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.

ObjectiveTo investigate the effects of targeted silencing of Runt-related Transcription Factor 3 （RUNX3） on the proliferation and migration of Mouse Hepatic Stellate Cells （HSCs）， as well as subsequent collagen deposition. MethodsMouse hepatic stellate cell line （JS-1） was selected and then morphologically observed and identified under a microscope. After the cells had fully adhered， they were treated with 5 ng/mL of transforming growth factor beta 1 （TGF-β₁） for 24 hours to induce hepatic stellate cell activation. Furthermore， a RUNX3 silencing model was established using RUNX3 lentiviral infection. The experiment was divided into four groups： Control group， TGF-β₁ group， TGF-β₁+siRNA-NC group， and TGF-β₁+siRNA-RUNX3 group. Protein expression changes of RUNX3， alpha-smooth muscle actin （α-SMA）， and Alpha 1 type I collagen （Collagen I） were detected using Western blot method. Cellular immunofluorescence assays were employed to investigate the deposition changes of α-SMA and RUNX3 in hepatic stellate cells. RT-qPCR was utilized to examine the mRNA expression changes of RUNX3， α-SMA， and Collagen I. The proliferative capacity of hepatic stellate cells was assessed using Edu staining. The migratory ability of hepatic stellate cells was evaluated through wound healing assays and Transwell migration experiments. ResultsCompared with Control group， a significant elevation in RUNX3 was observed in the TGF-β₁-induced activated HSCs （P<0.01）. Meanwhile， the protein and mRNA levels of fibrosis-related markers and α-SMA and Collagen I were significantly upregulated （P<0.001）. Additionally， the proliferation and migration capabilities of HSCs were significantly enhanced （P<0.001）. In contrast， when compared to TGF-β₁+siRNA-NC group， TGF-β₁+siRNA-RUNX3 group exhibited a notable decrease in RUNX3 and other related indicators， such as the protein and mRNA levels of α-SMA and Collagen I （P<0.05）. Concurrently， the proliferation and migration capabilities of HSCs were significantly inhibited in TGF-β₁+siRNA-RUNX3 group （P<0.01）. ConclusionSilencing RUNX3 can inhibit the deposition of collagen and the proliferation and migration of hepatic stellate cells. Conversely， RUNX3 promotes the proliferation and migration capabilities of HSCs， thereby facilitating the activation of HSC.

Objective:To describe the body mass index (BMI) level and long-term trends of Chinese older adults aged 65 and above.Methods:Older adults aged 65 and above from six waves (2002-2018) of the China Longitudinal Healthy Longevity Survey were selected as the study population. Multiple cross-sectional design with six survey waves conducted in 2002, 2005, 2008, 2011, 2014, and 2018 was adopted, enrolling 15 647, 15 358, 15 622, 9 166, 6 302, and 12 417 participants, respectively. Additionally, a total of 13, 755 participants were included in the cohort study design. Relevant information was collected through questionnaires and physical examinations. The χ2 trend test was used to compare the changes in the rates of underweight and overweight/obesity over the years, and the linear mixed-e?ects model (LMM) was used to fit trajectory curves of BMI changes with advancing age in older adults. Results:The baseline ages of the participants included in 2002, 2005, 2008, 2011, 2014, and 2018 were (85.16±11.26), (84.23±11.83), (84.99±12.16), (81.10±11.86), (78.89±11.30), and (83.08±12.42) years, respectively, with a relatively high proportion of females and rural residents. In the cohort study, the 13 755 participants had a median ( Q1, Q3) follow-up time of 6.5 (5.2, 10.0) years, with a cumulative follow-up duration of 109 041 person-years. In each wave, males had higher BMI than females, urban residents had higher BMI than rural residents, and BMI gradually decreased with increasing age (all P<0.001). The mean BMI of older adults in China increased from (19.37±3.80) kg/m2 in 2002 to (22.04±4.01) kg/m2 in 2018 ( P<0.001). Across all survey years, the prevalence of underweight was consistently higher in women than in men and in rural areas than in urban areas, with an upward trend as age increased (all P<0.001). In 2018, the underweight rates in the 65-79, 80-89, 90-99, and ≥100-year-old age groups were 8.0%, 16.7%, 26.2%, and 35.5%, respectively. Meanwhile, the prevalence of overweight/obesity was higher in men than in women and in urban areas than in rural areas, showing a declining trend with advancing age (all P<0.001). The prevalence of underweight among the older adults decreased significantly from 45.2% in 2002 to 18.9% in 2018 ( P<0.001), while the prevalence of overweight/obesity increased from 11.0% in 1998 to 29.6% in 2018 ( P<0.001). The trajectory curves fitted by the LMM model showed that individuals born in later decades had higher BMI levels at the same age compared to earlier cohorts. Conclusion:From 2002 to 2018, the BMI level among Chinese older adults showed an increasing trend. The prevalence of underweight showed a declining trend, while the rates of obesity and overweight increased. However, the underweight rate remained notably high among the oldest old.

Objective:To summarize the clinical characteristics of elderly patients with stage Ⅰ diffuse large B-cell lymphoma (DLBCL) and analyze the factors associated with prognosis.Methods:A case series study was conducted by retrospectively collecting clinical data from patients aged over 60 years with newly diagnosed stage Ⅰ DLBCL across 20 medical centers in Jiangsu Province, China, between June 2010 and April 2023. The involved site, classification and treatment plan were summarized. The primary endpoints were progression-free survival (PFS) and overall survival (OS). Statistical analyses were performed using the Kaplan-Meier method, and Cox regression model.Results:The study included 255 patients with a median age of 69 years, of whom 130 (51.0%) were male, 66 (25.9%) were aged ≥75 years and 26 (10.1%) had a high Charlson Comorbidity Index (CCI) score of ≥2. Extranodal involvement was observed in 163 (63.9%) patients, with the stomach (37.4%, 61/163), intestine (19.0%, 31/163), testes (11.0%, 18/163), and breast (7.4%, 12/163) being the most frequently affected sites. The non-germinal center B-cell (non-GCB) subtype was prevalent in 63.7% of patients (142/223), with no significant difference between the nodal and extranodal groups ( P=0.681). Furthermore, 73.9% (184/249) and 11.7% (29/249) of patients received the R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) and R-miniCHOP regimen, respectively. The overall 3-year PFS rate was 81.5%, and the 3-year OS rate was 85.6%. Patients aged ≥75 years ( HR=2.910, 95% CI 1.565-5.408, P=0.001) and/or with a CCI score ≥2 ( HR=2.324, 95% CI 1.141-4.732, P=0.020) had a significantly poorer PFS. Incorporating age ≥75 years and CCI score ≥2 into the stage-modified international prognostic index (sm-IPI) can better stratify the prognosis of elderly patients with stage Ⅰ DLBCL. The 3-year PFS rate was 48.7% in the high-risk group versus 85.7% in the low-risk group ( P<0.001). Conclusions:Our findings show that the elderly patients with stage Ⅰ DLBCL were predominantly characterized by extranodal involvement (particularly in the stomach and intestinal tract) and non-GCB subtype. Age ≥75 years and CCI ≥2 were identified as independent prognostic factors. The newly established sm-IPI-75-CCI incorporating these factors demonstrated superior prognostic discrimination compared to conventional risk assessment systems.

This research study focuses on addressing the limitations of current neuropathic pain(NP)treatments by developing a novel dual-target modulator,E0199,targeting both Nav1.7,Nay1.8,and Nay1.9 and Kv7 channels,a crucial regulator in controlling NP symptoms.The objective of the study was to synthesize a compound capable of modulating these channels to alleviate NP.Through an experimental design involving both in vitro and in vivo methods,E0199 was tested for its efficacy on ion channels and its therapeutic potential in a chronic constriction injury(CCI)mouse model.The results demonstrated that E0199 significantly inhibited Nav1.7,Nav1.8,and Nav1.9 channels with a particularly low half maximal inhibitory concentration(ICs0)for Nay1.9 by promoting sodium channel inactivation,and also effectively increased Kv7.2/73,Kv7.2,and Kv7.5 channels,excluding Kv7.1 by promoting potassium channel acti-vation.This dual action significantly reduced the excitability of dorsal root ganglion neurons and alle-viated pain hypersensitivity in mice at low doses,indicating a potent analgesic effect without affecting heart and skeletal muscle ion channels critically.The safety of E0199 was supported by neurobehavioral evaluations.Conclusively,E0199 represents a ground-breaking approach in NP treatment,showcasing the potential of dual-target small-molecule compounds in providing a more effective and safe thera-peutic option for NP.This study introduces a promising direction for the future development of NP therapeutics.

In recent years, the prevalence of myopia has shown a significant upward trend characterized by earlier onset and accelerated progression rates. This epidemic not only imposes an increasing socioeconomic burden but also leads to severe vision impairment through high myopia-related complications that profoundly affect daily life. Current research on the pathogenesis of myopia primarily focuses on four mechanistic theories, including scleral remodeling, choroidal hemodynamic abnormalities, dopamine synthesis and metabolism, and inflammatory responses. The advent of high-throughput sequencing technologies has revolutionized our investigative approaches, enabling deeper exploration into myopia development through multi-omics strategies encompassing genomics, proteomics, and metabolomics. These cutting-edge methodologies have provided novel insights for myopia prevention and control, while simultaneously identifying potential therapeutic targets for precision intervention. This review focuses on summarizing the aforementioned research findings.

Liuhetang is one of the classic prescriptions included in the Catalogue of Ancient Classic Prescriptions （the Second Batch）. This study adopts the method of literature review to systematically sort out the ancient literature about Liuhetang and obtained a total of 127 effective data records， involving 82 ancient books （including 2 Japanese books）. The origin， medicinal composition， compatibility， original plants and their processing methods， dosage， decocting method， usage， and indications of Liuhetang were analyzed. Liuhetang is first recorded in the Formulary of the Bureau of Taiping People's Welfare Pharmacy in the Song Dynasty， consisting of Amomi Fructus， Pinelliae Rhizoma， Armeniacae Semen Amarum， Ginseng Radix et Rhizoma， Glycyrrhizae Radix et Rhizoma， red Poria， Pogostemonis Herba， Lablab Semen Album， Chaenomelis Fructus， Moslae Herba， Magnoliae Officinalis Cortex， Zingiberis Rhizoma Recens， and Jujubae Fructus. The original plants of these herbal medicines follow those in the 2020 edition of the Pharmacopoeia of the People's Republic of China. The raw materials of Amomi Fructus， Armeniacae Semen Amarum， Ginseng Radix et Rhizoma， Glycyrrhizae Radix et Rhizoma， red Poria， Pogostemonis Herba， Chaenomelis Fructus， Moslae Herba， Magnoliae Officinalis Cortex， Zingiberis Rhizoma Recens， and Jujubae Fructus are used in this prescription. Pinelliae Rhizoma， Glycyrrhizae Radix et Rhizoma， Lablab Semen Album， and Magnoliae Officinalis Cortex are processed with alum， stir-fried， processed with Zingiberis Rhizoma Recens， and processed with Zingiberis Rhizoma Recens， respectively. The recommended formula is composed of 0.79 g Amomi Fructus， 0.79 g Pinelliae Rhizoma， 0.79 g Armeniacae Semen Amarum， 0.79 g Ginseng Radix et Rhizoma， 0.79 g Glycyrrhizae Radix et Rhizoma， 1.57 g red Poria， 1.57 g Pogostemonis Herba， 1.57 g Lablab Semen Album， 1.57 g Chaenomelis Fructus， 3.15 g Moslae Herba， and 3.15 g Magnoliae Officinalis Cortex. The above medicines should be pulverized to reach 10 meshes， mixed with 450 mL water， 3 g Zingiberis Rhizoma Recens， and 3 g Jujubae Fructus， and decocted to reach a volume of 240 mL. The filtrate should be taken three times a day. In ancient times， Liuhetang was mainly used to treat cholera， vomiting， diarrhea， phlegm， dyspnea， cough， chest distension， dizziness and pain in the head， swelling in the limbs， lethargy， loss of appetite， difficult urination and dark urine caused by heat and dampness damage to the spleen and disharmony between spleen and stomach. In modern times， Liuhetang is mainly used to treat the digestive system diseases such as gastroenteritis， hepatitis， stomach pain， and diarrhea. The above research confirmed the key information of Liuhetang， providing a basis for the clinical application of this prescription.

Objective:To develop a predictive model for the risk of post-traumatic hydrocephalus (PTH) in patients with severe traumatic brain injury (sTBI) and validate its predictive performance.Methods:A retrospective case control study was conducted to analyze the clinical data of 580 sTBI patients admitted to the 904th Hospital of the Joint Logistics Support Force of the PLA between January 2016 and December 2023, including 413 males and 167 females, aged 18-88 years [(54.3±14.6)years]. Patients were stratified into PTH group ( n=195) and non-PTH group ( n=385), based on the presence of PTH within 6 months after injury. Data collected from the two groups such as general baseline indicators, TBI-related clinical indicators (including surgical data), laboratory findings, and radiological features. Except for the data collected during the operation, all the above data are the results of the first examination at admission. Univariate analysis and Lasso regression analysis were used to screen predictors for the risk of PTH in sTBI patients. Subsequent multivariate Logistic regression was employed to identify predictors and construct a regression equation. Based on this equation, a nomogram prediction model was developed using the R language. Model discrimination was estimated through the receiver operating characteristic (ROC) curve, and calibration performance via the Hosmer-Lemeshow (H-L) goodness-of-fit test and calibration curve. Moreover, decision curve analysis (DCA) and clinical impact curve (CIC) were used for evaluating the clinical utility of the model. Results:Univariate analysis revealed statistically significant differences in 37 variables between the two groups, including age, age group, heart rate, oxygen saturation, Glasgow coma scale (GCS) score, left pupil size, right pupil size, pupillary light reflex, intracranial pressure (ICP) monitoring, type of decompressive craniectomy, neutrophil count, lymphocyte count, monocyte count, red blood cell count, platelet count, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), neutrophil-lymphocyte-platelet ratio (N/LP), lymphocyte-to-monocyte ratio (LMR), systemic inflammation response index (SIRI), systemic immune-inflammation index (SII), fibrinogen (FIB), D-dimer, D-dimer-to-fibrinogen ratio (DFR), serum albumin, prognostic nutritional index, blood glucose, status of basal cisterns, midline shift, degree of midline shift, cerebral herniation, epidural hematoma (EDH), subdural hematoma (SDH), intraventricular hemorrhage (IVH), subarachnoid hemorrhage (SAH), modified Fisher grade, and skull fracture ( P<0.05). Lasso regression analysis identified 24 potential predictors for PTH, including age, GCS score, pupillary light reflex, type of decompressive craniectomy, monocyte count, platelet count, NLR, PLR, N/LP, LMR, SII, D-dimer, DFR, serum albumin, prognostic nutritional index, blood glucose, status of basal cisterns, degree of midline shift, cerebral herniation, EDH, SDH, IVH, modified Fisher grade and skull fracture. Multivariate Logistic regression analysis demonstrated that age, unilateral pupillary light reflex, absent pupillary light reflex, bilateral decompressive craniectomy, monocyte count, PLR, cerebral herniation, SDH, IVH, linear skull fracture and depressed skull fracture were independent risk factors for PTH. In contrast, serum albumin was identified as an independent protective factor for PTH ( P<0.05). The regression equation derived from these factors was: Logit[ P/(1- P)]=0.05×"age"+1.65×"unilateral pupillary light reflex"+2.79×"absent pupillary light reflex"+1.60×"bilateral decompressive craniectomy"+1.90×"monocyte count"+0.02×"PLR"-0.12×"serum albumin"+2.07×"cerebral herniation"+2.59×"SDH"+2.23×"IVH"+1.24×"linear skull fracture"+ 1.66×"depressed skull fracture"-22.61. The prediction model built upon this equation achieved an area under the ROC curve (AUC) of 0.95(95% CI 0.93, 0.97), with a sensitivity of 91.79%, specificity of 85.97%, and Youden′s index of 0.78. The H-L goodness-of-fit test indicated good calibration ( χ2=7.90, P=0.545). DCA results showed that the bias-corrected curve closely aligned with the actual curve and approximated the ideal curve, indicating a high clinical net benefit. Furthermore, CIC results demonstrated that with threshold probabilities greater than 60%, the number of patients identified as high-risk by the model highly corresponded with the actual number of patients who developed PTH. Conclusion:The prediction model incorporating age, unilateral pupillary light reflex, absent pupillary light reflex, bilateral decompressive craniectomy, monocyte count, PLR, serum albumin, cerebral herniation, SDH, IVH, linear skull fracture and depressed skull fracture exhibits robust predictive performance for PTH in sTBI patients.

Objective:To investigate the impact of peripheral blood prolymphocyte percentage on the prognosis of patients with chronic lymphocytic leukemia (CLL) .Methods:This study included 300 patients diagnosed with CLL at the Department of Hematology of Jiangsu Provincial People’s Hospital from October 2011 to December 2020. The association between prolymphocyte percentage and other parameters was analyzed, and the optimal cutoff prolymphocyte percentage was determined by X-tile analysis. Further survival analysis and prognostic model construction were used to validate the predictive value of prolymphocyte percentage.Results:Of the 300 eligible patients with CLL who were enrolled, 50 received Bruton tyrosine kinase inhibitors (BTKi) as first-line treatment. The group with higher prolymphocyte percentage comprised more patients in the advanced stages ( P=0.010) and had higher β 2-microglobulin ( P<0.001), unmutated immunoglobulin heavy-chain variable region gene ( P<0.001), and TP53 aberration ( P=0.004). The optimal cutoff percentage of prolymphocytes was 1%. Patients with a prolymphocyte percentage >1% had significantly shorter treatment-free survival (TFS) ( P<0.001) and overall survival time ( P=0.007) than patients with a prolymphocyte percentage ≤1%. On multivariate analysis, prolymphocyte percentage >1% tended to have an independent prognostic value for TFS [ HR=1.405 (95% CI 0.971~2.032), P=0.071]. Compared with the nomogram of CLL international prognostic index (CLL-IPI) alone, the nomogram of CLL-IPI combined with prolymphocyte percentage showed better discrimination (area under the curve: 0.778 vs. 0.637; P=0.006). In addition, patients with a prolymphocyte percentage >1% were more likely to progress after BTKi treatment ( P=0.038) . Conclusion:Peripheral blood prolymphocyte percentage was associated with various clinical and biological parameters and prognosis among patients with treatment-naive CLL.

Objective: To investigate the effect of targeted silencing of DNA methyltransferase 3A(DNMT3A) on collagen deposition, proliferation and migration activity of mouse lung fibroblasts(PFs). Methods: In order to ensure the proliferation and migration activity of primary fibroblasts, the lung tissues of neonatal C57 suckling mice were taken, PFs were extracted after being sheared, and the morphology was observed and identified under the microscope. PFs cells were activated by 5 ng/ml TGF-β1for 24 h after cell attachment, and DNMT3A silencing model was constructed by small interfering RNA; The experiment was divided into control group, TGF-β1group, TGF-β1+ siRNA-NC group and TGF-β1+ siRNA-DNMT3A group. The protein expressions of DNMT3A, α-smooth muscle actin(α-SMA) and Collagen Ⅰ were detected by Western blot; Real time quantitative reverse transcription polymerase chain reaction(RT-qPCR) was used to detect the mRNA expression changes ofDNMT3A,α-SMAandCollagenⅠ. The proliferation ability of PFs was detected by CCK-8 and EdU staining; the migration ability of PFs was detected by scratch test and Transwell migration test. Results: Compared with the control group, TGF-β1induced the increase of DNMT3A in the activated PFs cell group(P<0.01), the protein and mRNA levels of fibrosis and proliferation related indicators α-SMA and Collagen Ⅰ also increased(allP<0.05), and the proliferation and migration ability of PFs increased(allP<0.000 1). Compared with the siRNA-NC group, the protein expression levels of DNMT3A(P<0.000 1) and related indicators α-SMA(P<0.01) and Collagen Ⅰ(P<0.01) significantly decreased in the DNMT3A silencing group by Western blot, and the mRNA levels ofDNMT3A,α-SMAandCollagenⅠby RT-qPCR also decreased(allP<0.001), and the proliferation(P<0.01) and migration ability(P<0.05) of PFs cells decreased compared with the control group. Conclusion Silencing DNMT3A can inhibit the deposition of collagen and the proliferation of PFs. DNMT3A can promote the proliferation and migration of PFs, and then promote the activation of PFs and the development of pulmonary fibrosis. This process may be regulated by DNA methylation modification.