ObjectiveTo establish the quality standards for Sennae Folium（Cassia angustifolia） dispensing granules based on standard decoctions. MethodsHigh performance liquid chromatography（HPLC） specific chromatograms were established for 15 batches of Sennae Folium（C. angustifolia） standard decoctions and 10 of Sennae Folium（C. angustifolia） dispensing granules from different manufacturers， and the similarity evaluation， hierarchical cluster analysis（HCA） and principal component analysis（PCA） were performed. Linear calibration with two reference substances（LCTRS） and quantitative analysis of multi-components by single-marker（QAMS） were established for the common peaks in the specific chromatograms to determine the contents of main components in the decoction pieces， standard decoctions and dispensing granules， and to calculate their transfer rates from decoction pieces to standard decoctions and dispensing granules. ResultsThe similarities of specific chromatograms of 15 batches of Sennae Folium（C. angustifolia） standard decoctions and 10 batches of Sennae Folium（C. angustifolia） dispensing granules were all greater than 0.95， and a total of 8 characteristic peaks were calibrated， and five of them were identified， including kaempferol-3，7-O-diglucoside， apigenin-6，8-di-C-glucoside， quercetin-3-O-gentianoside， sennoside B and sennoside A. HCA and PCA results showed that there were certain differences in the composition of different batches of standard decoctions， but no clustering was observed in the production area. As the standard decoctions， the extract rate of 15 batches of samples was 26.54%-45.38%， the contents of kaempferol-3，7-O-diglucoside， apigenin-6，8-di-C-glucoside， quercetin-3-O-gentianoside， sennoside B and sennoside A were 12.16-19.26， 2.57-4.94， 3.27-5.11， 6.75-11.39， 4.69-7.79 mg·g^-1， and their transfer rates from decoction pieces to standard decoctions were 45.41%-79.02%， 29.12%-55.07%， 40.52%-67.90%， 24.72%-49.12%， 27.54%-49.34%， respectively. The extract rates of Sennae Folium（C. angustifolia） dispensing granules（C8-C10） were 38.10%-39.50%， the transfer rates of the above five components from decoction pieces to dispensing granules were 72.85%-73.58%， 53.43%-53.94%， 40.19%-40.74%， 24.62%-25.00%， 28.65%-29.11%， respectively， which were generally consistent with the transfer rates from decoction pieces to standard decoctions. ConclusionCompared with the relative retention time method， LCTRS has higher prediction accuracy and is more suitable for chromatographic columns. The established quality control standard of Sennae Folium（C. angustifolia） dispensing granules based on standard decoction is reasonable and reliable， and all indicators of samples from different manufacturers are within the range specified based on the standard decoction， which can provide reference for the quality control and process research of this dispensing granules.

ObjectiveTo establish the specific chromatogram and quantitative analysis of multi-components by single-marker（QAMS） based on linear calibration using two reference substances（LCTRS）， explore the consistency between Hedyotis Herba dispensing granules and standard decoction， and evaluate the quality of the dispensing granules. MethodsHigh performance liquid chromatography（HPLC） specific chromatogram was established based on 15 batches of Hedyotis Herba standard decoction and 10 batches of the dispensing granules， and LCTRS was used to locate chromatographic peaks. The actual retention times of 7 characteristic peaks in the specific chromatogram was measured on 24 different types of C₁₈ columns， taking deacetyl asperulosidic acid and asperulosidic acid as the dual standard compounds， the retention times of the other 5 characteristic peaks were predicted and validated. Based on this， QAMS was developed to determine the contents of four components（deacetyl asperulosidic acid， deacetyl asperulosidic acid methyl ester， asperulosidic acid， and p-coumaric acid）. Then， the relative correction factors of deacetyl asperulosidic acid， deacetyl asperulosidic acid methyl ester and p-coumaric acid were calculated using the reference peak of asperulosidic acid in the dual standard compounds， and each component was quantified accordingly. Finally， the consistency between the dispensing granules and standard decoction was assessed by taking extract rate of the standard decoction， consistency of the specific chromatograms， contents and transfer rates of the indicator components as indexes， and the quality of the dispensing granules was evaluated. ResultsThere were 7 common peaks in the characteristic chromatogram of samples of Hedyotis Herba standard decoction and the dispensing granules， and four of them were identified by reference standards， namely deacetyl asperulosidic acid（peak 1）， deacetyl asperulosidic acid methyl ester（peak 3）， asperulosidic acid（peak 6） and p-coumaric acid（peak 7）. The similarity between the dispensing granules and the standard decoction was >0.9. The absolute deviation in the predicted retention time for each component by LCTRS was lower than that of the relative retention time method. The extract rate of the 15 batches of Hedyotis Herba standard decoction ranged from 7.89% to 14.60%， the contents of deacetyl asperulosidic acid， deacetyl asperulosidic acid methyl ester， asperulosidic acid and p-coumaric acid were 6.62-19.70， 3.83-17.99， 1.57-6.69， 1.62-4.52 mg·g^-1， and the transfer rates of these components from decoction pieces to the standard decoction were 22.89%-39.60%， 34.03%-62.24%， 24.25%-43.70%， and 40.58%-73.71%， respectively. The extract rate， index component contents and transfer rates from decoction pieces to the three batches of Hedyotis Herba dispensing granules（P1-P3）， produced by manufacturer A， were similar to those of the standard decoction prepared from the same batch of decoction pieces， and all fell within the specified range. The contents of the 4 indicator components in 7 batches of the dispensing granules（P4-P10） from manufacturers B-E were all within the range of the content converted from the standard decoction based on the quantity of the dispensing granules. ConclusionThe established specific chromatogram and QAMS based on LCTRS are reasonable and reliable. Based on the evaluation indicators of standard decoction yield， consistency of specific chromatograms， contents and transfer rates of the four index components， the 10 batches of Hedyotis Herba dispensing granules from various manufacturers have exhibited good consistency with the standard decoction， indicating that the current production process is relatively reasonable.

ObjectiveTo establish the specific chromatogram of Chuanxiong Rhizoma dispensing granules（CRdg）， and to evaluate its quality by chemometrics and two reference substances for determination of multiple components（TRSDMC）. MethodsHigh performance liquid chromatography（HPLC） specific chromatograms were established using 13 batches of CRdg from 7 manufacturers， and preliminary quality evaluation was performed by similarity evaluation and chemometrics analysis. Eight characteristic peaks in the specific chromatogram of CRdg were measured on 22 different types of C₁₈ columns， and the actual retention times were recorded. Taking chlorogenic acid（peak 1） and senkyunolide A（peak 8） as double standard compounds， the retention times of the eight characteristic peaks were predicted by linear calibration using two reference substances（LCTRS）， and the method was validated on three other columns of different brands. Taking chlorogenic acid as reference peak， the relative correction factor method（RCFM） was used to quantify cryptochlorogenic acid， caffeic acid， ferulic acid， senkyunolide I and senkyunolide A， and the results were compared with the external standard method（ESM）. ResultsThe similarities of specific chromatograms of 13 batches of CRdg were all >0.90， and a total of 8 characteristic peaks were calibrated， and six of them were identified， including chlorogenic acid（peak 1）， cryptochlorogenic acid（peak 2）， caffeic acid（peak 3）， ferulic acid（peak 5）， senkyunolide I（peak 6） and senkyunolide A（peak 8）. Through chemometric analysis， it was found that ferulic acid， chlorogenic acid， senkyunolide I and cryptochlorogenic acid were the main components causing quality difference in CRdg， and the accuracy of LCTRS in predicting the retention time of 8 characteristic peaks was superior to that of the relative retention time method（RRT）. Further comparison of the results obtained from RCFM and ESM showed that there was no statistically significant difference between the two methods. ConclusionA quality evaluation method for CRdg based on HPLC specific chromatogram and TRSDMC is established， its qualitative accuracy is better than that of RRT， the quantitative accuracy is similar to that of ESM， and 4 quality-differentiated components among different manufacturers are found. This method is stable and reliable， and has reference value for the quality evaluation of other dispensing granules.

ObjectiveTo establish the specific chromatogram of Chuanxiong Rhizoma dispensing granules（CRdg）， and to evaluate its quality by chemometrics and two reference substances for determination of multiple components（TRSDMC）. MethodsHigh performance liquid chromatography（HPLC） specific chromatograms were established using 13 batches of CRdg from 7 manufacturers， and preliminary quality evaluation was performed by similarity evaluation and chemometrics analysis. Eight characteristic peaks in the specific chromatogram of CRdg were measured on 22 different types of C₁₈ columns， and the actual retention times were recorded. Taking chlorogenic acid（peak 1） and senkyunolide A（peak 8） as double standard compounds， the retention times of the eight characteristic peaks were predicted by linear calibration using two reference substances（LCTRS）， and the method was validated on three other columns of different brands. Taking chlorogenic acid as reference peak， the relative correction factor method（RCFM） was used to quantify cryptochlorogenic acid， caffeic acid， ferulic acid， senkyunolide I and senkyunolide A， and the results were compared with the external standard method（ESM）. ResultsThe similarities of specific chromatograms of 13 batches of CRdg were all >0.90， and a total of 8 characteristic peaks were calibrated， and six of them were identified， including chlorogenic acid（peak 1）， cryptochlorogenic acid（peak 2）， caffeic acid（peak 3）， ferulic acid（peak 5）， senkyunolide I（peak 6） and senkyunolide A（peak 8）. Through chemometric analysis， it was found that ferulic acid， chlorogenic acid， senkyunolide I and cryptochlorogenic acid were the main components causing quality difference in CRdg， and the accuracy of LCTRS in predicting the retention time of 8 characteristic peaks was superior to that of the relative retention time method（RRT）. Further comparison of the results obtained from RCFM and ESM showed that there was no statistically significant difference between the two methods. ConclusionA quality evaluation method for CRdg based on HPLC specific chromatogram and TRSDMC is established， its qualitative accuracy is better than that of RRT， the quantitative accuracy is similar to that of ESM， and 4 quality-differentiated components among different manufacturers are found. This method is stable and reliable， and has reference value for the quality evaluation of other dispensing granules.

Objective To analyze the value of serum neutrophil count (NEUT), homocysteine (Hcy), adiponectin (APN) and blood glucose in predicting the occurrence of acute myocardial infarction (AMI) in patients with coronary heart disease. Methods The clinical data of 98 patients with coronary heart disease who were admitted to the hospital from March 2022 to March 2024 were collected retrospectively. Patients included were divided into AMI group (n=33) and non-AMI group (n=65) according to the presence and absence of AMI. Baseline data, complications, ultrasound examination data and laboratory examination data were collected. Multivariate logistic regression analysis was performed to identify the influencing factors of AMI in patients with coronary heart disease. The receiver operating characteristic curves were used to evaluate the predictive value of NEUT, Hcy, APN and blood glucose for AMI in patients with coronary heart disease. Results The levels of fasting plasma glucose (FPG), 2-hour postprandial plasma glucose (2hPG), glycosylated hemoglobin (HbA1c), NEUT, APN, Hcy, N-terminal pro B-type natriuretic peptide (NT-proBNP), C-reactive protein (CRP), red blood cell distribution width (RDW) and white blood cell (WBC) in the AMI group were higher than those in the non-AMI group (P<0.05). Logistic regression analysis found that FPG, 2hPG, HbA1c, NEUT, APN, Hcy, NT-proBNP, CRP, RDW, and WBC were independent influencing factors of AMI in patients with coronary heart disease (P<0.05). ROC curves indicated that the levels of FPG, 2hPG, HbA1c, NEUT, APN and Hcy were abnormally elevated in patients with coronary heart disease. Above indicators were helpful for predicting the occurrence of AMI. The area under the curve (AUC) and sensitivity of FPG for predicting AMI in patients with coronary heart disease were the best (P<0.05). Conclusion Abnormal elevated levels of FPG, 2hPG, HbA1c, NEUT, APN and Hcy are independent risk factors for AMI in patients with coronary heart disease. All of these indicators have predictive value.

Numerous c-mesenchymal-epithelial transition (c-MET) inhibitors have been reported as potential anticancer agents. However, most fail to enter clinical trials owing to poor efficacy or drug resistance. To date, the scaffold-based chemical space of small-molecule c-MET inhibitors has not been analyzed. In this study, we constructed the largest c-MET dataset, which included 2,278 molecules with different structures, by inhibiting the half maximal inhibitory concentration (IC₅₀) of kinase activity. No significant differences in drug-like properties were observed between active molecules (1,228) and inactive molecules (1,050), including chemical space coverage, physicochemical properties, and absorption, distribution, metabolism, excretion, and toxicity (ADMET) profiles. The higher chemical diversity of the active molecules was downscaled using t-distributed stochastic neighbor embedding (t-SNE) high-dimensional data. Further clustering and chemical space networks (CSNs) analyses revealed commonly used scaffolds for c-MET inhibitors, such as M5, M7, and M8. Activity cliffs and structural alerts were used to reveal "dead ends" and "safe bets" for c-MET, as well as dominant structural fragments consisting of pyridazinones, triazoles, and pyrazines. Finally, the decision tree model precisely indicated the key structural features required to constitute active c-MET inhibitor molecules, including at least three aromatic heterocycles, five aromatic nitrogen atoms, and eight nitrogen-oxygen atoms. Overall, our analyses revealed potential structure-activity relationship (SAR) patterns for c-MET inhibitors, which can inform the screening of new compounds and guide future optimization efforts.

Abstract In recent years, the prevalence of overweight and obesity among children and adolescents has risen rapidly, posing a serious threat to their physical and mental health. To provide scientific, systematic, and standardized weight management guidance for overweight and obese children and adolescents, the study focuses on the core concept of healthy lifestyle intervention, integrates multidisciplinary expert opinions and research findings,and proposes a comprehensive multidisciplinary intervention framework covering scientific exercise intervention, precise nutrition and diet, optimized sleep management, and standardized psychological support. It calls for the establishment of a multi agent collaborative management mechanism led by the government, implemented by families, fostered by schools, initiated by individuals, optimized by communities, reinforced by healthcare, and coordinated by multiple stakeholders. Emphasizing a child and adolescent centered approach, the consensus advocates for comprehensive, multi level, and personalized guidance strategies to promote the internalization and maintenance of a healthy lifestyle. It serves as a reference and provides recommendations for the effective prevention and control of overweight and obesity, and enhancing the health level of children and adolescents.

Lymphatic metastasis is the main metastatic route for colorectal cancer, which increases the risk of cancer recurrence and distant metastasis. The properties of the lymph node metastatic colorectal cancer (LNM-CRC) cells are poorly understood, and effective therapies are still lacking. Here, we found that hypoxia-induced fibroblast activation protein alpha (FAPα) expression in LNM-CRC cells. Gain- or loss-function experiments demonstrated that FAPα enhanced tumor cell migration, invasion, epithelial-mesenchymal transition, stemness, and lymphangiogenesis via activation of the STAT3 pathway. In addition, FAPα in tumor cells induced extracellular matrix remodeling and established an immunosuppressive environment via recruiting regulatory T cells, to promote colorectal cancer lymph node metastasis (CRCLNM). Z-GP-DAVLBH, a FAPα-activated prodrug, inhibited CRCLNM by targeting FAPα-positive LNM-CRC cells. Our study highlights the role of FAPα in tumor cells in CRCLNM and provides a potential therapeutic target and promising strategy for CRCLNM.

BACKGROUND:In recent years,computer-assisted navigation has gradually attracted attention in the medical field.Some scholars have reported that the clinical effects of computer navigation in total knee arthroplasty vary.To explore the clinical effect of the new generation of Brainlab Knee 3 navigation system,this study is conducted. OBJECTIVE:To analyze the application effect of computer navigation system(Brainlab Knee 3)combined with gap balance technology in total knee arthroplasty. METHODS:A total of 71 patients received total knee arthroplasty at the Department of Joint Surgery of Dalian Second People's Hospital from November 2020 to May 2021.In the navigation group,35 patients underwent total knee arthroplasty by computer navigation combined with gap balance.In the traditional group,36 patients underwent osteotomy with traditional surgical instruments.The difference between medial and lateral joint spaces,knee range of motion,hospital for special surgery knee score,hip-knee-ankle angle,deviation values of coronal femoral component angle,coronal tibial component angle,and sagittal tibial component angle were compared between the two groups. RESULTS AND CONCLUSION:(1)In the navigation group,the differences of intraoperative medial and lateral joint gap at knee extension 0,1,and 2 mm were found in 19,14,and 2 cases,respectively.The gap difference was 0 mm in 18 cases,1 mm in 15 cases and 2 mm in 2 cases at 90° degree knee flexion.In the traditional group,the gap difference at knee extention was 0 mm in 10 cases,1 mm in 20 cases,and 2 mm in 6 cases.The gap difference at 90 degree knee flexion was 0 mm in 10 cases,1 mm in 15 cases and 2 mm in 8 cases.(2)The operation time in the navigation group was longer than that in the traditional group(P<0.05),and two patients in the navigation group developed lower limb intermuscular vein thrombosis after surgery,and none of the patients in the traditional group had complications.(3)The range of motion between the two groups increased significantly at 6 and 12 months after surgery,and the range of motion in the navigation group was higher than that in the traditional group(P<0.05).(4)At 12 months after surgery,the hospital for special surgery knee scores of both groups increased significantly,and the hospital for special surgery knee score in the navigation group was higher than that in the traditional group(P<0.05).(5)At 6 months after surgery,the deviation values of hip-knee-ankle angle,coronal femoral component angle,coronal tibial component angle,and sagittal tibial component angle of navigation group were significantly lower than those in the traditional group(P<0.05).(6)The results showed that computer navigation technique combined with gap balance in total knee arthroplasty had advantages in postoperative range of motion,lower limb alignment and the accuracy of tibial prosthesis component position,and joint function recovered well.

Objective To explore the influencing factors of the efficacy of programmed death-1(PD-1)inhibitor pembrolizumab in the treatment of cervical cancer.Methods The clinical data of cervical cancer patients admitted to the Department of Obstetrics and Gynecology of Anhui Women and Children's Medical Center from January 2020 to October 2023 were retrospectively analyzed and the patients were divided into the ineffective group and the effective group according to the pembrolizumab treatment efficacy.The clinical data of patients in the two groups were compared[age,tumor type,pathological type,lesion size,differentiation degree,number of pregnancies,number of births,number of miscarriages,menopausal status,tumor mutation load(TMB),DNA repair gene mutation status,PD-L1 expression,diabetes mellitus,hypertension,mode of treatment,body mass index,tumor-infiltrating lymphocyte(TIL)expression,neoantigen intra-tumor heterogeneity(ITH)status,presence of liver disease,and family history],and logistic regression analysis was used to determine the risk factors affecting the efficacy of pembrolizumab in cervical cancer patients.Results A total of 60 patients were included in the study,with 42 in the effective group and 18 in the ineffective group.The proportion of patients with TMB＜143/Mb,no mutation in DNA repair genes,low expression of PD-L1,simple immunotherapy,TIL negative,and high PTH in the ineffective group was higher than that in the effective group(P＜0.05).Multivariate Logistic regression analysis showed that TMB＜143/Mb,non-mutated DNA repair genes,low PD-L1 expression,simple immunotherapy,TIL negative,and high PTH were risk factors affecting the efficacy of pembrolizumab in cervical cancer patients(P＜0.05).Conclusion The efficacy of the PD-1 inhibitor pembrolizumab in cervical cancer patients is influenced by factors such as TMB,DNA gene mutations,PD-L1 expression,treatment mode,TIL,and ETH.