OBJECTIVE To investigate the effect and mechanism of Jingangteng capsules in the treatment of non-alcoholic fatty liver disease （NAFLD）. METHODS Thirty-two SD rats were randomly divided into normal group and modeling group. The modeling group was fed a high-fat diet to establish a NAFLD model. The successfully modeled rats were then randomly divided into model group， atorvastatin group[positive control， 2 mg/（kg·d）]， and Jingangteng capsules low- and high-dose groups [0.63 and 2.52 mg/（kg·d）]， with 6 rats in each group. The pathological changes of the liver were observed by hematoxylin-eosin staining and oil red O staining. Enzyme-linked immunosorbent assay was performed to determine the serum levels of triglycerides （TG）， total cholesterol （TC）， high-density lipoprotein cholesterol （HDL-C）， low-density lipoprotein cholesterol （LDL-C）， alanine transaminase （ALT）， aspartate transaminase （AST）， tumour necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， IL-6， IL-18. 16S rDNA amplicon sequencing and metabolomics techniques were applied to explore the effects of Jingangteng capsules on gut microbiota and metabolisms in NAFLD rats. Based on the E-mail：591146765@qq.com metabolomics results， Western blot analysis was performed to detect proteins related to the nuclear factor kappa-B （NF-κB）/NOD-like receptor family protein 3 （NLRP3） signaling pathway in the livers of NAFLD rats. RESULTS The experimental results showed that Jingangteng capsules could significantly reduce the serum levels of TG， TC， LDL-C， AST， ALT， TNF-α， IL-1β， IL-6， IL-18， while increased the level of HDL-C， and alleviated the hepatic cellular steatosis and inflammatory infiltration in NAFLD rats. They could regulate the gut microbiota disorders in NAFLD rats， significantly increased the relative abundance of Romboutsia and Oscillospira， and significantly decreased the relative abundance of Blautia （P＜0.05）. They also regulated metabolic disorders primarily by affecting secondary bile acid biosynthesis， fatty acid degradation， O-antigen nucleotide sugar biosynthesis， etc. Results of Western blot assay showed that they significantly reduced the phosphorylation levels of NF-κB p65 and NF-κB inhibitor α， and the protein expression levels of NLRP3， caspase-1 and ASC （P＜0.05 or P＜0.01）. CONCLUSIONS Jingangteng capsules could improve inflammation， lipid accumulation and liver injury in NAFLD rats， regulate the disorders of gut microbiota and metabolisms， and inhibit NF-κB/NLRP3 signaling pathway. Their therapeutic effects against NAFLD are mediated through the inhibition of the NF-κB/NLRP3 signaling pathway.

ObjectiveTo investigate the expression level of lysophosphatidyllecithin acyltransferase 4 （LPCAT4） in pancreatic cancer and its effect on the proliferation of pancreatic cancer cells. MethodsIn this study， the differentially expressed genes of patients with KRAS mutant and wild-type pancreatic cancer were analyzed by online database LinkedOmics. The LPCAT4 expression in pancreatic cancer tissues was analyzed online by the University of Alabama at Birmingham Cancer Data Analysis （UALCAN）， Sangerbox and gene expression profile interaction analysis 2 （GEPIA2）. Kaplan-Meier Plotter database was used to explore the correlation between LPCAT4 and the prognosis of patients with pancreatic cancer. The expression of LPCAT4 in human pancreatic cancer cells were detected by quantitative real-time PCR and Western blot analysis. LPCAT4 was knocked down in the high-expressing SW1990 cell line and overexpressed in the low-expressing MIA PaCa-2 cell line. The effects of LPCAT4 expression on cell proliferation were assessed using CCK-8 and EdU assays. STRING and GEPIA2 databases were used to obtain LPCAT4 binding and coexpressed genes in tumors， which were then analyzed by GO and KEGG. ResultsAnalysis of the LinkedOmics online database revealed a significant upregulation of LPCAT4 in patients with KRAS mutant pancreatic cancer compared to patients with KRAS wild-type pancreatic cancer. The online analysis of GEPIA2， UALCAN and Sangerbox 3.0 showed that the expression of LPCAT4 was higher in pancreatic cancer than in normal tissues. Analysis of the Kaplan-Meier Plotter database revealed that high LPCAT4 expression was associated with poorer prognosis in pancreatic cancer patients.Western blot and qPCR results showed that expression of LPCAT4 in pancreatic cancer cell lines was significantly higher than in normal pancreatic ductal epithelial cells. Knockdown of LPCAT4 in SW1990 cells inhibited proliferation， while overexpression in MIA PaCa-2 cells promoted proliferation. Enrichment analysis indicated that LPCAT4 was closely related to sulfur metabolism. ConclusionsLPCAT4 is highly expressed in pancreatic cancer and is associated with poor prognosis of patients. It plays a significant regulatory role in the proliferation of pancreatic cancer cells， with its expression level closely correlated with cell proliferation capacity. These findings reveal the critical role of LPCAT4 in the malignant progression of pancreatic cancer and provide important evidence for its potential as a therapeutic target.

ObjectiveTo investigate pulmonary function levels and associated influencing factors among rural elderly in Guangzhou， to identify high-risk populations for poor pulmonary function， and to reveal the relationship between the influencing factors of pulmonary function. MethodsWe recruited 1 500 residents aged 60 to 94 years from rural area of Conghua District， Guangzhou City using convenience sampling in 2023. Data on demographics， body measurements， medical history and lifestyle were collected via face-to-face questionnaires and physical examination. Meanwhile， expiratory function parameters including forced expiratory volume in one second （FEV1）， forced vital capacity （FVC）， FEV1/FVC， and the prevalence of airflow obstruction （AFO） were assessed using a portable spirometer. Age and sex distribution of pulmonary function in older adults at 5-year intervals was reported， and risk factors of AFO using multifactorial logistic regression models were analyzed. Furthermore， path analysis was further employed to explore the role of lifestyle in the association between other influencing factors and lung function. ResultsAmong the 1 500 participants， the median age was 71 years （67-75）， and 44.2% were male. Subjects identified as AFOs were generally older， more likely male， less educated， and had lower rates of moderate to vigorous physical activity （＜1 time/week） and lower lean body mass. Mean FEV1/FVC ratio was （82.0±16.4） %. FEV1/FVC was （79.80±17.58） % in men and （83.66±15.22） % in women. Older age， lower education， male sex and leanness were negatively associated with all pulmonary function outcomes （all P values＜0.05）. Path analysis identified that age， gender， marital status， occupation and income may influence pulmonary function indirectly through lifestyle. ConclusionRural elderly in Guangzhou exhibited lower pulmonary function levels， and male sex， non-married status， advanced age， lower education， smoking habits， insufficient engagement in moderate to vigorous physical activity， and lean body type were all associated with worse pulmonary function.

Objective To explore the role and possible molecular mechanism of Isocitrate dehydrogenase 1(IDH1)gene in proliferation and migration of intrahepatic cholangiocarcinoma(iCCA)cell HuCCT1.Methods HuCCT1 cells with IDH1 gene knockout(HuCCT1IDH1-/-)were constructed by CRISPR/Cas9 gene editing technology.To investigate the capacities of proliferation,migration and invasion of HuCCT1WT(HuCCT1 cells with wild-type IDH1 gene)and HuCCT1IDH1-/-cells,assays of CCK-8,clone formation,scratch and transwell were performed.Western blotting was used to detect the expression levels of epithelial-mesenchymal transition(EMT)associated proteins E-cadherin,N-cadherin,Vimentin,MMP-9,Wnt3a and β-catenin in two groups of cells.The transcriptome sequencing data of HuCCT1WT and HuCCT1IDH1-/-cells were analyzed by bioinformatics methods,Western blotting was used to verify the expression of signaling pathway-related proteins.Results Compared with HuCCT1WT cells,HuCCT1IDH1-/-cells showed the number of proliferation and clone formation significantly reduced(P<0.05),the proportion of cells blocked in G2/M phase was significantly increased(P<0.01),the rate of scratch healing was significantly decreased(P<0.01),and the number of migrated cells(P<0.001)and invaded cells(P<0.05)was significantly reduced.qRT-PCR assay showed that the expression levels of IDH1,Vimentin,MMP-9 and genes related to the regulation of G2/M cycle proliferation,Cyclin A2,Cyclin B1 and CDK1 mRNA were down-regulated in HuCCT1IDH1-/-cells(P<0.05),and the expression of CDH1 mRNA encoding E-cadherin was up-regulated(P<0.01);Western blotting assay showed that the expression level of E-cadherin in HuCCT1IDH1-/-cells was significantly increased(P<0.05),and the expression level of N-cadherin,Vimentin and MMP-9 protein was significantly decreased(P<0.05)than that in HuCCT1WT cells.Data of transcriptome sequencing revealed 1476 differentially expressed genes(DEGs)between two groups of HuCCT1 cells.Go enrichment analysis showed the DEGs were significantly enriched in cell biological processes associated with inflammatory response,cell signaling and cell metabolism.Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis suggested that the DEGs may be involved in some signaling pathways such as Wnt,MAPK,Rap1,Hippo and TNF,which are closely related to the regulation of proliferation and invasion of tumor cells.Western blotting verification results showed that compared with HuCCT1WT cells,the relative expression of Wnt3a and β-catenin proteins of HuCCT1IDH1-/-cells was significantly decreased(P<0.05).Conclusions IDH1 gene may participate in the control of biological functions of HuCCT1 cells,including cell proliferation,migration,invasion and epithelial mesenchymal transition.The mechanism may be related to the activation of the Wnt/β-catenin signaling pathway.

Objective:To summarize the characteristics of autosomal recessive axonal neuropathy with neuromyotonia (ARAN-NM) caused by HINT1 gene mutation. Methods:Retrospective case summary.Clinical data of 2 Tibetan siblings diagnosed with ARAN-NM in the Department of Pediatrics of Peking University First Hospital in August 2023 were retrospectively analyzed.A review of literature reporting relevant Chinese patients was conducted.Results:The proband and her elder brother were aged 13 and 19, respectively.Both developed abnormal gait at the age of 11, followed by varus, claudication, and weak thumb strength.The proband also had neuromyotonia.Physical examinations showed that the proband and her elder brother had decreased muscle strength of the extremities, mainly in the thumbs and distal ends of lower limbs.The distal muscles of the proband′s lower extremities and the muscles of both hands of the proband′s elder brother were atrophied.Both feet showed talipes equinovarus in the proband and her elder brother.The proband′s electromyography (EMG) showed peripheral nerve injuries (motor and sensory axonal involvement, especially in distal ends) and myotonic potentials.The trio-whole exon sequencing detected homozygous pathogenic variation in HINT1 gene in both the proband and her elder brother, who were diagnosed as ARAN-NM based on c. 169A>G (p.K57E). After the Carbamazepine treatment, the proband′s neuromyotonia, numbness and weakness were relieved.Both the proband and her elder brother underwent orthopaedic surgery and rehabilitation.Their foot deformities and gait were significantly improved.Two Chinese literatures (2 patients) and four English literatures (8 patients) were retrieved.Including the proband and her elder brother in this study, there were 12 ARAN-NM patients, 10 of whom had clinical data.The ages of onset and diagnosis were 2-16 (1 case unknown) and 13-33 years old, respectively.Myasthenia was present in 9 patients, especially in distal ends.Eight patients were complicated with neuromyotonia, nine patients with muscle atrophy, seven patients with foot deformity, and two patients with sensory disturbance.Creatine kinase(CK) was elevated in all 9 patients tested or CK.EMG showed neurogenic injuries in all patients and neuromyotonia discharge in six patients.Three patients were treated with Carbamazepine, and some symptoms were relieved.Missense/nonsense mutations were found in the 12 patients, and the high-frequency variation was c. 112T>C (p.C38R). Conclusions:ARAN-NM is a rare autosomal recessive neuromuscular disease caused by HINT1 gene mutation.There is no ethnic difference in clinical manifestations, mainly distal limb weakness with neuromyotonia.Carbamazepine can alleviate some symptoms, and orthopaedic surgery can improve foot deformity and gait.

Objective:To analyze the treatment efficacy, safety and dose parameters of optimized hippocampus-avoidance prophylactic cranial irradiation (HA-PCI) in limited-stage small cell lung cancer (LS-SCLC) and explore the corresponding dosimetric parameters under the condition of narrowing the hippocampus avoidance region as hippocampus region plus 2 mm in three dimensions.Methods:Clinical data of patients with LS-SCLC receiving HA-PCI (hippocampus avoidance region defined as hippocampus region plus 2 mm in three dimensions) in Cancer Hospital Chinese Academy of Medical Sciences from August 2014 to June 2020 were retrospectively analyzed. Dose parameters of HA-PCI and adverse events were analyzed using descriptive statistics analysis. Changes of neurocognitive function, such as mini-mental state examination (MMSE) and Hopkins verbal learning test-revised (HVLT-R) scores, were evaluated by analysis of variance and Kruskal-Wallis H test. Overall survival (OS), progression-free survival (PFS) and intracranial PFS (iPFS) were calculated using Kaplan-Meier method. The cumulative incidence of local-regional recurrence (LRR), extracranial distant metastases (EDM), and locoregional recurrence (LR) were investigated under competing risk analysis. Results:A total of 112 patients were included, the median follow-up time was 50 months (95% CI: 45.61-54.38). The median volume of hippocampus was 4.85 ml (range: 2.65-8.34 ml), with the average dose ≤9 Gy in 106 patients (94.6%), ≤8 Gy in 92 patients (82.1%). The median volume of hippocampus avoidance area was 15.00 ml (range: 8.61-28.06 ml), with the average dose ≤12 Gy in 109 patients (97.3%), ≤10 Gy in 101 patients (90.2%). The 2-year cumulative LRR, EDM, LR rates were 16.9%, 23.2% and 28.5%, respectively. The 5-year cumulative LRR, EDM, LR rates were 23.2%, 26.9% and 33.3%, respectively. The 2-year iPFS, PFS and OS rates were 66.1% (95% CI: 57.9%-75.4%), 53.6% (95% CI: 45.1%-63.7%) and 80.4% (95% CI: 73.3%-88.1%), respectively. The most common grade I-Ⅱ adverse events were nausea (33.9%) and dizziness (31.3%), and only 1 patient developed grade Ⅲ nausea and dizziness. MMSE ( n=57) and HVLT-R tests ( n=56) showed no significant decline. Conclusions:Optimized HA-PCI can achieve similar dose limitation with favorable efficacy and light toxicity. No significant decline is observed in short-term neurocognitive function in evaluable patients.

Radiation therapy (RT) is a well-established and widely used treatment modality for prostate cancer. As prostate-rectum proximity contributes to rectal toxicity, there is growing interest in rectal protection. Technical advances have enabled the reduction of rectal injury. To improve the safety of prostate cancer radiotherapy and minimize the rectal toxicity of irradiation, the advances in rectal protection technique during prostate cancer radiotherapy, including technical advances of radiation therapy, image-guided radiotherapy, application of endorectal balloons, and use of rectum spacers, were reviewed, aiming to provide reference for improving the safety of prostate cancer radiotherapy and alleviating rectal radiation injury.

Traditional Chinese medicine can regulate the hypoxia-inducible factor-1α(HIF-1α)signalling pathway and slow down tumour progression mainly by inhibiting tumour angiogenesis,glycolysis,epithelial mesenchymal transition and other pathological processes.This paper,starting from HIF-1α and related factors,reviews its pathological mechanism in tumours and the research of traditional Chinese medicine interventions with the aim of providing theoretical references for the treatment of tumours with traditional Chinese medicine.

Most patients with stroke experience obstructive sleep apnea (OSA), which has a negative impact on functional outcome and cognitive function in patients with stroke and is associated with increased mortality. Continuous positive airway pressure (CPAP) is a gold standard for treating OSA. This article reviews the effect of CPAP on functional outcome and cognitive function in stroke patients with OSA.

Objective To investigate the effect of varying blood pressure stratification on renal function in the diabetic population.Methods A prospective cohort study was conducted,enrolling 9 489 diabetic patients from a total of 101 510 Kailuan Group employees who underwent health examinations between July 2006 and October 2007.The follow-up period was(8.6±4.0)years.Participants were categorized into four groups based on their baseline blood pressure levels:normal blood pressure(systolic blood pressure<120 mmHg and diastolic blood pressure<80 mmHg),elevated blood pressure(systolic blood pressure 120-130 mmHg and diastolic blood pressure<80 mmHg),stage 1 hypertension(systolic blood pressure 130-140 mmHg and/or diastolic blood pressure 80-90 mmHg),and stage 2 hypertension(systolic blood pressure≥140 mmHg and/or diastolic blood pressure≥90 mmHg).The incidence density of chronic kidney disease(CKD)was compared among these groups.A multivariate Cox proportional hazards regression model was employed to assess the effects of different blood pressure levels on renal function in diabetic patients,with the stability of the results confirmed using a multivariate time-dependent Cox proportional hazards model.Sensitivity analysis was conducted after excluding cases of cardiovascular disease(CVD)during follow-up,and cases using antihypertensive and antidiabetic medications at baseline.Results(1)At baseline,stage 1 hypertension patients demonstrated statistically significant higher differences with age and body mass index(BMI)compared to normal blood pressure group(P<0.05).(2)By the end of the follow-up,2 294 cases of CKD were identified,including 1 117 cases of estimated glomerular filtration rate(eGFR)decline and 1 575 cases of urinary protein.The incidences density of CKD,eGFR decline and urinary protein for stage 1 hypertension group were 39.4,16.3 and 25.5 per thousand person-years,respectively,all of which were statistically significant different from normal blood pressure group(log-rank test,P<0.01).(3)Multivariate Cox regression analysis revealed that,compared to the normal blood pressure group,stage 1 hypertension was associated with a 29%increased risk of CKD(HR=1.29,95%CI 1.09-1.52)and a 40%increased risk of eGFR decline(HR=1.40,95%CI 1.08-1.80)in diabetic individuals.Conclusion Stage 1 hypertension significantly increases the risk of CKD and eGFR decline in diabetic individuals,with a particularly notable effect on the risk of eGFR decline.