ObjectiveThis paper aims to investigate and evaluate the staged efficacy and safety of the representative empirical prescription of the “Zhu Ke Jiao” theory， Qijia Rougan prescription， combined with entecavir in the treatment of hepatic fibrosis in chronic hepatitis B. MethodsA multicenter randomized controlled clinical study was conducted， and 101 patients diagnosed with chronic hepatitis B-related hepatic fibrosis （CHB-HF） who met the diagnosis and inclusion criteria were randomly assigned to an observation group （Qijia Rougan prescription + entecavir） and a control group （entecavir）. The treatment duration was 24 weeks. Liver stiffness measurement （LSM）， fibrosis-4 index （FIB-4）， portal vein diameter， hepatitis B serology， biochemical indicators， hepatic fibrosis markers in serum ［hyaluronic acid （HA）， laminin （LN）， procollagen Ⅲ peptide （PⅢP）， and type Ⅳ collagen （Ⅳ-C）］， and traditional Chinese medicine syndrome scores were used as efficacy evaluation indicators. Efficacy assessments and explorations of different staged subgroups of Qijia Rougan prescription were conducted according to LSM values based on the Metavir pathological staging standard. ResultsA total of 98 cases were included for statistical analysis， with 49 cases in the observation group and 49 in the control group. The general data of the patients in both groups were comparable. Compared with the same group before treatment， the observation group showed a significant reduction in LSM and FIB-4 （P<0.01）， as well as notable improvements in LN， Ⅳ-C， and various TCM syndrome scores （P<0.05， P<0.01）. When compared to the control group after treatment， the observation group demonstrated significant improvements in LSM， FIB-4， and various TCM syndrome score indicators （P<0.05， P<0.01）， indicating that the observation group performed better than the control group. Subgroup analysis of the regression of hepatic fibrosis stages showed that compared to the same group before treatment， the observation group had better improvement in regression of stages F2 and F3 （P<0.05）. When compared to the control group after treatment， the observation group exhibited superior improvement in regression of stage F3 （P<0.05）. No adverse events occurred in either group during the treatment period. ConclusionCompared with entecavir alone， the combination of Qijia Rougan prescription and entecavir significantly improves the degree of hepatic fibrosis and clinical TCM symptoms in patients. The optimal intervention period is primarily during stage F3， which is a potential “interception” point of the “Zhu Ke Jiao” theory.

Diabetic kidney disease（DKD） is a chronic kidney structural and functional disorder caused by diabetes. With the global prevalence of diabetes continuing to rise， DKD has gradually become a major cause of chronic kidney disease and end-stage renal disease（ESRD）， posing a serious threat to patients' quality of life and long-term health outcomes. Studies have shown that apoptosis plays a pivotal role in the development and progression of DKD， with its mechanisms involving abnormal activation of multiple signaling pathways such as Toll-like receptor 4（TLR4）/nuclear transcription factor-κB（NF-κB）/B-cell lymphoma-2（Bcl-2）/cysteinyl aspartate-specific proteinase（Caspase）-3， protein kinase R-like endoplasmic reticulum kinase（PERK）/eukaryotic initiation factor 2α（eIF2α）/activating transcript factor 4（ATF4）/CCAAT enhancer-binding protein homologous protein（CHOP）， phosphatidylinositol 3-kinase（PI3K）/protein kinase B（Akt）/glycogen synthase kinase-3β（GSK-3β）， Janus kinase 2（JAK2）/signal transducer and activator of transcription 3（STAT3）， adenosine monophosphate-activated protein kinase（AMPK）/mammalian target of rapamycin（mTOR） and silent information regulator 1（SIRT1）/tumor suppressor protein 53（p53）， thereby accelerating renal pathological damage in DKD. Extensive evidence-based medical studies have confirmed that traditional Chinese medicine（TCM）， leveraging its unique therapeutic advantages of multi-target， multi-component and multi-pathway approaches， has demonstrated remarkable efficacy and favorable safety profiles in treating DKD. Recent studies have demonstrated that active components of TCM can specifically target and modulate key effectors in apoptotic signaling pathways. Meanwhile， traditional compound formulations exert synergistic effects through multiple approaches such as replenishing deficiency and activating blood circulation， detoxifying and dredging collaterals， tonifying kidney essence， and removing stasis and purging turbidity， thereby comprehensively regulating critical pathological processes including endoplasmic reticulum stress and mitochondrial apoptosis pathways. This combined therapeutic approach of molecular targeting and holistic regulation provides novel strategies for delaying the progression of DKD. Based on this， this paper provides an in-depth analysis of key apoptotic signaling pathways and their regulatory mechanisms， while systematically summarizing recent research advances regarding the therapeutic effects of TCM active components， compound formulations， and proprietary Chinese medicines on DKD through modulation of these pathways， with particular emphasis on their underlying molecular mechanisms. These findings not only elucidate the modern scientific connotation and theoretical basis of TCM in treating DKD but also establish a solid theoretical and practical foundation for promoting the wider clinical application and further research of TCM in the field of DKD treatment.

Hormone receptor (HR)-positive/HER2-negative early breast cancer is the most common subtype of breast cancer, and endocrine therapy serves as the cornerstone of adjuvant treatment. In recent years, with the publication of key clinical trials such as SOFT, TEXT, and monarchE, and breakthroughs in novel agents studies like lidERA, the endocrine therapy strategy for HR-positive/HER2-negative early breast cancer has evolved toward increased precision and intensity. This article systematically reviews the latest advances in endocrine therapy, focusing on the consolidation of ovarian function suppression as a standard for high-risk premenopausal patients with updated follow-up evidence, the benefit-risk assessment of extended endocrine therapy, and the current application and interdrug differences of CDK4/6 inhibitors in the adjuvant setting. This manuscript also addresses existing challenges, including optimizing treatment-related quality of life and precisely identifying beneficiary populations, and briefly introduces the clinical trial progress of novel agents, such as oral selective estrogen receptor degraders. Furthermore, it outlines evidence-based strategies for ovarian protection during chemotherapy and fertility preservation for young patients. This review aims to provide clinicians with a comprehensive perspective, balancing the pursuit of maximal efficacy with patients′ long-term quality of life and individualized needs.

Intervertebral disc degeneration （IVDD） is the core cause of chronic low back pain， which severely impairs patients’ quality of life and imposes a heavy social and medical burden. The hypoxia-pyroptosis-inflammation cascade mediated by hypoxia-inducible factor-1α （HIF-1α） is the core pathological mechanism driving the initiation and progression of IVDD. Natural active ingredients derived from traditional Chinese medicine （TCM） have become a research hotspot in the field of IVDD prevention and treatment due to their advantages of multi-target effects， favorable efficacy， and low toxicity. This paper systematically reviews the mechanism of HIF-1α-mediated hypoxia-pyroptosis-inflammation cascade in degenerative nucleus pulposus tissue and the intervention of related active ingredients. It is found that natural active ingredients such as baicalein， curcumin and resveratrol can intervene in the HIF-1α-mediated pathological cascade through four core links to delay IVDD progression： targeting the HIF-1α oxygen sensing pathway to block the initiation of pyroptosis cascade， inhibiting NOD-like receptor protein 3 inflammasome activation to cut off the cascade amplification of inflammatory signals， intervening in the Gasdermin D-mediated pyroptosis execution stage to protect cell membrane integrity， and regulating extracellular matrix metabolism to reconstruct intervertebral disc homeostasis.

Background In 2021, chronic obstructive pulmonary disease (COPD) emerged as the forth leading cause of death in the world. However, the impact of air pollutants on COPD is still inconsistent across current studies. Objective To analyze the relationship between ambient sulfur dioxide (SO₂) exposure and hospital admissions for COPD in Lanzhou, and to examine the modified effects of SO₂ across different genders, age groups, and seasons. Methods A total of 20718 hospital admission records for COPD were collected from Lanzhou between 2016 and 2020, alongside synchronized data on SO₂ concentration and meteorological variables. A generalized additive model integrated with a distributed lag nonlinear model was used to assess the relationship and the lag effects between SO₂ exposure and COPD admissions. Potential confounders, including meteorological factors, day-of-the-week effect, and holidays, were controlled for, with a maximum lag period set at 7 d. Two-pollutant models and sensitivity analyses were conducted to ensure robustness. Results are expressed as relative risks (RR) with 95% confidence intervals (95%CI). Results During the study period, the average daily number of COPD admissions was 11.34±7.03. The average mass concentration of SO₂ was (23.72±12.35) μg·m⁻³. SO₂ exposure was positively correlated with COPD admissions; specifically, each 10 μg·m⁻³ increase in SO₂ concentration was associated with an RR of 1.440 (95%CI: 1.317, 1.573). Stratified analyses found that at a cumulative lag of 7 d, the RRs were higher among females, individuals aged ≥65 years, and during the cold season. Conversely, no significant increase in COPD admission risk related to SO₂ was observed during the warm season. For every 10 μg·m⁻³ increase in SO₂ concentration, the RR was 1.483 (95%CI: 1.311, 1.678) for females, 1.441 (95%CI: 1.311, 1.583) for those aged > 65 years， and 1.595 (95%CI: 1.313, 1.937) during the cold season. Conclusion Short-term exposure to ambient SO₂ exposure in Lanzhou is associated with an increased risk of COPD admission. The association is more pronounced among females, the elderly (aged> 65 years) and during the cold season.

OBJECTIVE To construct a closed-loop management model for externally dispensed intravenous prescriptions， and to provide reference for standardized management of externally dispensed intravenous prescriptions. METHODS Based on the Expert Consensus on Closed-loop Management of Externally Dispensed Intravenous Prescriptions in Guangxi Zhuang Autonomous Region previously formulated by our hospital， risk points during the entire process were systematically identified through multidisciplinary team brainstorming and a fishbone diagram. A series of strategies were subsequently formulated and implemented， including qualifying designated external dispensing pharmacies and the drug catalogs， operating and maintaining the hospital information system and the Pharmacy Intravenous Admixture Service （PIVAS） intelligent management platform， and strengthening differentiated training for staff in the whole workflow. A whole-process closed-loop management system was constructed with PIVAS as the co re hub and the daytime chemotherapy center as the safety terminal. RESULTS A total of 3 cooperating pharmacies and an initial drug list comprising 35 product specifications were selected. A closed‑loop management process encompassing hospital outpatient prescribing， patient drug purchase in designated pharmacies， PIVAS drug dispensing， and medication use in daytime chemotherapy center was successfully established. This system enabled the mandatory grouping and association of externally dispensed intravenous prescriptions with in-hospital diluents， full-process verification based on drug traceability codes， intelligent monitoring of infusion parameters， and whole-process data traceability. CONCLUSIONS The constructed model effectively resolves the coordination and safety oversight during the use of externally dispensed intravenous drugs from out-of-hospital circulation to in-hospital use， and has preliminarily enabled procedural standardization， whole-process information traceability， and proactive control of medication risks.

ObjectiveThis paper aims to investigate the traditional Chinese medicine syndrome types in patients with chronic hepatitis B （CHB） complicated by metabolic dysfunction-associated fatty liver disease （MAFLD） and explore the correlations between these syndrome types and clinical indicators， as well as ocular manifestation characteristics， thereby providing a reference for syndrome differentiation and treatment strategies in traditional Chinese medicine. MethodsGeneral data， information from the four diagnostic methods of traditional Chinese medicine， clinical indicators， and ocular manifestation data were collected from 506 patients with CHB complicated by MAFLD enrolled at the Public Health Clinical Center of Chengdu between June 2024 and December 2024. Cluster analysis， principal component analysis， and complex network models were employed to identify the distribution patterns of traditional Chinese medicine syndromes. Correlations between different syndrome types and clinical indicators， as well as ocular manifestation characteristics， were further analyzed. ResultsThe predominant syndromes identified in patients with CHB complicated by MAFLD were dampness and heat accumulation （51.58%）， liver depression with spleen deficiency （31.62%）， blood stasis obstructing collaterals （8.89%）， and Qi-Yin deficiency （7.91%）. No statistically significant differences were found among the four syndrome types in routine blood tests and liver function indicators. However， patients with the dampness and heat accumulation type exhibited significantly higher levels of total cholesterol （TC）， triglycerides （TG）， low-density lipoprotein cholesterol （LDL-C）， liver stiffness measurement （LSM）， controlled attenuation parameter （CAP）， and alpha-fetoprotein （AFP）， along with lower levels of high-density lipoprotein cholesterol （HDL-C）， compared with those with other syndrome types. Regarding ocular manifestations， the incidence of moon halo signs was significantly higher in patients with the blood stasis obstructing collaterals type than in those with other syndrome types. Additionally， the incidence in scleral zone 3 （corresponding to the large intestine） was higher in patients with the damp and heat accumulation type. ConclusionDampness and heat accumulation is the core syndrome type in patients with CHB complicated by MAFLD， commonly accompanied by spleen deficiency， liver depression， blood stasis， and Yin deficiency. A complex syndrome pattern characterized by a predominance of dampness and heat， along with a mixture of deficiency and excess， is formed. Different traditional Chinese medicine syndrome types are associated with distinct clinical indicators and ocular manifestation characteristics. Among them， patients with the dampness and heat accumulation type exhibit more pronounced metabolic disturbances and liver injury， whereas those with the blood stasis type show a higher incidence of moon halo signs. Abnormalities in scleral zone 3 are also more prevalent in patients with dampness and heat type.

Background: Adrenocortical hormones, particularly 11-oxygenated androgens, are pivotal in female reproductive health and fertility. Standardized detection kits and population-specific reference intervals are lacking in China, hindering related clinical applications. Methods: A HPLC-tandem mass spectrometry (HPLC-MS/MS) pipeline was developed, rigorously validated, and applied to simultaneously quantify corticosterone, cortisone, cortisol, 18-OH cortisol, androstenedione (A4), 11β-hydroxyandrostenedione (11-OH A4), dehydroepiandrosterone, and dehydroepiandrosterone sulfate in serum samples from 455 reproductive-aged women (18–45 yrs) in Guangxi, China. Age-dependent concentration trends were analyzed, and reference intervals stratified by age (2.5th to 97.5th percentiles) were established. Correlations with body-composition metrics, ethnicity, and the menstrual cycle were investigated. Results: The HPLC-MS/MS method demonstrated high precision (intra- and inter-assay CVs < 15%), accuracy, and sensitivity. All eight hormones exhibited significant age-related declines (P < 0.001 for seven hormones; P = 0.001 for 11-OH A4). Notably, 11-OH A4 levels were significantly lower in the 35–45-yr (3.05 nmol/L) and 25–34-yr (3.09 nmol/L) age groups than in the 18–24-yr (3.57 nmol/L) age group, whereas no significant difference was observed between the 35–45-yr and 25–34-yr age groups. Weak negative correlations were observed between the body mass index and corticosterone and cortisone levels, whereas ethnicity and the menstrual cycle showed no significant associations with hormone levels. Conclusions We developed an HPLC-MS/MS-based method for simultaneously quantifying eight adrenocortical hormones, including 11-OH A4, and defined age-specific reference intervals for reproductive-aged Chinese women. These findings advance the clinical utility of adrenocortical hormones in diagnosing and managing reproductive disorders.

To analyze the epidemiological characteristics of COVID-19 in Fujian Province from the 49th week of 2022 to the 5th week of 2023,after further optimization of China's COVID-19 prevention and control measures on December 7,2022(the 49th week of 2022),this study used multi-dimensional surveillance data to dynamically assess population infection levels and their changing trends.The aim of the study was to provide a scientific basis for early warning of epidemic risk,medical resource allocation,and evalu-ation of socio-economic impact.A multi-source data surveillance system was constructed,encompassing surveillance of fever clinics at medical institutions(weekly collection of visits,positive nucleic acid and antigen test results,inpatients,and severe cases in sec-ondary or above hospitals),population nucleic acid test monitoring(weekly person-times and positivity rates of single-tube tests from the provincial system),sentinel hospital monitoring(weekly proportion of influenza-like illness visits at 18 sentinel hospitals and re-lated viral testing data),and monitoring of novel coronavirus variants(weekly systematic collection of genomic sequences of local and imported cases).Line charts were plotted weekly,and time series analysis,molecular epidemiological methods,and an improved SEIAR model were used to simulate epidemic spread.During the study period,the COVID-19 epidemic in Fujian Province exhibited three distinct stages.In the infection peak stage(52nd week of 2022),the provincial fever clinic visits reached 606 893 person-times,and a 49.2%positivity rate in population single-tube nucleic acid tests and 63.8%positivity rate in sentinel hospital monitoring were observed.In the medical load peak stage(2nd week of 2023),274 460 inpatients and 28 487 severe cases were recorded.In the epidemic decline stage(4th to 5th weeks of 2023),fever clinic visits decreased by 96.3%with respect to the peak,the single-tube nucleic acid test positivity rate decreased to 6.3%,and the sentinel hospital COVID-19 nucleic acid test positivity rate was 6.4%.All 508 sequenced local cases were Omicron variants,predominantly BA.5.2 and its sub-lineages(67.4%).Among 56 imported se-quenced cases,BA.5.2 and its sub-lineages accounted for 50.0%,and 16.1%comprised nine variants of interest including XBB and BQ.The model predicted the infection peak in the 52nd week of 2022,whereas the hospitalization peak lagged by approximately 10.6 days.Multi-source data monitoring revealed a three-stage development of the COVID-19 epidemic in Fujian.The BA.5.2 strain was dominant during the epidemic.The combination of multi-source monitoring data and modeling provides important references for epi-demic prevention and control,and highlights the need to improve the monitoring system in follow-up.

Objective To investigate the effects of inclined axial compressive force and flexion moment on the anterior and posterior shear stiffness of the lumbosacral segment.Methods Six fresh-frozen human cadaveric L5-S1 segments were tested under intact and two progressively impaired structural conditions:intact,a 4-mm bilateral facet joint gap,and anterior discectomy with nucleus pulposus removal plus circumferential release of the inner annular fibers(disc injury).A 300 N axial compressive force was applied either vertically downward or with a 10° or 20° anterior inclination through the disc's shear center.Anterior(0 N to 250 N)and posterior(-50 N to 0 N)shear tests were conducted using a material testing machine.These tests were repeated under a 5 N-m flexion moment.The relative motion between L5 and Si was measured using a three-dimensional motion capture system.Results In the intact state,the inclination of the axial compressive force did not significantly alter anterior or posterior shear stiffness.However,the application of a flexion moment increased anterior shear stiffness by 49.3％.Progressive structural damage resulted in incremental increases in anteroposterior shear translation and corresponding reductions in stiffness.Notably,under combined loading with axial compression and flexion moment,anterior stiffness decreased from 939 N/mm(intact)to 224 N/mm(disc injury),while posterior stiffness decreased from 572 N/mm to 217 N/mm.Within the low-load range,no significant differences in shear stiffness were observed across any structural conditions,regardless of axial force inclination or combined with a flexion moment.Conclusions This study supports the clinical view that retro-inclination of the pelvis serves as a compensatory mechanism to enhance segmental shear stability.However,this compensatory capacity gradually diminishes and ultimately fails as spinal degeneration progresses.