Increasing evidence shows that the early lesions of Parkinson's disease (PD) originate from gut, and correction of microbiota dysbiosis is a promising therapy for PD. FLZ is a neuroprotective agent on PD, which has been validated capable of alleviating microbiota dysbiosis in PD mice. However, the detailed mechanisms still need elucidated. Through metabolomics and 16S rRNA analysis, we identified glycoursodeoxycholic acid (GUDCA) was the most affected differential microbial metabolite by FLZ treatment, which was specially and negatively regulated by Clostridium innocuum, a differential microbiota with the strongest correlation to GUDCA production, through inhibiting bile salt hydrolase (BSH) enzyme. The protection of GUDCA on colon and brain were also clarified in PD models, showing that it could activate Nrf2 pathway, further validating that FLZ protected dopaminergic neurons through promoting GUDCA production. Our study uncovered that FLZ improved PD through microbiota-gut-brain axis, and also gave insights into modulation of microbial metabolites may serve as an important strategy for treating PD.

Although enteric glial cell (EGC) abnormal activation is reported to be involved in the pathogenesis of Parkinson's disease (PD), and inhibition of EGC gliosis alleviated gut and dopaminergic neuronal dysfunction was verified in our previous study, the potential role of gut microbiota on EGC function in PD still need to be addressed. In the present study, fecal microbiota transplantation revealed that EGC function was regulated by gut microbiota. By employing 16S rRNA and metabolomic analysis, we identified that 3-indolepropionic acid (IPA) was the most affected differential microbial metabolite that regulated EGC gliosis. The protective effects of IPA on PD were validated in rotenone-stimulated EGCs and rotenone (30 mg/kg i.g. for 4 weeks)-induced PD mice, as indicated by decreased inflammation, improved intestinal and brain barrier as well as dopaminergic neuronal function. Mechanistic study showed that IPA targeted pregnane X receptor (PXR) in EGCs, and inhibition of IL-13Rα1 involved cytokine-cytokine receptor interaction pathway, leading to inactivation of downstream JAK1-STAT6 pathway. Our data not only provided evidence that EGC gliosis was critical in spreading intestinal damage to brain, but also highlighted the potential role of microbial metabolite IPA in alleviating PD pathological damages through gut-brain axis.

[This corrects the article DOI: 10.1016/j.apsb.2025.02.029.].

OBJECTIVES: To investigate the effects of dihydroartemisinin (DHA) combined with doxorubicin (DOX) on proliferation and apoptosis of triple-negative breast cancer cells and explore the underlying molecular mechanism. METHODS: MDA-MB-231 cells were treated with 50, 100 or 150 μmol/L DHA, 0.5 μmol/L DOX, or with 50 μmol/L DHA combined with 0.5 μmol/L DOX. The changes in proliferation and survival of the treated cells were examined with MTT assay and colony-forming assay, and cell apoptosis was analyzed with flow cytometry. Western blotting was performed to detect the changes in protein expression levels of PCNA, cleaved PARP, Bcl-2, Bax, STAT3, p-STAT3, HIF-1α and survivin. RESULTS: The IC₅₀ of DHA was 131.37±29.87 μmol/L in MDA-MB-231 cells. The cells with the combined treatment with DHA and DOX showed significant suppression of cell proliferation. Treatment with DHA alone induced apoptosis of MDA-MB-231 cells in a dose-dependent manner, but the combined treatment produced a much stronger apoptosis-inducing effect than both DHA and DOX alone. DHA at 150 μmol/L significantly inhibited clone formation of MDA-MB-231 cells, markedly reduced cellular expression levels of PCNA, p-STAT3, HIF-1α and survivin proteins, and obviously increased the expression level of cleaved PARP protein and the Bax/Bcl-2 ratio, and the combined treatment further reduced the expression level of p-STAT3 protein and increased the Bax/Bcl-2 ratio. CONCLUSIONS DHA combined with DOX produces significantly enhanced effects for inhibiting cell proliferation and inducing apoptosis in MDA-MB-231 cells possibly as result of DHA-mediated negative regulation of the STAT3/HIF-1α pathway.
Humans ; STAT3 Transcription Factor/metabolism* ; Apoptosis/drug effects* ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism* ; Doxorubicin/pharmacology* ; Triple Negative Breast Neoplasms/metabolism* ; Cell Line, Tumor ; Artemisinins/pharmacology* ; Female ; Cell Proliferation/drug effects* ; Signal Transduction/drug effects* ; Survivin

Objective:To compare the diagnostic efficacy of the added 99Tc m-methoxyisobutylisonitrile (MIBI) SPECT/CT imaging (tomography imaging) after early or delayed planar imaging in different types of hyperparathyroidism, and to seek for the optimal timing of preoperative imaging. Methods:A total of 339 patients (148 males, 191 females, age (52±13) years) with primary or secondary hyperparathyroidism and pathological results from January 2016 to June 2024 in the Second Affiliated Hospital of Soochow University were retrospectively analyzed. The patients were divided into primary early tomography imaging group ( n=63) and delayed tomography imaging group ( n=47), secondary early tomography imaging group ( n=89) and delayed tomography imaging group ( n=140). χ2 test was used to compare the diagnostic efficacies of early and delayed tomography imaging. Results:The difference of accuracy between primary delayed (98.40%(185/188)) and early tomography imaging (94.84%(239/252)) was statistically significant ( χ2=3.90, P=0.048). There were significant differences in sensitivity (77.29%(405/524) and 85.40%(275/322)), accuracy (75.89%(425/560) and 83.99%(299/356)) and negative predictive value (14.39%(20/139) and 33.80%(24/71)) between secondary delayed and early tomography imaging ( χ2 values: 8.33, 8.61, 10.70, all P<0.01). Conclusion:The optimal timing of preoperative 99Tc m-MIBI SPECT/CT imaging for primary and secondary hyperparathyroidism is after delayed planar imaging and after early planar imaging respectively.

Objective: To investigate the spatio-temporal clustering characteristics of influenza in Shaoxing City, Zhejiang Province from 2015 to 2024, so as to provide the basis for formulating influenza prevention and control strategies. Methods: Influenza case data in Shaoxing City from 2015 to 2024 were collected through the Infectious Disease Surveillance Reporting System of the Chinese Disease Prevention and Control Information System. Descriptive epidemiological methods analyses were used to analyze the epidemiological characteristics of influenza. Spatial autocorrelation and spatio-temporal scanning were used to analyze the spatio-temporal clustering characteristics of influenza. Results: A total of 328 759 influenza cases were reported in Shaoxing City from 2015 to 2024, with an average annual reported incidence of 639.90/100 000, which showed an upward trend (AAPC=68.95%, P<0.05). The peak incidence period was from December to February of the following year, with 193 051 cases reported, accounting for 58.72%. There were 165 408 male cases and 163 351 female cases, with a male-to-female ratio of 1.01∶1. Children and adolescents aged 0-<15 years constituted the high-incidence population, while students represented the predominant occupational category, comprising 113 589 cases (34.55%). Keqiao District, Shengzhou City, and Yuecheng District had the top three average annual reported incidence of influenza, at 995.64/100 000, 734.66/100 000, and 687.44/100 000, respectively. Spatial autocorrelation analysis showed that, there were 155 high-high aggregation areas in Shaoxing City from 2015 to 2024, which gradually expanded from the local aggregation in the central part of Shengzhou City to Keqiao District and then spread to Yuecheng District. Spatio-temporal scanning analysis showed that, from November 2023 to February 2024, the strongest spatio-temporal clustering of influenza centered on Keqiao Street in Keqiao District, covering 11 towns (streets) in Yuecheng District and Keqiao District. From 2015 to 2018, the primary-type clustering of influenza was mainly concentrated in Xinchang County and Shengzhou City. After 2019, they gradually shifted to Yuecheng District and Keqiao District, with the main clustering period being from November to February of the following year. Conclusions The incidence of influenza in Shaoxing City from 2015 to 2024 showed an upward trend, with obvious spatio-temporal clustering. The clustering area expanded from Shengzhou City in the central region to Keqiao District and Yuecheng District in the northern region, mainly clustering from November to February of the following year.

Objective:To evaluate the short-term efficacy of minimally invasive treatment of Sanders Ⅱ and Ⅲ calcaneal fractures in diabetes patients using subtalar arthroscopy assisted by preoperative musculoskeletal ultrasound to localize the lateral calcaneal branch of the sural nerve and a medial calcanetalar distractor.Methods:The clinical data of the 52 patients with diabetes mellitus were retrospectively analyzed who had been treated for Sanders Ⅱ and Ⅲ calcaneal fractures from March 2016 to August 2020 at Department of Traumatic Orthopedics, The Third Affiliated Hospital of Soochow University. There were 34 males and 18 females with an age of (61.7±14.5) years. According to the Sanders' classification, there were 23 cases of type Ⅱ and 29 cases of type Ⅲ. Preoperative musculoskeletal ultrasonography was routinely performed to locate the lateral calcaneal branch of the sural nerve in all patients. The surgical procedures were subtalar arthroscopy combined with percutaneous prying reduction and screw fixation assisted by a calcanetalar joint distractor. Incision healing, local skin paraesthesia and other conditions were observed regularly in all patients. The short-term efficacy was assessed by comparing calcaneal lengths, calcaneal widths, calcaneal heights, B?hler angles and Gissane angles at pre-surgery, 3 days, 12 months and the last follow-up after surgery, as well as by comparing visual analogue scale (VAS) pain scores, American Orthopedic Foot and Ankle Society (AOFAS) ankle-hindfoot scores and Maryland scores at pre-surgery, 12 months and the last follow-up after surgery.Results:All the 52 patients were followed up for (23.7±3.2) months after successful surgery. No incision-related complications were reported. The calcaneal radiographic parameters (calcaneal lengths, calcaneal widths, calcaneal heights, B?hler angles and Gissane angles) at 3 days, 12 months and the last follow-up after surgery were significantly improved compared with the values before surgery ( P<0.05), but there were no significant differences regarding the calcaneal radiographic parameters between 3 days, 12 months and the last follow-up after surgery ( P>0.05). The VAS pain scores, AOFAS ankle-hindfoot scores and Maryland scores at 12 months and the last follow-up after surgery were significantly improved compared with those before surgery ( P<0.05). Conclusion:In the minimally invasive treatment of Sanders Ⅱ and Ⅲ calcaneal fractures in diabetes patients, preoperative musculoskeletal ultrasonography to locate the lateral calcaneal branch of the sural nerve, followed by subtalar arthroscopy combined with percutaneous prying reduction and screw fixation assisted by a calcanetalar joint distractor can lead to good short-term efficacy.

Objective To investigate the distribution and antimicrobial resistance profiles of common pathogens isolated from cerebrospinal fluid(CSF)in CHINET program from 2015 to 2021.Methods The bacterial strains isolated from CSF were identified in accordance with clinical microbiology practice standards.Antimicrobial susceptibility test was conducted using Kirby-Bauer method and automated systems per the unified CHINET protocol.Results A total of 14 014 bacterial strains were isolated from CSF samples from 2015 to 2021,including the strains isolated from inpatients(95.3％)and from outpatient and emergency care patients(4.7％).Overall,19.6％of the isolates were from children and 80.4％were from adults.Gram-positive and Gram-negative bacteria accounted for 68.0％and 32.0％,respectively.Coagulase negative Staphylococcus accounted for 73.0％of the total Gram-positive bacterial isolates.The prevalence of MRSA was 38.2％in children and 45.6％in adults.The prevalence of MRCNS was 67.6％in adults and 69.5％in children.A small number of vancomycin-resistant Enterococcus faecium(2.2％)and linezolid-resistant Enterococcus faecalis(3.1％)were isolated from adult patients.The resistance rates of Escherichia coli and Klebsiella pneumoniae to ceftriaxone were 52.2％and 76.4％in children,70.5％and 63.5％in adults.The prevalence of carbapenem-resistant E.coli and K.pneumoniae(CRKP)was 1.3％and 47.7％in children,6.4％and 47.9％in adults.The prevalence of carbapenem-resistant Acinetobacter baumannii(CRAB)and Pseudomonas aeruginosa(CRPA)was 74.0％and 37.1％in children,81.7％and 39.9％in adults.Conclusions The data derived from antimicrobial resistance surveillance are crucial for clinicians to make evidence-based decisions regarding antibiotic therapy.Attention should be paid to the Gram-negative bacteria,especially CRKP and CRAB in central nervous system(CNS)infections.Ongoing antimicrobial resistance surveillance is helpful for optimizing antibiotic use in CNS infections.

Objective To investigate the antimicrobial resistance of clinical isolates from elderly patients(≥65 years)in major medical institutions across China.Methods Bacterial strains were isolated from elderly patients in 52 hospitals participating in the CHINET Antimicrobial Resistance Surveillance Program during the period from 2015 to 2021.Antimicrobial susceptibility test was carried out by disk diffusion method and automated systems according to the same CHINET protocol.The data were interpreted in accordance with the breakpoints recommended by the Clinical and Laboratory Standards Institute(CLSI)in 2021.Results A total of 514 715 nonduplicate clinical isolates were collected from elderly patients in 52 hospitals from January 1,2015 to December 31,2021.The number of isolates accounted for 34.3％of the total number of clinical isolates from all patients.Overall,21.8％of the 514 715 strains were gram-positive bacteria,and 78.2％were gram-negative bacteria.Majority(90.9％)of the strains were isolated from inpatients.About 42.9％of the strains were isolated from respiratory specimens,and 22.9％were isolated from urine.More than half(60.7％)of the strains were isolated from male patients,and 39.3％isolated from females.About 51.1％of the strains were isolated from patients aged 65-＜75 years.The prevalence of methicillin-resistant strains(MRSA)was 38.8％in 32 190 strains of Staphylococcus aureus.No vancomycin-or linezolid-resistant strains were found.The resistance rate of E.faecalis to most antibiotics was significantly lower than that of Enterococcus faecium,but a few vancomycin-resistant strains(0.2％,1.5％)and linezolid-resistant strains(3.4％,0.3％)were found in E.faecalis and E.faecium.The prevalence of penicillin-susceptible S.pneumoniae(PSSP),penicillin-intermediate S.pneumoniae(PISP),and penicillin-resistant S.pneumoniae(PRSP)was 94.3％,4.0％,and 1.7％in nonmeningitis S.pneumoniae isolates.The resistance rates of Klebsiella spp.(Klebsiella pneumoniae 93.2％)to imipenem and meropenem were 20.9％and 22.3％,respectively.Other Enterobacterales species were highly sensitive to carbapenem antibiotics.Only 1.7％-7.8％of other Enterobacterales strains were resistant to carbapenems.The resistance rates of Acinetobacter spp.(Acinetobacter baumannii 90.6％)to imipenem and meropenem were 68.4％and 70.6％respectively,while 28.5％and 24.3％of P.aeruginosa strains were resistant to imipenem and meropenem,respectively.Conclusions The number of clinical isolates from elderly patients is increasing year by year,especially in the 65-＜75 age group.Respiratory tract isolates were more prevalent in male elderly patients,and urinary tract isolates were more prevalent in female elderly patients.Klebsiella isolates were increasingly resistant to multiple antimicrobial agents,especially carbapenems.Antimicrobial resistance surveillance is helpful for accurate empirical antimicrobial therapy in elderly patients.