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.

Yuejuwan is a classic formula widely used by doctors to relieve liver and depression， with precise clinical efficacy in traditional Chinese medicine （TCM）. The authors used bibliometric methods to collect and collate 495 ancient data related to Yuejuwan， and 105 valid data were screened out， involving 68 ancient Chinese medical books. After systematic verification of the origin of the formula of Yuejuwan， the main treatment symptoms， the principle of the formula， the composition of the drug， the dosage， the preparation method， the decoction method， and other information， the results showed that Yuejuwan originated from the Danxi Xinfa （《丹溪心法》） of the Yuan Dynasty by ZHU Zhenheng， and it is composed of five medicines， namely Atractylodis Rhizoma， Cyperi Rhizom， Chuanxiong Rhizoma， Massa Medicata Fermentata， and Gardeniae Fructus. In terms of drug base， Atractylodis Rhizoma， Cyperi Rhizom， Chuanxiong Rhizoma， and Gardeniae Fructus are in line with the records in the 2020 edition of Chinese Pharmacopoeia， and Massa Medicata Fermentata is used. The preparation method is as follows： Massa Medicata Fermentata and Gardeniae Fructus are fried， and Cyperi Rhizoma is roasted in vinegar. Chuanxiong Rhizoma is used in the raw form， and Atractylodis Rhizoma is prepared with rice swill. The formula can regulate Qi and relieve depression and broaden the middle and remove fullness. It is clinically used for the treatment of six types of depression syndromes， chest and diaphragm plumpness， abdominal distension and leg acid， acid swallowing and vomiting， eating and drinking disharmony， toothache， mouth and tongue sores， and other diseases. The most used dosage of the formula in the ancient records through the ages is converted into the modern dosage， namely 3.05 g Atractylodis Rhizoma， 3.05 g Cyperi Rhizoma， 3.05 g Chuanxiong Rhizoma， 3.05 g Massa Medicata Fermentata， and 3.05 g Gardeniae Fructus， and the daily dosage is 15.25 g. The converted dosage is similar to that recorded in the 2020 edition of the Chinese Pharmacopoeia. The formula is in pill form， and medicine should be taken with lukewarm boiled water after the meal. Through the excavation of the ancient literature related to Yuejuwan， the key information of the formula is identified， with a view to providing a more accurate reference for the clinical application of Yuejuwan and subsequent in-depth investigation.

Yuejuwan is a classic formula widely used by doctors to relieve liver and depression， with precise clinical efficacy in traditional Chinese medicine （TCM）. The authors used bibliometric methods to collect and collate 495 ancient data related to Yuejuwan， and 105 valid data were screened out， involving 68 ancient Chinese medical books. After systematic verification of the origin of the formula of Yuejuwan， the main treatment symptoms， the principle of the formula， the composition of the drug， the dosage， the preparation method， the decoction method， and other information， the results showed that Yuejuwan originated from the Danxi Xinfa （《丹溪心法》） of the Yuan Dynasty by ZHU Zhenheng， and it is composed of five medicines， namely Atractylodis Rhizoma， Cyperi Rhizom， Chuanxiong Rhizoma， Massa Medicata Fermentata， and Gardeniae Fructus. In terms of drug base， Atractylodis Rhizoma， Cyperi Rhizom， Chuanxiong Rhizoma， and Gardeniae Fructus are in line with the records in the 2020 edition of Chinese Pharmacopoeia， and Massa Medicata Fermentata is used. The preparation method is as follows： Massa Medicata Fermentata and Gardeniae Fructus are fried， and Cyperi Rhizoma is roasted in vinegar. Chuanxiong Rhizoma is used in the raw form， and Atractylodis Rhizoma is prepared with rice swill. The formula can regulate Qi and relieve depression and broaden the middle and remove fullness. It is clinically used for the treatment of six types of depression syndromes， chest and diaphragm plumpness， abdominal distension and leg acid， acid swallowing and vomiting， eating and drinking disharmony， toothache， mouth and tongue sores， and other diseases. The most used dosage of the formula in the ancient records through the ages is converted into the modern dosage， namely 3.05 g Atractylodis Rhizoma， 3.05 g Cyperi Rhizoma， 3.05 g Chuanxiong Rhizoma， 3.05 g Massa Medicata Fermentata， and 3.05 g Gardeniae Fructus， and the daily dosage is 15.25 g. The converted dosage is similar to that recorded in the 2020 edition of the Chinese Pharmacopoeia. The formula is in pill form， and medicine should be taken with lukewarm boiled water after the meal. Through the excavation of the ancient literature related to Yuejuwan， the key information of the formula is identified， with a view to providing a more accurate reference for the clinical application of Yuejuwan and subsequent in-depth investigation.

ObjectiveTo investigate the dynamic expression profiles and potential regulatory mechanisms of long non-coding RNAs （lncRNAs） in male reproductive system aging. MethodsA naturally aging C57BL/6 mouse model was used and 4 mice were selected each at 3， 15， and 21 months of age. RNA was extracted from seven regions of the male reproductive tract （testis， efferent duct， initial segment of epididymis， caput epididymis， corpus epididymis， cauda epididymis， and vas deferens）， followed by RNA sequencing and bioinformatics analysis. ResultsRegion-specific dynamic expression profiles of lncRNAs were constructed in the testis， epididymis （efferent duct， initial segment， caput， corpus， and cauda）， and vas deferens of male mice. Combined with gene functional enrichment analysis， the functional associations of lncRNAs were elucidated in reproductive system aging. The differentially expressed lncRNAs in the aging testis were primarily involved in hormone biosynthesis and extracellular matrix organization， while those in the initial segment of the epididymis were closely related to cell recognition and epithelial cell migration. A comprehensive lncRNA expression atlas associated with male reproductive aging was established. ConclusionLncRNAs may participate in male reproductive aging through the regulation of the reproductive microenvironment， which provides key molecular targets and a research foundation for understanding age-related fertility decline.

Objective: To investigate the willingness to receive the pneumococcal vaccine and its influencing factors among middle-aged and elderly population in Zhejiang Province, so as to provide a basis for increasing the vaccination rate of pueumococcal among middle-aged and elderly population. Methods: From March to May 2024, a multi-stage random sampling method was employed to recruit residents aged ≥50 years from 35 counties (cities or districts) in Zhejiang Province. Data on basic information, knowledge of pneumonia, pneumococcal vaccine, and willingness to receive pneumococcal vaccine were collected through questionnaire surveys. A multivariable logistic regression model was used to analyze influencing factors for the willingness to receive pneumococcal vaccine among middle-aged and elderly population. Results: A total of 10 500 middle-aged and elderly population were surveyed. Among them, there were 5 202 males, accounting for 49.54%, and 5 298 females, accounting for 50.46%. The mean age was (65.11±9.05) years. Of the participants, 7 732 individuals were aware of pneumonia, accounting for 73.64%. A total of 1 724 individuals had received pneumococcal vaccine, corresponding to a vaccination rate of 16.42%. Furthermore, 5 138 participants expressed willingness to receive pneumococcal vaccine, with a willingness rate of 48.93%. The multivariable logistic regression analysis showed that middle-aged and elderly population aged ≥60 years (60-<70 years, OR=1.577, 95%CI: 1.433-1.736; ≥70 years, OR=2.110, 95%CI: 1.918-2.321), those with a history of chronic diseases (OR=1.250, 95%CI: 1.154-1.353), those who were recommended to receive the pneumonia vaccine by doctors (OR=4.896, 95%CI: 4.507-5.318), those who were aware of pneumonia (OR=1.460, 95%CI: 1.338-1.594), those who were aware that the elderly are prone to pneumonia (OR=1.490, 95%CI: 1.375-1.614), those who were aware of the causes of pneumonia (OR=1.559, 95%CI: 1.434-1.694), those who were aware that vaccination can prevent pneumonia (OR=2.196, 95%CI: 2.031-2.375), and those who were aware of the immunization schedule for pneumonia vaccine (OR=1.897, 95%CI: 1.683-2.124) had a higher willingness to receive pneumonia vaccine. Conclusions The willingness of middle-aged and elderly population in Zhejiang Province to receive pneumonia vaccine is related to age, history of chronic diseases, awareness of pneumonia, and awareness of pneumonia vaccine. It is recommended to strengthen health education on pneumonia and pneumonia vaccine for middle-aged and elderly population, in order to increase the willingness to receive the vaccine and vaccination rate.

OBJECTIVE To develop a population pharmacokinetic （PPK） model for mycophenolate mofetil active metabolite mycophenolic acid （MPA） in children with primary IgA nephropathy， explore the factors affecting the pharmacokinetic parameters of MPA， and provide a basis for clinical individualized therapy. METHODS Retrospective collection was conducted on 636 concentrations and clinical data from 47 pediatric patients with primary IgA nephropathy. PPK analysis was carried out by using the nonlinear mixed-effects model； the covariates were tested with a stepwise method. Goodness-of-fit plots， Bootstrap and visual predictive check were employed to evaluate the final model. RESULTS The pharmacokinetics of MPA in children with IgA nephropathy in vivo conformed to the first-order absorption and elimination two-compartment model （objective function value of 3 276.31）. Covariate analysis suggested that body weight and albumin （ALB） levels were significant influencing factors on apparent clearance rate and apparent distribution volume. The typical values of PPK parameters of MPA in the final model were as follows： the central room had a distributed volume of 5.79 L， the clearance rate was 4.06 L/h， the volume of peripheral ventricular distribution was 430.93 L， the clearance rate between compartments was 15.40 L/h， the oral absorption rate constant was 1.29 h－1. After verification， most of the predicted corrected observed concentration points were within the 90% confidence interval of the predicted corrected simulated concentration， indicating that the MPA final model had good predictive performance. CONCLUSIONS The PPK model of MPA in children with primary IgA nephropathy is established in this study， identifying body weight and ALB levels are significant factors affecting MPA metabolism.

OBJECTIVE To study the protective effect and mechanism of Bupleurum chinense polysaccharides （BCP） on acute liver injury （ALI） in mice. METHODS Overall 40 mice were randomly divided into normal group， model group， positive control group （Baogan tablet， 550 mg/kg）， BCP high-dose and low-dose groups （400， 100 mg/kg）， with 8 mice in each group. The drug was administered intragastrical once a day for 7 days. One hour after the last administration， except for the normal group， mice in other groups were injected with 20 mg/kg concanavalin A solution through the tail vein to establish ALI model. After injection of concanavalin A solution for 12 h， the liver and spleen indexes of mice were measured， and the pathological changes of liver and spleen tissue were observed； the serum levels of aspartate aminotransferase （AST）， alanine aminotransferase （ALT） and lactate dehydrogenase （LDH） were detected， and the levels of superoxide dismutase （SOD） and malondialdehyde （MDA） in liver tissue were detected. The levels of tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6） and IL-1β in serum and liver tissue of mice were determined， as well as the protein expression levels of nuclear factor-κB （NF-κB）， Toll-like receptor 4 （TLR4）， nuclear factor erythroid 2-related factor 2 （Nrf2） and heme oxygenase-1 （HO-1） in liver tissue were also detected. RESULTS Compared with the normal group， the liver tissue of mice in the model group was necrotic and infiltrated with inflammatory cells； spleen enlargement， increased bleeding and decreased lymphocytes were observed， liver and spleen indexes were increased significantly （P＜0.01）； the serum levels of AST， ALT and LDH， the levels of TNF-α， IL-6 and IL-1β in serum and liver tissue， as well as the MDA level， protein expressions of TLR4， NF- κB and HO-1 in liver tissue were all increased significantly （P＜0.05 or P＜0.01）. The levels of SOD and protein expression of Nrf2 in liver tissue were all decreased significantly （P＜0.05）. Compared with the model group， the pathological damages of the liver and the spleen tissues in mice alleviated in BCP high-dose and low-dose groups， and most of liver and spleen indexes， the above indexes of serum and liver tissue were reversed significantly （P＜0.05 or P＜0.01）. CONCLUSIONS BCP has a protective effect on ALI， the mechanism of which may be related to the inhibition of TLR4/NF-κB signaling pathway and the activation of the Nrf2/HO-1 signaling pathway.

Gualou Niubangtang is a classic formula for eliminating swelling and dispersing lumps， commonly used in the clinical treatment of breast diseases in traditional Chinese medicine （TCM）. This paper employed bibliometric methods to collect and organize 12 pieces of data from ancient texts related to Gualou Niubangtang， ultimately screening 10 valid references from 10 ancient Chinese medical books. Information regarding the prescription origin， main indications， formulation principles， drug composition， dosages， preparation methods， and decoction techniques was systematically verified. The results indicate that Gualou Niubangtang originates from the Orthodox Manual of External Medicine （Wai Ke Zheng Zong） by Chen Shigong in the Ming Dynasty. The formula consists of 12 Chinese medicines， including Citri Reticulatae Pericarpium， Arctii Fructus， Gardeniae Fructus， Lonicerae Japonicae Flos， Glycyrrhizae Radix et Rhizoma， Trichosanthis Semen， Scutellariae Radix， Trichosanthis Radix， Forsythiae Fructus， Gleditsiae Spina， Bupleuri Radix， and Citri Reticulatae Pericarpium Viridm. In terms of drug origins， the dominant radical for Trichosanthis Semen and Trichosanthis Radix is Trichosanthes kirilowii， and the historical dominant radical for Glycyrrhizae Radix et Rhizoma is Glycyrrhiza uralensis. The nine medicines， Citri Reticulatae Pericarpium， Arctii Fructus， Gardeniae Fructus， Lonicerae Japonicae Flos， Scutellariae Radix， Forsythiae Fructus， Gleditsiae Spina， Bupleuri Radix， and Citri Reticulatae Pericarpium Viridm， are consistent with the 2020 edition of the Chinese Pharmacopoeia. The preparation methods involve frying Arctii Fructus， removing the heart from Forsythiae Fructus， while the remaining 10 medicines are used raw. The efficacy includes clearing heat， removing toxins， reducing swelling， and dispersing lumps. Clinically， it is used to treat conditions such as breast carbuncles， breast gangrene， and knot-like swellings and pain. The dosage， converted to modern standards， includes 3.73 g of Trichosanthis Semen， 3.73 g of Trichosanthis Radix， 3.73 g of Arctii Fructus， 3.73 g of Scutellariae Radix， 3.73 g of Gardeniae Fructus， 3.73 g of Forsythiae Fructus， 3.73 g of Gleditsiae Spina， 3.73 g of Lonicerae Japonicae Flos， 3.73 g of Glycyrrhizae Radix et Rhizoma， 3.73 g of Citri Reticulatae Pericarpium， 1.85 g of Citri Reticulatae Pericarpium Viridm， and 1.85 g of Bupleuri Radix. The preparation is in the form of a decoction， with the 12 medicines added to 400 mL of water and decocted until 160 mL. The liquid is then mixed with 200 mL of yellow wine and taken before meals three times a day. Through the excavation and organization of ancient literature regarding Gualou Niubangtang， key information has been identified to provide a scientific basis for its clinical application and further development.

ObjectiveTo observe the efficacy and safety of Uyghur medicine Yangxin Dawayimixike Honey Paste （养心达瓦依米西克蜜膏， YDMHP） in the treatment of stable angina pectoris （SAP） of qi stagnation and blood stasis syndrome. MethodsA randomized ， double-blind， positive-controlled，multi-center clinical trial was conducted， in which 370 patients with SAP of qi stagnation and blood stasis syndrome were randomly divided into treatment group（279 cases）and control group（91cases）at a ratio of 3∶1. The treatment group was orally administered with YDMHP， 3 g each time， and placebo of Xuefu Zhuyu Capsule （血府逐瘀胶囊）， 2.4 g each time， while the control group was treated with Xuefu Zhuyu Capsule， 2.4 g each time， and placebo of YDMHP， 3 g each time， both twice a day for a course of 12 weeks. The primary outcome was the effect of angina pectoris symptom. The secondary outcomes include single angina symptom scores such as number of attacks， duration of attacks， pain intensity and usae of nitroglycerin scores， the total angina symptom score before and after the treatment， the usage of nitroglycerin， the exercise duration in treadmill exercise test （TET） and the Duck treadmill score among patients，the scores of Seattle Angina Questionnaire （SAQ） on five dimensions including physical limitations， anginal stability， anginal frequency， treatment satisfaction， and disease perception， and efficacy of TCM syndrome and of each single TCM symptom after treatment. The safety were evaluated by examine blood routine， urine routine， liver and kidney function， fasting blood sugar， electrocardiogram， adverse events. ResultsThe total effective rate of angina symptom in the treatment group was 71.69% （200/279）， significantly higher than 51.64% （47/91） in the control group （P＜0.01）. The curative and markedly effective rate of TCM syndrome in the treatment group was 53.05% （148/279）， which was significantly higher than 25.27% （23/91） in the control group （P＜0.01）. After treatment， scores of the number as well as duration of angina attacks and pain severity， the total score of angina symptoms， and the usage of nitroglycerin significantly decreased in both groups， and more changes were seen in the treatment group than in the control group； the scores of physical limitations， anginal stability， anginal frequency， treatment satisfaction， and disease perception in both groups significantly increased， and more improvement were shown in the experimental group regarding the anginal stability， anginal frequency and treatment satisfaction （P＜0.05 or P＜0.01）. The effects of chest pain， chest tightness， palpitation， shortness of breath and fatigue in experimental group were significantly higher than those in control group （P＜0.05 or P＜0.01）. There was no significant difference in the exercise duration of treadmill test and Duke score among patients between the two groups either before or after treatment （P＞0.05）. Adverse events occurred in 66 cases （23.66%） of the experimental group and 16 cases （17.58%） of the control group， with no statistical significance between the two groups （P＞0.05）. ConclusionThe Uyghur medicine YDMHP can effectively improve symptoms of angina pectoris， reduce the number， duration， and intensity of attacks， decrease the dosage of nitrogly-cerin and improve the individual TCM symptoms and has good safety in the treatment of SAP patients of qi stagnation and blood stasis.

OBJECTIVE To investigate the metabolic changes in MEG-01 megakaryocytes after treatment with linezolid （LZD） from metabolomic perspective and its impact on the the proliferation of cells and generation of platelet precursors. METHODS MEG-01 cells were seeded in proliferation medium and divided into blank control group （untreated）， solvent control group （4‰DMSO）， and 100， 200， 400， 800 μg/mL LZD groups. The proliferation status of cells in each group was observed under the microscope； cell proliferation and viability were assessed. Cells were also seeded in differentiation medium and divided into blank control group （untreated）， solvent control group （4‰DMSO）， and 400 μg/mL LZD group； after 14 days of culture， platelet precursor generation was observed under the microscope； immunofluorescence staining was performed to count the proportion of cells producing pseudopodia， the relative length of pseudopodia was measured， and the expression levels of CD41 and CD42b mRNA were assessed. Cells from the solvent control group and the 400 μg/mL LZD group， cultured in differentiation medium for 14 days， were extracted and subjected to non-targeted metabolomics and targeted energy metabolomics analysis using liquid chromatography-tandem mass spectrometry. The relative content of pyruvate in cells， after being cultured for 14 days with the addition of pyruvate （10 mmol/L） or LZD （400 μg/mL）+pyruvate （10 mmol/L）， was measured and observed， as well as its effects on cell proliferation and platelet precursor generation. RESULTS 400 μg/mL LZD could significantly inhibit the proliferation of MEG-01 cells and the generation of platelet precursors （P＜0.01）. Non-targeted metabolomic analysis of MEG-01 cells after 400 μg/mL LZD treatment revealed significant changes in energy metabolism-related pathways such as mTOR signaling pathway， alanine， aspartate and glutamate metabolism， and central carbon metabolism in cancer. Targeted energy metabolomic analysis further showed that the relative contents of adenosine triphosphate， guanosine triphosphate， and pyruvate in MEG-01 cells were significantly reduced （P＜0.01）， while the relative contents of lactate were significantly increased （P＜0.01）. Compared with the LZD group， the relative content of pyruvate， cell count， the proportion of cells producing pseudopodia and the relative length of pseudopodia were significantly increased in the LZD+pyruvate group （P＜0.01）. CONCLUSIONS LZD may reduce pyruvate production by inhibiting mitochondrial energy metabolism， thereby suppressing megakaryocyte proliferation and platelet precursor production， ultimately leading to the occurrence of thrombocytopenia.