiveness of UPLC-MS/MS assay. Following spraying PBU at a dose of 1 kg/667 m², the half-life of PBU was 6.24 d in rice plants and 3.43 d in paddy water samples, respectively. The final residues of PBU were lower than the LOQ of 0.005 mg/kg in brown rice and rice husk samples 98 d following spraying PBU. Following spraying PBU at a dose of 5 kg/667 m², the half-life of PBU was 15.75 d in rice plants and 7.62 d in paddy water samples, respectively. The final residue of PBU was lower than the LOQ of 0.005 mg/kg in brown rice 98 d following spraying PBU, and the final residue of PBU was 0.049 mg/kg in rice husks. Conclusions A simple, and highly accurate and precise UPLC-MS/MS assay has been developed for determination of PBU residues in rice plants and paddy environments through extraction and purification of PBU from matrix samples using QuEChERS pretreatment. After spraying PBU in paddies, the concentration of PBU gradually decreases in rice plants and paddy water over time, and the final residual concentration is low.

Objective To examine the value of breast ultrasound for diagnosis of benign and malignant breast masses among female patients with nipple discharges, and to provide a reference for the diagnosis of patients with nipple discharges. Methods A total of 317 female patients with nipple discharges underwent breast examinations in Changzhou Maternal and Child Health Care Hospital between April 2021 and May 2024 were enrolled, and all patients underwent ultrasound, mammography, and pathologic examinations of the breast. With pathologic examination as the gold standard, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of breast ultrasound and mammography for diagnosis of benign and malignant breast masses were compared. The diagnostic value of breast ultrasound for benign and malignant breast masses was evaluated among female patients with nipple discharges. Results The study subjects had a mean age of (43.27 ± 10.71) years, and a mean nipple discharge duration of (1.11 ± 0.53) years. Moreover, 51.74% of nipple discharges were in the right-sided breast, 52.05% were spontaneous, 32.49% were bloody, and 53.63% were classified as Breast Imaging Reporting and Data System category 1 to 3. Of the 317 female patients with nipple discharges, histopathology detected 137 malignant breast masses and 180 benign masses, and the 53 masses with Breast Imaging Reporting and Data System category 5 were all malignant. The diagnostic sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 64.23%, 77.22%, 68.22%, 73.94% and 71.61% for breast ultrasound, and 80.29%, 35.00%, 48.46%, 70.00% and 54.57% for breast mammography. The specificity (χ²=8.81, P < 0.01), positive predictive value (χ²=13.01, P < 0.01), and accuracy (χ²=19.75, P < 0.01) of breast ultrasound were significantly higher than breast mammography, while the sensitivity of breast ultrasound was significantly lower than breast mammography (χ²=65.15, P < 0.01). However, there was no significant difference in the negative predictive value between breast ultrasound and mammography (χ²=0.47, P > 0.05). Conclusion Breast ultrasound has a high accuracy for diagnosis of benign and malignant breast masses among female patients with nipple discharges, which may serve as an auxiliary tool for diagnosis of breast masses among patients with nipple discharges.