Background/Aims: Natural killer (NK) cell function is generally considered dampened in chronic hepatitis B virus (HBV) infection; however, the NK cell pool exhibits phenotypic and functional heterogeneity, and the antibody--mediated effect of NK cells remains less characterized. This study evaluated the dynamic changes in antibody-mediated NK cell responses and the involvement of distinct NK subsets across disease stages and during antiviral treatment. Methods: A T-cell receptor-like antibody specific for the HBV core 18–27 peptide (cTCRL-Ab) was used to determine the antibody-mediated effect of NK cells, and an array of NK cell surface markers were analyzed in cross-sectional and longitudinal cohorts of patients with chronic HBV infection. Single-cell RNA sequencing (scRNA-seq) was performed to identify the heterogeneity of NK subsets. Results: The cTCRL-Ab enabled the detection of NK cell cytolytic activity and IFNγ production. Notably, cTCRL-Ab-mediated NK cell responses were compromised in chronically HBV-infected patients, particularly in those receiving pegylated interferon-α (Peg-IFNα), which was associated with the downregulation of CD16 expression. Correspondingly, Peg-IFNα inhibited cTCRL-Ab-mediated NK cell function by reducing CD16 expression in vitro. scRNA-seq revealed that CD16 downregulation occurred mainly within a dysfunctional CD16hi NK subset exhibiting exhaustion properties. In contrast, an activated CD16hiNK subpopulation (CX3CR1⁺KLRC2–CD16hi) with high cytotoxicity was enriched in patients who experienced favorable treatment responses. Furthermore, the intrahepatic CX3CR1+KLRC2–CD16hi subset tended to exhibit functional restoration in HBsAg-loss individuals. Conclusions Our data contribute to the understanding of antibody-mediated responses of NK cells in chronic HBV infection, and highlight a previously unappreciated functional CX3CR1+KLRC2–CD16hiNK subset as a potential therapeutic target.

Esophageal cancer cases in China account for more than 50% of the world, among which approximately 90% are histological subtypes of esophageal squamous cell carcinoma. Over 50% of esophageal cancer patients are initially diagnosed at locally advanced or advanced stages. The R0 resection rate with surgical treatment alone is relatively low, and local recurrence and distant metastasis are prone to occur, resulting in a low 5-year survival rate. Recent research has focused on neoadjuvant therapy for esophageal cancer, but the most effective form of such therapy remains undetermined. Immunotherapy is currently the most active research field in tumor treatment. Further exploration of the treatment model combing immunotherapy with neoadjuvant chemotherapy or chemoradiotherapy is expected to improve the therapeutic effect and survival benefit in patients with locally advanced resectable esophageal squamous cell carcinoma.

Background:To compare the efficacy and safety of monthly administrations of gonadotropin releasing hormone (GnRH) agonists LY01005 and Zoladex ? in Chinese patients with premenopausal breast cancer. Methods:From October 2020 to November 2021, 188 premenopausal breast cancer patients were enrolled in 34 hospitals and randomized 1:1 to receive either LY01005 or Zoladex ? every 28 days for a total of three injections. All patients concomitantly received oral tamoxifen (TAM). The primary efficacy endpoint was cumulative probability of maintaining menopausal level [oestradiol (E2) ≤30 pg/ml] from day 29 to day 85. The second efficacy endpoint included changes in E2, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) compared with the baseline. Pharmacokinetics (PK), pharmacodynamics (PD), and safety were analyzed. The study also evaluated the pharmacokinetic and pharmacodynamic characteristics of LY01005. Results:A total of 188 patients were randomised and 187 patients received either LY01005 or Zoladex ?. Cumulative probabilities of maintaining menopausal level (E2≤30 pg/ml) from day 29 to day 85 were 93.1% for LY01005 and 86.3% for Zoladex ?. The between-group difference was 6.8% (95% CI: -2.3%, 15.9%) and primary efficacy in the LY01005 group was not inferior to that in the Zoladex ? group. Changes in E2, LH, and FSH levels compared with the baseline were equivalent between the two groups (E2: 89.34% to 90.23% vs. 82.11% to 85.02%; LH: 88.89% to 95.52% vs. 89.70% to 97.02%; FSH: 75.36% to 80.85% vs.73.07% to 80.24%, respectively). After three consecutive doses of LY01005, the LH and FSH levels of the subjects showed a transient increase after the first dose, reached a peak on the second day and then started to decrease. The LH and FSH reached a lower level and remained at or below that level until the 85th day. Both treatments were well-tolerated. Conclusion:LY01005 is as effective as Zoladex ? in suppressing E2 to menopausal levels in Chinese patients with premenopausal breast cancer, with a similar safety profile.

Background:To compare the efficacy and safety of monthly administrations of gonadotropin releasing hormone (GnRH) agonists LY01005 and Zoladex ? in Chinese patients with premenopausal breast cancer. Methods:From October 2020 to November 2021, 188 premenopausal breast cancer patients were enrolled in 34 hospitals and randomized 1:1 to receive either LY01005 or Zoladex ? every 28 days for a total of three injections. All patients concomitantly received oral tamoxifen (TAM). The primary efficacy endpoint was cumulative probability of maintaining menopausal level [oestradiol (E2) ≤30 pg/ml] from day 29 to day 85. The second efficacy endpoint included changes in E2, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) compared with the baseline. Pharmacokinetics (PK), pharmacodynamics (PD), and safety were analyzed. The study also evaluated the pharmacokinetic and pharmacodynamic characteristics of LY01005. Results:A total of 188 patients were randomised and 187 patients received either LY01005 or Zoladex ?. Cumulative probabilities of maintaining menopausal level (E2≤30 pg/ml) from day 29 to day 85 were 93.1% for LY01005 and 86.3% for Zoladex ?. The between-group difference was 6.8% (95% CI: -2.3%, 15.9%) and primary efficacy in the LY01005 group was not inferior to that in the Zoladex ? group. Changes in E2, LH, and FSH levels compared with the baseline were equivalent between the two groups (E2: 89.34% to 90.23% vs. 82.11% to 85.02%; LH: 88.89% to 95.52% vs. 89.70% to 97.02%; FSH: 75.36% to 80.85% vs.73.07% to 80.24%, respectively). After three consecutive doses of LY01005, the LH and FSH levels of the subjects showed a transient increase after the first dose, reached a peak on the second day and then started to decrease. The LH and FSH reached a lower level and remained at or below that level until the 85th day. Both treatments were well-tolerated. Conclusion:LY01005 is as effective as Zoladex ? in suppressing E2 to menopausal levels in Chinese patients with premenopausal breast cancer, with a similar safety profile.

Ferroptosis is an iron-dependent, apoptotic cell death caused by massive lipid peroxidation-mediated cell membrane damage. Recent evidence suggests that exosomes, as a 30-100 nm diameter follicular body, contain a variety of active ingredients such as proteins, various RNAs and lipids that can have a great impact on the diagnosis and treatment of related diseases by regulating cellular iron death. To this end, this paper elaborates the research significance of exosomes in the regulation of cell ferroptosis, analyzes their role in disease treatment, and reviews the relevant reports and studies on exosomes regulating cell ferroptosis in recent years.

Steroid-induced avascular necrosis of the femoral head (SANFH) is the death of the femoral head caused by long-term use of glucocorticoid (GC). Its pathological manifestations are mainly trabecular bone collapse and increased empty bone lacunas, osteocyte apoptosis rate and autophagy rate. Its pathogenesis is complicated, and the exact pathogenesis is still unclear. MicroRNAs (miRNAs) are a group of endogenous, non-coding small RNAs with an average length of 23 nucleotides. They are responsible for negatively regulating gene expression after transcription by inhibiting target messenger RNAs (mRNAs). MiRNAs play an important role in physiological processes, including cell development, proliferation, differentiation, metabolism, migration and apoptosis. According to bioinformatics analysis, MiRNAs play an important role in regulating gene expression, and it is estimated that more than one-third of human genes are regulated by them. In the past few years, more and more miRNAs have been found to be related to osteonecrosis, such as regulating the proliferation and differentiation of mesenchymal stem cells and osteoblasts. This article aims to review the relationship between steroid-induced femoral head necrosis and miRNAs.

Objective To evaluate the efficacy and safety of percutaneous balloon aortic valvuloplasty (PBAV) in retrograde,antegrade way or right ventricular pacing in children.Methods This was retrospective clinical study included 32 children who were treated with PBAV for congenital aortic stenosis from January 2008 to June 2017 in Guangdong Cardiovascular Institute.The general clinical data including residual stenosis and aortic stenosis again,and degree of artery injury,aortic regurgitation were particularly assessed.Results A total of 32 patients consisting of 27 boys and 5 girls underwent the procedure,with age of (55.8 ± 52.0) months (ranging from 20 days to 15 years) and body weight (18.2 ± 14.0) kg (ranging from 3.5 kg to 59.0 kg).Two infants accepted left cardiac catheterization through femoral vein and one with interventional indication then accepted PBAV through the patent foramen ovale.The others underwent the retrograde way,including 24 cases with rapid right ventricular pacing.The catheter-measured peak systolic the aortic valve gradient decreased from (81.6 ± 28.0) mmHg(1 mmHg =0.133 kPa) to (41.4 ± 19.0) mmHg immediately after percutaneous interventional treatment,and the difference was statistically significant (t =9.543,P =0.000).The peak systolic valve gradient mea-sured pre-PBAV and on the second day after PBAV measured by Doppler echocardiography decreased from (82.7 ±23.0) mmHg to (44.6 ± 18.0) mmHg,and the difference was statistically significant (t =11.732,P =0.000).The diameters of the aortic valve were (13.8 ± 3.0) mm(ranging from 6.5 mm to 21.0 mm) and the balloons were (14.1 ±4.0) mm(ranging from 6 mm to 23 mm).The follow-up period was 1 to 72 months.The peak systolic valve gradient measured by Doppler echocardiography increased from (44.6 ±18.0) mmHg to (58.6 ± 30.0) mmHg,and the difference was statistically significant (t =-2.549,P =0.016).During the procedure,5 children (14.7％) accepted surgery for restenosis or regurgitation.Seven had regurgitation,one had femoral artery embolism and one died on the second day after the procedure.Conclusions With the diversification of procedures and the continuous improvement of interventional devices,PBAV can play a very good role in alleviating congenital aortic stenosis in children,and the safety has been continuously improved.

Objective: To conduct a comprehensive and systematic review of the efficacy and safety of Wenxin Keli (WXKL) in the treatment of atrial fibrillation (AF) . Methods: Seven databases (PubMed, The Cochrane Library, Web ofScience, CNKI, Wanfang Database, VIP and SinoMed) were searched to identify relevant randomized controlled trials (RCTs) from inceptions to 1 October, 2018. Two review authors independently assessed the methodological quality andanalyzed data by Cochrane handbook and the Rev Man 5.3 software. Begg.s test was conducted to assess publication biasvia Stata 14 software. Results: Twenty-four RCTs with 2246 patients were included in this review. Compared with blankcontrol, placebo or western medicine alone, WXKL alone or combined with western medicine could effectively reducerapid ventricular rate (MD=-7.14, 95％CI:-8.42——5.87), the frequency and duration of AF. It could also shorten thesinus rhythm conversion time (MD=-3.04, 95％CI:-3.47——2.61), increase the sinus rhythm conversion rate (RR=1.19, 95％ CI: 1.09～1.29) and decrease recurrence rate of AF (RR=0.28, 95％ CI: 0.13-0.59) . Besides, WXKL alone orcombined with western medicine was beneficial for improving the left ventricular ejection fraction (LVEF) (MD=3.44, 95％ CI: 0.87-6.01), left ventricular end diastolic diameter (LVEDD) (MD=-2.47, 95％ CI:-2.86——2.08), left atrialdiameter (LAd) (MD=-0.91, 95％CI:-1.58——0.25) and P wave dispersion (Pd) (MD=-4.04, 95％CI:-4.15——3.93) .WXKL combined with low-dose amiodarone was superior to conventional-dose amiodarone alone in improving themaximum P wave (Pmax) (MD=-8.25, 95％ CI:-10.33——6.17), and WXKL combined with conventional-doseamiodarone is more effective (MD=-13.10, 95％CI:-13.65——12.55) . Compared with the control group, the treatmentgroup had fewer adverse reactions, and the Begg.s test did not find any publication bias. Conclusion: WXKL alone orcombined with western medicine exhibited better therapeutic effects in the treatment of AF, but these results still needhigh-quality evidence to verify.

The research outputs from 2010 to 2014 in clinical medicine of the top 10 universities announced by the Academic Degrees Center under Education Ministry of China in 2012 were analyzed and assessed according to the index system for assessment of research outputs in clinical medicine we established on the basis of bibliometrics.

This paper summed up the medical professionalism as taking patients'interests first , reshaping the medical good faith , improving business ability and promoting social justice .Also proposed that in order to have rea-sonable human resource allocation , ensure the construction of rural health personnel team and stability , the follow-ings are necessary:medical staff at villages and towns setting up the medical ethics , strengthening the altruism spir-it;changing the traditional model of the doctor -patient relationship , adhering to the principle of patient autonomy;cultivating professional sense of responsibility , building moral education;intensive training and striving to improve the level of medical technology;increasing the doctor -patient communication , restoring patients'interests first , re-shaping medical doctor -patient trust integrity , improving business ability and promoting social justice as well as fully exerting the social , moral and cultural supporting factors etc .