Objective To explore characteristics of clinical parameters and cytokines in patients with drug-induced liver injury(DILI)caused by different drugs and their correlation with clinical indicators. Method The study was conducted on patients who were up to Review of Uncertainties in Confidence Assessment for Medical Tests(RUCAM)scoring criteria and clinically diagnosed with DILI.Based on Chinese herbal medicine,cardiovascular drugs,non-steroidal anti-inflammatory drugs(NSAIDs),anti-infective drugs,and other drugs,patients were divided into five groups.Cytokines were measured by Luminex technology.Baseline characteristics of clinical biochemical indicators and cytokines in DILI patients and their correlation were analyzed. Results 73 patients were enrolled.Age among five groups was statistically different(P=0.032).Alanine aminotransferase(ALT)(P=0.033)and aspartate aminotransferase(AST)(P=0.007)in NSAIDs group were higher than those in chinese herbal medicine group.Interleukin-6(IL-6)and tumor necrosis factor alpha(TNF-α)in patients with Chinese herbal medicine(IL-6:P<0.001;TNF-α:P<0.001)and cardiovascular medicine(IL-6:P=0.020;TNF-α:P=0.001)were lower than those in NSAIDs group.There was a positive correlation between ALT(r=0.697,P=0.025),AST(r=0.721,P=0.019),and IL-6 in NSAIDs group. Conclusion Older age may be more prone to DILI.Patients with NSAIDs have more severe liver damage in early stages of DILI,TNF-α and IL-6 may partake the inflammatory process of DILI.

Objective This study aimed to investigate the effect and underlying mechanism of Fructus lycii in improving exercise fatigue.Methods A network pharmacological approach was used to explore potential mechanisms of action of Fructus lycii. Skeletal muscle C2C12 cells and immunofluorescence were employed to verify the effect and mechanism of the representative components in Fructus lycii predicted by network pharmacological analysis.Results Six potential active components, namely quercetin, β-sitosterol, stigmasterol, 7-O-methylluteolin-6-C-beta-glucoside_qt, atropine, and glycitein, were identified to have potency in improving exercise fatigue via multiple pathways, such as the PI3K-Akt, neuroactive ligand-receptor interaction, IL-17, TNF, and MAPK signaling pathways. The immunofluorescence results indicated that quercetin, a significant active component in Fructus lycii, increased the mean staining area of 2-NBDG, TMRM, and MitoTracker, and decreased the area of CellRox compared to the control. Furthermore, the protein expression levels of p-38 MAPK, p-MAPK, p-JNK, p-PI3K, and p-AKT markedly increased after quercetin treatment.Conclusion Fructus lycii might alleviate exercise fatigue through multiple components and pathways. Among these, quercetin appears to improve exercise fatigue by enhancing energy metabolism and reducing oxidative stress. The PI3K-AKT and MAPK signaling pathways also appear to play a role in this process.

Objective:To investigate the current situation of the use of transjugular intrahepatic portosystemic shunt (TIPS) for portal hypertension, which should aid the development of TIPS in China.Methods:The China Portal Hypertension Alliance (CHESS) initiated this study that comprehensively investigated the basic situation of TIPS for portal hypertension in China through network research. The survey included the following: the number of surgical cases, main indications, the development of Early-TIPS, TIPS for portal vein cavernous transformation, collateral circulation embolization, intraoperative portal pressure gradient measurement, commonly used stent types, conventional anticoagulation and time, postoperative follow-up, obstacles, and the application of domestic instruments.Results:According to the survey, a total of 13 527 TIPS operations were carried out in 545 hospitals participating in the survey in 2021, and 94.1% of the hospital had the habit of routine follow-up after TIPS. Most hospitals believed that the main indications of TIPS were the control of acute bleeding (42.6%) and the prevention of rebleeding (40.7%). 48.1% of the teams carried out early or priority TIPS, 53.0% of the teams carried out TIPS for the cavernous transformation of the portal vein, and 81.0% chose routine embolization of collateral circulation during operation. Most of them used coils and biological glue as embolic materials, and 78.5% of the team routinely performed intraoperative portal pressure gradient measurements. In selecting TIPS stents, 57.1% of the hospitals woulel choose Viator-specific stents, 57.2% woulel choose conventional anticoagulation after TIPS, and the duration of anticoagulation was between 3-6 months (55.4%). The limitation of TIPS surgery was mainly due to cost (72.3%) and insufficient understanding of doctors in related departments (77.4%). Most teams accepted the domestic instruments used in TIPS (92.7%).Conclusions:This survey shows that TIPS treatment is an essential part of treating portal hypertension in China. The total number of TIPS cases is far from that of patients with portal hypertension. In the future, it is still necessary to popularize TIPS technology and further standardize surgical indications, routine operations, and instrument application.

Objective:To review and analyze the clinical diagnosis and treatment of renal Ewing's sar-coma with venous tumor embolus,to follow up the survival and prognosis of the patients,and to provide help for the diagnosis and treatment of the disease.Methods:Clinical data(including general data,sur-gical data and postoperative pathological data)of patients diagnosed with renal Ewing's sarcoma with ve-nous tumor embolus in Peking University Third Hospital from June 2016 to June 2022 were collected,and the prognosis of the patients was followed up to analyze the influence of diagnosis and treatment process on the prognosis of the disease.Results:There were 6 patients,including 1 male and 5 females.There were 4 cases of left renal tumor and 2 cases of right renal tumor.The median age at diagnosis was 28 years(16-52 years).The imaging findings were all exogenous tumors with internal necrotic tissue and hemorrhage.The mean maximum tumor diameter was 12.6 cm,and the mean tumor thrombus length was 7.8 cm.Four patients underwent open surgery and 2 patients underwent laparoscopic surgery.The post-operative pathological results were renal Ewing sarcoma.Immunohistochemical results showed 3 cases of CD99(+),2 cases of FLI-1(+),and 1 case of CD99,FLI-1(-).3 patients received chemothera-py(cyclophosphamide,doxorubicin,vincristine/ifosfamide,etoposide),1 case received chemotherapy combined with radiotherapy,and 2 cases received no adjuvant therapy.The mean overall survival(OS)of the 6 patients was 37 months,and the mean OS of the 4 patients(47 months)who received chemo-therapy was significantly higher than that of the 2 patients(16 months)who did not receive chemotherapy(P=0.031).Conclusion:Renal Ewing's sarcoma with venous tumor embolus is rare in clinic,and it is common in young female patients.The operation is difficult and the prognosis is poor.Surgical resection,adjuvant radiotherapy and chemotherapy can improve the overall survival rate of the patients.

Recently,inductively coupled plasma mass spectrometry(ICP-MS)has shown great potential in the quantitative analysis of biomolecules due to its high sensitivity,high accuracy,anti-interference ability and multi-element detection capability.Elemental tags enable specific labeling of target biomolecules with element-reporter groups,playing a critical role in the performance of bioanalysis using ICP-MS.Antibodies are highly specific to antigens on cell surfaces and are one of the most commonly used targeted delivery vehicles.Traditional random chemical coupling methods are difficult to control the coupling sites and loading numbers of element reporters,which lead to heterogeneity of antibody conjugates,affecting the specific recognition and binding ability of antibodies and antigens,and thus reducing the targeting ability and quantitative accuracy.To solve these issues,site-specific coupling of antibodies with element reporter was studied in this work.By using peptide-mediated affinity labeling technology,a short chain DNA was specifically labeled to immunoglobulin G(IgG)antibody K248,and then DNA base complementary pairing was used to realize accurate assembly of monoclonal antibodies and Eu-modified phage MS2 capsid,resulting in the preparation of highly sensitive and selective element tags.This method overcame the heterogeneity problem of element tags caused by random coupling,and ensured the targeting specificity,affinity and signal amplification ability of element tags.The element tag prepared here showed a specificity to bind/label with epidermal growth factor receptor(EGFR)biomarker on the surface of cancer cells,realizing single cancer cell analysis using ICP-MS.

Objective To investigate the cumulative incidence of recurrence(CIR)in children with acute lymphoblastic leukemia(ALL)after treatment with the Chinese Children's Cancer Group ALL-2015(CCCG-ALL-2015)protocol and the risk factors for recurrence.Methods A retrospective analysis was conducted on the clinical data of 852 children who were treated with the CCCG-ALL-2015 protocol from January 2015 to December 2019.CIR was calculated,and the risk factors for the recurrence of B-lineage acute lymphoblastic leukemia(B-ALL)were analyzed.Results Among the 852 children with ALL,146(17.1%)experienced recurrence,with an 8-year CIR of 19.8%±1.6%.There was no significant difference in 8-year CIR between the B-ALL group and the acute T lymphocyte leukemia group(P>0.05).For the 146 children with recurrence,recurrence was mainly observed in the very early stage(n=62,42.5%)and the early stage(n=46,31.5%),and there were 42 children with bone marrow recurrence alone(28.8%)in the very early stage and 27 children with bone marrow recurrence alone(18.5%)in the early stage.The Cox proportional-hazards regression model analysis showed that positive MLLr fusion gene(HR=4.177,95%CI:2.086-8.364,P<0.001)and minimal residual disease≥0.01%on day 46(HR=2.013,95%CI:1.163-3.483,P=0.012)were independent risk factors for recurrence in children with B-ALL after treatment with the CCCG-ALL-2015 protocol.Conclusions There is still a relatively high recurrence rate in children with ALL after treatment with the CCCG-ALL-2015 protocol,mainly bone marrow recurrence alone in the very early stage and the early stage,and minimal residual disease≥0.01%on day 46 and positive MLLr fusion gene are closely associated with the recurrence of B-ALL.

Objective To understand the epidemiological and clinical characteristics of healthcare-associated infec-tion(HAI)in neonates with different gestational ages and birth weights,and provide guidance for personalized cli-nical diagnosis and treatment.Methods According to the inclusion and exclusion criteria,240 neonates with HAI in the neonatal intensive care unit(NICU)of a hospital in Handan City from January 2018 to December 2022 were selected as the study group,720 neonates without HAI were selected as the control group based on systematic sam-pling method with a ratio of 1∶3.The incidence of HAI,distribution characteristics of infection site,pathogenic features of HAI,as well as the effect of different delivery modes on HAI in neonates with different gestational ages and birth weights were analyzed.Results Neonates with gestational age＜28 weeks and birth weight＜1 000 g had the highest incidence of HAI,which were 19.48％and 20.41％,respectively.Among neonates with gestational age＜28 weeks,unidentified site infection were the most(37.50％),while in all gestational age groups within 28-36+6 weeks,bloodstream infection(BSI)and respiratory system infection were predominant.For neonates with gestational age ≥37 weeks,BSI and unidentified site infection occurred frequently.Among neonates in all weight groups,BSI was the most frequent,followed by respiratory system infection.Pathogens from different sites of in-fections in neonates with different gestational ages and birth weights varied.Among neonates with gestational age of 28-31+6 weeks and birth weight of 1 000-1 499 g,the constituent of birth modes showed statistically significant difference between neonates with and without HAI(both P＜0.05).Conclusion Epidemiological and clinical chara-cteristics of HAI in neonates with different gestational ages and birth weights are different.For the prevention and control of HAI,individualized diagnosis and treatment plans should be developed to achieve precise prevention and control,reduce the incidence of HAI,and improve the overall treatment level of neonates.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in tertiary hospitals in major regions of China in 2022.Methods Clinical isolates from 58 hospitals in China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2022 Clinical &Laboratory Standards Institute(CLSI)breakpoints.Results A total of 318 013 clinical isolates were collected from January 1,2022 to December 31,2022,of which 29.5％were gram-positive and 70.5％were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species(excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi)was 28.3％,76.7％and 77.9％,respectively.Overall,94.0％of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 90.8％of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis showed significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 94.2％in the isolates from children and 95.7％in the isolates from adults.The resistance rate to carbapenems was lower than 13.1％in most Enterobacterales species except for Klebsiella,21.7％-23.1％of which were resistant to carbapenems.Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.1％to 13.3％.The prevalence of meropenem-resistant strains decreased from 23.5％in 2019 to 18.0％in 2022 in Pseudomonas aeruginosa,and decreased from 79.0％in 2019 to 72.5％in 2022 in Acinetobacter baumannii.Conclusions The resistance of clinical isolates to the commonly used antimicrobial agents is still increasing in tertiary hospitals.However,the prevalence of important carbapenem-resistant organisms such as carbapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a downward trend in recent years.This finding suggests that the strategy of combining antimicrobial resistance surveillance with multidisciplinary concerted action works well in curbing the spread of resistant bacteria.

Objective:To evaluate the effect of low-dose recombinant interleukin-2(rIL-2)therapy on immunocyte subsets and its side effects in children with solid tumor.Methods:A total of 22 children(11 males and 11 females)with solid tumor in our department from December 2012 to November 2017 were selected,with a median age of 9(3-16)years old when starting IL-2 therapy.ALL surgeries and chemotherapy of children had been completed before low-dose rIL-2 therapy,and 17 cases achieved complete remission(CR)and 5 cases achieved partial remission(PR).A low-dose rIL-2 therapy was given 1 month after chemotherapy for 1 year:4 × 105 IU/(m2·d),s.c.for every other day,3 times per week.The immunocyte subsets were detected every 3 months until the end of treatment,meanwhile,disease condition and therapy-related side effects were followed up.Results:After low-dose rIL-2 therapy in 22 children,the absolute values of CD3+T cells,CD3-CD56+natural killer cells,CD3+CD4+helper T cells(Th)and CD3+CD8+cytotoxic T cells were up-regulated remarkably,as well as Th/suppressor T cells(all P＜0.05).While,there were no significant differences in absolute value and proportion of CD4+CD25+CD127-Treg cells during therapy.Among the 17 children who achieved CR before rIL-2 therapy,14 cases continued to maintain CR after therapy,while 3 cases relapsed,and with 2 died after treatment abandonment.The 5 children who achieved PR before low-dose rIL-2 therapy were evaluated CR by PET/CT scan after treatment.In the early stage of low-dose rIL-2 therapy,1 child developed skin rashes at the injection sites,and 2 children ran a slight to mild transient fever.Their symptoms disappeared without any organ damage after symptomatic treatment.Conclusion:Low-dose rIL-2 therapy has good drug tolerance,and changes the distribution of anti-tumor immune-cell subgroup in peripheral blood of children with solid tumor remarkably without up-regulation of absolute value and ratio of Treg cells.

Objective:To investigate the value of serum free light chain(sFLC)and serum calcium ion in the diagnosis and prognosis of multiple myeloma(MM).Methods:Forty patients with MM treated in Henan Provincial People's Hospital from January 2018 to January 2022 were selected as the observation group,and 40 healthy volunteers were selected as the control group.The differences of sFLC-κ,sFLC-λ,sFLC-κ/λ,serum calcium ions,etc between the two groups were compared.Meanwhile,the differences of sFLC-κ,sFLC-λ,sFLC-κ/λ,serum calcium ions,etc in different international staging systems(ISS),chemotherapy efficacy and prognosis patients were analyzed.Results:The levels of sFLC-κ[(98.39±21.19)vs(12.01±4.45)mg/L],sFLC-λ[(210.20±45.54)vs(14.10±5.11)mg/L]and proportions of hypocalcemia(65％vs 0)in the observation group were significantly higher than those in the control group(P＜0.05),while sFLC-κ/λ ratio[(0.44±0.10)vs(0.87±0.12)]and serum calcium ions[(1.98±0.46)vs(2.42±0.40)mmol/L]were significantly lower than those in the control group(P＜0.05).The sFLC-κ,sFLC-λ,the proportion of hypocalcemia and the course of hypocalcemia in ISS stage Ⅲ patients in the observation group were significantly higher than those in stage Ⅰ and Ⅱ patients(P＜0.05),while sFLC-κ/λ ratio,and serum calcium ions were significantly lower than those in stage Ⅰ and Ⅱ patients(P＜0.05).The levels of sFLC-κ[(107.76±21.22)vs(94.67 ±20.11)mg/L],sFLC-λ[(245.54±41.12)vs(205.54±50.22)mg/L]of patients with hypocalcemia in the observation group was significantly higher than those without hypocalcemia(P＜0.05),while the sFLC-κ/λ ratio was significantly lower than those without hypocalcemia[(0.42±0.04)vs(0.47±0.06);P＜0.05].The levels of sFLC-κ[(107.29±20.14)vs(91.11±18.92)mg/L],sFLC-λ[(247.98±42.26)vs(179.29±39.32)mg/L]in patients with ineffective chemotherapy were significantly higher than those in patients with effective chemotherapy(P＜0.05),while the sFLC-κ/λ ratio was significantly lower than those in patients with effective chemotherapy[(0.43± 0.10)vs(0.50±0.09);P＜0.05)].The area under the ROC curve for sFLC-κ,sFLC-λ,sFLC-κ/λ predicting ineffective chemotherapy was 0.803,0.793 and 0.699 respectively,P＜0.05.There was no significant difference in sFLC-κ,sFLC-λ,sFLC-κ/λ ratio,serum calcium ion,hypocalcemia ratio and hypocalcemia course between survival and death patients(P＞0.05).Conclusion:sFLC and serum calcium are related to 1SS stage of MM patients.sFLC level has a certain value to predict the curative effect of chemotherapy in MM patients.However,the prognostic values of sFLC and serum calcium are not yet confirmed for MM patients.