ObjectiveTo evaluate the clinical efficacy and safety of acupuncture in treating severe Bell's palsy and to explore its potential mechanism by investigating the effect on serum levels of glial cell line-derived neurotrophic factor （GDNF） and nerve growth factor （NGF）. MethodsA randomized， subject-blinded， sham-acupuncture controlled trial was conducted. A total of 130 patients with severe Bell's palsy were randomly allocated into a treatment group or a control group at a 1∶1 ratio. Both groups received conventional western medicine. In addition， the treatment group received acupuncture， while the control group received sham acupuncture， with each session lasting 30 minutes. The treatment course lasted 8 weeks for both groups， followed by a follow-up assessment at week 12. The primary outcome was the proportion of patients achieving House-Brackmann （H-B） grade Ⅱ or lower at week 8. Secondary outcomes included Sunnybrook facial grading system scores at week 0， 4， 8， and 12， the time to satisfactory recovery（the time required to achieve H-B grade≤Ⅱ）， distribution of H-B grades and facial disability index （FDI） scores including the physical function subscale （FDIP） and social/well-being function subscale （FDIS） scores at week 0， 4， 8， and 12， and serum GDNF and NGF levels at week 0， 4， and 8. Adverse events and participants' self-assessments of treatment efficacy were also recorded. ResultsA total of 122 participants completed the study， including 62 in the treatment group and 60 in the control group. An intention-to-treat （ITT） analysis was performed， and missing data were handled using the last observation carried forward （LOCF） method. The proportion of patients achieving H-B grade ≤grade Ⅱ at week 8 was 78.5% （51/65） in the treatment group， significantly higher than 49.2% （32/65） in the control group （P＜0.05）. The Sunnybrook scores， FDIP and FDIS scores increased， while H-B grades decreased at week 4， 8， and 12 in both groups compared to week 0； moreover， improvements in all outcome measures were significantly greater in the treatment group than in the control group （P＜0.05）. The median time to satisfactory recovery was 6 weeks （95%CI： 5.697-6.303） in the treatment group， significantly shorter than 12 weeks （95%CI： 8.314-15.686） in the control group （P＜0.05）. Serum levels of GDNF and NGF were significantly higher in the treatment group at weeks 4 and 8 （P＜0.05）. No serious acupuncture-related adverse events occurred in either group. Adverse events were reported in 5 patients （7.69%） in the treatment group and 4 patients （6.15%） in the control group， with no statistically significant difference between groups （P＞0.05）. Patients' self-assessment of treatment efficacy after 8 weeks treatment was significantly better in the treatment group （P＜0.05）. ConclusionAcupuncture can effectively improve facial nerve function and shorten recovery time in patients with severe Bell's palsy， with a favorable safety profile. The therapeutic mechanism may be associated with the upregulation of serum GDNF and NGF levels.

Objective To optimize the extraction process of Xuetong capsules and establish its quality control method. Methods The extraction process was optimized by orthogonal experiment using ethanol reflux method to investigate the effects of different factors on diphenylstilbene, aloin and extraction yield. The content of 5 anthraquinone compounds in Xuetong capsule was determined by HPLC. Results The optimal extraction process was to add 10 times ethanol, with an ethanol concentration of 70%, and extract 3 times, each time for 1 h; 5 components had a good linear relationship with peak area within a certain concentration range, r>0.999 7; The range of sample recovery rate was 93.66%-96.85%, RSD range of 1.48%-1.66%. The content determination results of the 5 components in three batches of Xuetong capsules were （0.632-0.641）, （0.660-0.681）, （1.968-1.991）, （2.547-2.580）, and （1.076-1.101） mg/g. Conclusion The method was accurate, reproducible, and highly feasible, which could be references for producing and improving the quality control standards of Xuetong capsules.

ObjectiveTo investigate the incidence of stroke in patients with type 2 diabetes mellitus (T2DM) in the community of Shanghai, and to explore its influencing factors. MethodsA two-way cohort study was used to observe the incidence of stroke in a dynamic cohort of14 743 community-based T2DM patients who were enrolled for management from January 2016 to December 2018 in Hongkou District, Shanghai. All the research subjects were followed up for 3 years to observe the stroke occurrence. Outcome events were retrospectively collected from the Shanghai Stroke and Acute Myocardial Infarction Registry Reporting Information System and the Cause of Death Registry System, and information on stroke onset and verification of past medical history were collected by family physicians through clinic follow-up, home follow-up, and telephone follow-up. Cox proportional hazards model was used to identify the risk factors of stroke in TDM2 patients, and the hazard ratio (HR) and its 95% confidence interval (CI) were calculated. ResultsAfter a mean follow up of 3.5 years, the standardized incidence of stroke in patients with T2DM was 8.65‰, and the risk of standardized incidence was 3.50 (95%CI: 3.26‒3.77) compared with that of the total national population. Cox proportional hazards regression analysis showed that age (HR=1.18, 95%CI: 1.13‒1.23), being female (HR=1.14, 95%CI: 1.01‒1.29), physical activity <600 metabolic equivalent (MET)·min·week^-1 (HR=1.24, 95%CI: 1.06‒1.44), substandard of HbA1c control (HR=1.16, 95%CI: 1.03‒1.30), occasional smoker(HR=1.23, 95%CI: 1.04‒1.45), and those who took insulin therapy (HR=1.36, 95%CI: 1.11‒1.66) were associated with an increased risk of stroke, while those received contracted services from family doctors were associated with a decreased risk of stroke(HR=0.78, 95%CI: 0.71‒0.88). ConclusionCommunity T2DM population in Shanghai has a high risk of stroke. It is necessary to continue to explore the positive role of family doctor contract service management model, strengthen individualized exercise, smoking cessation and other lifestyle interventions, and strictly control blood glucose as soon as one can to delay or avoid the occurrence of complications.

Chronic thromboembolic pulmonary hypertension(CTEPH)is a severe form of pulmonary hypertension(PH),and is classified as the fourth major category of pulmonary arterial hypertension.CTEPH is primarily caused by chronic thrombosis,leading to the obstruction of blood flow in the pulmonary arteries and result ing in a sustained increase in pulmonary artery pressure.The unclear pathogenesis of CTEPH,however,means that its early diagnosis is challenging,treatment options are limited,and prognosis assessment is often inaccurate.In-depth research into these mechanisms will thus improve our understanding of the pathophysiological processes of CTEPH,and also provide a theoretical basis for developing new therapeutic strategies.This review focuses on the current method of establishing CTEPH rat models and their advantages and disadvantages,offering researchers a reference for selecting and constructing CTEPH rat models.

Objective:Exploring the association between Life's Crucial 9 (LC9) and the risk of thyroid dysfunction (TD), as well as its potential predictive capacity.Methods:A total of 247 600 TD-free participants from the UK Biobank were enrolled in the study. The LC9 score was divided into three CVH groups: low (0-), medium (50-), and high (80-100). Cox proportional hazards regression models were used to calculate the HRs and 95% CIs of the risk of TD with LC9 CVH status. Calculate Harrell's concordance index ( C-index), net reclassification improvement (NRI), and integrated discrimination improvement (IDI) to evaluate the predictive ability of the LC9 score and Life's Essential 8 (LE8) score. Results:During a median follow-up of 12.3 years, 5 515, 911, and 4 869 new cases of TD, hyperthyroidism, and hypothyroidism were documented, respectively. Participants with a high LE8 CVH group had 57.00% ( HR=0.43, 95% CI: 0.38-0.49), 55.00% ( HR=0.45, 95% CI: 0.34-0.60), and 58.00% ( HR=0.42, 95% CI: 0.37-0.47) lower risk of TD, hyperthyroidism, and hypothyroidism, respectively, than those with low CVH group. Compared with the LE8 score, the improvement in C-index for the LC9 score predicted TD risk was 0.004 (95% CI: 0.001-0.007), the NRI was 0.101 (95% CI: 0.021-0.103), and the IDI was 0.001 (95% CI: 0.000-0.001). Conclusions:The better CVH status, defined by LC9, was associated with a lower risk of TD. Compared to the LE8 score, the LC9 score demonstrated a significant enhancement in both risk discrimination and reclassification capability for TD risk.

Objective To explore the inhibitory effect of guggulsterone(GS)on diethylnitrosamine(DEN)-induced liver fibrosis in rats and its mechanism.Methods DEN-induced liver fibrosis model was established in SD rats.The successful model rats were randomly divided into model group(n=6),GS group(n=6,50 mg/kg,intraperitoneal injection for 4 weeks),GS+SRI group(n=6,50 mg/kg+30 mg/kg,intraperitoneal injection for 4 weeks),and control group(n=6,without DEN-induced).Rats in the control group and the model group were injected with the same amount of normal saline.The pathological changes of the liver were detected by HE staining.Serum liver function indexes including alanine aminotransferase(ALT),aspartate aminotransferase(AST),albumin(ALB)and alkaline phosphatase(ALP)were detected by automatic biochemical analyzer.The serum levels of pro-collagen Ⅲ(PC-Ⅲ),collagen Ⅳ(Ⅳ-C),hyaluronidase(HA),laminin(LN),malondialdehyde(MDA),reduced glutathione(GSH),superoxide dismutase(SOD),and catalase(CAT)were detected by ELISA assay.The mRNA and protein expression of TGF-β1,Smad2,and p-Smad3/Smad3 were detected by Real-time PCR and Western blotting.Results Compared with the control group,the model group showed typical pathological changes of liver fibrosis;the serum ALB,GSH,SOD and CAT levels were significantly decreased(P＜0.05);the serum levels of ALT,AST,ALP,MDA,PC-Ⅲ,Ⅳ-C,HA,LN and the mRNA expression of TGF-β1,Smad3 and protein expression of TGF-β1,p-Smad3 in liver tissues were significantly increased(P＜0.05).Compared with the model group,the pathological changes of liver fibrosis in the GS group were alleviated,and the serum levels of ALB,GSH,SOD and CAT were significantly increased(P＜0.05),the serum levels of ALT,AST,ALP,MDA,PC-Ⅲ,Ⅳ-C,HA and LN,the mRNA expression of TGF-β1 and Smad3,and protein expression of TGF-β1 and p-Smad3 in liver tissues were significantly decreased(P＜0.05).In addition,after the administration of SRI,TGF-β1 signaling pathway activator,compared with the GS group,the GS+SRI group showed significantly decreased serum ALB,GSH,SOD and CAT levels(P＜0.05),but significantly increased serum levels of ALT,AST,ALP,MDA,PC-Ⅲ,Ⅳ-C,HA and LN as well as the mRNA expression of TGF-β1 and Smad3 and protein expression of TGF-β1 and p-Smad3 in liver tissues(P＜0.05).Therefore,SRI attenuated the anti-fibrotic effect of GS on rats with liver fibrosis.Conclusion GS has certain inhibitory effect on DEN-induced liver fibrosis in rats,and its mechanism may be related to the reduction of oxidative stress level and the inhibition of the activation of TGF-β1/Smad3 signaling pathway.

OBJECTIVE: To develop a method for identifying high-risk patients among septic populations requiring mechanical ventilation, and to conduct phenotypic analysis based on this method. METHODS: Data from four sources were utilized: the Medical Information Mart for Intensive Care (MIMIC-IV 2.0, MIMIC-III 1.4), the Philips eICU-Collaborative Research Database 2.0 (eICU-CRD 2.0), and the Anhui Medical University Second Affiliated Hospital dataset. The adult patients in intensive care unit (ICU) who met Sepsis-3 and received invasive mechanical ventilation (IMV) on the first day of first admission were enrolled. The MIMIC-IV dataset with the highest data integrity was divided into a training set and a test set at a 6:1 ratio, while the remaining datasets were served as validation sets. The demographic information, comorbidities, laboratory indicators, commonly used ICU scores, and treatment measures of patients were extracted. Clinical data collected within first day of ICU admission were used to calculate the sequential organ failure assessment (SOFA) score. K-means clustering was applied to cluster SOFA score components, and the sum of squared errors (SSE) and Davies-Bouldin index (DBI) were used to determine the optimal number of disease subtypes. For clustering results, normalized methods were employed to compare baseline characteristics by visualization, and Kaplan-Meier curves were used to analyze clinical outcomes across phenotypes. RESULTS: This study enrolled patients from MIMIC-IV dataset (n = 11 166), MIMIC-III dataset (n = 4 821), eICU-CRD dataset (n = 6 624), and a local dataset (n = 110), with the four datasets showing similar median ages and male proportions exceeding 50%; using 85% of the MIMIC-IV dataset as the training set, 15% as the test set, and the rest dataset as the validation set. K-means clustering based on the six-item SOFA score was performed to determine the optimal number of clusters as 3, and patients were finally classified into three phenotypes. In the training set, compared with the patients with phenotype II and phenotype III, those with phenotype I had the more severe circulatory and respiratory dysfunction, a higher proportion of vasoactive drug usage, more obvious metabolic acidosis and hypoxia, and a higher incidence of congestive heart failure. The patients with phenotype II was dominated by respiratory dysfunction with higher visceral injury. The patients with phenotype III had relatively stable organ function. The above characteristics were consistent in both the test and validation sets. Analysis of infection-related indicators showed that the patients with phenotype I had the highest SOFA score within 7 days after ICU admission, initial decreases and later increases in platelet count (PLT), and higher counts of neutrophils, lymphocytes, and monocytes as compared with those with phenotype II and phenotype III, their blood cultures had a higher positivity rates for Gram-positive bacteria, Gram-negative bacteria and fungi as compared with those with phenotype II and phenotype III. The Kaplan-Meier curve indicated that in the training, test, and validation sets, the 28-day cumulative mortality of patients with phenotype I was significantly higher than that of patients with phenotypes II and phenotype III. CONCLUSIONS Three distinct phenotypes in septic patients receiving IMV based on unsupervised machine learning is derived, among which phenotype I, characterized by cardiorespiratory failure, can be used for the early identification of high-risk patients in this population. Moreover, this population is more prone to bloodstream infections, posing a high risk and having a poor prognosis.
Humans ; Machine Learning ; Sepsis/therapy* ; Respiration, Artificial ; Intensive Care Units ; Organ Dysfunction Scores ; Male ; Female ; Middle Aged ; Adult

BACKGROUND:The definitive cause of adolescent idiopathic scoliosis is not yet known.The search for a clinical approach to address adolescent idiopathic scoliosis is imminent.OBJECTIVE:To investigate the effect of Schroth therapy combined with core strength training on mild adolescent idiopathic scoliosis and to provide more bases for the clinical treatment of mild adolescent idiopathic scoliosis.METHODS:110 patients with mild adolescent idiopathic scoliosis attending the Department of Rehabilitation Medicine and Department of Spine Surgery of Affiliated Hospital of Nantong University from July 2022 to January 2024 were selected as the study subjects.They were divided into the trial group and the control group according to the wishes of the patients and their parents,with 55 cases in each group.The control group was observed and followed up,and the trial group underwent Schroth therapy combined with core strength training for 45 minutes a day for 24 weeks.The differences in imaging parameters,body surface indexes,three-dimensional ultrasound imaging angle,and quality of life were compared between the two groups before and after treatment.RESULTS AND CONCLUSION:(1)At 24 weeks after treatment,major curve Cobb,apical vertebral translation,and cervical lordosis were significantly improved in the trial group(P＜0.05),while there was no significant difference in the control group(P＞0.05).Major curve Cobb and apical vertebral translation in the trial group were significantly better than those in the control group(P＜0.05).(2)At 24 weeks after treatment,angle of trunk rotation in the trial group was significantly lower than that before treatment(P＜0.05),while there was no significant difference between before and after treatment in the control group(P＞0.05),and angle of trunk rotation in the trial group was significantly lower than that of the control group(P＜0.05).(3)At 24 weeks after treatment,the center of laminae angle of three-dimensional ultrasound imaging was significantly reduced in the trial group(P＜0.05),while there was no significant difference in the control group before and after treatment(P＞0.05).The center of laminae angle of three-dimensional ultrasound imaging was smaller in the trial group than that in the control group(P＜0.05).(4)At 24 weeks after treatment,in terms of the quality of life,pain dimension score in the trial group was significantly increased(P＜0.05).Both trial and control groups showed significantly higher scores in the self-image dimension compared with that before treatment(P＜0.05).Both groups had significantly lower scores in the mental health dimension compared with that before treatment(P＜0.05).In the dimensions of pain,self-image,mental health,and satisfaction,the trial group was significantly higher than the control group(P＜0.05).(5)It is indicated that Schroth therapy combined with core strength training can improve the major curve Cobb,apical vertebral translation,and cervical lordosis angle,reduce the angle of trunk rotation,decrease the center of laminae angle of three-dimensional ultrasound imaging,and improve the quality of life,and it is effective in the treatment of mild adolescent idiopathic scoliosis.

Objective To evaluate the quality of Xi xiong(Gansu Chuanxiong)based on the combination of intelligent sensory technology,HPLC and HS-SPME-GC-MS.Methods The chromaticity values of 10 batches of Gansu Chuanxiong Rhizoma samples were measured using a colorimeter and clustering analysis was performed;an electronic nose was used to measure the odor of Gansu Chuanxiong Rhizoma,and Loadings and PCA were conducted;According to the method under the Chuanxiaong Rhizoma section of the Chinese Pharmacopoeia,the moisture,ash content and extract were determined;HPLC was used to determine the contents of ferulic acid,chlorogenic acid and ligustrazine;the volatile components were analyzed by HS-SPME-GC-MS;the quality of Gansu Chuanxiong Rhizoma was evaluated by analyzing the correlation between chromaticity value,odor and active components.Results The total color value of Gansu Chuanxiong Rhizoma ranged from 31.210 1±1.193 7 to 43.976 3±0.721 4,at the Euclidean distance of 10,and the 10 batches of Gansu Chuanxiong Rhizoma could be clustered into four categories;Loadings and PCA showed that the higher contribution of sensors W2S,W5S,W2W,W1W and W1S to Gansu Chuanxiong Rhizoma samples,the variance contribution of the first and second principal components was 62.6%and 22.4%,respectively;water,ash and extract in 10 batches of Gansu Chuanxiong Rhizoma all met the standards of Chinese Pharmacopoeia;the HPLC determination results indicated that the content of ferulic acid in Gansu Chuanxiong Rhizoma was greater than 0.192 6%,ligustrazine content was between 0.001 2%and 0.006 1%,chlorogenic acid content was greater than 0.016 4%;HS-SPME-GC-MS results indicated 52 volatile components were identified in Gansu Chuanxiong Rhizoma samples,the olefin compounds were rich in species,phenyphthalide compounds had the highest relative content;the correlation analysis showed that the color values ΔL*,Δb* and ΔE showed a high degree of correlation with ferulic acid and ligusticum tecidate A.Conclusion This study clarifies the intrinsic quality of Gansu Chuanxiong Rhizoma and provides a theoretical basis for research on Gansu Chuanxiong Rhizoma.

Objective:To explore the mechanism of BNIP3-mediated mitophagy in m. 3635G>A related Leber′s hereditary optic neuropathy (LHON).Methods:A transmitochondrial cybrid cell line derived from a Chinese LHON patient carrying the m. 3635G>A, diagnosed at the Eye Hospital of Wenzhou Medical University in September 2013, was selected as the study subject. A transmitochondrial cybrid cell line from a healthy control with an identical mitochondrial background was included as a control. Immunofluorescence, real-time quantitative PCR (RT-qPCR), and Western blotting were employed to assess the expression of autophagy-related proteins, aiming to explore the role of BNIP3-mediated mitophagy in m. 3635G>A related LHON. This study was approved by the Medical Ethics Committee of the Eye Hospital of Wenzhou Medical University (Ethics No. 2023-J-096).Results:① Compared with the control group, the protein expression levels of autophagy-related markers LC3 (LC3-Ⅱ/LC3-Ⅰ) and LAMP1 were significantly reduced in the variant group ( P<0.05). Additionally, the protein levels of macroautophagy-related proteins ATG12, ATG7, and ATG5 were also significantly decreased ( P<0.05). ② Compared with the control cells, the mRNA and protein expression levels of mitophagy-associated protein BNIP3 were significantly reduced in the cells of the variant group ( P<0.05). Compared with the control group, both mRNA and protein expression levels of the mitophagy-related protein BNIP3 were significantly reduced in the variant group ( P<0.05). Conclusion:The m. 3635G>A inhibits BNIP3-mediated mitophagy, thereby contributing to the pathogenesis of LHON.