OBJECTIVE To investigate the neuroprotective effect and mechanism of eleutheroside B （ELB） on Parkinson’s disease （PD） model mice by regulating the IκB kinase β （IKKβ）/nuclear factor-κB （NF-κB） signaling pathway. METHODS Fifty mice were randomly divided into normal control group， model group， positive control group （selegiline hydrochloride， 10 mg/kg）， and ELB low-dose and high-dose groups （80， 160 mg/kg）， with 10 mice in each group. Each group was given relevant medicine or normal saline intragastrically for 14 consecutive days. Starting from the 10th day of administration， the model group and all administration groups were intraperitoneally injected with 1-methyl-4-phenyl-1，2，3，6-tetrahydropyridine （MPTP） 30 mg/kg， for five consecutive days to establish the chronic PD model. After the last administration for 24 h， six mice were randomly selected from each group to test their behavioral abilities； detect the levels of interleukin-1β （IL-1β）， IL-10， tumor necrosis factor-α （TNF-α） in brain tissue and their mRNA expressions were measured， and positive expression of tyrosine hydroxylase （TH）， protein expressions of TH， α -synuclein （ α -syn）， ionized calcium-binding adaptor molecule 1 （Iba-1）， as well as phosphorylation levels of IKKβ and NF-κB p65 proteins in the brain tissue were detected. The ultrastructure of neurons in substantia nigra was observed. RESULTS Compared with the model group， rotarod endurance time and climbing score of each administration group （except for the ELB low-dose group） were increased significantly （ P ＜0.05）， while the levels and mRNA expressions of IL-1β， TNF-α， α -syn， and Iba-1， as well as phosphorylation levels of IKKβ and NF-κB p65 proteins in brain tissue were decreased significantly （except for TNF-α in the ELB low-dose group）. Conversely， the level and mRNA expression of IL-10 （except for the ELB low-dose group）， TH positive expression and protein expressions were significantly increased （ P ＜0.05）. Typical neurodegenerative pathological changes， such as neuronal karyopyknosis， mitochondrial swelling and vacuolization， and endoplasmic reticulum dilation， all showed varying degrees of improvement. CONCLUSIONS ELB may exert neuroprotective effects by inhibiting the activation of the IKKβ/NF-κB signaling pathway， alleviating inflammatory responses， reducing abnormal α -syn aggregation and neuronal loss， and further improving motor dysfunction in PD mice.

Objective:To investigate the pathogen distribution characteristics and related risk factors for postoperative infection in liver transplant recipients.Method:A retrospective analysis was conducted on the clinical data of 153 recipients who underwent liver transplantation and received postoperative treatment in the intensive care unit (ICU) of China-Japan Friendship Hospital from January 2019 to December 2023. According to whether postoperative infection occurred, the recipients were divided into the infection group (33 cases) and the non-infection group (120 cases). Pathogen-related data were collected from multiple postoperative body fluid sites of liver transplant recipients. Univariate analysis and multivariate logistic regression analysis were performed to identify independent risk factors.Result:Among the 153 recipients, 105 were male and 48 were female, with a mean age of (52.2 ± 9.5) years. During the ICU stay after liver transplantation, 33 recipients developed infections, including 15 cases of single-pathogen infection and 18 cases of mixed-pathogen infection. The most common site of infection was the lung, accounting for 22 cases (66.67%). Eleven recipients (33.33%) in the infection group died, with septic shock being the leading cause of death (7 cases, 63.63%), and the median survival time was 14 days. Infected recipients had Gram-negative bacteria (171 strains), mainly Stenotrophomonas maltophilia[54 strains (31.57%)] and Pseudomonas aeruginosa[52 strains (30.41%)]. Gram-positive bacteria (47 strains) were dominated by Enterococcus faecalis[25 strains (53.19%)]. Multivariate regression analysis showed that postoperative mechanical ventilation for more than 48 hours was an independent risk factor for infection in liver transplant recipients ( OR=10.878, 95% CI: 3.632-32.580, P<0.001). Conclusion:It is necessary to prevent ventilator-associated pneumonia in liver transplant recipients. Early removal of the tracheal tube and strengthening hospital infection prevention and control are of great significance in reducing the risk of postoperative infection in liver transplant recipients.

Objective:To study the relationship between the type of hypertriglyceridemia(HTG) and the severity and prognosis of acute pancreatitis (AP).Methods:A total of 112 AP patients with HTG diagnosed and treated in Bozhou People's Hospital from June 2022 to June 2024 were retrospectively selected as the study objects, the AP severity and complication rate of patients with different types of HTG were compared. According to the discharge status of AP patients, they were divided into poor prognosis group (26 cases) and good prognosis group (86 cases). Univariate and multivariate Logistic regression were used to analyze the risk factors of poor prognosis in HTG patients with AP.Results:The main types of HTG in AP patients were type Ⅰ, type Ⅳ and type Ⅴ. The proportion of severe disease in AP patients with type Ⅰ HTG was higher than that of other HTG types, there were statistical differences ( P<0.05). The incidence of pancreatic pseudocyst and infectious pancreatic necrosis in AP patients with different HTG types had no statistical differences ( P>0.05). The incidence of systemic inflammatory response syndrome and organ failure in AP patients with HTG type Ⅰ was higher than that with other HTG types, there were statistical differences ( P<0.05). The proportion of type I HTG and severe AP in the poor prognosis group were higher than those in the good prognosis group : 88.46%(23/26) vs. 68.60%(59/86), 76.92%(20/26) vs. 13.95%(12/86); the triglycerides (TG), very low-density lipoprotein (VLDL), total cholesterol (TC) and fasting plasma glucose (FPG) in the poor prognosis group were higher than those in the good prognosis group: (17.29 ± 3.48) mmol/L vs. (12.29 ± 2.45) mmol/L, (3.04 ± 0.46) mmol/L vs.(2.46 ± 0.68) mmol/L,(6.03 ± 1.13) mmol/L vs.(5.25 ± 1.23) mmol/L, (12.01 ± 1.67) mmol/L vs. (11.14 ± 1.82)mmol/L; while albumin and blood calcium were lower than those in the good prognosis group: (36.28 ± 1.53) g/L vs. (37.33 ± 1.65) g/L, (1.65 ± 0.57) mmol/L vs. (2.04 ± 0.72) mmol/L; there were statistical differences ( P<0.05). The results of single factor analysis showed that combined HTG type, AP severity, triglyceride (TG), very low density lipoprotein (VLDL), total cholesterol (TC), fasting blood glucose (FPG), albumin and blood calcium levels were risk factors affecting the prognosis of AP patients ( P<0.05). Multivariate Logistic regression analysis showed that combined HTG type, AP severity, TG, VLDL, TC, FPG, blood calcium and albumin levels were independent risk factors affecting the prognosis of AP patients ( P<0.05). Conclusions:The type of HTG is closely related to the severity and prognosis of AP patients. Among them, AP patients with type Ⅰ HTG have a higher rate of severe disease. The combination of type Ⅰ HTG, the severity of AP, and abnormal lipid metabolism indexes are all important independent risk factors affecting the prognosis of AP patients.

Objective To investigate the distribution and antimicrobial resistance profiles of clinically isolated Haemophilus influenzae and Moraxella catarrhalis in hospitals across China from 2015 to 2021,and provide evidence for rational use of antimicrobial agents.Methods Data of H.influenzae and M.catarrhalis strains isolated from 2015 to 2021 in CHINET program were collected for analysis,and antimicrobial susceptibility testing was performed by disc diffusion method or automated systems according to the uniform protocol of CHINET.The results were interpreted according to the CLSI breakpoints in 2022.Beta-lactamases was detected by using nitrocefin disk.Results From 2015 to 2021,a total of 43 642 strains of Haemophilus species were isolated,accounting for 2.91％of the total clinical isolates and 4.07％of Gram-negative bacteria in CHINET program.Among the 40 437 strains of H.influenzae,66.89％were isolated from children and 33.11％were isolated from adults.More than 90％of the H.influenzae strains were isolated from respiratory tract specimens.The prevalence of β-lactamase was 53.79％in H.influenzae strains.The H.influenzae strains isolated from children showed higher resistance rate than the strains isolated from adults.Overall,779 strains of H.influenzae did not produce β-lactamase but were resistant to ampicillin(BLNAR).Beta-lactamase-producing strains showed significantly higher resistance rates to these antimicrobial agents than the β-lactamase-nonproducing strains.Of the 16 191 M.catarrhalis strains,80.06％were isolated from children and 19.94％isolated from adults.M.catarrhalis strains were mostly susceptible to both amoxicillin-clavulanic acid and cefuroxime,evidenced by resistance rate lower than 2.0％.Conclusions The emergence of antibiotic-resistant H.influenzae due to β-lactamase production poses a challenge for clinical anti-infective treatment.Therefore,it is very important to implement antibiotic resistance surveillance for H.influenzae and guide rational antibiotic use.All local clinical microbiology laboratories should actively improve antibiotic susceptibility testing and strengthen antibiotic resistance surveillance for H.influenzae.

Objective To understand the changing composition and antibiotic resistance of bacterial species in the clinical isolates from outpatient and emergency department(hereinafter referred to as outpatients)and inpatient children over time in various hospitals,and to provide laboratory evidence for rational antibiotic use.Methods The data on clinically isolated pathogenic bacteria and antimicrobial susceptibility of isolates from outpatients and inpatient children in the CHINET program from 2015 to 2021 were collected and analyzed.Results A total of 278 471 isolates were isolated from pediatric patients in the CHINET program from 2015 to 2021.About 17.1％of the strains were isolated from outpatients,primarily group A β-hemolytic Streptococcus,Escherichia coli,and Staphylococcus aureus.Most of the strains(82.9％)were isolated from inpatients,mainly SS.aureus,E.coli,and H.influenzae.The prevalence of methicillin-resistant S.aureus(MRSA)in outpatients(24.5％)was lower than that in inpatient children(31.5％).The MRSA isolates from outpatients showed lower resistance rates to the antibiotics tested than the strains isolated from inpatient children.The prevalence of vancomycin-resistant Enterococcus faecalis or E.faecium and penicillin-resistant S.pneumoniae was low in either outpatients or inpatient children.S.pneumoniae,β-hemolytic Streptococcus and S.viridans showed high resistance rates to erythromycin.The prevalence of erythromycin-resistant group A β-hemolytic Streptococcus was higher in outpatients than that in inpatient children.The prevalence of β-lactamase-producing H.influenzae showed an overall upward trend in children,but lower in outpatients(45.1％)than in inpatient children(59.4％).The prevalence of carbapenem-resistant Klebsiella pneumoniae(CRKpn),carbapenem-resistant Pseudomonas aeruginosa(CRPae)and carbapenem-resistant Acinetobacter baumannii(CRAba)was 14％,11.7％,47.8％in outpatients,but 24.2％,20.6％,and 52.8％in inpatient children,respectively.The prevalence of multidrug-resistant E.coli,K.pneumoniae,Proteus mirabilis,P.aeruginosa and A.baumannii strains was lower in outpatients than in inpatient children.The prevalence of fluoroquinolone-resistant E.coli,ESBLs-producing K.pneumoniae,ESBLs-producing P.mirabilis,carbapenem-resistant E.coli(CREco),CRKpn,and CRPae was lower in children in outpatients than in inpatient children,but the prevalence of CRAba in 2021 was higher than in inpatient children.Conclusions The distribution of clinical isolates from children is different between outpatients and inpatients.The prevalence of MRSA,ESBL,and CRO was higher in inpatient children than in outpatients.Antibiotics should be used rationally in clinical practice based on etiological diagnosis and antimicrobial susceptibility test results.Ongoing antimicrobial resistance surveillance and prevention and control of hospital infections are crucial to curbing bacterial resistance.

Objective To investigate the changing antibiotic resistance profiles of E.coli isolated from patients in the 52 hospitals participating in the CHINET program from 2015 to 2021.Methods Antimicrobial susceptibility was tested for clinical isolates of E.coli according to the unified protocol of CHINET program.WHONET 5.6 and SPSS 20.0 software were used for data analysis.Results Atotal of 289 760 nonduplicate clinical strains ofE.coli were isolated from 2015 to 2021,mainly from urine samples(44.7±3.2)％.The proportion of E.coli strains isolated from urine samples was higher in females than in males(59.0％vs 29.5％).The proportion of E.coli strains isolated from respiratory tract and cerebrospinal fluid samples was significantly higher in children than in adults(16.7％vs 7.8％,0.8％vs 0.1％,both P＜0.05).The isolates from internal medicine department accounted for the largest proportion(28.9±2.8)％with an increasing trend over years.Overall,the prevalence of ESBLs-producing E.coli and carbapenem resistant E.coli(CREco)was 55.9％and 1.8％,respectively during the 7-year period.The prevalence of ESBLs-producing E.coli was the highest in tertiary hospitals each year from 2015 to 2021 compared to secondary hospitals.The prevalence of CREco was higher in children's hospitals compared to secondary and tertiary hospitals each year from 2015 to 2021.The prevalence of ESBLs-producing E.coli in tertiary hospitals and children's hospitals and the prevalence of CREco in children's hospitals showed a decreasing trend over the 7-year period.The prevalence of CREco in secondary and tertiary hospitals increased slowly.Antibiotic resistance rates changed slowly from 2015 to 2021.Carbapenem drugs(imipenem,meropenem)were the most active drugs amongβ-lactams against E.coli(resistance rate≤2.1％).The resistance rates of E.coli to β-lactam/β-lactam inhibitor combinations(piperacillin-tazobactam,cefoperazone-sulbactam),aminoglycosides(amikacin),nitrofurantoin and fosfomycin(for urinary isolates only)were all less than 10％.The resistance rate of E.coli strains to antibiotics varied with the level of hospitals and the departments where the strains were isolated,especially for cefazolin and ciprofloxacin,to which the resistance rate of E.coli strains from children in non-ICU departments was significantly lower than that of the strains isolated from other departments(P＜0.05).The E.coli isolates from ICU showed higher resistance rate to most antimicrobial agents tested(excluding tigecycline)than the strains isolated from other departments.The E.coli strains isolated from tertiary hospitals showed higher resistance rates to the antimicrobial agents tested(excluding tigecycline,polymyxin B,cefepime and carbapenems)than the strains from secondary hospitals and children's hospitals.Conclusions E.coli is an important pathogen causing clinical infection.More than half of the clinical isolates produced ESBL.The prevalence of CREco is increasing in secondary and tertiary hospitals over the 7-year period even though the overall prevalence is still low.This is an issue of concern.

BACKGROUND: Generalized pustular psoriasis (GPP), a rare and recurrent autoinflammatory disease, imposes a substantial burden on patients and society. Awareness of GPP in China remains limited. METHODS: This cross-sectional survey, conducted between September 2021 and May 2023 across 14 hospitals in China, included GPP patients of all ages and disease phases. Data collected encompassed demographics, clinical characteristics, economic impact, disease severity, quality of life, and treatment-related complications. Risk factors for GPP recurrence were analyzed. RESULTS: Among 127 patients (female/male ratio = 1.35:1), the mean age of disease onset was 25 years (1st quartile [Q1]-3rd quartile [Q3]: 11-44 years); 29.2% had experienced GPP for more than 10 years. Recurrence occurred in 75.6% of patients, and nearly half reported no identifiable triggers. Younger age at disease onset ( P  = 0.021) and transitioning to plaque psoriasis ( P  = 0.022) were associated with higher recurrence rates. The median diagnostic delay was 8 months (Q1-Q3: 2-41 months), and 32.3% of patients reported misdiagnoses. Comorbidities were present in 53.5% of patients, whereas 51.1% experienced systemic complications during treatment. Depression and anxiety affected 84.5% and 95.6% of patients, respectively. During GPP flares, the median Dermatology Life Quality Index score was 19.0 (Q1-Q3: 13.0-23.5). This score showed significant differences between patients with and without systemic symptoms; it demonstrated correlations with both depression and anxiety scores. Treatment costs caused financial hardship in 55.9% of patients, underscoring the burden associated with GPP. CONCLUSIONS The substantial disease and economic burdens among Chinese GPP patients warrant increased attention. Patients with early onset disease and those transitioning to plaque psoriasis require targeted interventions to mitigate the high recurrence risk.
Humans ; Male ; Female ; Psoriasis/pathology* ; Adult ; Cross-Sectional Studies ; Adolescent ; Child ; Young Adult ; Quality of Life ; Middle Aged ; China/epidemiology* ; Recurrence ; Risk Factors ; Surveys and Questionnaires ; East Asian People

ADC189 is a novel drug of cap-dependent endonuclease inhibitor. In our study, its antiviral efficacy was evaluated in vitro and in vivo, and compared with baloxavir marboxil and oseltamivir. A first-in-human phase I study in healthy volunteers included single ascending dose (SAD) and food effect (FE) parts. In the preclinical study, ADC189 showed potent antiviral activity against various types of influenza viruses, including H1N1, H3N2, influenza B virus, and highly pathogenic avian influenza, comparable to baloxavir marboxil. Additionally, ADC189 exhibited much better antiviral efficacy than oseltamivir in H1N1 infected mice. In the phase I study, ADC189 was rapidly metabolized to ADC189-I07, and its exposure increased proportionally with the dose. The terminal elimination half-life (T_1/2) ranged from 76.69 to 98.28 hours. Of note, food had no effect on the concentration, clearance, and exposure of ADC189. It was well tolerated, with few treatment-emergent adverse events (TEAEs) reported and no serious adverse events (SAEs). ADC189 demonstrated excellent antiviral efficacy both in vitro and in vivo. It was safe, well-tolerated, and had favorable pharmacokinetic characteristics in healthy volunteers, supporting its potential for single oral dosing in clinical practice.
Humans ; Antiviral Agents/therapeutic use* ; Animals ; Male ; Adult ; Mice ; Female ; Endonucleases/antagonists & inhibitors* ; Influenza, Human/drug therapy* ; Young Adult ; Dibenzothiepins/pharmacology* ; Oseltamivir/pharmacology* ; Middle Aged ; Triazines/pharmacology* ; Thiepins/pharmacology* ; Influenza B virus/drug effects* ; Influenza A Virus, H1N1 Subtype/drug effects* ; Pyridines/pharmacology* ; Morpholines ; Pyridones

Objective:To observe the efficacy and safety of Tianchan capsule on chemotherapy-induced peripheral neuropathic pain (CIPNP) .Methods:A total of 120 CIPNP patients with Karnofsky performance status (KPS) score higher than 60 admitted to the Nantong Tumor Hospital, Jiangsu Province and Suzhou Hospital of Traditional Chinese Medicine from April 2023 to April 2024 were selected as study objects. Patients were divided into control group (cisplatin/paclitaxel) and observation group (cisplatin/paclitaxel+Tianchan capsule) according to random number table method, with 60 cases in each group. After 28 days of treatment, the clinical efficacy, adverse reactions, numberical rating scale (NRS) score, quality of life score, Traditional Chinese Medicine (TCM) syndrome score and neurotoxicity grading score before and after treatment were observed and compared between the two groups.Results:Twenty-eight days after treatment, the total effective rate of the control group was 0 (0/60) , while the total effective rate of the observation group was 83.33% (50/60) , with a statistically significant difference ( χ2=85.71, P<0.001) . The NRS scores of the control group before treatment and at 7, 14, and 28 days after treatment were 6.18±1.71, 6.17±1.72, 6.20±1.70 and 6.22±1.70, respectively, with no statistically significant difference ( F=-1.43, P=0.160) . The NRS scores of the observation group before treatment and at 7, 14, and 28 days after treatment were 6.05±1.76, 5.17±1.42, 3.76±1.16, and 2.00±0.80, respectively, with a statistically significant difference ( F=22.89, P<0.001) . The NRS scores of the observation group at 7, 14, and 28 days after treatment were all lower than those of the control group, with statistically significant differences (all P<0.001) . Further pairwise comparison showed that, NRS scores in the observation group gradually decreased from before treatment to after 7, 14 and 28 days of treatment (all P<0.05) . Before treatment and 7, 14, and 28 days after treatment in the control group, the KPS scores were 67.33±6.43, 67.25±6.29, 67.08±6.14 and 66.75±5.80, respectively, with no statistically significant difference ( F=2.18, P=0.340) . Before treatment and 7, 14, and 28 days after treatment in the observation group, the KPS scores were 67.17±6.49, 68.33±6.32, 71.25±7.68 and 79.42±5.30, respectively, with a statistically significant difference ( F=-19.33, P<0.001) . The KPS scores of the observation group at 14 and 28 days after treatment were both higher than those of the control group, with statistically significant differences ( t=-3.33, P<0.001; t=-12.66, P<0.001) . Further pairwise comparison showed that, the KPS scores of the observation group were higher at 28 days after treatment compared to pre-treatment levels, as well as to those at 7 and 14 days after treatment (all P<0.05) . The scores of TCM syndrome showed that the scores of burnout and fatigue were 3.03±0.66 before treatment and 3.03±0.66 after 28 days of treatment in the control group, respectively, with no statistically significant difference ( t<0.01, P>0.999) . In the observation group, the scores were 3.02±0.60 and 1.97±0.52, respectively, with a statistically significant difference ( t=21.00, P<0.001) . The scores of hypochondriac pain were 3.05±0.68 before treatment and 3.07±0.63 after 28 days of treatment in the control group, respectively, with no statistically significant difference ( t=-0.57, P=0.568) . In the observation group, the scores were 3.03±0.66 and 2.02±0.57, respectively, with a statistically significant difference ( t=18.25, P<0.001) . The scores of pale complexion were 2.87±0.50 and 2.85±0.48 in the control group before treatment and 28 days after treatment, respectively, with no statistically significant difference ( t=-0.57, P=0.568) . In the observation group, the scores were 2.93±0.55 and 1.93±0.55, respectively, with a statistically significant difference ( t=24.29, P<0.001) . The scores of loss of appetite were 2.90±0.60 and 2.90±0.63 in the control group before treatment and after 28 days of treatment, respectively, with no statistically significant difference ( t<0.01, P>0.999) . In the observation group, the scores were 2.95±0.57 and 1.98±0.60, respectively, with a statistically significant difference ( t=20.42, P<0.001) . After 28 days of treatment, the scores of burnout and fatigue, hypochondriac pain, pale complexion and loss of appetite in the observation group were lower than those in the control group (all P<0.001) . Comparison of neurotoxicity grading showed that the scores of peripheral sensory nerve disorder were 2.54±0.50 before treatment and 2.58±0.49 after 28 days of treatment in the control group, respectively, with no statistically significant difference ( t=-0.40, P=0.690) . The scores in the observation group were 2.52±0.50 and 2.00±0.00, respectively, with a statistically significant difference ( t=7.29, P<0.001) . The scores of peripheral motor nerve disorder were 2.44±0.51 before treatment and 2.36±0.48 after 28 days of treatment, respectively, with no statistically significant difference ( t=0.81, P=0.419) . In the observation group, the scores were 2.46±0.50 and 2.00±0.10, respectively, with a statistically significant difference ( t=6.49, P<0.001) . Neuralgia score: Before treatment and after 28 days of treatment, the scores in the control group were 2.14±0.49 and 2.18±0.48, respectively, with no statistically significant difference ( t=-0.41, P=0.683) . The scores in the observation group were 2.16±0.51 and 1.72±0.46, respectively, with a statistically significant difference ( t=4.56, P<0.001) . After 28 days of treatment, the scores of peripheral sensory nerve disorder, peripheral motor nerve disorder and neuralgia in the observation group were lower than those in the control group (all P<0.001) . Patients in both control group and observation group had different degrees of diarrhea, nausea and vomiting, but there was no statistically significant difference in total incidence of adverse reactions between the two groups ( χ2=0.22, P=0.637) . Conclusions:Tianchan capsule can effectively reduce the pain degree of patients with CIPNP, improve the quality of life of patients and has good safety.