Objective To explore the value of combining quantitative indicators of rectus femoris muscle obtained through ultrasound technology with clinical data in identifying protein energy wasting(PEW)in patients with chronic kidney disease(CKD)undergoing maintenance hemodialysis.Methods 90 CKD patients undergoing regular hemodialysis treatment in Guangzhou Red Cross Hospital from November 2023 to August 2024 were selected and divided into experimental group(30 cases with PEW)and control group(60 cases without PEW)according to PEW diagnostic criteria.Clinical indicators and quadriceps ultrasound quantitative data were measured and compared between two groups.Independent predictors of PEW were screened through multivariate Logistic regression analysis.A prediction model was constructed and receiver operating characteristic curve were drawn to evaluate its diagnostic performance.Results Significant differences were observed between experimental group and control group in body mass index(BMI),serum albumin,age,gender,rectus femoris thickness,and cross-sectional area(P＜0.05).Multivariate Logistic regression analysis showed that BMI and rectus femoris thickness were independent factors affecting PEW in CKD patients.A diagnostic model based on these two indicators,Logit(P)=1/[1+e-(10.292-0.378×BMI-2.992×rectus femoris thickness)],demonstrated good diagnostic performance(area under the curve=0.853,95％CI:0.764-0.943,P＜0.05).Conclusion Ultrasound assessment of rectus femoris thickness can objectively reflect the degree of skeletal muscle atrophy in CKD patients,and the prediction model constructed in combination with BMI helps in early identification of PEW and clinical intervention decision-making.

Objective The aim of this study was to investigate the microbiological characteristics and antimicrobial resistance of Nocardia isolates in Hebei Province during the 9-year period.Methods The medical records of all hospitalized patients from whom Nocardia was isolated from 2015 to 2023 were analyzed retrospectively.The isolates were identified to the species level by amplification and sequencing of 16S rRNA,secA1 and ropB genes of Nocardia.Antimicrobial susceptibility of Nocardia isolates were tested by microbroth dilution method.Results Of the 162 strains of Nocardia,128(79.0％)were isolated from respiratory tract specimens,followed by skin and soft tissue infection(25/162,15.4％).Most of the patients with respiratory tract infection were elderly(＞65 years old).Most of the patients with skin and soft tissue infection were middle-aged and elderly(＞45 years old).Twelve species were identified among the 162 isolates.The most common species were N.cyriacigeorgica(36.4％,59/162),N.farcinica(25.3％,41/162),and N.otitidiscaviarum(9.9％,16/162).The most common Nocardia species isolated from the respiratory tract was N.cyriacigeorgica,followed by N.farcinica.The most common species causing skin and soft tissue infection were N.cyriacigeorgica,N.farcinica and N.brasiliensis.All Nocardia strains were susceptible to linezolid,followed by 98.8％susceptible to amikacin and 98.1％susceptible to trimethoprim-sulfamethoxazole(TMP-SMZ).Conclusions Nocardia is mainly isolated from respiratory tract,skin and soft tissues.N.cyriacigeorgica and N.farcinica are the most prevalent species.TMP-SMZ is the first choice for treatment of nocardiosis.Combination therapy may be appropriate for moderate and severe infections according to the results of antimicrobial susceptibility testing.

Objective To explore the value of combining quantitative indicators of rectus femoris muscle obtained through ultrasound technology with clinical data in identifying protein energy wasting(PEW)in patients with chronic kidney disease(CKD)undergoing maintenance hemodialysis.Methods 90 CKD patients undergoing regular hemodialysis treatment in Guangzhou Red Cross Hospital from November 2023 to August 2024 were selected and divided into experimental group(30 cases with PEW)and control group(60 cases without PEW)according to PEW diagnostic criteria.Clinical indicators and quadriceps ultrasound quantitative data were measured and compared between two groups.Independent predictors of PEW were screened through multivariate Logistic regression analysis.A prediction model was constructed and receiver operating characteristic curve were drawn to evaluate its diagnostic performance.Results Significant differences were observed between experimental group and control group in body mass index(BMI),serum albumin,age,gender,rectus femoris thickness,and cross-sectional area(P＜0.05).Multivariate Logistic regression analysis showed that BMI and rectus femoris thickness were independent factors affecting PEW in CKD patients.A diagnostic model based on these two indicators,Logit(P)=1/[1+e-(10.292-0.378×BMI-2.992×rectus femoris thickness)],demonstrated good diagnostic performance(area under the curve=0.853,95％CI:0.764-0.943,P＜0.05).Conclusion Ultrasound assessment of rectus femoris thickness can objectively reflect the degree of skeletal muscle atrophy in CKD patients,and the prediction model constructed in combination with BMI helps in early identification of PEW and clinical intervention decision-making.

Objective The aim of this study was to investigate the microbiological characteristics and antimicrobial resistance of Nocardia isolates in Hebei Province during the 9-year period.Methods The medical records of all hospitalized patients from whom Nocardia was isolated from 2015 to 2023 were analyzed retrospectively.The isolates were identified to the species level by amplification and sequencing of 16S rRNA,secA1 and ropB genes of Nocardia.Antimicrobial susceptibility of Nocardia isolates were tested by microbroth dilution method.Results Of the 162 strains of Nocardia,128(79.0％)were isolated from respiratory tract specimens,followed by skin and soft tissue infection(25/162,15.4％).Most of the patients with respiratory tract infection were elderly(＞65 years old).Most of the patients with skin and soft tissue infection were middle-aged and elderly(＞45 years old).Twelve species were identified among the 162 isolates.The most common species were N.cyriacigeorgica(36.4％,59/162),N.farcinica(25.3％,41/162),and N.otitidiscaviarum(9.9％,16/162).The most common Nocardia species isolated from the respiratory tract was N.cyriacigeorgica,followed by N.farcinica.The most common species causing skin and soft tissue infection were N.cyriacigeorgica,N.farcinica and N.brasiliensis.All Nocardia strains were susceptible to linezolid,followed by 98.8％susceptible to amikacin and 98.1％susceptible to trimethoprim-sulfamethoxazole(TMP-SMZ).Conclusions Nocardia is mainly isolated from respiratory tract,skin and soft tissues.N.cyriacigeorgica and N.farcinica are the most prevalent species.TMP-SMZ is the first choice for treatment of nocardiosis.Combination therapy may be appropriate for moderate and severe infections according to the results of antimicrobial susceptibility testing.

Objective: To evaluate the efficacy and safety of adding toripalimab to bevacizumab and platinum-based chemotherapy as first-line treatment for refractory recurrent or metastatic (R/M) cervical cancer (CC). Methods: Patients were administered toripalimab (240 mg) + bevacizumab (7.5 mg/kg) combined with platinum-based chemotherapy once every three weeks for six cycles, followed by the maintenance therapy involving toripalimab + bevacizumab once every 3 weeks for 12 months or when disease progression or intolerable toxicity occurred. The primary endpoint was the objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors version 1.1. The secondary endpoints were safety profiles, disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). Results: Twenty-four patients were enrolled in this study and in the final analysis. The median follow-up duration was 18.6 (range, 3.3–28.5) months. The ORR was 83.3% (95% confidence interval [CI]=62.6–95.3) and the DCR was 95.8% (95% CI=78.9–99.9); 9 (37.5%) patients achieved complete response, 11 (45.8%) achieved partial response, and 3 (12.5%) had stable disease. The median PFS was 22.6 (95% CI=10.4–34.7) months and the median OS was not reached. The most common grade 3 treatment-related adverse events (AEs) were neutropenia (41.7%) and leukopenia (16.7%). The most common immune-related AEs (irAEs) were thyroid dysfunction (37.5%) and increased adrenocorticotropic hormone (37.5%) and serum cortisol levels (33.3%). No grade ≥3 irAEs were observed. Conclusion Toripalimab combined with bevacizumab and platinum-based chemotherapy show promising clinical efficacy and favorable safety profile, providing an alternative firstline treatment option for patients with R/M CC.

OBJECTIVE To optimize the heart-nourishing granule extraction process by network pharmacology and Box-Behnken response surface method. METHODS The active ingredients of heart-nourishing granule were excavated through network pharmacology and their mechanism of action in the treatment of coronary heart disease was preliminarily explored. Molecular docking technology was used to predict the binding ability of the active ingredients to the main targets. At the same time, based on the compatibility relationship between the monarch, minister, assistant and guide of the prescription, the pharmacological effects of the ingredients, and the content determination index components of each medicinal flavor in the 2020 edition of the Chinese Pharmacopoeia, the process evaluation index components of heart-nourishing granule were further determined. In addition, combined with the analytic hierarchy process to determine the weight of each component, the Box-Behnken response surface method was used to optimize the extraction process of heart-nourishing granule. RESULTS The main active components of heart-nourishing granule screened were catalpol, Rhmannioside D, acteoside, ferulic acid and lobetyolin. By acting on core targets such as AKT1, IL-6, IL-1b, VEGFA, JUN and MAPK3, they regulated lipid and atherosclerosis, MAPK signaling and other pathways played a role in the treatment of coronary heart disease. Molecular docking results showed that the binding energies of active components and core targets predicted by network pharmacology were all < -5.0 kJ·mol-1. Five components catalpol, Rhmannioside D, acteoside, ferulic acid and lobetyolin were calculated by analytic hierarchy process method. The weight coefficients of arginyl glycosides were 0.329 7, 0.329 7, 0.164 8, 0.109 9, and 0.065 9, respectively. The Box-Behnken response surface method obtained the optimal water extraction process: 10 times the amount of water was used to extract twice, and each time was decocted for 1.5 h. The verification test showed that the contents of the five components were consistent with the predicted values, and the RSD values were all <5%. CONCLUSION The extraction process of heart-nourishing granule based on network pharmacology and Box-Behnken response surface methodology is stable and feasible, which provided an experimental basis for its further quality improvement.

OBJECTIVES: To determine the potential molecular mechanisms underlying the therapeutic effect of curcumin on hepatocellular carcinoma (HCC) by network pharmacology and experimental in vitro validation. METHODS: The predictive targets of curcumin or HCC were collected from several databases. the identified overlapping targets were crossed with Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses using the Database for Annotation, Visualization, and Integrated Discovery (DAVID) platform. Two of the candidate pathways were selected to conduct an experimental verification. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide tetrazolium (MTT) assay was used to determine the effect of curcumin on the viability of HepG2 and LO2 cells. The apoptosis and autophagy of HepG2 cells were respectively detected by flow cytometry and transmission electron microscopy. Besides, western blot and real-time polymerase chain reaction (PCR) were employed to verify the p53 apoptotic pathway and adenosine 5'-monophosphate (AMP)‍-activated protein kinase (AMPK) autophagy pathway. HepG2 cells were pretreated with pifithrin-‍α (PFT-‍α) and GSK690693 for further investigation. RESULTS: The 167 pathways analyzed by KEGG included apoptosis, autophagy, p53, and AMPK pathways. The GO enrichment analysis demonstrated that curcumin was involved in cellular response to drug, regulation of apoptotic pathway, and so on. The in vitro experiments also confirmed that curcumin can inhibit the growth of HepG2 cells by promoting the apoptosis of p53 pathway and autophagy through the AMPK pathway. Furthermore, the protein and messenger RNA (mRNA) of the two pathways were downregulated in the inhibitor-pretreated group compared with the experimental group. The damage-regulated autophagy modulator (DRAM) in the PFT-‍α-pretreated group was downregulated, and p62 in the GSK690693-pretreated group was upregulated. CONCLUSIONS Curcumin can treat HCC through the p53 apoptotic pathway and the AMPK/Unc-51-like kinase 1 (ULK1) autophagy pathway, in which the mutual transformation of autophagy and apoptosis may occur through DRAM and p62.
AMP-Activated Protein Kinases/pharmacology* ; Apoptosis ; Carcinoma, Hepatocellular/pathology* ; Curcumin/pharmacology* ; Humans ; Liver Neoplasms/pathology* ; Network Pharmacology ; Tumor Suppressor Protein p53/metabolism*

Immunotherapy combined with targeted therapy can benefit the survival of patients with unresectable hepatocellular carcinoma. Atezolizumab combined with bevacizumab has achieved remarkable efficacy in patients with advanced hepatocellular carcinoma, but the efficacy of conversion therapy in patients with unresectable hepatocellular carcinoma still needs more evidences. The authors report the clinical efficacy of a case of unresectable hepatocellular carcinoma with hepatitis B virus related liver cirrhosis who was treated with immunotherapy plus targeted therapy combined with local treatment. Results show a good effect in patient without tumor recurrence after postoperative 9 months.

【Objective】 To investigate the main causes of blood donor deferral in domestic blood center. 【Methods】 The causes of donor deferral were classified into 12 categories as previous medical history, drug use, alcohol consumption, menstrual period, underweight, abnormal blood pressure, abnormal body temperature, abnormal hemoglobin (Hb), lipemic blood, positive hepatitis B surface antigen (HBsAg), elevated alanine aminotransferase (ALT) and others according to the comparison indicators of Asia-Pacific Blood Network (APBN) and the national standard Blood Donor Health Examination Requirements. The relevant data of the top 3 causes of donor deferral, voluntarily reported by the members of Practice Comparison Working Group of China’s Mainland Blood Collection and Supply Institutions from 2014 to 2019, were collected and a histogram was generated. 【Results】 The median donor deferral rate of 20 domestic blood centers from 2014 to 2019 was 12.14%, with the lowest at 0.18% and highest at 32.32%, respectively. The top three causes for donor deferral were elevated ALT, abnormal Hb and abnormal blood pressure in year 2014, 2015, 2018 and 2019; elevated ALT, lipemic blood and abnormal blood pressure in 2016; elevated ALT, abnormal Hb, and lipemic blood in 2017. 【Conclusion】 The main causes of donor deferral were elevated ALT, abnormal Hb, abnormal blood pressure and lipemic blood.

Objective:To analyze the clinical efficacy and pregnancy outcomes of gonadotropin-releasing hormone agonist (GnRH-a) based fertility-sparing re-treatment in women with endometrial carcinoma (EC) and atypical endometrial hyperplasia (AEH) who failed with oral progestin therapy.Methods:Forty cases with EC or AEH who failed to respond to oral progestin were included from January 2012 to December 2020 at Peking Union Medical College Hospital. Combination of GnRH-a with levonorgestrel-releasing intrauterine system (group GLI: a subcutaneous injection of GnRH-a every 4 weeks and LNG-IUS insertion constantly) or the combination of GnRH-a with aromatase inhibitor (group GAI: a subcutaneous injection of GnRH-a every 4 weeks and oral letrozole 2.5 mg, daily) were used for these patients. Histological evaluation were performed at the end of each course (every 3-4 months) by hysteroscopy and curettage. After the complete remission (CR), all patients were followed up regularly.Results:(1) Clinical characteristics:among the 40 patients with EC or AEH, the median age at diagnosis was 31 years (range: 22-40 years) and the median body mass index was 24.7 kg/m 2 (range: 18.9-39.5 kg/m 2). (2) Efficacy of fertility-sparing re-treatment: 37 (92%, 37/40) patients achieved CR, 6 (6/7) in AEH and 31 (94%, 31/33) in EC patients. The CR rate was 93% (26/28) and 11/12 in group GLI and GAI, respectively. The median time to CR was 5 months (range: 3-12 months). At the end of the first therapy course, the CR rates in AEH and EC were 5/7 and 42% (14/33), at the second course, the CR rates were 6/7 and 82% (27/33), respectively. (3) Recurrence: after 25 months of median follow-up duration (range: 10-75 months), 8 (22%, 8/37) women developed recurrence, 1/6 in AEH and 7 (23%, 7/31) in EC patients, with the median recurrence time of 18 months (range: 9-26 months). Among them, two cases who had completed childbirth chose to receive hysterectomy directly. Six patients met the criteria of fertility-preserving therapy and received conservative treatment again and 5 (5/6) of them achieved CR. (4) Pregnancy: of the 37 patients with CR, 33 desired to conceive. Ten women attempted to get pregnancy spontaneously and 23 cases with assisted reproductive technology. Fourteen (42%, 14/33) patients became pregnant, including 9 (27%, 9/33) live births, 3 (9%, 3/33) missed abortions, and 2 (6%, 2/33) miscarriages at the second trimester. Conclusions:GnRH-a based fertility-sparing re-treatment in AEH or EC patients who failed with oral progestin therapy achieved good treatment effect and reproductive outcomes. It is an encouraging alternative regime for patients who failed with oral progestin therapy.