Parkinson's disease （PD） is a complex neurodegenerative disease involving multiple systems and neurotransmitters. Due to the high clinical heterogeneity of PD，it is urgent to establish a comprehensive and long-term traditional Chinese medicine （TCM） management model. In this paper，the conceptual framework of full-cycle management of PD is preliminarily constructed：based on the evolution of the pathophysiological mechanisms of protein deposition and neurotransmitter disorder in PD，the three-stage syndrome characteristics of the prodromal stage （predominant healthy Qi with subtle pathogenic factors），the early clinical stage （declining healthy Qi with growing pathogenic factors） and the middle and late stages （overwhelming pathogenic factors with deficient healthy Qi） are longitudinally described. Through the syndrome differentiation of visceral manifestations，the etiology and pathogenesis of PD motor and non-motor symptoms were comprehensively analyzed，while the matching treatment methods and prescriptions were inferred，and the modular scheme of the combining main symptoms，accompanying symptoms and secondary symptoms was proposed. The conceptual gap of TCM regarding motor complications （'variable syndrome'） and PD-related hyperpyrexia syndrome （'critical syndrome'） was explained. This framework reflects the characteristics of combination of disease and syndrome and overall constant motion，and provides new theories and research ideas for individualized and whole-process management of PD in TCM.

Parkinson's disease （PD） is a complex neurodegenerative disease involving multiple systems and neurotransmitters. Due to the high clinical heterogeneity of PD，it is urgent to establish a comprehensive and long-term traditional Chinese medicine （TCM） management model. In this paper，the conceptual framework of full-cycle management of PD is preliminarily constructed：based on the evolution of the pathophysiological mechanisms of protein deposition and neurotransmitter disorder in PD，the three-stage syndrome characteristics of the prodromal stage （predominant healthy Qi with subtle pathogenic factors），the early clinical stage （declining healthy Qi with growing pathogenic factors） and the middle and late stages （overwhelming pathogenic factors with deficient healthy Qi） are longitudinally described. Through the syndrome differentiation of visceral manifestations，the etiology and pathogenesis of PD motor and non-motor symptoms were comprehensively analyzed，while the matching treatment methods and prescriptions were inferred，and the modular scheme of the combining main symptoms，accompanying symptoms and secondary symptoms was proposed. The conceptual gap of TCM regarding motor complications （'variable syndrome'） and PD-related hyperpyrexia syndrome （'critical syndrome'） was explained. This framework reflects the characteristics of combination of disease and syndrome and overall constant motion，and provides new theories and research ideas for individualized and whole-process management of PD in TCM.

Objective To summarize the changing prevalence of carbapenem resistance in Enterobacterales based on the data of CHINET Antimicrobial Resistance Surveillance Program from 2015 to 2021 for improving antimicrobial treatment in clinical practice.Methods Antimicrobial susceptibility testing was performed using a commercial automated susceptibility testing system according to the unified CHINET protocol.The results were interpreted according to the breakpoints of the Clinical & Laboratory Standards Institute(CLSI)M100 31st ed in 2021.Results Over the seven-year period(2015-2021),the overall prevalence of carbapenem-resistant Enterobacterales(CRE)was 9.43％(62 342/661 235).The prevalence of CRE strains in Klebsiella pneumoniae,Citrobacter freundii,and Enterobacter cloacae was 22.38％,9.73％,and 8.47％,respectively.The prevalence of CRE strains in Escherichia coli was 1.99％.A few CRE strains were also identified in Salmonella and Shigella.The CRE strains were mainly isolated from respiratory specimens(44.23±2.80)％,followed by blood(20.88±3.40)％and urine(18.40±3.45)％.Intensive care units(ICUs)were the major source of the CRE strains(27.43±5.20)％.CRE strains were resistant to all the β-lactam antibiotics tested and most non-β-lactam antimicrobial agents.The CRE strains were relatively susceptible to tigecycline and polymyxins with low resistance rates.Conclusions The prevalence of CRE strains was increasing from 2015 to 2021.CRE strains were highly resistant to most of the antibacterial drugs used in clinical practice.Clinicians should prescribe antimicrobial agents rationally.Hospitals should strengthen antibiotic stewardship in key clinical settings such as ICUs,and take effective infection control measures to curb CRE outbreak and epidemic in hospitals.

Objective To characterize the changing species distribution and antibiotic resistance profiles of respiratory isolates in hospitals participating in the CHINET Antimicrobial Resistance Surveillance Program from 2015 to 2021.Methods Commercial automated antimicrobial susceptibility testing systems and disk diffusion method were used to test the susceptibility of respiratory bacterial isolates to antimicrobial agents following the standardized technical protocol established by the CHINET program.Results A total of 589 746 respiratory isolates were collected from 2015 to 2021.Overall,82.6％of the isolates were Gram-negative bacteria and 17.4％were Gram-positive bacteria.The bacterial isolates from outpatients and inpatients accounted for(6.0±0.9)％and(94.0±0.1)％,respectively.The top microorganisms were Klebsiella spp.,Acinetobacter spp.,Pseudomonas aeruginosa,Staphylococcus aureus,Haemophilus spp.,Stenotrophomonas maltophilia,Escherichia coli,and Streptococcus pneumoniae.Each microorganism was isolated from significantly more males than from females(P＜0.05).The overall prevalence of methicillin-resistant S.aureus(MRSA)was 39.9％.The prevalence of penicillin-resistant S.pneumoniae was 1.4％.The prevalence of extended-spectrum β-lactamase(ESBL)-producing E.coli and K.pneumoniae was 67.8％and 41.3％,respectively.The overall prevalence of carbapenem-resistant E.coli,K.pneumoniae,Enterobacter cloacae,Pseudomonas aeruginosa,and Acinetobacter baumannii was 3.7％,20.8％,9.4％,29.8％,and 73.3％,respectively.The prevalence of β-lactamase was 96.1％in Moraxella catarrhalis and 60.0％in Haemophilus influenzae.The H.influenzae isolates from children(＜18 years)showed significantly higher resistance rates to β-lactam antibiotics than the isolates from adults(P＜0.05).Conclusions Gram-negative bacteria are still predominant in respiratory isolates associated with serious antibiotic resistance.Antimicrobial resistance surveillance should be strengthened in clinical practice to support accurate etiological diagnosis and appropriate antimicrobial therapy based on antimicrobial susceptibility testing results.

Objective:To assess the relationship between basophil levels and mortality in patients with intra-abdominal infection.Methods:Information on patients with intraperitoneal infection admitted to the intensive care unit were extracted from the MIMIC database.A time-dependent Cox regression model was used to adjust for confounders associated with 28-day mortality.Propensity score matching(PSM)was used to balance the baseline differences be-tween groups with different basophil levels,and a restricted cube chart(RCS)was used to show the relationship between basophil count and 28-day mortality in patients with intra-abdominal infection.Results:A total of 4403 patients with intra-abdominal infection were enrolled in the MIMIC database.Patients with high basophil levels have lower mortality than those with low basophil levels.There was an L-shaped curve between basophil level and 28-day mortality,with a cut-off value of 0.47×109/L.Cox regression analysis showed that basophil levels were an independent protective factor for mortal-ity in patients with intra-abdominal infection after adjusting for potential confounders(HR=0.586,95%CI:0.443-0.769).Protective factors for death at basophil levels remained after PSM adjusted for potential confounders(HR=0.628,95%CI:0.470-0.832).Conclusion:Basophil level is an independent protective factor for mortality in patients with intra-abdominal infection,and basophil levels should be dynamically monitored to better evaluate the prognosis of patients.

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.

Background Mitochondrial biogenesis is pivotal in coal workers' pneumoconiosis fibrosis, yet the role of the peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α)-nuclear respiratory factor 1 (NRF1)-mitochondrial transcription factor A (TFAM) pathway inmitochondrial biogenesis remains elusive, warranting further investigation. Objective To elucidate the role of the PGC-1α-NRF1-TFAM pathway in mitochondrial biogenesis in a rat coal workers' pneumoconiosis model through in vivo and in vitro experiments. Methods (1)n vivo: twelve SPF male SD rats (200-220 g) were randomized into a control group and a coal dust group (n=6 per group). After acclimatization, the coal dust group received 1 mL 50 mg·mL⁻¹ coal dust suspension via intratracheal instillation; the controls received saline. Lung tissues were harvested after two months for histopathology [HE, Masson, and transmission electron microscopy (TEM) ], protein and mRNA analysis, and mitochondrial DNA (mtDNA) quantification by quantitative real-time polymerase chain reaction (qPCR). (2) In vitro: rat lung type II epithelial cells (RLE-6TN) cells were exposed to coal dust (50, 100, 200, and 400 mg·L⁻¹, 24 h). CCK-8 assay determined optimal doses. Ultrastructural changes were analyzed by TEM. Cells were transfected with OE-PGC-1α (PGC-1α overexpression) or shRNA-PGC-1α plasmids (PGC-1α knockdown), and the transfection efficiency was determined by reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR). The expression levels of alpah-smooth muscle actin (α-SMA), citrate synthase (CS), PGC-1α, NRF1, TFAM, and fibronectin (Fn) proteins and their corresponding mRNA were detected using Western blot and RT-qPCR, respectively. The relative content of mtDNA was determined by qPCR. Results In vivo: the control group lung samples exhibited soft, pink parenchyma, while the coal dust-exposed lungs showed blackened surfaces with soft texture. The histopathological evaluation revealed intact alveolar walls in the controls versus structural destruction, micro-nodules, and fibrotic areas in the coal dust group. After Masson staining, coal dust deposits were found surrounded by blue collagen fibers in the exposed lungs, but absent in the controls. The coal dust group displayed significant upregulation of fibrotic marker α-SMA and downregulation of mitochondrial biogenesis markers (CS, PGC-1α, NRF1, TFAM) and mtDNA compared to the controls (P<0.05). In vitro: coal dust exposure reduced cell density and induced morphological alterations. TEM revealed evenly distributed normal mitochondria in controls versus mitochondrial swelling, disrupted cristae, and reduced numbers in exposed cells. The mitochondrial biogenesis markers were elevated in the coal dust + OE-PGC-1α group compared to the coal dust + OE-NC group (P<0.05); in contrast, they were decreased in the coal dust + shRNA-PGC-1α group compared to the coal dust + shRNA-NC group (P<0.05). Compared to the control group, the expression levels of the fibrosis marker α-SMA mRNA and protein were increased in the coal dust group (P<0.05). Overexpression of PGC-1α reduced α-SMA expression, while downregulation of PGC-1α increased its expression (P<0.05). Conclusion Coal dust exposure induces mitochondrial dysfunction and pulmonary fibrosis in vivo and in vitro via the PGC-1α-NRF1-TFAM pathway dysregulation. Targeting this pathway may mitigate coal dust-induced fibrosis by restoring mitochondrial biogenesis.

Objective To investigate the diagnostic value of our regression model based on quantitative parameters of dual-energy CT and clinical features for stages T2 and T3 colorectal cancer.Methods A cross-section study was performed on 91 patients with colorectal cancer confirmed by postoperative pathology in our hospital from January 2022 to November 2023.All of them underwent dual-energy CT examination.According to the pathological T staging criteria of Chinese Colorectal Cancer Diagnosis and Treatment Standard(2020 Edition),they were divided into T2 group(n=43)and T3 group(n=48).Univariate analysis was used to compare the differences in quantitative CT parameters and clinical features between the 2 groups,and the obtained significant variables were employed to construct diagnosis models by univariate or multivariate logistic regression analysis.The area under receiver operating characteristic curve(AUC)of the CT parametric model and the model combined with clinical features was compared to evaluate the efficacy of diagnosing T2 and T3 stages.Results Univariate analysis showed that carcinoembryonic antigen(CEA),N stage,tumor location,tumor longest diameter(LD),CT value of virtual noncontrast(CT-VNC),fat fraction,electron density(Rho)and dual energy index(DEI)were significantly different between the T2 and T3 groups(P＜0.05).Multivariate logistic regression analysis found that N stage,tumor location,LD,fat fraction and DEI were independent risk factors for the diagnosis of stage T3.The AUC value of the model of above CT parameters in diagnosing stage T3 colorectal cancer was 0.671(95％CI:0.558～0.783),and the AUC value of the combined model of above CT parameters and clinical features was 0.886(95％CI:0.815～0.957),and statistical difference was observed in the AUC value between the combined model and the CT parametric model(P＜0.01).Conclusion The regression model constructed with dual-energy CT quantitative parameters combined with clinical features has high value in the preoperative diagnosis of stages T2 and T3 colorectal cancer before surgery.

The development of breast cancer is closely related to the information transfer in its microenvironment.As a novel information communication tool,exosomes present non-coding RNAs that are involved in breast cancer cell proliferation,migration,invasion,tumour-associated fibroblasts ogenesis,cell cycle,degradation of oncogenes,etc.This paper reviews the relationship between exosomes and the tumour microenvironment and the role of their presenting non-coding RNAs on breast cancer as well as their clinical applications in order to provide new ideas for biological research and therapeutic strategies.