Based on the theory of "sweet-flavored medicinals retaining and restoring body fluid"， this paper proposed that the core pathogenesis of hypercoagulable state in malignant tumors is qi deficiency and fluid consumption， blood stasis and vessels stagnation， which evolves dynamically according to the pattern "qi deficiency → fluid consumption → blood stasis". Accordingly， a staged treatment system is established with the general principle of "fortifying the middle jiao， restoring fluid and activating blood circulation". In the initial stage， invigorating the spleen and boosting qi to generate body fluid， targeting the onset of middle jiao deficiency and body fluid consumption； in the middle stage， nourishing yin and unblocking collaterals to facilitate body fluid circulation， addressing the disorder of body fluid transportation and collateral injury caused by internal dryness； in the late stage， consolidating yin and resolving blood stasis to retain body fluid， resolving yin impairment， fluid exhaustion， and binding of stasis and toxin. By regulating body fluid metabolism to improve the hypercoagulable state， this system is intended to provide insights for the prevention and treatment of hypercoagulable state in malignant tumors with traditional Chinese medicine.

ObjectiveTo observe the clinical efficacy and safety of Yuyin Lidan granules （YYLD） in preventing the recurrence of common bile duct stones （CBDS） in patients with liver and gallbladder dampness-heat syndrome following endoscopic retrograde cholangiopancreatography （ERCP）. MethodsThis randomized， parallel， controlled trial enrolled postoperative CBDS-ERCP patients who met the inclusion and exclusion criteria. Sixty-four patients were randomly assigned to an observation group or a control group， with 32 cases in each. Both groups received conventional Western medical treatment after ERCP， while the observation group additionally received YYLD for 8 weeks. The follow-up period lasted for 1 year. The efficacy indicators included bile bilirubin levels， traditional Chinese medicine （TCM） syndrome scores， clinical efficacy rate， pancreatitis and inflammation markers， postoperative liver function， and CBDS recurrence rate at 1-year follow-up， which were used to jointly evaluate the clinical efficacy and safety of both groups. ResultsA total of 56 patients completed the study and were included in the final analysis， i.e.， 29 in the observation group and 27 in the control group. Baseline characteristics were comparable between the two groups. Compared with pre-treatment and with the control group after treatment， the bile bilirubin level in the observation group significantly decreased （P<0.05）. After treatment， the clinical cure and marked improvement rates were higher in the observation group than in the control group， showing a statistically significant difference in overall clinical efficacy （P<0.05）. Compared with pre-treatment， the primary and secondary symptoms in the observation group， as well as the primary symptom and the secondary symptom of nausea and vomiting in the control group （weeks 4 and 8）， were significantly reduced （P<0.05）. Compared with the control group after treatment， the observation group showed significant reductions in the primary symptom of loose stools/constipation （day 5 and week 4） and in three secondary symptoms， i.e.， bitter taste and sticky dry mouth， abdominal distension and poor appetite （throughout the treatment period）， and general heaviness and fatigue （day 5 and week 4）， with statistical differences （P<0.05）. Compared with pre-treatment， both groups showed decreased lipase and urinary amylase levels （P<0.05）. However， no significant between-group differences were observed in pancreatitis or inflammation-related indices after treatment. Compared with pre-treatment， all liver function indicators in the observation group and alanine aminotransferase （ ALT ）， γ-glutamyl transferase （ γ-GT ）， alkaline phosphatase （ALP）， and conjugated bilirubin in the control group significantly decreased at weeks 4 and 8 （P<0.05）. Compared with the control group after treatment， only serum total bilirubin and unconjugated bilirubin were significantly reduced in the observation group during the treatment period （P<0.05）. ConclusionYYLD combined with conventional Western medical treatment can effectively regulate bilirubin metabolism （in bile and serum）， improve TCM clinical symptoms， and prevent CBDS recurrence after ERCP in patients with liver and gallbladder dampness-heat syndrome. This regimen is safe and effective and is worthy of further clinical research and promotion.

In recent years, China’s capacity for new drug research and development has been significantly strengthened, with major breakthroughs across multiple therapeutic areas, including cancer, autoimmune diseases, and metabolic disorders. An increasing number of domestically developed innovative drugs have been approved for marketing, gradually establishing a competitive position against imported drugs and expanding into global markets. This article systematically reviews the latest research progress of Class 1 innovative drugs in China from 2023 to 2024, categorizes representative approved drugs by therapeutic area, summarizes the clinical advantages and characteristics of representative drugs approved, analyzes in depth the current development trends of and challenges for China’s innovative pharmaceutical industry, and explores future directions, aiming to provide some reference for innovative drug research, industrial development, and policy-making in China.

Objective To investigate the expression characteristics of the transcription factor E2F2 in clear cell renal cell carcinoma (ccRCC), its impact on patient prognosis, and its potential role in the tumor immune microenvironment, with validation using clinical samples and functional assays. Methods RNA sequencing data and clinical information of ccRCC patients were obtained from the TCGA database; GSE53757 and GSE66272 datasets were downloaded from the GEO database as external validation cohorts. The expression difference of E2F2 between ccRCC tissue and normal tissue was compared, and the relationship between E2F2 expression and clinical pathological characteristics was analyzed. Kaplan-Meier (KM) survival analysis with log-rank test was performed to evaluate the effects of E2F2 on overall survival (OS), progression-free survival (PFS), and disease-specific survival (DSS). The prognostic efficacy of E2F2 in predicting 1-, 3- and 5-year survival was evaluated using receiver operating characteristic (ROC) curve. GSEA was performed to identify E2F2-related signaling pathways, and the ESTIMATE and CIBERSORT algorithms were used to assess the relationship between E2F2 expression level and tumor immune cell infiltration and immune microenvironment. Twenty pairs of surgically resected and pathologically confirmed ccRCC tissues and matched adjacent non-tumor tissues were collected from our hospital, and immunohistochemistry (IHC) was performed to detect the protein expression of E2F2. Human ccRCC cell line 786-O was used for functional assays;shRNA was used to knock down E2F2 expression (constructing stable shE2F2#1 and shE2F2#2 cell lines), and qRT-PCR and Western blot were performed to verify knockdown efficiency, followed by MTT, colony formation, and Transwell migration assays to evaluate the effects of E2F2 on the biological behaviors of ccRCC cells. Results E2F2 was significantly upregulated in ccRCC tissues (the same results in the verification set). Higher E2F2 expression was associated with advanced histological grade, clinical stage and higher TNM classification (P＜0.05). KM analysis showed that patients in the E2F2 high-expression group had worse OS, PFS, and DSS (P=0.019, 0.036, ＜0.001); the ROC curves showed area under the curve (AUC) of E2F2 of predicting 1-, 3- and 5- year survival of ccRCC patients were 0.844, 0.851 and 0.815, respectively. GSEA revealed that the E2F2 low-expression group was enriched in multiple metabolism-related pathways, whereas the E2F2 high-expression group was associated with immune-related pathways. Immune analysis demonstrated that high E2F2 expression was associated with increased immune scores, increased proportion of immune cells, higher tumor mutation burden, and potentially stronger immunotherapy response. IHC results showed that the E2F2 immunoreactivity score in ccRCC tissues was significantly higher than that in adjacent non-tumor tissues (P＜0.05). Functional assays indicated that E2F2 knockdown significantly inhibited the proliferation, colony formation, and migration of ccRCC cells. Conclusion E2F2 is highly expressed in ccRCC and may be involved in tumorigenesis and progression through modulation of the immune microenvironment. Its expression level is closely associated with patient prognosis, and E2F2 has the potential to serve as a prognostic biomarker and immunotherapeutic target in ccRCC.

Introduction: Primary bilateral macronodular adrenal hyperplasia (PBMAH), characterized by bilateral adrenal macronodules >1 cm, is a rare genetic disease contributing to <2% of Cushing syndrome. Case: A 56-year-old male with underlying diabetes mellitus and hypertension presented with worsening proximal muscle weakness. Detailed neurological assessment was unremarkable. Re-assessment revealed more apparent cushingoid features, prompting referral to endocrinology. Basal cortisol was markedly elevated at 957 nmol/L (145.4– 619.4 nmol/L). Unsuppressed cortisol after 1 mg overnight dexamethasone and low-dose dexamethasone test confirmed Cushing Syndrome. Suppressed adrenocorticotropic hormone (ACTH <0.33 pmol/L) suggested autonomous cortisol secretion from adrenal glands. Computed tomography adrenal reported massively enlarged hypodense multinodular adrenal glands of varying sizes. Oral ketoconazole, an adrenal steroidogenesis inhibitor, was initiated. Despite careful titration to keep serum cortisol 400–500 nmol/L, he experienced glucocorticoid withdrawal syndrome. Bilateral adrenalectomy was planned but deferred as he continued to lose weight despite persistent hypercortisolism. Extensive investigations were conducted for possible opportunistic infections or malignancy. His chest X-ray revealed a suspicious right lung cavity. Positive serum galactomannan and bronchial alveolar lavage galactomannan suggested pulmonary aspergillosis. Voriconazole was introduced, with drug-drug interaction judiciously addressed. He underwent bilateral adrenalectomy and required lifelong glucocorticoid and mineralocorticoid replacement. Histopathological report confirms bilateral macronodular adrenocortical disease. A referral to a genetic clinic was made to explore the potential hereditary basis. Conclusion PBMAH is a highly heterogeneous disease with variable presentation and a wide spectrum of hypercortisolism. Definitive management remained controversial and individualized. Multidisciplinary discussion is crucial, and genetic study is highly recommended for long-term prognostication and familial screening.

Introduction: Diabetes literacy represents personal knowledge and competencies related to diabetes mellitus (DM) among people living with DM (PLWD). It is a crucial component for optimizing care and empowering effective selfmanagement. Methodology: A cross-sectional study was conducted at Hospital Tuanku Ja’afar Seremban (HTJS) and Klinik Kesihatan Seremban (KKS) using a validated simplified Diabetes Knowledge Test (DKT). DKT assessed understanding in six domains, namely, awareness, lifestyle modification, diet and monitoring, general knowledge, preventive screening, and insulin. A score of >75% was classified as adequate diabetes literacy. Significant predictive factors identified from univariate Pearson Chi Square were further analyzed using multivariate logistic regression. Results: A total of 250 PLWDs, with equal contribution from each centre, were recruited with a mean (SD) age of 50.3 (13.6) years, 58.4% female, and 43.2% Malays. A total of 21.2% demonstrated adequate diabetes literacy. The results demonstrated the highest proficiency in the preventive screening domain (92.6%) and the lowest in the awareness domain (50.2%). Unemployed PLWDs had significantly lower odds of adequate diabetes literacy (odds ratio [OR] = 0.20, p = 0.010). Similarly, PLWDs with hemoglobin A1c levels >10% exhibited approximately 2.6-fold lower odds of adequate diabetes literacy. In contrast, PLWDs who reported healthcare personnel as their primary source of diabetes-related information had significantly higher odds of adequate literacy (OR = 1.59, p = 0.017). No significant association was demonstrated between diabetes literacy and frequency of hospital admissions, medication adherence, and diabetes-related target organ damage Conclusion Diabetes literacy among PLWD in HTJS and KKS is suboptimal, with notable gaps in awareness of the disease. Targeted, culturally tailored education strategies are essential to address these disparities and to empower them for effective diabetes self-management.
Literacy ; Diabetes Mellitus

Objective To investigate the effect of sodium-glucose cotransporter 2 inhibitor (empagliflozin, EMPA) on myocardial remodeling in a mouse uremic cardiomyopathy (UCM) model induced by 5/6 nephrectomy, through the phosphatidylinositol 3 kinase (PI3K)/protein kinase B (PKB/AKT)/p65 signaling pathway. Methods The animals were divided into three groups: Sham group (n=6), UCM group (n=8), and UCM＋EMPA group (n=8). A UCM model was established in C57BL/6N mice using the 5/6 nephrectomy. Starting from 5 weeks post-surgery, EMPA or a placebo was administered. After 16 weeks, blood pressure, serum creatinine, blood urea nitrogen, 24-hour urine glucose and urine sodium were measured. Cardiac structure and function were assessed by echocardiography. Hematoxylin-eosin (HE) staining and Masson trichrome staining were used to observe pathological changes in the heart and kidneys. Wheat germ agglutinin (WGA) staining was used to evaluate myocardial hypertrophy. The real-time quantitative PCR (RT-qPCR) was used to detect the expression levels of myocardial hypertrophy- and fibrosis-related mRNAs. Western blotting was used to detect the expression levels of PI3K, AKT and p65 in myocardial tissues. Results After 16 weeks, UCM group exhibited significantly higher blood pressure, serum creatinine, blood urea nitrogen than sham group (P＜0.01); UCM＋EMPA group exhibited lower blood pressure, serum creatinine, blood urea nitrogen, and higher 24 h urine sodium and glucose than UCM group (P＜0.05). Echocardiographic results showed ventricular remodeling in the UCM group, evidenced by left ventricular wall thickening, left ventricular enlargement, increased left ventricular mass, and decreased systolic function (P＜0.05); ventricular remodeling was alleviated (P＜0.05), though there was no significant improvement in systolic function in UCM＋EMPA group. HE and Masson stainings revealed myocardial degeneration, necrosis, and interstitial fibrosis in UCM group (P＜0.01); the myocardial pathology improved with reduced collagen deposition in UCM＋EMPA group (P＜0.01). WGA staining confirmed myocardial hypertrophy in UCM group (P＜0.01), while myocardial hypertrophy was alleviated in UCM＋EMPA group (P＜0.01). RT-qPCR results showed myocardial hypertrophy- and fibrosis-related genes (NPPA, NPPB, MYH7, COL1A1, COL3A1, TGF-β1) were upregulated in UCM group (P＜0.05), but downregulated in UCM＋EMPA group. Western blotting showed PI3K, p-AKT/AKT ratio, and p-p65/p65 ratio were increased in UCM group, but decreased in UCM＋EMPA group (P＜0.05). Conclusion EMPA can improve myocardial hypertrophy and fibrosis in the UCM mouse model, and it may play the role through inhibiting the PI3K/AKT/p65 signaling pathway.

AIM:This study aims to investigate the protective effect of α-lipoic acid(α-LA)against alcohol-induced damage in H9c2 rat cardiomyocytes and to explore the underlying mechanisms.METHODS:An alcohol-induced injury model of H9c2 cells was established,and the cells were divided into 4 groups:control group,alcohol group,α-LA group,and alcohol+α-LA group.Additionally,H9c2 cells overexpressing aldehyde dehydrogenase 2(ALDH2)were cre-ated and further divided into 6 groups:normal control group,normal cells treated with alcohol group,normal cells treated with alcohol+α-LA group,ALDH2 overexpression group,ALDH2-overexpressing cardiomyocytes treated with alcohol group,and ALDH2-overexpressing cardiomyocytes treated with alcohol+α-LA group.Cell proliferation was assessed using 5-ethynyl-2'-deoxyuridine(EdU)staining.Reactive oxygen species(ROS)levels in each group were measured using di-hydroethidium(DHE)staining,while the expression levels of ALDH2,silent information regulator 1(SIRT1),heme oxy-genase 1(HO1)and P53 proteins were detected by Western blot analysis.RESULTS:(1)Alcohol exposure resulted in a decrease in the proliferation of H9c2 cells and an increase in intracellular oxidative stress,evidenced by elevated ROS levels and decreased expression of related proteins(ALDH2,SIRT1 and HO1).However,α-LA treatment significantly mitigated the decline in cell proliferation and the oxidative stress induced by alcohol.(2)Alcohol may induce cellular se-nescence,as demonstrated by the up-regulation of P53 expression,which were reversed by α-LA.(3)The H9c2 cells with high ALDH2 expression markedly improved the cell proliferation in the presence of alcohol,suppressed the ROS pro-duction,prevented the down-regulation of oxidative stress-related proteins(ALDH2,SIRT1 and HO1),and reversed the enhanced expression of the senescence marker P53.CONCLUSION:Treatment with α-LA may counteract oxidative stress and attenuate cellular senescence by activating ALDH2,thereby protecting cardiomyocytes from alcohol-induced damage.

Objective The experimental method of cervical vestibular evoked myogenic potential(cVEMP)with high retest reliability was designed to verify the accuracy of locating sternocleidomastoid muscle in mice.Methods Three 2-month-old ICR male mice were selected,one of which was dissected to locate the sternocleidomastoid muscle,while the other two were used to design the experimental plan to verify the accuracy of localization.Results The recording electrode positioned on the sternocleidomastoid muscle of mice can repeatedly elicit clear cVEMP waveform.Conclusion The cVEMP waveform with high retest reliability can be measured in both experimental mice,suggesting that the localization of sternocleidomastoid muscle in this research is accurate.

AIM:To evaluate the value of ultra-sound-guided erector spinae plane block(ESPB)combined with opioid-sparing anaesthesia in extra-corporeal shock wave lithotripsy(ESWL)for pancre-atic stones.METHODS:A total of 96 patients(60 males and 36 females,aged 20-65 years,ASA Ⅰ-Ⅱ,BMI 16-30 kg/m2)undergoing elective extracorpo-real shock wave lithotripsy for pancreatic duct stones were selected in our hospital from March 2022 to April 2023.The patients were randomly di-vided into conventional intravenous anesthesia group(group C,48 cases)and ESPB+opioid-sparing group(group E,48 cases).Patients in group C un-derwent general anesthesia with target-controlled infusion of propofol and remifentanil with sponta-neous breathing.Patients in group E underwent ul-trasound-guided bilateral ESPB before intravenous general anesthesia.The changes of hemodynamic indexes(HR,MAP)in the two groups were ob-served and recorded.The anesthetic effect,dosage of remifentanil,quality of anesthesia recovery,postoperative analgesic effect and incidence of perioperative adverse reactions(respiratory depres-sion,nausea and vomiting,pruritus,etc.)were ob-served in the two groups.RESULTS:Compared with group C,the incidence of intraoperative respiratory depression was significantly decreased,the intraop-erative consumption of remifentanil was de-creased,and the postoperative recovery time was shortened in group E(P＜0.05).The VAS scores of rest and cough pain and the incidence of postoper-ative nausea and vomiting were significantly de-creased in group E(P＜0.05).There was no signifi-cant difference in HR and MAP between the two groups(P＞0.05).CONCLUSION:Ultrasound-guided ESPB in ESWL for pancreatic duct stones is satisfac-tory and can save opioids with few complications.