OBJECTIVE To provide a scientific basis for the quality evaluation and clinical application of Qingwen hufei granules. METHODS Fourteen batches of Qingwen hufei granules were used as samples to establish high-performance liquid chromatography （HPLC） fingerprints using the Similarity Evaluation System for Chromatographic Fingerprint of Traditional Chinese Medicine （2012 Edition）. The chromatographic peaks were identified and the similarity was evaluated. Cluster analysis （CA）， principal component analysis （PCA）， and orthogonal partial least squares-discriminant analysis （OPLS-DA） were used to conduct chemical pattern recognition analysis on the 14 batches of samples. Meanwhile， the contents of neochlorogenic acid （NGA）， chlorogenic acid （CHA）， cryptochlorogenic acid （CGA）， forsythoside A （FTA）， 3，5-O-dicaffeoylquinic acid （3，5-O- DA）， 4，5-O-dicaffeoylquinic acid （4，5-O-DA）， and angoroside C （AGC） in the samples were determined by HPLC. RESULTS The methodological investigation results of both the fingerprint and the content determination complied with the relevant requirements. Fourteen common peaks were indicated in the HPLC fingerprints of the 14 batches of samples， and 7 of them were identified [NGA （peak 2）， CHA （peak 3）， CGA （peak 5）， FTA （peak 11）， 3，5-O-DA （peak 12）， 4，5-O-DA （peak 13）， and AGC （peak 14）]； the similarity of each sample was greater than 0.94. The results of CA and PCA showed that the samples could be classified into 3 categories； the results of OPLS-DA indicated that peak 4 （unknown）， peak 11 （FTA）， peak 8 （unknown）， peak 9 （unknown）， and peak 1 （unknown） were the differential components. The content ranges of NGA， CHA， CGA， 3，5-O-DA， FTA， 4，5-O-DA and AGC in the 14 batches of samples were 0.210 4-0.458 7， 0.269 1-0.506 3， 0.228 1-0.461 1， 0.443 9-1.044 6， 0.066 7-0.155 7， 0.062 8-0.143 8， and 0.057 4-0.105 7 mg/g， respectively. CONCLUSIONS The HPLC fingerprint and multi-component content determination methods established in this study are efficient and reliable， and can be used for the quality evaluation of Qingwen hufei granules.

ObjectiveTo investigate the mechanism of modified Si Junzitang and Shashen Maidong Tang ［Yiqi Yangyin Jiedu prescription （YQYYJD）］ in enhancing the sensitivity of cisplatin in epidermal growth factor receptor tyrosine kinase inhibitor （EGFR-TKI）-resistant lung adenocarcinoma cells based on aerobic glycolysis. MethodsThe effects of different concentrations of YQYYJD （0， 2， 3， 4， 5， 6， 7， 8 g·L^-1） and cisplatin （0， 3， 6， 9， 12， 15， 18， 21， 24， 27 mg·L^-1） on the proliferation and activity of PC9/GR cells were detected by the cell counting kit-8 （CCK-8） assay after 24 hours of intervention. The half-maximal inhibitory concentration （IC₅₀） for PC9/GR cells was calculated to determine the concentrations used in subsequent experiments. PC9/GR cells were divided into blank group （complete medium）， YQYYJD group （5 g·L^-1）， cisplatin group （12 mg·L^-1）， and combined group （YQYYJD 5 g·L^-1 + cisplatin 12 mg·L^-1）. After 24 hours of intervention， cell viability was measured using CCK-8 assay. Cell proliferation was assessed by colony formation assay， and cell migration was evaluated by scratch and Transwell assays. Glucose consumption， lactate production， and adenosine triphosphate （ATP） levels were measured by colorimetric assays. The expression levels of glycolysis-related proteins， including hexokinase 2 （HK2）， phosphofructokinase P （PFKP）， pyruvate kinase M2 （PKM2）， lactate dehydrogenase A （LDHA）， glucose transporter 1 （GLUT1）， and monocarboxylate transporter 4 （MCT4）， were determined by Western blot. ResultsBoth YQYYJD and cisplatin inhibited the viability of PC9/GR cells in a concentration-dependent manner. The IC₅₀ of PC9/GR cells for YQYYJD and cisplatin were 5.15 g·L^-1 and 12.91 mg·L^-1， respectively. In terms of cell proliferation， compared with the blank group， the cell survival rate and the number of colonies formed in the YQYYJD group， cisplatin group， and combined group were significantly decreased （P<0.01）. Compared with the YQYYJD and cisplatin groups， the combined group showed a further significant reduction in cell survival rate and colony formation （P<0.01）. In terms of cell migration， compared with the blank group， the cell migration rate and the number of cells passing through the Transwell membrane in the YQYYJD group， cisplatin group， and combined group were significantly decreased （P<0.01）. Compared with the YQYYJD and cisplatin groups， the combined group exhibited a further significant reduction in cell migration rate and the number of cells passing through the Transwell membrane （P<0.01）. In terms of glycolysis， compared with the blank group， glucose consumption， lactate production， and ATP levels in the YQYYJD group， cisplatin group， and combined group were significantly decreased （P<0.01）. Compared with the YQYYJD and cisplatin groups， the combined group showed a further significant reduction in glucose consumption， lactate production， and ATP levels （P<0.05）. Compared with the blank group， the protein expression levels of HK2， PFKP， PKM2， and LDHA in the YQYYJD， cisplatin， and combined groups were significantly decreased （P<0.01）. The combined group showed a further significant reduction in the expression levels of these proteins compared with the YQYYJD and cisplatin groups （P<0.01）. No significant differences were observed in the protein expression levels of GLUT1 and MCT4 among the groups. ConclusionYQYYJD can synergistically inhibit the proliferation and migration of PC9/GR cells and enhance their sensitivity to cisplatin. The mechanism may be related to the downregulation of the expression of glycolysis-related rate-limiting enzymes， including HK2， PFKP， PKM2， and LDHA， thereby inhibiting glycolysis.

ObjectiveThrough qualitatively and quantitatively analysis of the differences in chemical composition between the combined decoction and single decoction of Huaganjian and comparison of their core efficacy， to explore the rationality of the flexible clinical application of Huaganjian compound preparations and single-flavored dispensing granules. MethodsUltra performance liquid chromatography-quadrupole-electrostatic field orbitrap high resolution mass spectrometry（UPLC-Q-Exactive Orbitrap MS） was used to qualitatively analyze the combined decoction and single decoction samples of Huaganjian， and meanwhile， the contents of four index components（geniposide， paeoniflorin， hesperidin and paeonol） were quantitatively analyzed by high performance liquid chromatography（HPLC）. Nonalcoholic fatty liver disease（NAFLD） rat model induced by high-fat diet was applied to compare the efficacy of combined decoction and single decoction of Huaganjian. A total of 30 male SD rats were randomly divided into the control group， model group， lovastatin group（1.8 mg·kg^-1）， combined decoction group（1.26 g·kg^-1） and single decoction group（1.18 g·kg^-1）. After successful modeling， lovastatin group， combined decoction group and single decoction group were given corresponding doses of drugs by intragastric administration every day， and the control group and model group were given equal amounts of normal saline by intragastric administration， after 4 weeks of administration， the serum and liver tissues were collected， and the contents of alanine aminotransferase（ALT）， aspartate aminotransferase（AST）， total cholesterol（TC）， triglyceride（TG）， low-density lipoprotein cholesterol（LDL-C） and high-density lipoprotein cholesterol（HDL-C） in serum of rats were detected， and the liver pathological examination was carried out by hematoxylin-eosin（HE） staining and oil red O staining， so as to compare differences of their efficacy. ResultsSeventy chemical components were initially identified and attributed from the lyophilized powder of the combined decoction and single decoction samples of Huaganjian， and there was no obvious difference in composition between the two. Further quantitative analysis showed that the contents of geniposide， paeoniflorin， hesperidin and paeonol in the combined decoction samples were significantly increased when compared with those of the single decoction samples（P<0.01）. The pharmacodynamic results showed that compared with the model group， both the combined and single decoction groups of Huaganjian could improve the liver index of NAFLD rats， reduce the serum levels of AST， ALT， TC， TG and LDL-C， increase the serum level of HDL-C， and ameliorate the pathological changes of liver cell steatosis and fat accumulation. However， there was no significant difference in pharmacodynamic effects between the combined decoction group and the single decoction group. ConclusionThere is no significant difference between the combined decoction and single decoction of Huaganjian in terms of chemical composition， but the contents of the four index components show significantly difference. Both of them can significantly improve the fat accumulation and liver function in NAFLD rats. This study provides a reference basis for the rational clinical application and evaluation of famous classical formula compound preparations and single-flavored dispensing granules.

OBJECTIVE To systematically investigate the current status and effectiveness of the standardized on-the-job training program for community clinical pharmacists in Shanghai， and to provide a scientific basis for optimizing the training scheme. METHODS A questionnaire survey was conducted to collect the data from trainees and mentor pharmacists who participated in the program between 2016 and 2024. The survey examined their basic information， evaluations of the training scheme， satisfaction with training outcomes， and suggestions for improvement. Statistical analyses were also conducted. RESULTS A total of 420 valid responses were collected， including 340 from trainees and 80 from mentor pharmacists. Before training， only 30.29% of trainees were engaged in clinical pharmacy-related work， whereas this proportion increased to 73.24% after training. Most mentor pharmacists had extensive experience in clinical pharmacy （76.25% with ≥5 years of experience） and mentoring （78.75% with ≥3 teaching sessions）. Totally 65.59% of trainees and 55.00% of mentor pharmacists believed that blended training yielded the best learning outcomes. Over 80.00% of both trainees and mentor pharmacists considered the overall training duration， theoretical study time， and practical training time to be reasonable. More than 95.00% of trainees and mentor pharmacists agreed that the homework and assessment schemes were appropriate. Trainees rated the relevance of training content to their actual work highly （with an average relevance score ＞4.5）， though they perceived the chronic disease medication therapy management module as significantly more challenging than the prescription review and evaluation module and the home-based pharmaceutical care module. The average satisfaction score of trainees and mentor pharmacists with the training effectiveness of each project was above 4 points， indicating a high overall satisfaction. Inadequate provision of teaching resources was unanimously recognized by trainees and mentor pharmacists as the key area requiring improvement. CONCLUSIONS The standardized on-the-job training program for community clinical pharmacists in Shanghai has contributed to improving pharmaceutical services in community healthcare settings. However， ongoing improvements must concentrate on content design， resource development， and faculty cultivation.

Objective: To analyze the association of participation in non-sports extracurricular tutoring classes with the prevalence of screening myopia, axial length (AL) and axial length to corneal radius ratio (AL/CR) among primary school students, so as to provide evidences for formulating myopia prevention and control policies. Methods: In December 2024, combination of convenience and cluster sampling method was used to select 2 273 students from two primary schools in Hefei City, Anhui Province. Ophthalmic examinations and questionnaire surveys were conducted to obtain information on myopia, AL, AL/CR and participation in various types of extracurricular tutoring. A binary Logistic regression model was used to analyze the association between non-sports tutoring and screening myopia, and multiple linear regression models were used to examine the associations between non-sports tutoring and AL and AL/CR. Results: Among the surveyed students, the participation rate in non-sports extracurricular tutoring classes was 64.9% , and the overall prevalence of screening myopia was 39.1%. The average AL and AL/CR were (23.60± 1.01 ) mm and (3.00±0.12), respectively. Univariate analysis showed that students who attended non-sports, music, or academic tutoring classes for ≥2 h per week had higher risks of screening myopia and greater AL/CR values than non-participants (screening myopia: OR =1.38, 1.82, 1.55; AL/CR: β =0.01, 0.03, 0.03; all P <0.05). After adjusting for sex, grade, and participation in sports tutoring, multivariate analysis indicated that participation in non-sports and musical instrument tutoring classes for ≥2 h per week remained significantly associated with higher risks of screening myopia ( OR =1.26, 1.49, both P <0.05). Multiple linear regression showed that participation in musical instrument tutoring for ≥2 h per week was positively correlated with AL ( β=0.14, P < 0.05). Conclusions Participation in non-sports extracurricular tutoring is common among primary school students. Attending non-sports tutoring classes for ≥2 h per week increases the risk of screening myopia.

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

Musculoskeletal disorders (MSDs) are characterized by extensive pathological involvement and high prevalence and cause a significant disease burden. Long-term drug administration often causes by adverse effects with poor therapeutic efficacy. Low-intensity pulsed ultrasound (LIPUS), as a specialized therapeutic modality, delivers acoustic energy at a low intensity in a pulsed wave mode, thus ensuring stable energy transmission to the target tissues while minimizing thermal effects. This non-invasive approach has demonstrated significant potential for MSD treatment by delivering effective physical stimulations. Extensive animal and clinical studies have demonstrated the efficacy of LIPUS for accelerating the healing process of fresh fractures and nonunions, promoting soft tissue regeneration and suppressing inflammatory responses. Emerging evidence suggests promising applications of LIPUS in skeletal muscle injury treatment and promoting tissue regeneration and repair. This review outlines the recent advancements and mechanistic studies of LIPUS for treatment of common MSDs including fractures, nonunions, muscle injuries, and osteoarthritis, addressing also the technical parameters of commercially available LIPUS devices, current therapeutic approaches, the existing challenges, and future research directions.
Humans ; Ultrasonic Therapy/methods* ; Musculoskeletal Diseases/therapy* ; Ultrasonic Waves ; Osteoarthritis/therapy* ; Muscle, Skeletal/injuries*

Objective:To investigate the diagnostic value of plasma cytokines such as interleukin (IL)-2, IL-6 and interferon (IFN)-γ in non-Hodgkin lymphoma (NHL).Methods:A retrospective case-control study was conducted. A total of 48 NHL patients admitted to the Second Affiliated Hospital of Xuzhou Medical University between January 2020 and December 2022 were selected as NHL group, and another 34 healthy people who underwent physical examimation during the same period were selected as the healthy control group. The levels of IL-2, IL-4, IL-6, IL-10, IL-17, tumor necrosis factor (TNF) - α and IFN-γ in the plasma of patients at first admission and healthy subjects during physical examination were detected by using flow cytometry. The differences in general data and all cytokines levels of both groups were compared. The collinearity stepwise screening was made in 7 cytokines levels, and the screened variables were included in multivariate binary logistic regression model. Plasma cytokines with independent effects on the pathogenesis of NHL were screened. Taking local biopsy, histopathological examination or immunohistochemical examination as the gold standard, the receiver operating characteristic (ROC) curves of individual and combined diagnosis of NHL based on the selected cytokines were drawn to judge the diagnostic effect of all indicators on NHL.Results:There were 32 males (66.7%) and 16 females (33.3%) in NHL group, with the median age [ M ( Q1, Q3)] of 56.50 (45.75, 67.50) years; there were 28 males (82.4%) and 6 females (17.6%) in the healthy control group, with the median age of 52.00 (47.50, 55.50) years. There were no statistically significant differences in age and gender composition between the 2 groups (all P > 0.05). The levels of IL-2 [1.44 (1.36, 1.85) pg/ml vs. 1.19 (0.86, 1.68) pg/ml] and TNF-α [3.46 (2.68, 4.06) pg/ml vs. 2.23 (1.52, 3.46) pg/ml] in NHL group were higher than those in the healthy control group, and the differences were statistically significant (all P < 0.05). There were no statistically significant differences in IL-4, IL-6, IL-10, IL-17, IFN-γ levels (all P > 0.05). According to collinear stepwise screening of independent variables, IL-4 and TNF-α were excluded from 7 cytokines, and the other 5 cytokines were included in multivariate logistic regression model, and the result showed that the decreased level of IL-2 ( OR = 0.20, 95% CI: 0.08-0.53, P = 0.001) and the increased levels of IL-6 ( OR = 1.18, 95% CI: 1.04-1.33, P = 0.009) and IFN-γ ( OR = 1.26, 95% CI: 1.08-1.46, P = 0.003) were independent risk factors for the onset of NHL. The results showed that the area under the curve of IL-2, IL-6, IFN-γ and the combination of 3 indexes for the diagnosis of NHL was 0.760 (95% CI: 0.651-0.870), 0.595 (95% CI: 0.468-0.722), 0.508 (95% CI: 0.373-0.642), 0.847 (95% CI: 0.763-0.930), and the optimal cut-off value of the combination of 3 indexes was 0.730 which was calculated by logistic regression model formula; the corresponding sensitivity and specificity were 70.2% and 94.1%, respectively. Conclusions:The decreased level of IL-2 and increased levels of IL-6 and IFN-γ at initial diagnosis are risk factors for the onset of NHL. The combined detection of the 3 indexes shows a good value in the diagnosis of NHL.

Objective To investigate the therapeutic effects and mechanisms of Hibiseu Manihot L.fructus on type 2 diabetes mellitus(T2DM)mice.Methods T2DM mice were randomly divided into normal group,model group,positive drug group,Hibiseu Manihot L.fructus total extract group,water-solube part group,and Hibiseu Manihot L.fructus ethyl acetate fraction group,with 10 mice in each group.After 4 weeks of treatment,anti-diabetic effects were evaluated by monitoring body mass,fasting blood glucose(FBG),oral glucose tolerance test(OGTT),fasting insulin(FINS),homeostasis model assessment of insulin resistance(HOMA-IR),and area under the blood glucose curve(AUC).Liver tissue status was assessed through liver index and hematoxylin-eosin(HE)staining.Results Compared with the model group,the water-solube part and total extract group showed significant improvements in mental status,food intake,body mass,excretion,and the FBG elevation was effectively suppressed,OGTT,FINS,AUC,HOMA-IR and liver index were significantly decreased(P＜0.05 or P＜0.01),the histopathological analysis revealed improved liver tissue morphology.Regarding channel protein expression,compared with the model group,the water-solube part group exhibited significantly upregulated phosphorylation levels of protein kinase B(AKT)and phosphatidylinositol 3-kinase(PI3K)in mouse liver tissue(P＜0.05),furthermore,the positive drug group,total extract group,and water-solube part group all demonstrated markedly increased phosphorylation of adenosine monophosphate-activated protein kinase(AMPK)in hepatic tissues(P＜0.05).Conclusion The water-solube part of fructus of Hibiseu Manihot L fructus.effectively alleviates T2DM symptoms(polyphagia,polydipsia,polyuria,weight loss)and glucose metabolism disorders,with hepatoprotective effects potentially mediated through PI3K/AKT pathway activation and enhanced p-AMPK expression.

OBJECTIVE To conduct rapid health technology assessment （HTA） of ulinastatin （UTI）， and to evaluate the efficacy， safety and cost-effectiveness of UTI in the treatment of acute pancreatitis （AP）. METHODS Retrieved from PubMed， Embase， the Cochrane Library， CNKI， Wanfang database， CBM and official websites of HTA institutions， the systematic review （SR）/meta-analysis， economic evaluation and HTA reports of UTI in the treatment of AP were collected from the inception to Apr. 2024. Two researchers independently conducted screening， quality evaluation and data extraction according to the admission and exclusion criteria， and descriptive analysis was adopted to analyze and summarize the data. RESULTS A total of 19 studies were included， involving 15 SR/meta-analysis and 4 economic studies， and no HTA report was retrieved. In the treatment of AP， UTI showed clear advantages over conventional treatment alone in terms of improving the overall effective rate， shortening the recovery time of amylase， reducing the time required to relieve abdominal pain and distension， lowering the mortality rate， and decreasing the average hospital stay. Compared to other positive drugs （carbendate mesylate， octreotide， somatostatin， etc.）， its efficacy is similar， with a favorable safety profile. As far as the current research was concerned， UTI had obvious economic advantages over other positive drugs. CONCLUSIONS UTI is safe and effective in the treatment of AP， and has economic advantages.