Objective: To investigate the mechanism of Yishen Tongluo Formula in ameliorating renal pyroptosis in diabetic nephropathy mice by regulating the toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88)/nuclear factor-κB (NF-κB) signaling pathway. Methods: Sixty C57BL/6 male mice were randomly divided into control (10 mice) and intervention groups (50 mice) using random number table method. The diabetes nephropathy model was established by intraperitoneally injecting streptozotocin(50 mg/kg). After modeling, the intervention group was further divided into model, semaglutide (40 μg/kg), and high-, medium-, and low-dose Yishen Tongluo Formula groups (15.6, 7.8, and 3.9 g/kg, respectively) using random number table method. The high-, medium-, and low-dose Yishen Tongluo Formula groups were administered corresponding doses of medication by gavage, the semaglutide group received a subcutaneous injection of semaglutide injection, and the control group and model groups were administered distilled water by gavage for 12 consecutive weeks. Random blood glucose levels of mice in each group were monitored, and the 24-h urinary protein content was measured using biochemical method every 4 weeks; after treatment, the serum creatinine and urea nitrogen levels were measured using biochemical method. The weight of the kidneys was measured, and the renal index was calculated. Hematoxylin and eosin, periodic acid-Schiff, periodic Schiff-methenamine, and Masson staining were used to observe the pathological changes in renal tissue. An enzyme-linked immunosorbent assay was used to detect urinary β2-microglobulin (β2-MG), neutrophil gelatinase-associated lipocalin (NGAL), and kidney injury molecule-1 (KIM-1) levels. Western blotting and real-time fluorescence PCR were used to detect the relative protein and mRNA expression levels of nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3 (NLRP3), Caspase-1, gasdermin D (GSDMD), interleukin-1β (IL-1β), and interleukin-18 (IL-18) in renal tissue. Immunohistochemistry was used to detect the proportion of protein staining area of the TLR4, MyD88, and NF-κB in renal tissue. Results: Compared with the control group, the random blood glucose, 24-h urinary protein, serum creatinine, urea nitrogen, and renal index of the model group increased, and the urine β2-MG, NGAL, and KIM-1 levels increased. The relative protein and mRNA expression levels of NLRP3, Caspase-1, GSDMD, IL-1β, and IL-18 in renal tissue increased, and the proportion of TLR4, MyD88, and NF-κB protein positive staining areas increased (P<0.05). Pathological changes such as glomerular hypertrophy were observed in the renal tissue of the model group. Compared with the model group, the Yishen Tongluo Formula high-dose group showed a decrease in random blood glucose after 12 weeks of treatment (P<0.05). The Yishen Tongluo Formula high- and medium-dose groups showed a decrease in 24-h urinary protein, creatinine, urea nitrogen, and renal index, as well as decreased β2-MG, NGAL, and KIM-1 levels. NLRP3, Caspase-1, GSDMD, IL-1 β, and IL-18 relative protein and mRNA expression levels were also reduced, and the proportion of TLR4, MyD88, and NF-κB protein positive staining areas was reduced (P<0.05). Pathological damage to renal tissue was ameliorated. Conclusion Yishen Tongluo Formula may exert protective renal effects by inhibiting renal pyroptosis and alleviating tubular interstitial injury in diabetic nephropathy mice by regulating the TLR4/MyD88/NF-κB signaling pathway.

ObjectiveTo explore the therapeutic effects and mechanisms of modified Danggui Shaoyaosan on acne based on the c-Jun N-terminal kinase （JNK）/p38 mitogen-activated protein kinase （p38 MAPK） pathway. MethodsA rat ear acne model was established in SD rats， and the rats were divided into a blank group， a model group， and low-， medium-， and high-dose groups of modified Danggui Shaoyaosan （7.15， 14.30， 28.60 g·kg·d^-1）， with six rats in each group. After the administration for 14 consecutive days， morphological changes in the rats' auricles were observed， and hematoxylin-eosin （HE） staining was used to examine the pathological changes in the acne-affected ear tissue. Enzyme-linked immunosorbent assay （ELISA） was employed to measure the levels of interleukin-1β （IL-1β） and tumor necrosis factor-α （TNF-α） in the ear tissue. Quantitative reverse transcription polymerase chain reaction （Real-time PCR） was performed to detect the mRNA expression levels of Caspase-3， B cell lymphoma-2 （Bcl-2）， Bcl-2-associated X protein （Bax）， JNK， and p38 MAPK in the ear tissue. Additionally， Western blot analysis was conducted to assess the protein levels of Caspase-3， Bcl-2， Bax， JNK， and p38 MAPK in the ear tissue. The active components and key targets of modified Danggui Shaoyaosan in the treatment of acne were identified through network pharmacology analysis. Molecular docking was then employed to evaluate the interactions between the main active components and the key targets. ResultsThe results of the animal experiment demonstrated that compared with those in the blank group， rats in the model group exhibited redness， swelling， thickening， hardening， dryness， and roughness of the auricle. The surface showed sebaceous scales and desquamation， accompanied by acne-like lesions such as papule-like elevations or cysts. Histopathological changes included keratinization， epidermal thickening， dermal collagen fiber degeneration and necrosis， subcutaneous muscle degeneration and necrosis， inflammatory cell infiltration， and fibrous tissue proliferation. The mRNA and protein expression levels of IL-1β， TNF-α， Caspase-3， Bax， JNK， and p38 MAPK were significantly increased （P<0.01）， while those of Bcl-2 were significantly decreased （P<0.01）. In comparison to the model group， the modified Danggui Shaoyaosan groups showed marked improvement in acne-like lesions of the auricle， with varying degrees of histopathological damage reduction. Additionally， the mRNA and protein expression levels of IL-1β， TNF-α， Caspase-3， Bax， JNK， and p38 MAPK in the tissue were significantly decreased （P<0.05， P<0.01）， while those of Bcl-2 were significantly increased （P<0.05， P<0.01）. Network pharmacology analysis indicated that the key compounds in modified Danggui Shaoyaosan responsible for its effects in treating acne may include acacetin， kaempferol， luteolin， quercetin， wogonin， and baicalein. These compounds exerted their effects by modulating core targets such as TNF， IL-1β， Caspase-3， and Bcl-2， thereby alleviating inflammation and apoptosis and ultimately improving acne symptoms. ConclusionModified Danggui Shaoyaosan may exert its therapeutic effects on acne by inhibiting the activation of the JNK/p38 MAPK pathway， thereby alleviating inflammation and apoptosis.

ObjectiveTo investigate the effect and mechanism of Yishen Tongluo prescription in protecting mice from oxidative stress injury in diabetic kidney disease （DKD） via the nuclear factor erythroid 2-related factor 2 （Nrf2）/heme oxygenase-1 （HO-1）/NAD（P）H quinone oxidoreductase 1 （NQO1） signaling pathway. MethodsSpecific pathogen-free （SPF） male C57BL/6 mice were assigned into a control group （n=10） and a modeling group （n=50）. The DKD model was established by intraperitoneal injection of streptozotocin. The mice in the modeling group were randomized into a model group， a semaglutide （40 μg·kg^-1） group， and high-， medium-， and low-dose （18.2， 9.1， 4.55 g·kg^-1， respectively） Yishen Tongluo prescription groups， with 10 mice in each group. The treatment lasted for 12 weeks. Blood glucose and 24-h urine protein levels were measured， and the kidney index （KI） was calculated. Serum levels of creatinine （SCr）， blood urea nitrogen （BUN）， alanine aminotransferase （ALT）， and aspartate aminotransferase （AST） were assessed. The pathological changes in the renal tissue were evaluated by hematoxylin-eosin， periodic acid-Schiff， periodic acid-silver methenamine， and Masson’s trichrome staining. Enzyme-linked immunosorbent assay kits were used to measure the levels of β2-microglobulin （β2-MG）， neutrophil gelatinase-associated lipocalin （NGAL）， kidney injury molecule-1 （KIM-1）， liver fatty acid-binding protein （L-FABP）， nitric oxide synthase （NOS）， glutathione （GSH）， total antioxidant capacity （T-AOC）， and 8-hydroxy-2'-deoxyguanosine （8-OHdG）. Immunohistochemical staining was performed to examine the expression of Kelch-like ECH-associated protein 1 （Keap1） and malondialdehyde （MDA）. Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR） and Western blot were employed to determine the mRNA and protein levels， respectively， of factors in the Nrf2/HO-1/NQO1 signaling pathway. ResultsCompared with the control group， the DKD model group showed rises in blood glucose， 24-h urine protein， KI， SCr， BUN， and ALT levels， along with glomerular hypertrophy， renal tubular dilation， thickened basement membrane， mesangial expansion， and collagen deposition. Additionally， the model group showed elevated levels of β2-MG， NGAL， KIM-1， L-FABP， NOS， and 8-OHdG， lowered levels of GSH and T-AOC， up-regulated expression of MDA and Keap1， and down-regulated expression of Nrf2， HO-1， NQO1， and glutamate-cysteine ligase catalytic subunit （GCLC） （P<0.05）. Compared with the model group， the semaglutide group and the medium- and high-dose Yishen Tongluo prescription groups showed reductions in blood glucose， 24-h urine protein， KI， SCr， BUN， and ALT levels， along with alleviated pathological injuries in the renal tissue. In addition， the three groups showed lowered levels of β2-MG， NGAL， KIM-1， L-FABP， NOS， and 8-OHdG， elevated levels of GSH and T-AOC， down-regulated expression of MDA and Keap1， and up-regulated expression of Nrf2， HO-1， NQO1， and GCLC （P<0.05）. ConclusionYishen Tongluo prescription exerts renoprotective effects in the mouse model of DKD by modulating the Nrf2/HO-1/NQO1 signaling pathway， mitigating oxidative stress， and reducing renal tubular injuries.

OBJECTIVE To explore optimization pathways for the drug traceability code management model in outpatient pharmacy workflows， providing practical evidence for enhancing the efficiency of pharmaceutical service. METHODS Taking the outpatient pharmacy of the First Affiliated Hospital of Sun Yat-sen University as the research subject， a comprehensive drug traceability system was established through three key interventions： upgrading the information system architecture [including integration of the hospital information system （HIS） with the traceability platform]， workflow optimization （reorganizing the inventory-dispensing-verification tripartite process）， and designing a dual-mode traceability data collection mechanism （primary data capture at dispensing stations and supplementary capture at verification stations）. Operational efficiency differences before and after implementation were analyzed using the medical insurance data and service timeliness metrics in September 2024. RESULTS After the implementation of drug traceability code management， in terms of data collection: Mode Ⅰ （verification-stage capture） uploaded 26 144 records， while Mode Ⅲ （inventory-as-sales capture） uploaded 443 061 records， totaling 469 205 entries； in terms of time efficiency： average drug dispensing time increased from 28.74 s to 43.37 s （enhanced by 51%）. Through dynamic staffing adjustments， patient wait time only extended from 8.04 min to 8.67 min （enhanced by 8%）. CONCLUSIONS Drug traceability code management can be effectively implemented via a “system reconstruction-process reengineering-human-machine collaboration” trinity strategy， leveraging informatization （e.g.， dual-mode data capture） to offset manual operation delays， which validates the feasibility of balancing national traceability demands with service efficiency in outpatient pharmacies.

Rice is the world's largest food crop, and its yield and quality are directly related to food security and human health. Grain size, as one of the important factors determining the rice yield, has been widely concerned by breeders and researchers for a long time. To decipher the regulatory mechanism of rice grain size, we obtained a multi-tiller, dwarf, and small-grain mutant htd1 by ethyl methanesulfonate (EMS) mutation from the Japonica rice cultivar 'Zhonghua 11' ('ZH11'). Genetic analysis indicated that the phenotype of htd1 was controlled by a single recessive gene. Using the mutation site map (Mutmap) method, we identified the candidate gene OsHTD1, which encoded a carotenoid cleavage dioxygenase involved in the biosynthesis of strigolactone (SL). The SL content in htd1 was significantly lower than that in 'ZH11'. Cytological analysis showed that the grain size of the mutant decreased due to the reductions in the length and width of glume cells. The function of htd1 was further verified by the CRISPR/cas9 gene editing technology. The plants with the gene knockout exhibited similar grain size to the mutant. In addition, gene expression analysis showed that the expression levels of multiple grain size-related genes in the mutant changed significantly, suggesting that HTD1 may interact with other genes regulating grain size. This study provides a new theoretical basis for research on the regulatory mechanism of rice grain size and potential genetic resources for breeding the rice cultivars with high yields.
Oryza/growth & development* ; Mutation ; Edible Grain/growth & development* ; Alleles ; Plant Proteins/genetics* ; Dioxygenases/genetics* ; Lactones/metabolism* ; Gene Expression Regulation, Plant ; Genes, Plant ; Gene Editing ; CRISPR-Cas Systems ; Phenotype

ObjectiveTo investigate the association of the dynamic changes of serum total bilirubin （ΔTBil） and alpha-fetoprotein （AFP） with the short-term prognosis of patients with hepatitis B virus-associated acute-on-chronic liver failure （HBV-ACLF）， to establish a new scoring model， and to investigate the value of this model in evaluating the short-term prognosis of HBV-ACLF through comparison with Model for End-Stage Liver Disease （MELD） score and other scoring systems. MethodsThe patients with HBV-ACLF who were hospitalized and treated in Department of Gastroenterology， The General Hospital of Western Theater Command， from January 2015 to December 2022 were enrolled as the retrospective study cohort. Clinical data within 24 hours after admission were collected from all patients， and the patients were divided into survival group and death group according to the survival after 90 days of follow-up. The independent-samples t test was used for comparison of normally distributed continuous data between groups； the Mann-Whitney U test was used for comparison of continuous data with skewed distribution between groups； the chi-square test or the corrected chi-square test was used for comparison of categorical data between two groups. A multivariate Logistic regression analysis was used to determine the risk factors for the prognosis of HBV-ACLF patients and establish a predictive model for prognosis， and the receiver operating characteristic （ROC） curve was used to investigate the value of the new model in predicting the short-term prognosis of HBV-ACLF patients. ResultsA total of 361 patients were included in the analysis， with a 90-day survival rate of 67.3% （243/361）. Compared with the survival group （n=243）， the death group （n=118） had significantly higher age， incidence rates of upper gastrointestinal bleeding and hepatic encephalopathy， international normalized ratio， prothrombin time （PT）， leukocytes， monocytes， neutrophils， creatinine， ΔTBil， MELD score， and ALBI score （all P<0.05）， as well as significantly lower levels of total cholesterol， high-density lipoprotein， low-density lipoprotein， albumin， AFP， platelet count， lymphocytes， and Na⁺ （all P<0.05）. The multivariate Logistic regression analysis showed that AFP， PT， Na⁺， and ΔTBil were independent influencing factors for the 90-day prognosis of patients with HBV-ACLF （all P<0.05）. The new ΔTBil-AFP scoring model was established as 11.987+1.168×ΔTBil （%）－0.095×Na⁺ （mmol/L）+0.25×PT （s）－0.002×AFP （ng/mL）， which had a relatively high predictive value， with an area under the ROC curve of 0.796， a sensitivity of 0.766， and a specificity of 0.723， and the decision curve showed good benefits. ConclusionCompared with the commonly used prediction models such as MELD score and ALBI score， the ΔTBil-AFP scoring model has a better prediction performance.

Objective:To analyze the influencing factors of achieving textbook outcome (TO) after pancreaticoduodenectomy (PD) in patients with pancreatic ductal adenocarcinoma, and to construct a nomograph model to explore its predictive value in TO.Methods:The clinical data of 205 patients with pancreatic ductal adenocarcinoma treated by PD in Henan University People's Hospital from January 2019 to December 2022 were analyzed retrospectively, including 88 males and 117 females with the age of (61.3±9.8) years old. Patients were divided into two groups based on whether they achieved TO after surgery: TO group ( n=113) and non-TO group ( n=92). Clinical data such as age, gender, intraoperative blood loss, operation time, blood transfusion volume, pancreatic CT value, and tumor differentiation degree were collected. Logistic regression analysis screened the influencing factors of PD postoperative TO and built a nomogram model. The performance of the nomogram model was evaluated using receiver operating characteristic (ROC) curve, calibration diagram, and decision curve analysis. Results:Multivariate logistic regression analysis showed that the higher the degree of tumor differentiation was in patients with pancreatic ductal adenocarcinoma (high differentiation to medium differentiation: OR=7.20, 95% CI: 1.20-43.28; high differentiation to low differentiation: OR=16.55, 95% CI: 2.01-136.11), CT value>38.45 Hu ( OR=0.29, 95% CI: 0.13-0.65), blood transfusion volume ≤350 ml ( OR=8.05, 95% CI: 2.94-22.01) and operative time ≤407.5 min ( OR=10.88, 95% CI: 3.90-30.41), the easier it was to achieve TO after PD (all P<0.05). Based on the above influencing factors, a nomogram model of the postoperative effect of PD on TO was established, and the consistency index of this column graph model was 0.863 (95% CI: 0.816-0.911). The sensitivity and specificity of ROC curve were 0.804 and 0.752, respectively. The calibration diagram showed that the calibration curve fits well with the ideal curve, and the decision curve showed that the model had obvious positive net benefit. Conclusion:The degree of tumor differentiation, CT value, blood transfusion volume, and operation time are independent influencing factors for the achievement of TO after PD in patients with pancreatic ductal adenocarcinoma, and the nomogram model constructed based on which has good predictive performance for TO.

Objective:To analyze the influencing factors of not achieving textbook outcome (TO) after laparoscopic radical surgery in patients with malignant pancreatic body and tail tumor, and to establish and evaluate a nomogram for predicting the failure to achieve TO.Methods:The clinical data of 111 patients with malignant pancreatic body and tail tumors undergoing laparoscopic radical surgery in the Department of Hepatobiliary and Pancreatic Surgery in Henan Provincial People's Hospital from January 2020 to December 2022 were retrospectively analyzed, including 44 males and 67 females, aged (53.8±14.7) years. All patients were staged TNM I to II, including pancreatic ductal adenocarcinoma ( n=102, 91.9%), pancreatic neuroendocrine tumor ( n=5, 4.5%), and pancreatic intraductal papillary mucinous tumors ( n=4, 3.6%). The patients were randomly divided into a training set ( n=78) and a test set ( n=33) at a ratio of 7∶3. The 78 patients in the training set were further divided into TO group ( n=28) and control group ( n=50, not achieving TO). Based on the univariate and multivariate logistic regression analysis of training set, the influencing factors of failure to achieve TO after laparoscopic radical surgery in patients with pancreatic body and tail tumor were analyzed. A nomogram based on the multi-factors were established to predict the failure to achieve TO. Receiver operating characteristic (ROC) curve, calibration curve, decision curve analysis (DCA) were utilized to evaluate the nomogram. Results:There were significant differences in tumor diameter, positive lymph nodes, operation time and CT value of pancreas between the TO and control groups (all P<0.05). Multivariate logistic regression analysis showed that tumor diameter >4 cm ( OR=9.673, 95% CI: 2.198-42.579), positive lymph node ( OR=5.385, 95% CI: 1.514-19.154), pancreatic CT value ( OR=0.594, 95% CI: 0.392-0.902) were the influencing factors for patients who did not achieve TO (all P<0.05). Based on the results of multiple factors, a nomogram was established to predict the failure to achieve TO after laparoscopic radical surgery. The area under the ROC curve of the nomogram was 0.849 (95% CI: 0.757-0.940) and 0.873 (95% CI: 0.730-1.000) in the training and test sets, respectively. The calibration curve was close to the ideal curve and the predicted results of the nomogram matched well with the actual results. The DCA showed that the nomogram has obvious positive net benefit. Conclusion:The nomogram constructed with tumor diameter > 4 cm, positive lymph nodes and CT value of pancreas for prediction of the patients with pancreatic body and tail malignant tumor after laparoscopic radical surgery did not achieve TO has good performance.

Objective:To analyze the effect of sarcopenia on the prognosis of patients with hepatocellular carcinoma (HCC) after laparoscopic radical resection.Methods:Clinical data of 165 patients with HCC undergoing laparoscopic radical resection in Henan University People's Hospital from January 2018 to December 2021 were retrospectively analyzed, including 122 males and 43 females, aged (55.5±11.4) years. Patients were divided into sarcopenia group ( n=79) and control group (non-sarcopenia, n=86) according to the skeletal muscle index. The survivals were analyzed using the Kaplan-Meier method, and were compared by the log-rank test. Univariate and multivariate Cox regression were utilized to analyze the effect of sarcopenia on the prognosis of HCC after laparoscopic radical surgery. Results:The 1- and 3-year cumulative survival rates of control group were 96.4% and 81.2%, which were higher than those of the sarcopenia group (83.2% and 48.9%, respectively, χ2=19.67, P<0.001). The 1- and 3-year recurrence-free survival (RFS) rates of control group were 88.4% and 66.1%, which were higher than those of sarcopenia group (70.9% and 37.7%, respectively, χ2=18.80, P<0.001). Multivariate Cox regression analysis showed that the risk of recurrence ( HR=1.35, 95% CI: 1.20-1.59, P<0.001) and the risk of death ( HR=2.21, 95% CI: 1.23-3.41, P=0.001) after laparoscopic radical resection for HCC in patients with sarcopenia rises compared to non-sarcopenic patients. Conclusion:Sarcopenia is a risk factor for the survival and recurrence of HCC after laparoscopic radical surgery.

Objective:To compare the therapeutic efficacy of laparoscopic versus open hepatectomy based on three-dimensional image reconstruction in the treatment of hepatocellular carcinoma (HCC) in the central region of liver.Methods:Clinical data of 118 patients with HCC located in the central region of liver undergoing hepatectomy in the People's Hospital of Zhengzhou University from January 2020 to December 2023 were retrospectively analyzed, including 85 males and 33 females, aged (57.5±8.9) years old. According to surgical approach, patients were divided into two groups: the open surgery group ( n=66) and laparoscopic surgery group ( n=52). All patients underwent three-dimensional image reconstruction preoperatively to determine the tumor location and its relationship with the hepatic vessels. The operative duration, intraoperative blood loss, incidence of postoperative complications, postoperative hospital stay, and prognosis were compared between the groups. Results:Compared to open surgery, patients in laparoscopic group were younger [(55±9) years old vs. (59±8) years old], and experienced a longer operative time [212.5 (152.5, 262.3) min vs. 161.5 (135.8, 210.0) min] and a shorter postoperative hospital stay [11.0(9.0, 13.0) d vs. 13.0(11.0, 15.3) d] (all P<0.05). Postoperative pathology indicated that R0 resection was achieved in both groups. The incidence of postoperative complications were comparable between the two groups [34.6% (18/52) vs. 39.4% (26/66), χ2=0.28, P=0.594]. The 1-year and 3-year recurrence-free survivals were 69.7% and 53.0% in laparoscopic group, similar to those in open group (71.2% and 53.8%, respetctively, P=0.953). Conclusion:Laparoscopic hepatectomy based on three-dimensional image reconstruction is safe and feasible for HCC in central region in terms of clinical prognosis. Laparoscopic surgery is also associated with a shorter postoperative hospital stay.