Objective:To investigate the efficacy and safety of percutaneous trans-hepatic choledochoscopic lithotripsy (PTCSL) in the treatment of recurrent hepatobiliary calculi under enhanced recovery after surgery (ERAS) mode.Methods:Clinical data of 88 patients with recurrent hepatobiliary calculi, who were treated with PTCSL at Zhengzhou Central Hospital Affiliated to Zhengzhou University and the First Affiliated Hospital of Xi'an Jiaotong University between June 2022 and June 2024 were retrospectively analyzed, including 34 males and 54 females, aged (52.0±13.8) years. The scheme includes preoperative education, prophylactic antibiotic application, ensuring the quality of surgery, early postoperative feeding and activity, etc. The operation can be divided into two fashions: percutaneous transhepatic cholangial drainage and PTCSL, which can be completed in one stage (one-stage expansion method) or in two stages (staged expansion method). Clinical data such as gender, age, operative time, intraoperative blood loss, residual stone, and surgical complications were recorded.Results:All 88 patients underwent PTCSL under ERAS mode successfully, including 52 cases using one-stage expansion method and 36 cases using staged expansion method. The operative time was (53±20) min, the intraoperative blood loss was (9.7±3.8) ml, the postoperative hospital stay was (3.6±1.7) d, and the hospitalization cost was (17 500±4 700) yuan. Sixty-nine patients (78.4%, 69/88) had one-time stone removal in the first PTCSL. A total of 19 cases of residual stones were managed again by percutaneous sinus soft choledochoscopy, of which 12 cases were managed by one-time choledochoscopy, five cases by two-time choledochoscopy, and two cases by three-time choledochoscopy. The rate of residual stone was significantly higher in one-stage expansion method compared to staged expansion method [28.8% (15/52) vs. 11.1% (4/36), P=0.040]. No death, conversion to open surgery, or severe complications such as intra-abdominal hemorrhage or bile leakage occurred in the patients. No residual stones or recurrence were found during the follow-ups of (7.5±2.1) months after discharge. Conclusion:PTCSL under ERAS mode is safe and effective in the treatment of recurrent hepatobiliary calculi.

An analysis of 24 144 norovirus sequences from Asia and Russia deposited in GenBank between 1995 and 2023 was conducted,to understand the temporal and spatial variations in norovirus genotypes in these regions.Norovirus sequences from Asia and Russia were downloaded in FASTA format from GenBank for the years 1995-2023,and analyzed in Excel,R language,and GraphPad Prism for data visualization.The number of norovirus sequences submitted to GenBank increased annually from 2004 and peaked in 2015.Notably,China and Japan contributed 62.3％of all submitted norovirus sequences.These sequences encompassed 31 capsid genotypes(C-type),with GⅠ accounting for 9％and GⅡ accounting for 90％.Additionally,49 polymerase types(P-type)were identified,along with 68 combinations of CP types;among the analyzed recombinant sequences(4 460 entries in total),approxi-mately 41％belonged to three predominant recombinant strains:GⅡ.2[P16],GⅡ.4[P31],and GⅡ.4[P16].This analysis provides valuable insights into the distribution characteristics of norovirus genotypes across Asia and Russia over time,thereby supporting vac-cine design and evaluation efforts.

Objective:To study the risk factors and the molecular epidemiology characteristics for Carbapenem-resistant Enterobacteriaceae(CRE) colonization in neonatal inpatients in Shenzhen region, China, which provide reference for the prevention and control of clinical CRE infection.Methods:This study is a prospective case-control study.Anal samples from inpatients between January 2023 and December 2023 at Longgang Maternity and Child Institute of Shantou University Medical College and Shenzhen Children's Hospital were collected for screening CRE strain. Drug susceptibility test, modified Carbapenem Inactivation Method (mCIM) test, drug resistance-related gene sequencing and multilocus sequence typing (MLST) were performed for isolated CRE strains.Meanwhile, the clinical data were collected for analyzing the risk factors of CRE intestinal colonization by multivariate regression analysis.Results:A total of 1 517 patients were screened, 26 CRE(1.7%, 26/1 517) were identified which including 14 Escherichia coli(53.8%, 14/26), 11 Klebsiella pneumoniae(42.3%, 11/26), 1 Enterobacter cloacae(3.9%, 1/26). The predominant carbapenemase gene was New Delhi Metallo(NDM) (92.4%, 24/26), followed by Imipenem (IMP) (3.8%, 1/26) and Guiana extended spectrum gene (GES) (3.8%, 1/26).Among the carried NDM resistance genes, New Delhi Metallo 5 (NDM5) was the main one, accounting for 84.6% (22/26).The MLST typing of Escherichia coli was mainly Sequence Type 48 (ST48) (6/14), while that of Klebsiella pneumoniae was mainly Sequence Type 35 (ST35) (10/11). All CRE isolates were resistant to penicillin, penicillinase inhibitors, cephalosporins, ertapenem and imipenem.The resistance rates of Escherichia coli to amikacin, levofloxacin was 1/14, 4/14, respectively. All isolates of Klebsiella pneumoniae were sensitive to amikacin, and the resistance rate to levofloxacin is 1/11. Risk factors for CRE colonization include the older age, length of hospital stay, tracheal intubation, invasive respiration, lumbar puncture, Apgar <7 score, and exposure to antibiotics.Conclusions:NDM5 is the predominant resistant gene in CRE isolated from neonatal patients feces in Shenzhen region.It is necessary to strengthen the screening of CRE colonization in neonate for prevention and control of CRE infection.

Cancer cachexia is a complex syndrome caused by multiple factors,which seriously affects the quality of life and prognosis of patients.Its overall pathogenesis is related to the deficiency of spleen qi,insufficiency of kidney essence,internal generation of turbid toxins,and the obstruction of the production of qi,blood and essential qi,which cannot nourish the muscles and bones.Under the guidance of the dynamic diagnosis and treatment system of"spleen and kidney exhaustion as the root cause and internal accumulation of turbid toxins as the manifestation",the overall regulation is carried out from four dimensions:opening and closing the spleen and stomach,nourishing the kidney and promoting transportation,transforming turbid toxins and detoxification,and tonifying qi and nourishing yin.It has shown unique value in the intervention of cancer cachexia and can provide ideas and references for the clinical practice of TCM in treating cancer cachexia.

Cognitive frailty, as one of the independent dimensions of frailty syndrome, has received increasing attention from researchers in recent years. Cognitive frailty not only reduces the quality of life for elderly people, but also increases the risk of adverse outcomes such as falls, disabilities, hospitalization, dementia, and death. This article introduces the concept, assessment methods, influencing factors, and intervention measures of cognitive frailty, emphasizing the important role of general practitioners in screening and management of cognitive frailty.

The interaction between skeletal aging and systemic aging has emerged as a frontier in the field of aging biology research.Recent studies have indicated that bones serve not only as mechanical support organs but also as endocrine organs that regulate systemic homeostasis through bone-derived factors.This review systematically elaborates the characteristics and mechanisms of skeletal aging, including tissue structural remodeling, cellular phenotypic changes, microenvironmental disruption, and molecular network disorders, etc.In aging organisms, bones interact with other organs to form a "bone-system aging axis", thereby promoting the occurrence and development of geriatric comorbidities.Accordingly, multi-target intervention strategies targeting the "bone-system aging axis" show the potential in decelerating the progression of systemic aging.In-depth research on the characteristic changes in inter-organ communication during the aging process of the body is not only conducive to facilitating the development of more comprehensive systemic anti-aging strategies, but also provides a new perspective for treating geriatric comorbidities and achieving healthy aging.

Background High-sensitivity C-reactive protein (hs-CRP) is a sensitive biomarker for cardiovascular disease (CVD) and can independently predict the risk of cardiovascular events. Although the association between per- and polyfluoroalkyl substances (PFAS) exposure and CVD risk has been widely reported, studies on the association between hs-CRP and PFAS remain limited. Objective To investigate the association between PFAS and hs-CRP levels, to provide a scientific basis for early identification and prevention of environment-related cardiovascular events. Methods This study utilized data from the National Health and Nutrition Examination Survey (NHANES) database (2015–2018). Based on predefined inclusion and exclusion criteria, a total of 3219 participants were included for subsequent analysis. Five PFAS with detection rates exceeding 90% were selected as exposure factors and log-transformed (lnPFAS) for subsequent analysis, including perfluorohexane sulfonic acid (PFHxS), perfluorononanoic acid (PFNA), perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS), and perfluorodecanoic acid (PFDA). After selecting potential confounders through a change-in-estimate approach, logistic regression was employed to examine the effects of individual PFAS on serum hs-CRP level. Additionally, quantile g-computation and Bayesian kernel machine regression (BKMR) were applied to assess the combined effects of PFAS mixtures on hs-CRP. Results The study included 3219 participants with a mean age of (50.4±17.6) years, of whom 1554 (48.28%) were male. The median concentrations of the five PFAS compounds were: 1.20 ng·mL⁻¹ (PFHxS), 0.50 ng·mL⁻¹ (PFNA), 1.50 ng·mL⁻¹ (PFOA), 5.20 ng·mL⁻¹ (PFOS), and 0.20 ng·mL⁻¹ (PFDA). The Wilcoxon rank-sum tests revealed statistically significant differences between the elevated serum hs-CRP (≥2 mg·L⁻¹) and normal (<2 mg·L⁻¹) groups for all five PFAS compounds (PFHxS: P=0.005; PFNA: P=0.009; PFOA: P<0.001; PFOS: P<0.001; PFDA: P<0.001). After adjusting for potential confounders, the analysis of individual PFAS exposure demonstrated significant negative associations between serum hs-CRP levels and both ln-PFOS (OR: 0.87; 95%CI: 0.79, 0.96; P=0.0036) and lnPFDA (OR: 0.78; 95%CI: 0.71, 0.86; P < 0.001). The joint effect analysis using quantile g-computation revealed an overall inverse association between PFAS mixtures and hs-CRP, with lnPFDA emerging as a primary contributor; an similar association was observed in males, but not significant in females. Further evaluation through BKMR showed that when PFAS mixture concentrations reached or exceeded P₇₀, their combined effect on hs-CRP became significantly lower than when all PFAS concentrations were at P₅₀, establishing a clear negative dose-response relationship. Conclusion The mixed exposure to PFAS showed a significant negative joint effect on serum hs-CRP levels, with PFDA being the key component contributing to this combined effect. Future prospective cohort studies are warranted to further validate these findings and elucidate the underlying mechanisms involved.

Post-orgasmic illness syndrome (POIS) is a rare condition characterized by the rapid onset of extreme fatigue, flu-like symptoms, difficulty concentrating, depression, nasal congestion, rhinorrhea, itchy eyes, and other physical and psychological discomforts following ejaculation. This report presents the outcomes of two patients with POIS who underwent a two-year course of autologous seminal plasma subcutaneous cluster immunotherapy. Treatment efficacy was assessed using methods such as the symptom Visual Analogue Scale (VAS), the Union Physio-Psycho-Social Assessment Questionnaire (UPPSAQ)-70, and the Short Form 36 Health Survey (SF-36). The results suggest that autologous seminal plasma subcutaneous cluster immunother-apy may be a safe and effective therapeutic approach for POIS.

ObjectiveTo explore the effectiveness and potential mechanism of Shugan Jianpi Granules （疏肝健脾颗粒） combined with Chushi Zhiyang Ointment （除湿止痒软膏） in the treatment of atopic dermatitis with sleep disturbance of liver constraint and spleen deficiency syndrome. MethodsSixty-six patients with atopic dermatitis combined with sleep disturbance of liver constraint and spleen deficiency syndrome were randomly divided into 33 cases each in the treatment group and the control group. Both groups were treated with Chushi Zhiyang Ointment for external use. The treatment group additionally received Shugan Jianpi Granules orally， one dose per day； and the control group received cetirizine hydrochloride tablets orally， 10mg per day， taken before bedtime. Both groups were under the treatment for 4 weeks. Clinical effectiveness was evaluated after treatment， and the SCORing Atopic Dermatitis （SCORAD） index， pruritus visual analog scale （VAS） score， Insomnia Severity Index （ISI） score， and Pittsburgh Sleep Quality Index （PSQI） score were recorded before and after treatment， and serum levels of melatonin （MLT）， interleukin-4 （IL-4）， interleukin-6 （IL-6）， interleukin-13 （IL-13）， and tumor necrosis factor-α （TNF-α） were measured. The patients were also tested for blood routine， liver function and kidney function before and after treatment， and the occurrence of adverse events was also observed. ResultsThe total effective rate in the treatment group （90.63%， 29/32） was significantly higher than that in the control group （66.67%， 20/30， P＜0.05）. After the interventions， the scores for SCORAD， VAS， ISI， and PSQI， as well as the levels of IL-4， IL-6， IL-13， and TNF-α， were significantly reduced in both groups. In contrast， the MLT levels in treatment group significantly elevated compared to that before treatment （P＜0.05）. Comparing between the two groups after treatment， the scores of SCORAD， ISI， PSQI， and VAS， as well as the levels of serum IL-4 and IL-13 in the treatment group were significantly lower than those in the control group， while the MLT levels were markedly higher than that in the control group （P＜0.05 or P＜0.01）. There was no obvious abnormality in blood routine， liver function and kidney function in both groups when compared before and after treatment. The incidence rate of adverse reactions was 9.38% （3/32） in the treatment group and 13.33% （4/30） in the control group， and the difference between groups showed no statistical difference （P＞0.05）. ConclusionOn the basis of topical application of Chushi Zhiyang Ointment， the combined application of Shugan Jianpi Granules can significantly alleviate the degree of skin lesions and itching， and improve the quality of sleep in atopic dermatitis patients with sleep disturbance of liver constraint and spleen deficiency syndrome， and its mechanism may be related to regulating the immune balance， reducing the secretion of inflammatory factors， and elevating the level of MLT.

HDAC7, a member of class IIa HDACs, plays a pivotal regulatory role in tumor, immune, fibrosis, and angiogenesis, rendering it a potential therapeutic target. Nevertheless, due to the high similarity in the enzyme active sites of class IIa HDACs, inhibitors encounter challenges in discerning differences among them. Furthermore, the substitution of key residue in the active pocket of class IIa HDACs renders them pseudo-enzymes, leading to a limited impact of enzymatic inhibitors on their function. In this study, proteolysis targeting chimera (PROTAC) technology was employed to develop HDAC7 drugs. We developed an exceedingly selective HDAC7 PROTAC degrader B14 which showcased superior inhibitory effects on cell proliferation compared to TMP269 in various diffuse large B cell lymphoma (DLBCL) and acute myeloid leukemia (AML) cells. Subsequent investigations unveiled that B14 disrupts BCL6 forming a transcriptional inhibition complex by degrading HDAC7, thereby exerting proliferative inhibition in DLBCL. Our study broadened the understanding of the non-enzymatic functions of HDAC7 and underscored the importance of HDAC7 in the treatment of hematologic malignancies, particularly in DLBCL and AML.