ObjectiveTo investigate the risk factors for bleeding within 5 days and 2 weeks after endoscopic variceal ligation （EVL） or endoscopic cyanoacrylate injection （ECI） for the treatment of esophagogastric varices in patients with liver cirrhosis， as well as the safety of EVL/ECI in patients with thrombocytopenia. MethodsA total of 489 patients with liver cirrhosis and esophagogastric varices who underwent EVL/ECI in Guangzhou Eighth People’s Hospital， Guangzhou Medical University， from January 2018 to December 2023 were enrolled as subjects， and according to the presence or absence of bleeding after surgery， they were divided into bleeding group and non-bleeding group. The risk factors for bleeding within 5 days and 2 weeks after surgery were analyzed. The independent-samples t test or the Mann-Whitney U test was used for comparison of continuous data between groups， and the chi-square test or the continuity-corrected chi-square test was used for comparison of categorical data between groups； the receiver operating characteristic （ROC） curve was plotted to determine the cut-off value of MELD score； a multivariate logistic regression analysis was used to identify the independent risk factors for postoperative bleeding. ResultsThere were no significant differences in the bleeding rates within 5 days and 2 weeks after EVL/ECI between the 386 patients with a platelet count of ≥50×10⁹/L and the 103 patients with a platelet count of （25 — 49）×10⁹/L （5 days： 1.94% vs 2.85%， P=0.870； 2 weeks： 2.91% vs 4.92%， P=0.544）. The overall bleeding rate was 2.66% （13/489） and 4.50% （22/489）， respectively， within 5 days and 2 weeks after EVL/ECI. The multivariate logistic regression analysis showed that MELD score was an independent risk factor for bleeding within 5 days （odds ratio ［OR］=3.726， 95% confidence interval ［CI］： 1.214 — 11.429， P=0.021） and 2 weeks （OR=5.760， 95%CI： 1.779 — 18.651， P=0.003） after EVL/ECI， while hemoglobin （Hb） was a protective factor against bleeding within 5 days （OR=0.972， 95%CI： 0.948 — 0.996， P=0.025） and 2 weeks （OR=0.976， 95%CI： 0.957 — 0.995， P=0.016） after surgery； portal vein tumor thrombus （OR=2.667， 95%CI： 1.000 — 7.117， P=0.050） was an independent risk factor for bleeding within 2 weeks after surgery， while platelet count ［（25 — 49）×10⁹/L］ was not a risk factor for postoperative bleeding （P>0.05）. ConclusionBoth EVL and ECI have good safety in patients with liver diseases and grade 3 thrombocytopenia. MELD score is an independent risk factor for bleeding within 5 days and 2 weeks after EVL/ECI， while Hb is a protective factor； portal vein tumor thrombus is an independent risk factor for bleeding within 2 weeks after surgery.

ObjectiveTo investigate the potential mechanism of Qingguangan Ⅱ Formula （青光安Ⅱ号方， QGAⅡ） in the treatment of glaucoma from the perspectives of oxidative stress and the cyclic adenosine monophosphate/ protein kinase A （cAMP/PKA） signaling pathway. MethodsForty SD rats were randomly assigned to a medicated serum group （n=30）， which received QGAⅡby intragastric administration at 6.741 g/（kg·d）， and a blank group （n=10）， which received normal saline at 10 ml/（kg·d）. After 7 consecutive days of administration， medicated serum and blank serum were prepared. The optimal concentration of medicated serum for R28 cell intervention was determined using CCK-8 assay. An in vitro glaucoma model was established by exposing R28 cells to continuous hydrostatic pressure combined with oxygen-glucose deprivation （OGD） for 24 h to simulate the pathological microenvironment of glaucomatous optic nerve injury. The experiment set a control group （complete medium）， model group （glucose-free medium + tri-gas incubator）， medicated serum group （selected concentration of QGA-medicated serum + glucose-free medium + tri-gas incubator）， and blank serum group （blank serum + glucose-free medium + trigas incubator）. The total culture medium volume in each culture dish was 5 ml. After 24 h of culture， cell proliferation was assessed using the EdU immunofluorescence assay， and apoptosis was determined by flow cytometry. Malondialdehyde （MDA） content and superoxide dismutase （SOD） activity were measured using biochemical assays. Western Blotting was performed to detect the expression of oxidative stress-related proteins including 4-hydroxynonenal （4-HNE） and heme oxygenase-1 （HO-1）， apoptosis-related proteins including B-cell lymphoma-2 （Bcl-2）， Bcl-2-associated X protein （Bax）， and cleaved caspase-3 （C-caspase-3）， and cAMP/PKA signaling pathway-related proteins including protein kinase A （PKA）， phosphorylated PKA （p-PKA）， cAMP response element-binding protein （CREB）， and phosphorylated CREB （p-CREB）. Intracellular cyclic adenosine monophosphate （cAMP） levels were determined by ELISA. In addition， a forskolin （agonist） group， an H89 （inhibitor） group， and a 7.5% medicated serum plus inhibitor group were established to further investigate the effects of QGAⅡ-medicated serum on oxidative stress and the cAMP/PKA signaling pathway in R28 cells. ResultsA concentration of 7.5% QGAⅡ-medicated serum was identified as the optimal concentration for subsequent experiments. Compared to the control group， the model group exhibited significantly decreased cell proliferation， SOD activity， Bcl-2 protein expression， p-PKA/PKA ratio， p-CREB/CREB ratio， and cAMP content， as well as increased apoptosis rate， MDA content， and the protein expression levels of 4-HNE， HO-1， Bax， and C-caspase-3 （P＜0.01）. Compared to the model group， the 7.5% medicated serum group showed significant improvements in all of the above parameters （P＜0.01）. In the forskolin group， the apoptosis rate and the expression levels of C-caspase-3 and Bax significantly decreased， whereas Bcl-2 expression and the p-PKA/PKA and p-CREB/CREB ratios increased compared to those in the model group （P＜0.01）. Compared to the 7.5% medicated serum group， the 7.5% medicated serum plus inhibitor group exhibited significantly increased expression of C-caspase-3 and Bax， together with significantly decreased Bcl-2 expression and reduced p-PKA/PKA and p-CREB/CREB ratios （P＜0.01）. ConclusionUnder continuous hydrostatic pressure and OGD-induced injury conditions， QGAⅡ- containing serum effectively mitigates oxidative stress in R28 cells， activates the cAMP/PKA signaling pathway， and inhibits apoptosis， thereby exerting a neuroprotective effect on retinal ganglion cells

Glaucoma is a multifactorial degenerative optic neuropathy, and its irreversible and blinding pathological characteristics mainly come from the damage to the optic nerve, namely glaucomatous optic neuropathy(GON). The difficulty in the treatment of GON lies in the early intervention, and currently there is no optic neuroprotective drug for the treatment of all types of GON. The death of retinal ganglion cells(RGCs)is the core pathological change caused by various pathogenic mechanisms of GON. Recent studies have found that the widespread second messenger cyclic adenosine 3', 5' -monophosphate(cAMP)and its downstream effector protein kinase A(PKA)signal cascade play an important role in the pathogenesis of GON. It can also inhibit the apoptosis of RGCs and play a protective and therapeutic role in glaucoma. Therefore, this article reviews the role of cAMP/PKA pathway in the pathophysiological development of GON, focusing on its effects on glaucoma intraocular pressure regulation, oxidative stress, neuroinflammation and optic nerve degeneration, in order to find a common central regulatory target for the optic nerve damage caused by different pathological mechanisms of GON and promote the further understanding and clinical treatment of this disease.

The theory of "turbid pathogen harming the clarity" was proposed by YE Tianshi in his book Wenre Lun, which can be applied to clear orifices diseases such as ear, eye, nose, and mouth. Based on the location and characteristics of vitreous opacity, as well as its understanding by medical professionals throughout history, this article points out that the core pathogenesis of vitreous opacity is "turbid pathogen harming the clarity" and the obstruction of the spirit light, and the basic pathogenesis is: unfavorable liver and gallbladder conditions, damp heat accumulation and turbidity; imbalance of middle jiao, qi deficiency leading to turbidity; kidney failure with yang deficiency, stagnant water and fluids; and stagnation entering the collaterals for an extended time, causing blockage and turbidity. And based on the pathogenesis of "turbid pathogen harming the clarity" , corresponding treatment principles are proposed: soothing liver and promoting bile flow, clearing heat and eliminating turbidity; cultivating soil to produce gold, enhancing clarity and reducing turbidity; tonifying kidney and promoting yang, warming and dispelling turbid pathogens; and removing blood stasis and activating collaterals, dispelling turbidity and unblocking the orifices. Based on the theory of "turbid pathogen harming the clarity" , this article summarizes the pathogenesis and treatment of vitreous opacity, in order to provide new ideas for traditional Chinese medicine treatment of this disease.

BACKGROUND: Molecular subtyping is an essential complementarity after pathological analyses for targeted therapy. This study aimed to investigate the consistency of next-generation sequencing (NGS) results between circulating tumor DNA (ctDNA)-based and tissue-based in non-small cell lung cancer (NSCLC) and identify the patient characteristics that favor ctDNA testing. METHODS: Patients who diagnosed with NSCLC and received both ctDNA- and cancer tissue-based NGS before surgery or systemic treatment in Lung Cancer Center, Sichuan University West China Hospital between December 2017 and August 2022 were enrolled. A 425-cancer panel with a HiSeq 4000 NGS platform was used for NGS. The unweighted Cohen's kappa coefficient was employed to discriminate the high-concordance group from the low-concordance group with a cutoff value of 0.6. Six machine learning models were used to identify patient characteristics that relate to high concordance between ctDNA-based and tissue-based NGS. RESULTS: A total of 85 patients were enrolled, of which 22.4% (19/85) had stage III disease and 56.5% (48/85) had stage IV disease. Forty-four patients (51.8%) showed consistent gene mutation types between ctDNA-based and tissue-based NGS, while one patient (1.2%) tested negative in both approaches. Patients with advanced diseases and metastases to other organs would be suitable for the ctDNA-based NGS, and the generalized linear model showed that T stage, M stage, and tumor mutation burden were the critical discriminators to predict the consistency of results between ctDNA-based and tissue-based NGS. CONCLUSION ctDNA-based NGS showed comparable detection performance in the targeted gene mutations compared with tissue-based NGS, and it could be considered in advanced or metastatic NSCLC.
Humans ; Carcinoma, Non-Small-Cell Lung/pathology* ; Circulating Tumor DNA/blood* ; High-Throughput Nucleotide Sequencing/methods* ; Female ; Male ; Lung Neoplasms/pathology* ; Middle Aged ; Mutation/genetics* ; Aged ; Adult ; Aged, 80 and over

Objective:To investigate whether intratumoral Gemella haemolysans(G.haemolysans)enhances the efficacy of neoadjuvant chemoimmunotherapy(NACI)in esophageal squamous cell carcinoma(ESCC)-bearing mice and the underlying mechanism.Methods:Twenty-five 4-week-old female C57BL/6 mice were randomized into five groups(n=5 per group):negative control(NC)group,chemo-therapy group,G.haemolysans+chemotherapy group,NACI group,and G.haemolysans+NACI group.A germ-free mouse model was established in each group by administering antibiotic cocktail for 2 weeks.On day 0,ESCC-bearing mouse models were built through subcutaneous inoculation of either murine esophageal cancer cell line AKR or G.haemolysans-AKR cells.On day 7 when tumors formed under the skin,drugs were injected into the abdomen thrice weekly.On day 28 when the treatments were finished,the mice were sacrificed to harvest their tumors,and then the tumors were fixed in 4%paraformaldehyde.We located and quantified G.haemolysans within the tumors through fluorescence in situ hybridization,and characterized immune cell composition in the tumor immune microen-vironment(TIME)of the mice treated with NACI through multiplex immunohistochemistry and flow cytometry.Results:G.haemolysans significantly strengthened the efficacy of NACI in ESCC(P<0.05),whereas no chemosensitizing effects were observed on chemo-therapy in ESCC-bearing mice.G.haemolysans significantly en-hanced natural killer(NK)cell infiltration within the TIME(P<0.01).Conclusion:G.haemolysans improves NACI efficacy in ESCC-bearing mice by increasing NK cell recruitment in the TIME.

Objective To systematically evaluate the psychometric properties of specific self-reported outcome assessment tools for patients undergoing Endoscopic Transnasal Transsphenoidal Surgery(ETTS),with the aim of pro-viding clinical healthcare professionals with evidence to guide the selection of appropriate assessment tools.Methods A systematic search was performed across multiple databases,including the North American Skull Base Society,PubMed,Embase,CINAHL,Web of Science,Cochrane Library,CNKI,VIP database,Wanfang database,and the China Biomedical Literature Database,for studies published from the inception of each database to January 9,2025,that are related to ETTS-specific symptom assessment tools.Totally 2 independent researchers screened the literature and extracted relevant data.The consensus-based health measurement tool selection bias risk checklist and quality standards were used to evaluate the methodological quality and psychometric properties of the included studies,which helped to form the development of recommendations.Results A total of 11 articles were included,covering 8 specific self-reported outcome assessment tools for patients undergoing endonasal transsphenoidal pituitary tumor resection.Of these,the Pituitary Outcome Score and the Leiden Bother and Needs Questionnaire for patients with pituitary disease 2 tools were rated as Grade A recommendations,and 6 tools were rated as Grade B recommendations.Conclusion POS and LBNQ-Pituitary are recommended due to their relatively strong overall methodological quality and psychometric properties.However,further validation with larger sample sizes is necessary.

This paper presents a rare case of renal amyloidosis complicated with primary minimal change disease. The patient initially presented with edema and proteinuria, accompanied by IgG-λ monoclonal immunoglobulinemia, leading to a diagnosis of primary systemic immunoglobulin light chain amyloidosis with renal involvement. Following treatment, the patient achieved both hematologic and renal remission. However, a renal relapse occurred two years later, presenting as nephrotic syndrome without hematologic disease recurrence. A repeat renal biopsy revealed no obvious change in amyloid deposition, but demonstrated markedly enlarged effacement of podocyte foot processes. Based on these findings, a secondary diagnosis of primary minimal change disease was established. The patient exhibited a rapid response to immunosuppressive therapy, achieving sustained long-term remission. This case underscores the importance of remaining vigilant to etiological changes in the treatment of renal diseases and highlights the role of repeated renal biopsy in refining the diagnosis and guiding treatment.

Objective To develop the Ego Depletion Scale for Type 2 Diabetes Patients and evaluate its reliability and validity,and to provide a specific assessment tool for evaluating ego-depletion in self-management.Methods Guided by the self-control strength model,the initial scale was constructed through literature review,semi-structured interviews,2 rounds of expert consultation,and a pilot survey.A convenience sampling method was employed to recruit 460 patients with Type 2 Diabetes from the endocrinology department of a tertiary hospital in Wuhan,Hubei Province,between April and July 2024.They were randomly divided into 2 subsets for exploratory factor analysis and confirmatory factor analysis.Results A total of 451 valid questionnaires were collected.Exploratory factor analysis extracted 6 common factors,with a cumulative variance contribution of 73.231％.In confirmatory factor analysis,an item was deleted due to failing to meet the standardized loading value criterion.The revised Ego Depletion Scale for Type 2 Diabetes Patients comprised 6 dimensions and 22 items.The total Cronbach's α coefficient was 0.911;split-half reliability was 0.744;the content validity index was 0.860.Correlation coefficients between the total score and scores of each dimension of the scale and the total score of the Self-Regulatory Fatigue Scale ranged from 0.558 to 0.946(P＜0.001).Conclusion The scale exhibits robust reliability and validity,serving as a scientifically instrument for assessing ego depletion in patients with Type 2 Diabetes.

OBJECTIIVE:The positive role of exercise intervention in the prevention and treatment of sarcopenia has received widespread attention,but the optimal exercise dose for elderly sarcopenic patients still needs to be further determined.The article explored the dose-effect relationship between various elements of exercise prescription and the improvement of muscle mass,muscle strength and physical function in community-dwelling elderly patients with sarcopenia,aiming to provide scientific support for the development of exercise prescription for community-dwelling elderly patients with sarcopenia.METHODS:Literature published from the inception to October 9,2024 in PubMed,EMBASE,Scopus,Web of Science,CNKI,WanFang,VIP,and CBMdisc databases was systematically searched.Meta-analysis was performed using RevMan 5.3 software.Standardized mean difference(SMD)and its 95％CI were used as effect statistics.RESULTS:(1)A total of 11 randomized controlled trials were included,with 348 in the trial group and 304 in the control group.(2)Meta-analysis results showed that exercise improved appendicular skeletal muscle mass index,grip strength,and walking speed in elderly patients with sarcopenia(SMDs 0.46,0.63,0.67,P＜0.05).(3)When the frequency of exercise was 2-3 days/week,appendicular skeletal muscle mass index(SMD=0.57,95％CI:0.28-0.86,P＜0.001),grip strength(SMD=0.70,95％CI:0.37-1.02,P＜0.001),and walking speed(SMD=0.69,95％CI:0.20-1.18,P=0.006)were effectively improved in elderly patients with sarcopenia.(4)When the duration of exercise was 25-60 minutes per session,appendicular skeletal muscle mass index(SMD=0.28,95％CI:0.07-0.50,P=0.01),grip strength(SMD=0.37,95％CI:0.16-0.59,P＜0.001),and walking speed(SMD=0.39,95％CI:0.06-0.73,P=0.02)were effectively improved in elderly patients with sarcopenia.(5)When the exercise intensity was moderate,appendicular skeletal muscle mass index(SMD=0.69,95％CI:0.35-1.03,P＜0.001),and grip strength(SMD=0.36,95％CI:0.09-0.64,P=0.009),and walking speed(SMD=0.91,95％CI:0.34-1.47,P=0.002)were effectively improved in elderly patients with sarcopenia.(6)When the dose of exercise cycle was 8-12 weeks,appendicular skeletal muscle mass index(SMD=0.42,95％CI:0.20-0.64,P＜0.001),grip strength(SMD=0.45,95％CI:0.26-0.64,P＜0.001),and walking speed(SMD=0.76,95％CI:0.27-1.25,P=0.002)were effectively improved in elderly patients with sarcopenia.CONCLUSION:Active,regular exercise can improve muscle health in older adults with sarcopenia.It is recommended that older patients with sarcopenia exercise at least 2 to 3 days per week,25 to 60 minutes each time,lasting for 8 to 12 weeks of moderate intensity exercise to improve muscle health.