Objective To investigate the effect and mechanism of miglitol on regulating the energy metabolism of brown adipocytes by activating UCP1 and preventing cold injury in mice after cold exposure. Methods Primary brown adipocytes were induced into mature adipocytes, the effect of miglitol on the viability of brown adipocytes was investigated by MTT method, the lipid droplet consumption level of cells after drug administration was investigated by Oil Red O staining technology, and the level of UCP1, a key protein of thermogenesis in brown adipocytes, was detected by Western blotting. The activity of anti-frostbite was investigated in cold exposure at 4 ℃ and −20 ℃. KM mice, which were randomly divided into control group, cold exposure group, miglitol group and all-trans retinoic acid group, and after 7 days of repeated administration, the body surface temperature of mice was detected by infrared thermal imaging system, the anal temperature change was detected by anal thermometer, and the expression levels of UCP1 and PGC1-α in adipose tissue were detected by immunoblotting. Results Compared with the control group, the lipid droplet consumption and UCP1 expression levels in brown adipocytes in the miglitol group were significantly increased. The levels of body surface temperature and rectal temperature increased significantly after cold exposure, and the levels of UCP1 and PGC1α in the brown adipose tissue of mice increased significantly, which indicated that the miglitol could activate the critical proteins UCP1 and PGC1α of the thermogenesis pathway, increase the thermogenesis of mice after cold exposure, and thus improve the effect of cold injury for toe swelling. Conclusion Miglitol could play a role in improving cold injury and body temperature in mice by increasing the level of UCP1 and PGC1α, which are key targets of the thermogenesis pathway to promote the thermogenesis of brown fat.

OBJECTIVE: To evaluate the dynamic changes of glucocorticoid (GC) dose and the feasibility of GC discontinuation in rheumatoid arthritis (RA) patients under the background of Chinese medicine (CM). METHODS: This multicenter retrospective cohort study included 1,196 RA patients enrolled in the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine (CERTAIN) from September 1, 2019 to December 4, 2023, who initiated GC therapy. Participants were divided into the Western medicine (WM) and integrative medicine (IM, combination of CM and WM) groups based on medication regimen. Follow-up was performed at least every 3 months to assess dynamic changes in GC dose. Changes in GC dose were analyzed by generalized estimator equation, the probability of GC discontinuation was assessed using Kaplan-Meier curve, and predictors of GC discontinuation were analyzed by Cox regression. Patients with <12 months of follow-up were excluded for the sensitivity analysis. RESULTS: Among 1,196 patients (85.4% female; median age 56.4 years), 880 (73.6%) received IM. Over a median 12-month follow-up, 34.3% (410 cases) discontinued GC, with significantly higher rates in the IM group (40.8% vs. 16.1% in WM; P<0.05). GC dose declined progressively, with IM patients demonstrating faster reductions (median 3.75 mg vs. 5.00 mg in WM at 12 months; P<0.05). Multivariate Cox analysis identified age <60 years [P<0.001, hazard ratios (HR)=2.142, 95% confidence interval (CI): 1.523-3.012], IM therapy (P=0.001, HR=2.175, 95% CI: 1.369-3.456), baseline GC dose ⩽7.5 mg (P=0.003, HR=1.637, 95% CI: 1.177-2.275), and absence of non-steroidal anti-inflammatory drugs use (P=0.001, HR=2.546, 95% CI: 1.432-4.527) as significant predictors of GC discontinuation. Sensitivity analysis (545 cases) confirmed these findings. CONCLUSIONS RA patients receiving CM face difficulties in following guideline-recommended GC discontinuation protocols. IM can promote GC discontinuation and is a promising strategy to reduce GC dependency in RA management. (Trial registration: ClinicalTrials.gov, No. NCT05219214).
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Arthritis, Rheumatoid/drug therapy* ; Glucocorticoids/therapeutic use* ; Medicine, Chinese Traditional ; Retrospective Studies

To investigate the impact of high salt stress on the metabolic pathways and regulatory mecha-nisms involved in synthesizing hydroxyectoine(5-HE)in Virgibacillus salexigens,cultures were supple-mented with 1.5 and 2.5 mol/L NaCl as control and experimental groups,respectively.High-perform-ance liquid chromatography(HPLC)was used to detect the difference in the amount of 5-HE synthesis.Transcriptomic and metabolomic analyses identified differential genes and metabolites under varying salt concentrations.Key differential gene expressions related to 5-HE synthesis were validated using qRT-PCR.Results showed that 5-HE synthesis reached 121.9 mg/L at 2.5 mol/L NaCl.Transcriptomic anal-ysis identified 652 differentially expressed genes across 348 KEGG pathways,with 210 upregulated and 442 downregulated,primarily enriched in pathways such as purine metabolism,amino acid biosynthesis,sulfur metabolism,and biotin metabolism.Validation of 13 genes,including lysC,asd,ectA,ectB,ectC,ectD,thrB,thrC,ilvA,ilvE,AGXT,YckA and GlnQ,showed expression trends consistent with transcriptome data.Metabolomic analysis identified 1153 metabolites predominantly enriched in histidine metabolism,lysine degradation,and arginine and proline metabolism.This study preliminarily elucidated the effect of high salt on the 5-HE synthesis pathway,and provided a basis for the subsequent construc-tion of 5-HE high-yielding strains.

Objective:This study aims to systematically compare the differences in severity, clinical manifestations, and treatment processes between patients with foodborne and iatrogenic botulism, thereby providing evidence-based support for clinical diagnosis and management.Methods:A retrospective analysis was conducted on botulism patients admitted to the Second Hospital of Hebei Medical University between January 2010 and July 2024. The foodborne group was diagnosed according to the WS/T 83-1996 standard. The iatrogenic group required a documented history of type A botulinum toxin injection and typical clinical manifestations. Individuals with comorbid neurological disorders or incomplete clinical data were excluded. The severity of poisoning was classified into three groups: mild, moderate, and severe, according to the "Diagnosis and Treatment Protocol for Botulism". SPSS 26.0 software was used to statistically analyze the distribution of poisoning severity between groups and to compare clinical symptoms and course indicators across severity grades.Results:A total of 220 botulism patients were included in this study, comprising 86 cases of foodborne poisoning (39.1%) and 134 cases of iatrogenic poisoning (60.9%). There was a significant difference in the distribution of poisoning severity between the two groups ( P=0.001), the proportion of severe poisoning was significantly higher in the foodborne group. Analysis of clinical symptoms indicated that, among patients with mild poisoning, the incidence of nausea and vomiting was significantly higher in the foodborne group, compared to that in the iatrogenic group (44.0% vs. 16.4%, P=0.006). In patients with moderate poisoning, the iatrogenic group exhibited a significantly higher prevalence of hoarseness (60.5% vs. 35.7%, P=0.041) and neck weakness (53.5% vs. 17.9%, P=0.003) compared to the foodborne group. Conversely, the foodborne cohort experienced a notably longer interval before seeking medical attention when compared to their iatrogenic counterparts (2.25 d vs. 1.50 d, P=0.003). Among severe poisoning patients, the foodborne group exhibited a higher likelihood of experiencing fever (51.5% vs. 25.0%, P=0.044) and abdominal distension accompanied by constipation (69.7% vs. 41.7%, P=0.034) when compared to the iatrogenic group. Furthermore, the foodborne cohort demonstrated a significantly shorter incubation period (1.00 d vs. 2.45 d, P<0.001), an extended length of hospitalization (22.0 d vs. 16.00 d, P=0.001), and a prolonged duration of antitoxin therapy (14.00 d vs. 9.50 d, P<0.001), alongside a markedly higher total dosage administered (315 900 U vs. 163 300 U, P<0.001) compared to their iatrogenic counterparts. Conclusions:Statistically significant differences exist between food-borne and iatrogenic botulism. Food-borne botulism is characterized by acute onset, greater severity, and a prolonged course, predominantly featuring systemic symptoms and gastrointestinal dysfunction. In contrast, iatrogenic botulism primarily manifests with ocular and oropharyngeal muscle symptoms and is generally less severe.

To investigate the impact of high salt stress on the metabolic pathways and regulatory mecha-nisms involved in synthesizing hydroxyectoine(5-HE)in Virgibacillus salexigens,cultures were supple-mented with 1.5 and 2.5 mol/L NaCl as control and experimental groups,respectively.High-perform-ance liquid chromatography(HPLC)was used to detect the difference in the amount of 5-HE synthesis.Transcriptomic and metabolomic analyses identified differential genes and metabolites under varying salt concentrations.Key differential gene expressions related to 5-HE synthesis were validated using qRT-PCR.Results showed that 5-HE synthesis reached 121.9 mg/L at 2.5 mol/L NaCl.Transcriptomic anal-ysis identified 652 differentially expressed genes across 348 KEGG pathways,with 210 upregulated and 442 downregulated,primarily enriched in pathways such as purine metabolism,amino acid biosynthesis,sulfur metabolism,and biotin metabolism.Validation of 13 genes,including lysC,asd,ectA,ectB,ectC,ectD,thrB,thrC,ilvA,ilvE,AGXT,YckA and GlnQ,showed expression trends consistent with transcriptome data.Metabolomic analysis identified 1153 metabolites predominantly enriched in histidine metabolism,lysine degradation,and arginine and proline metabolism.This study preliminarily elucidated the effect of high salt on the 5-HE synthesis pathway,and provided a basis for the subsequent construc-tion of 5-HE high-yielding strains.

OBJECTIVE Healthcare-associated infection(HAI)surveillance is a crucial tool for healthcare manage-ment and public health prevention,the World Health Organization(WHO)released simplified technical guidelines of HAI surveillance to enhance the HAI surveillance in areas with limited medical resources.This study explores the applicability and implementation pathways of the WHO's simplified standards for HAI surveillance in China.METHODS This study used text analysis and qualitative interviews to compare the differences of HAI sur-veillance criteria between China and WHO.Interviews were conducted with professionals of infection prevention and control(IPC)to explore the opportunities and challenges of implementing WHO simplified standards in China.RESULTS Twenty-two IPC professionals with long-term experiences participated in the interviews.Main themes derived from the interview were:WHO simplified standards could enhance the sensitivity of HAI surveil-lance,this approach provided insights for a risk early warning surveillance and improved surveillance in primary healthcare institutions.It also increased the international comparability of Chinese HAI surveillance results.How-ever,the implementation of the WHO simplified standards required further pilot validation,higher levels of infor-matic surveillance and clinical diagnostic capabilities.CONCLUSION This study explores the feasibility and accept-ability of the WHO's simplified HAI surveillance in China,provides references for the transformation of China's HAI surveillance models and systems.

OBJECTIVE Healthcare-associated infection(HAI)surveillance is a crucial tool for healthcare manage-ment and public health prevention,the World Health Organization(WHO)released simplified technical guidelines of HAI surveillance to enhance the HAI surveillance in areas with limited medical resources.This study explores the applicability and implementation pathways of the WHO's simplified standards for HAI surveillance in China.METHODS This study used text analysis and qualitative interviews to compare the differences of HAI sur-veillance criteria between China and WHO.Interviews were conducted with professionals of infection prevention and control(IPC)to explore the opportunities and challenges of implementing WHO simplified standards in China.RESULTS Twenty-two IPC professionals with long-term experiences participated in the interviews.Main themes derived from the interview were:WHO simplified standards could enhance the sensitivity of HAI surveil-lance,this approach provided insights for a risk early warning surveillance and improved surveillance in primary healthcare institutions.It also increased the international comparability of Chinese HAI surveillance results.How-ever,the implementation of the WHO simplified standards required further pilot validation,higher levels of infor-matic surveillance and clinical diagnostic capabilities.CONCLUSION This study explores the feasibility and accept-ability of the WHO's simplified HAI surveillance in China,provides references for the transformation of China's HAI surveillance models and systems.

BACKGROUND:Early identification of patients requiring ventilator support will be beneficial for the outcomes of botulism.The present study aimed to establish a new scoring system to predict mechanical ventilation(MV)for botulism patients. METHODS:A single-center retrospective study was conducted to identify risk factors associated with MV in botulism patients from 2007 to 2022.Univariate analysis and multivariate logistic regression analysis were used to screen out risk factors for constructing a prognostic scoring system.The area under the receiver operating characteristic(ROC)curve was calculated. RESULTS:A total of 153 patients with botulism(66 males and 87 females,with an average age of 43 years)were included.Of these,49 patients(32.0%)required MV,including 21(13.7%)with invasive ventilation and 28(18.3%)with non-invasive ventilation.Multivariate analysis revealed that botulinum toxin type,pneumonia,incubation period,degree of hypoxia,and severity of muscle involvement were independent risk factors for MV.These risk factors were incorporated into a multivariate logistic regression analysis to establish a prognostic scoring system.Each risk factor was scored by allocating a weight based on its regression coefficient and rounded to whole numbers for practical utilization([botulinum toxin type A:1],[pneumonia:2],[incubation period≤1 day:2],[hypoxia<90%:2],[severity of muscle involvement:grade II,3;grade III,7;grade IV,11]).The scoring system achieved an area under the ROC curve of 0.82(95%CI 0.75-0.89,P<0.001).At the optimal threshold of 9,the scoring system achieved a sensitivity of 83.7%and a specificity of 70.2%. CONCLUSION:Our study identified botulinum toxin type,pneumonia,incubation period,degree of hypoxia,and severity of muscle involvement as independent risk factors for MV in botulism patients.A score≥9 in our scoring system is associated with a higher likelihood of requiring MV in botulism patients.This scoring system needs to be validated externally before it can be applied in clinical settings.

Objective:To compare the diagnostic efficacy of 22 G fine needle aspiration (FNA) needles and 22 G end-cutting fine needle biopsy (FNB) needles for solid pancreatic lesion using both cytological and histological examination.Methods:Clinical data of 116 patients who underwent endoscopic ultrasound-guided fine needle aspiration/biopsy (EUS-FNA/FNB) at the Digestive Endoscopy Center of Ruijin Hospital, Shanghai Jiao Tong University School of Medicine from June 2022 to March 2023 were retrospectively analyzed. Sixty-three patients sampled with 22 G FNA needles were the FNA group, and 53 sampled with 22 G FNB needles were the FNB group. The diagnostic accuracy, sensitivity, specificity, positive predictive value, negative predictive value, and cytological and histological diagnostic yield of FNA needles and FNB needles for solid pancreatic lesions were compared.Results:There were no significant differences in age, gender, lesion location, lesion size, or the number of passes between the FNA group and the FNB group ( P>0.05). There were no significant differences in the diagnostic accuracy [93.7% (59/63) VS 90.6% (48/53), P=0.730], sensitivity [93.0% (53/57) VS 90.2% (46/51), P=0.732], specificity [100.0% (6/6) VS 100.0% (2/2), P=1.000], positive predictive value [100.0% (53/53) VS 100.0% (46/46), P=1.000] and negative predictive value [60.0% (6/10) VS 28.6% (2/7), P=0.335] of combined cytology and histology in distinguishing benign and malignant lesions between the two groups. In the FNA group, the diagnostic accuracy of combined cytology and histology was higher than cytology alone [93.7% (59/63) VS 81.0% (51/63), P=0.008], and was higher than histology alone without statistical significance [93.7% (59/63) VS 87.3% (55/63), P=0.125]. In the FNB group, the diagnostic accuracy of combined cytology and histology was higher than cytology alone [90.6% (48/53) VS 69.8% (37/53), P=0.001], but not than histology alone [90.6% (48/53) VS 90.6% (48/53)， P=1.000]. For solid masses located in pancreatic body/tail, the diagnostic accuracy for malignancy by histology using FNB needles tended to be higher than that of FNA needles [100.0% (17/17) VS 81.3% (26/32), P=0.080]. Conclusion:Both FNA needles and FNB needles exhibit adequate diagnostic yield for solid pancreatic masses when combining cytology and histology. FNB needles may offer a higher histological diagnostic yield.