ObjectiveTo investigate the effect and mechanism of modified Sini San in ameliorating intestinal mucosal barrier by observing its effects on short chain fatty acids （SCFAs） and high mobility group protein B1 （HMGB1）/receptor of advanced glycation end products （RAGE） signaling pathways in chronic stress rats. MethodsThe 50 male SD rats were randomly divided into control group，model group，low-dose modified Sini San group （7.34 g·kg^-1·d^-1），high-dose modified Sini San group （14.68 g·kg^-1·d^-1），and Fructo-oligosaccharides group （3.15 g·kg^-1·d^-1），with 10 rats in each group. Except for the control group，all other groups were subjected to chronic unpredictable stress/social isolation to create a chronic stress model for 6 weeks. After 4 weeks of modeling，each treatment group was given corresponding drugs by gavage for 2 weeks while modeling. The control group and model group were given the same volume of physiological saline. The effects of Modified Sini San on behaviors，body weight，Bristol score in feces and fecal moisture content in chronic stress rats were observed. Hematoxylin and eosin （HE） staining was used to observe the pathological changes in the cecum. The content of SCFAs in the cecal contents of rats were detected by Gas chromatography-mass spectrometry （GC-MS）. Immunohistochemistry and Western blot were used to detect the expression of HMGB1/RAGE pathway related proteins in cecal tissue. The levels of ZO-1，Occludin，and Claudin-1 in the cecal tissue were detected by enzyme linked immunosorbent assay （ELISA）. ResultsCompared with the model group，the sucrose preference rate，total distance traveled and the number of grid crossings in the open field test of rats in the low-dose modified Sini San group were obviously increased （P<0.05， P<0.01），and the immobility time in the open field test and the immobility time in the forced swimming test of rats in the low-dose and high-dose modified Sini San groups were obviously reduced （P<0.05， P<0.01）. Meanwhile，the Bristol score and fecal moisture content of rats in the low and high dose groups of modified Sini San were obviously increased （P<0.05）. The low-dose group of modified Sini San had intact mucosal layer structure in the cecal tissue and reduced infiltration of inflammatory cells. The content of SCFAs in the cecal contents increased，with a obviously increase in the content of acetic acid，propionic acid，butyric acid，and isovaleric acid （P<0.05， P<0.01） and the expression levels of HMGB1，RAGE，Toll-like receptor 2（TLR2），Toll-like receptor 4（TLR4），tumor necrosis factor-α（TNF-α），and nuclear factor kappa-B p65（NF-κB p65） proteins in cecal tissue were significantly decreased （P<0.05， P<0.01） in low-dose group of modified Sini San. Meanwhile，the contents of ZO-1，Occludin，and Claudin-1 in the cecal tissue were obviously increased （P<0.01） in low-dose group of modified Sini San. ConclusionModified Sini San can improve the function of intestinal mucosal barrier in chronic stress rats by increasing the content of SCFAs in the intestine and inhibiting the HMGB1/RAGE pathway.

Coronavirus,a major pathogen infecting humans,mammals,and birds,causes primarily respiratory diseases af-ter infecting humans.Seven coronaviruses have been found to infect humans and subsequently cause varying degrees of respira-tory symptoms.From 2019 to 2023,millions of people died from severe acute respiratory syndrome coronavirus 2 infections,and the virus continues to mutate.Therefore,drug screening research must urgently be expanded to develop more effective,broad-spectrum anti-coronavirus drugs.In-depth research has indicated that the coronavirus 3C-like protease and RNA polymer-ase are necessary for viral reproduction and are highly conserved among strains,and consequently are anti-virus targets of great interest.This article summarizes the enzymes encoded by coronaviruses and drug screening methods,to provide a reference for coronavirus prevention and control.

Chemiluminescence,as a self-luminous phenomenon that does not require light,heat,acoustic,electric and magnetic excitation,has been widely used in the fields of analytical chemistry,cold light source and bio-imaging because of its advantages including high sensitivity,wide linear range,simple equipment and fast detection speed compared with other analytical techniques.Carbon dots(CDs)are a class of nanomaterials with excellent photoluminescence properties and high biocompatibility.CDs are stable,easy to prepare and abundant in types,and researchers have introduced many types of CDs into different chemiluminescence systems.In this paper,the applications of CDs in common chemiluminescence systems and the possible mechanisms of action were discussed,and the research progresses on the application of CDs in different chemiluminescence detection fields in recent years were summarized.Finally,the development trend of CDs in chemiluminescence was analyzed.

Near infrared spectroscopy(NIRS)analysis technology has become an important process analysis tool in industrial and agricultural production,and has been widely used for qualitative and quantitative analysis in the fields of tobacco,agriculture,and pharmaceuticals.To address issues such as poor generalization ability and low prediction accuracy in NIRS modeling,a two-dimensional convolutional neural network(2DCNN)quantitative analysis model based on competitive adaptive reweighted sampling(CARS)and Gramian angular difference field(GADF)(CARS-GADF-2DCNN)was proposed.CARS-GADF-2DCNN used the CARS method to select an optimal wavelength set from the full spectrum,then employed GADF to encode the selection results into two-dimensional images,and finally used 2DCNN for prediction analysis.The 2DCNN model consisted of convolutional layers,parallel convolution modules,flattening layer,and fully connected layers.Simulation experiments were conducted on three public near-infrared(NIR)spectral datasets encompassing soil,tablet,and grain datasets to evaluate the CARS-GADF-2DCNN model.The results demonstrated that,compared to the one-dimensional convolutional neural network(1DCNN),the GADF-2DCNN model achieved 16.74％,23.40％,and 7.13％improvement in prediction accuracy for the soil,tablet,and grain datasets,respectively.Compared to GADF-2DCNN,VCPA-GADF-2DCNN,and IRIV-GADF-2DCNN models,the CARS-GADF-2DCNN model further improved prediction accuracy.For the soil dataset,prediction accuracy improved by 39.00％,30.78％and 4.13％;for the tablet dataset,the improvements were 9.52％,6.94％and 2.56％;for the grain dataset,the improvements were 20.57％,9.85％and 15.66％.In conclusion,CARS-GADF-2DCNN effectively selected the optimal wavelength subset from near infrared spectra,and revealed the latent features between different wavelengths.CARS-GADF-2DCNN addresses the issues of high complexity in prediction models and low prediction accuracy in near infrared spectral modeling,and could be effectively applied to near infrared spectral prediction analysis of different substances.

Objective:To construct a predictive model for mortality in patients with multiple trauma combined with thoracic injuries and evaluate its predictive value.Methods:A retrospective cohort study was conducted to analyze the clinical data of 184 patients with multiple trauma combined with thoracic injuries admitted to the International Zhuang Medicine Hospital Affiliated to Guangxi University of Chinese Medicine from April 2019 to December 2023, including 129 males and 55 females, aged 19-85 years [(46.1±13.7)years]. According to the prognostic outcomes at 3-month follow-up after discharge, the patients were divided into survival group ( n=145) and death group ( n=39). Data were recorded in both groups at admission, including gender, age, and cause of injury, laboratory tests such as systolic blood pressure, oxygen saturation (SaO 2), hemoglobin (Hb), neutrophil-to-lymphocyte ratio (NLR), and lactate, combined injuries such as the number of combined injuries, number of rib fracture, bilateral rib fracture, first-rib fracture, sternum fracture, thoracic vertebral fracture, bilateral pulmonary contusion, bilateral pneumothorax, subarachnoid hemorrhage, subdural hematoma, epidural hematoma, skull fracture, skull base fracture, cervical vertebral fracture, brain herniation, cerebral contusion, lumbar vertebral fracture, pelvic and abdominal cavity hematoma, liver injury, kidney injury, spleen injury, clavicle fracture, scapular fracture, femoral fracture, and pelvic fracture, and injury scores such as shock index (SI), modified shock index (MSI), injury severity score (ISS), revised trauma score (RTS), Glasgow coma score (GCS), and thoracic trauma severity (TTS) score. Univariate binary logistic regression analysis was used to screen for risk factors of death in patients with multiple trauma combined with thoracic injuries. LASSO regression and multivariate logistic regression analysis were employed to identify predictive variables and independent risk factors for mortality in those patients and to construct a regression equation. A nomogram prediction model based on the regression equation was developed using R language. Receiver operating characteristic (ROC) curves were plotted to evaluate the discrimination of the model. The ROC curves were internally validated using the Bootstrap method with 1 000 resamples. The calibration of the model was assessed using the Hosmer-Lemeshow (H-L) goodness-of-fit test. The clinical application value of the model was evaluated using decision curve analysis (DCA) and clinical impact curve (CIC) analysis. Results:There were statistically significant differences between the survival group and the death group in systolic blood pressure, SaO 2, NLR, lactate, number of combined injuries, subarachnoid hemorrhage, subdural hematoma, skull fracture, skull base fracture, brain herniation, liver injury, SI, MSI, ISS, RTS, GCS, and TTS ( P<0.05 or 0.01). The results of the univariate binary logistic regression analysis showed that the above-mentioned related variables except for systolic blood pressure were all significantly associated with death in patients with multiple trauma combined with thoracic injuries ( P<0.05 or 0.01). Five predictive variables, TTS, GCS, brain herniation, ISS, and lactate were obtained in LASSO regression analysis. The results of the multivariate logistic regression analysis showed that GCS ( OR=0.70, 95% CI 0.58, 0.83), brain herniation ( OR=46.18, 95% CI 4.27, 499.26), TTS ( OR=1.71, 95% CI 1.30, 2.24), and lactate ( OR=1.35, 95% CI 1.01, 1.80) were independent risk factors for death in patients with multiple trauma combined with thoracic injuries ( P<0.05 or 0.01). Based on the aforementioned independent risk factors, a regression formula was constructed as follows: P=e x/(1+e x), with the x=-0.36×"GCS"+3.83×"brain herniation"+0.53×"TTS"+0.30×"lactate levels"-11.03. The area under the ROC curve (AUC) of the predictive model for mortality in patients with multiple trauma combined with thoracic injuries based on the equation was 0.97 (95% CI 0.93, 1.00). The AUC was internally validated using the Bootstrap method with 1 000 samples, resulting in an AUC of 0.97 (95% CI 0.91, 1.00). The results of the H-L goodness-of-fit test showed that the bias-corrected calibration curve of the model was in good consistence with the actual curve and both of them were close to the ideal curve. In the evaluation of the clinical application value of the predictive model, the DCA results showed that the predictive model could achieve good clinical net benefit. The CIC results showed that when the threshold probability was greater than 0.7, the model-identified high-risk patients for death highly matched the patients who actually died. Conclusion:The predictive model for mortality in patients with multiple trauma combined with thoracic injuries based on GCS, brain herniation, TTS, and lactate has good predictive performance and clinical application value.

OBJECTIVE: To investigate the protective effects of stir-fried Semen Armeniacae Amarum (SAA) against aristolochic acid I (AAI)-induced nephrotoxicity and DNA adducts and elucidate the underlying mechanism involved for ensuring the safe use of Asari Radix et Rhizoma. METHODS: In vitro, HEK293T cells overexpressing Flag-tagged multidrug resistance-associated protein 3 (MRP3) were constructed by Lentiviral transduction, and inhibitory effect of top 10 common pairs of medicinal herbs with Asari Radix et Rhizoma in clinic on MRP3 activity was verified using a self-constructed fluorescence screening system. The mRNA, protein expressions, and enzyme activity levels of NAD(P)H quinone dehydrogenase 1 (NQO1) and cytochrome P450 1A2 (CYP1A2) were measured in differentiated HepaRG cells. Hepatocyte toxicity after inhibition of AAI metabolite transport was detected using cell counting kit-8 assay. In vivo, C57BL/6 mice were randomly divided into 5 groups according to a random number table, including: control (1% sodium bicarbonate), AAI (10 mg/kg), stir-fried SAA (1.75 g/kg) and AAI + stir-fried SAA (1.75 and 8.75 g/kg) groups, 6 mice in each group. After 7 days of continuous gavage administration, liver and kidney damages were assessed, and the protein expressions and enzyme activity of liver metabolic enzymes NQO1 and CYP1A2 were determined simultaneously. RESULTS: In vivo, combination of 1.75 g/kg SAA and 10 mg/kg AAI suppressed AAI-induced nephrotoxicity and reduced dA-ALI formation by 26.7%, and these detoxification effects in a dose-dependent manner (P<0.01). Mechanistically, SAA inhibited MRP3 transport in vitro, downregulated NQO1 expression in vivo, increased CYP1A2 expression and enzymatic activity in vitro and in vivo, respectively (P<0.05 or P<0.01). Notably, SAA also reduced AAI-induced hepatotoxicity throughout the detoxification process, as indicated by a 41.3% reduction in the number of liver adducts (P<0.01). CONCLUSIONS Stir-fried SAA is a novel drug candidate for the suppression of AAI-induced liver and kidney damages. The protective mechanism may be closely related to the regulation of transporters and metabolic enzymes.
Aristolochic Acids/toxicity* ; Animals ; Humans ; NAD(P)H Dehydrogenase (Quinone)/genetics* ; HEK293 Cells ; Kidney/pathology* ; Cytochrome P-450 CYP1A2/genetics* ; Mice, Inbred C57BL ; DNA Adducts/drug effects* ; Male ; Kidney Diseases/drug therapy* ; Drugs, Chinese Herbal/therapeutic use* ; Mice ; Prunus armeniaca ; Plant Extracts

OBJECTIVES: To evaluate whether adding Fuzheng Jiedu Xiaoji (FZJDXJ) therapy improves survival in advanced hepatitis B virus-related HCC (HBV-HCC) patients. METHODS: This prospective, randomized controlled study was performed at a major academic medical center in Beijing, China from October 2020 to October 2022. Eligible patients with advanced HBV-HCC were randomly divided equally (1:1) to receive either the combination of FZJDXJ and conventional Western medical therapy (63 cases, FZJDXJ group) or solely Western medicine (66 cases, control group). The study endpoints consisted of overall survival (OS) as the primary outcome, with progression-free survival (PFS), disease control rate (DCR), and adverse events (AEs) as secondary measures. RESULTS: The median OS was significantly prolonged in the FZJDXJ group at 8.9 months (95% CI: 6.0-11.9) vs. 4.4 months (95% CI: 3.2-7.3) in the control group (P<0.05). The hazard ratio for mortality in the FZJDXJ group was 0.59 (95% CI: 0.40-0.89), suggesting a 41% lower risk of death compared to the control group. The results revealed that patients receiving FZJDXJ therapy achieved a PFS of 5.1 months (95% CI: 4.1 to 7.2 months), compared to only 2.9 months (95% CI: 2.0 to 4.6 months) in the control group (P<0.05). Additionally, DCR was significantly elevated in the FZJDXJ group (20.6%) compared to the control group (10.6%, P<0.05). Subgroup analysis demonstrated that FZJDXJ significantly improved OS in patients with alpha-fetoprotein levels <400 ng/mL, age <60 years, Barcelona Clinic Liver Cancer (BCLC) stage C, and compensated liver function (Child-Pugh A and B, P<0.05). Multivariate analysis revealed that FZJDXJ therapy acted as an independent factor protecting against mortality within 1 year. Gastrointestinal symptoms are rare side effects, and no fatalities associated with the treatment were reported. CONCLUSION This randomized controlled trial demonstrated that FZJDXJ combined Western conventional therapy significantly improves OS and PFS in patients with advanced HBV-HCC. (registration No. ChiCTR2000033941).
Humans ; Drugs, Chinese Herbal/adverse effects* ; Male ; Female ; Middle Aged ; Liver Neoplasms/virology* ; Carcinoma, Hepatocellular/virology* ; Treatment Outcome ; Hepatitis B virus ; Adult ; Aged ; Hepatitis B/drug therapy*

Eightly-four novel thioheterocyclic nucleoside derivatives were designed, synthesized, and evaluated for antitumor activity in vitro and in vivo. Most of the compounds inhibited the growth of HCT116 and HeLa cancer cells in vitro, among them 33a and 36b exhibited potent activity against HCT116 cells (IC₅₀ = 0.27 and 0.49 μmol/L, respectively). Both compounds 33a and 36b inhibited cell metastasis, arrested the cell cycle in the G₂/M phase, and induced apoptosis in vitro. Mechanistic studies revealed that 33a and 36b increased ROS levels, led to DNA damage, ER stress, and mitochondrial dysfunction, and inhibited autophagy in HCT116 cells. Biological information analysis, RNA-sequencing, Gene Set Enrichment Analysis (GSEA), drug affinity responsive target stability (DARTS) assay, cellular thermal shift assay (CETSA), and SPR experiments identified that compounds 33a and 36b showed antitumor activity by suppressing the c-MYC pathway. c-MYC silencing assays indicated that c-MYC proteins participated in 33a-mediated anticancer activities in HCT116 cells. More importantly, compound 33a presented favorable pharmacokinetic properties in mice (T _1/2 = 6.8 h) and showed significant antitumor efficacy in vivo without obvious toxicity, showing promising potential for further clinical development.

Analyzing the spatial distribution pattern and formation factors of medicinal plant resources can provide a scientific basis for the protection and development of traditional Chinese medicine(TCM) resources. This study is based on the survey data of medicinal plant resources in 104 county-level administrative regions of Anhui province in the Fourth National Survey of TCM Resources. The global spatial autocorrelation analysis, trend surface analysis, local spatial autocorrelation analysis, hotspot analysis, and a geodetector were employed to analyze the spatial distribution pattern of medicinal plant richness, and its relationship with natural factors was explored. The results can provide a basis for the formulation of development strategies such as the protection and utilization of TCM resources, as well as offer a scientific foundation for the establishment of regional planning schemes for TCM resources in Anhui province. The results indicated that the richness of medicinal plant resources in Anhui province had significant spatial heterogeneity, exhibiting highly clustered distribution characteristics. Cold spots and hot spots presented clustered distribution patterns, with cold spots mostly located north of the Huaihe River and hot spots south of the Yangtze River. Overall, the distribution of medicinal plant resources in Anhui province showed an overall trend of high in the south and low in the north, which was consistent with the overall geomorphic trend of this province. In addition, natural factors such as altitude, precipitation, and vegetation type played an important role in the diversity and spatial distribution pattern formation of medicinal plant resources. The extraction and analysis of the spatial distribution characteristics of natural factors in cold and hot spot regions discovered that the heterogeneity of eco-environments constituted a fundamental condition for the formation of species diversity.
Plants, Medicinal/classification* ; China ; Spatial Analysis ; Conservation of Natural Resources ; Biodiversity

OBJECTIVE: To investigate the variability of bone metabolism levels among different populations and its association with knee osteoarthritis (KOA) pain. METHODS: A total of 50 people (control group) who participated in physical examination from January 2023 to June 2023 were selected, including 26 males and 24 females, wtih a mean aged of (52.14±9.04) years old ranging 41 to 65 years old. The other 50 patients with knee osteoarthritis(case group) who attended the outpatient clinic of the Orthopedics and Traumatology Department in the same time period, including 19 males and 31 females, with a mean age of (53.60±7.76) years old ranging 40 to 65 years. The two groups of Western Ontario and McMaster Universities Osteoarthritis Index(WOMAC) and bone metabolism markers, such as 25-hydroxy-cholecalciferol[25(OH)D], β-isomerized typeⅠcollagen C-telopeptide breakdown products (β-CTX), total typeⅠprocollagen N-terminal propeptide (t-PINP), osteocalcin (OC), parathormone (PTH) levels were compared. Pearson correlation analysis was used to compare the correlation between two groups of bone metabolism related markers and WOMAC. RESULTS: The WOMAC score of the case group (39.90±2.34) was higher than that of the control group (3.60±0.57), with significant difference (P<0.05). There was no significant difference between the two groups of 25 (OH)D, β-CTX and PTH (P>0.05). The t-PINP and OC of the case group were (62.90±52.40) and (19.88±10.15) ng·ml-1, respectively, and those of the control group were (38.86±10.82) and (14.90±3.62) ng·ml^-1, respectively;the t-PINP and OC of the case group were higher than those of the control group, with significant difference (P<0.05). Pearson correlation analysis showed that t-PINP was positively correlated with WOMAC pain score in the case group (r²=0.045, P<0.01). CONCLUSION Bone metabolism levels in the serum of patients with knee osteoarthritis are different from those of healthy people, and the difference between OC and t-PINP is the most obvious, and the concentration of t-PINP levels is positively correlated with pain symptoms in patients with KOA. However, the specific mechanism of correlation between the bone metabolism levels of patients with KOA and their pain symptoms needs to be further elucidated by basic experimental research as well as by enlarging the samples.
Humans ; Female ; Male ; Middle Aged ; Osteoarthritis, Knee/metabolism* ; Aged ; Adult ; Bone and Bones/metabolism* ; Pain/etiology* ; Biomarkers/metabolism*