1.Dissecting antibody-mediated natural killer cell effects reveals a cytotoxic CX3CR1+KLRC2–CD16hi subset linked to hepatitis B virus outcomes
Libo TANG ; Yuhao WANG ; Zihan JIN ; Yurong GU ; Zhaofeng ZENG ; Linnan SONG ; Xuan YI ; Lingtao ZHANG ; Yujing ZHANG ; Weiying HE ; Liping WANG ; Weixin HE ; Jianru SUN ; Xiaoqin LAN ; Xiangyong LI ; Shihong ZHONG ; Yongyin LI
Clinical and Molecular Hepatology 2026;32(2):683-705
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.
2.Mid-and-long clinical outcomes of Dynesys dynamic internal fixation combined with decompression for the treatment of lumbar degenerative diseases
Yong HU ; Jianbin ZHONG ; Zhenshan YUAN ; Weixin DONG ; Quanliang TIAN ; Xiaoyang SUN ; Oujie LAI ; Bingke ZHU ; Kailun ZHANG
Chinese Journal of Orthopaedics 2021;41(17):1188-1197
Objective:To evaluate the medium and long-term clinical efficacy of the treatment of lumbar degenerative diseases in Dynesys dynamic internal fixation combined with decompression.Methods:From March 2008 to March 2015, 145 patients (84 males and 61 females, mean age 55.9±7.1 years old) with symptoms of lumbar degenerative diseases (69 lumbar disc herniation, 53 lumbar spinal stenosis and 23 I grade lumbar degenerative spondylolisthesis) were treated by the lumbar discectomy using Dynesys dynamic internal fixation combined with decompression. The clinical symptoms before and after surgery were assessed by visual analogue scale (VAS), Japanese Orthopaedic Association (JOA) and Oswestry disability index (ODI). Lumbar lateral radiographs were used to measure the height of intervertebral space between the surgical segment and the adjacent segment. The range of motion (ROM) between the surgical segment and the adjacent segment was measured by lumbar dynamic position X-ray. Surgical and adjacent segments degenerative were classified according to the Pfirrmann grade classification.Results:The VAS score, ODI and JOA score of lower back and lower limbs in patients with lumbar disc herniation were improved from 6.6±1.7, 7.1±1.4, 63.1%±10.2%, 12.5±2.4 preoperatively to 2.6±1.0, 2.8±0.9, 30.9%±9.8%, 22.4±2.1 at the latest follow-up. The differences were statistically significant. The VAS score, ODI score and JOA score of lower back and lower limbs in patients with lumbar spinal stenosis were improved from 6.3±2.2, 6.9±1.3, 63.4%±8.5%, 12.8±2.7 preoperatively to 2.4±1.2, 2.8±1.0, 35.1%±12.0%, 22.2±2.2 at the latest follow-up. The differences were statistically significant. The VAS score, ODI score and JOA score of lower back and lower limbs in patients with I degree lumbar degenerative spondylolisthesis were improved from 5.7±2.3, 6.7±0.9, 65.7%±10.0%, 12.5±2.7 preoperatively to 2.2±1.2, 2.7±1.1, 37.0%±11.8%, 22.4±2.6 at the latest follow-up. The differences were statistically significant. Comparing to preoperational value, the height of the operative segment and caudal intervertebral space were decreased at the 1 year postoperatively and last follow-up. But the difference was not significant. As for cranial adjacent segment, the height of intervertebral space preoperatively was decreased from 12.1±1.9 mm preoperatively to 11.7±1.6 mm at 1 year postoperatively, and to 11.3±1.8 mm at the latest follow-up. The difference between them was statistically significant ( F=6.46, P=0.001). The ROM of surgical segments was decreased from 7.6°±2.2° preoperatively to 5.5°±1.6° at 1 year postoperatively, and to 2.9°±1.4° at the latest follow-up. The difference between them was statistically significant ( F=267.9, P<0.001). Conversely, the ROM of cranial and caudal segments was increased from 8.2°±2.4°, 6.5°±1.6° preoperatively to 9.1°±2.1°, 7.1°±1.9° at 1 year postoperatively, and to 10.6°±2.5°, 7.2°±1.8° at the latest follow-up. The difference between them was statistically significant ( F=38.66, 3.81, P<0.001, 0.023). At the latest follow-up, 120 (51.9%) adjacent segments were to be defined adjacent segment degeneration which includes 103 radiological adjacent segment degeneration and 17 symptomatic adjacent segment degenerations. Conclusion:Dynesys dynamic internal fixation combined with decompression could achieve satisfying mid- and long-term therapeutic effect in the treatment of lumbar degenerative diseases. The ROM of surgical segments decreased with time, although part of the ROM was still retained at the latest follow-up. However, it does not seem to avoid the degeneration of adjacent segment.
3.Role of HSP70 in ozone preconditioning-induced reduction of hepatic ischemia-reperfusion injury in rats
Weixin ZHONG ; Lianghui LI ; Lanlan WANG ; Wenhua CHEN
Chinese Journal of Anesthesiology 2018;38(4):493-496
Objective To evaluate the role of heat shock protein 70 (HSP70) in ozone preconditioning-induced reduction of hepatic ischemia-reperfusion (I/R) injury in rats.Methods Twenty-four pathogen-free healthy male Sprague-Dawley rats,aged 8 weeks,weighing 250-300 g,were divided into 4 groups (n=6 each) using a random number table:sham operation group (group S),group I/R,ozone preconditioning group (group OP) and HSP70 inhibitor quercetin group (group Q).Hepatic I/R injury was induced by clamping the branches of hepatic artery supplying left and middle lobes of the liver,portal vein and bile vessel for 45 min,followed by 2 h of reperfusion.In group OP,the mixture of ozone and oxygen was intraperitoneally injected at the concentration of ozone 50 μg/ml and bolus dose 1 mg/kg once a day for 5 consecutive days before operation.In group Q,quercetin 7 mg/kg was intraperitoneally injected at 1 h before injecting the mixture of ozone and oxygen.Blood samples from the abdominal aorta were collected at 2 h of reperfusion for determination of serum alanine transaminase (ALT) and aspartate transaminase (AST) activities and concentrations of interleukin-1beta (IL-1β),IL-6 and tumor necrosis factor-alpha (TNF-α) in serum (by enzyme-linked immunosorbent assay).The animals were sacrificed after blood sampling,and hepatic tissue specimens were collected for detection of activated caspase-3 expression (by Western blot) and cell apoptosis (by TUNEL).Apoptotic index (AI) was calculated.Results Compared with group S,the serum ALT and AST activities,concentrations of IL-1β,IL-6 and TNF-α in serum and AI were significantly increased,and the expression of activated caspase-3 was up-regulated in group I/R (P<0.05 or 0.01).Compared with group I/R,the serum ALT and AST activities,concentrations of IL-1β,IL-6 and TNF-α in serum and AI were significantly decreased,and the expression of activated caspase-3 was downregulated in group OP (P<0.05 or 0.01).Compared with group OP,the serum ALT and AST activities,concentrations of IL-1β,IL-6 and TNF-α in serum and AI were significantly increased,and the expression of activated caspase-3 was up-regulated in group Q (P<0.05 or 0.01).Conclusion The mechanism by which ozone preconditioning reduces hepatic I/R injury is related to activating HSP70 and inhibiting inflammatory responses and cell apoptosis in rats.
4.The curative effect and safety of collagen sponge with different pH and content of protein implanted into orthopedic bone defect.
Gang TONG ; Jing LEI ; Cuihong ZHONG ; Weixin CAI ; Xuewei LIN
Journal of Biomedical Engineering 2012;29(6):1125-1130
This paper presents a 3mm fracture model of radial bone of rabbits using operation method. The bone defect was treated with collagen sponge with different pH and different content. After the operation, the body temperature, blood routine measurement, serum antibody, X-ray examination and histological observation in each group were examined to evaluate and study the curative effect and safety of collagen sponge. Collagen sponge had a good result of safety, but there was slightly change in blood routine, serum antibody, and histological observation, etc, with the pH changing and different content of collagen. The results showed that there was no obvious influence of safety to tissues after treatment of the collagen sponge at different pH implanted into bone defect. Collagen sponge at lower pH could promote the healing of bone defect partly, while the safety of collagen sponge with lower content was better.
Animals
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Collagen Type I
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adverse effects
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chemistry
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therapeutic use
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Hydrogen-Ion Concentration
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Male
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Prostheses and Implants
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Proteins
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analysis
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Rabbits
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Radius Fractures
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surgery
5.Preoperative hepatic and regional arterial infusion chemotherapy in the prevention of liver metastasis after colorectai cancer surgery
Yunshi ZHONG ; Jianmin XU ; Weixin NIU ; Li REN ; Ye WEI ; Shixu LU ; Jianhua WANG ; Zhiping YAN ; Jiemin CHENG ; Sheng QIAN ; Xinyu QIN
Chinese Journal of General Surgery 2008;23(9):672-675
Objective To investigate the safety of preoperative hepatic and regional arterial infusion chemotherapy in the prevention of liver metastasis and improving survival after curative colorectal cancer resection.Methods Patients admitted from 2001 to 2007 with Stage Ⅱ or Stage Ⅲ colorectal cancer were randomly assigned to receive preoperative hepatic and regional arterial infusion chemotherapy (PHRAIC group,n=256)or surgery alone(control group,n=253).Toxity of liver,hematology,immunology and post-operative complication of PHRAIC and the control were evaluated.Results Grade Ⅲ hepatic toxity,leukemia,anemia and platelet decrease in PHRAIC group was 3.1%(8/256),5.5% (14/256),7.4%(19/256)and 6.6%(17/256).There were no grade Ⅳ toxities,and all the patients in PHRAIC group received surgery.Morbidity rate in PHRAIC and the control group was 9.8%(25/256)vs 8.3%(21/253)(X2=1.86,P>0.05).All patients were followed up,with mean follow up of 42±14 months until Oct 30.2007.For stage Ⅲ patients,5-year overall survival and liver metastasis rate were 81.0% in PHRAIc group vs.60.4% in control group(X2=5.15,P<0.05)and 18.9%(28/148)vs 27.3%(41/150)(X2=5.41,P<0.05),respectively.Conclusion Preoperative hepatic and regional arterial infusion chemotherapy 7 days before surgery was safe and could reduce liver metastasis and improve survival rate in patients with Stage Ⅲ colorectal cancer.
6.Balloon catheter dilation of esophageal caustic ingestion stenosis in children
Juming YU ; Guoping FAN ; Weixin ZHONG
Journal of Interventional Radiology 2001;0(05):-
Objective To evaluate the methods and effect of balloon catheter dilation of esophageal caustic ingestion stenosis in children. Methods We analysed 18 cases, including 10 cases of esophageal stenosis due to ingestion of sulphuric acid, 7 cases of esophageal stenosis caused by ingestion of sodium carbonate and the last one through ingestion of chemical materials include zinc sulphate. Barium esophagogram was taken before dilation for every patient and the balloon size varied from 4 mm?40 mm to 16 mm?40 mm or 20 mm?40 mm in diameter was selected for the procedure. Results 18 cases were all successful in dilation by balloon catheter, without esophageal perforation and other complications. The satisfactory results maintained from six months to thirty months with remarkable improvement clinicoly. Conclusions Balloon catheter dilation is a simple, safe and reliable method for the treatment of esophageal caustic ingestion stenosis in children, and should be recommended as the first choice.
7.Pharmacological Study on Yiqipingchuan Pills(Radix Ginseng,Cornu Cervi Pantotrichum,etc.)
Chinese Traditional Patent Medicine 1992;0(11):-
This experiment showed that Yiqipingchuan Pills possessed obvious treatment action of cough and asthma,and expectorant action.It could cause a striking increase in the immunity-organ weight and carbon-particle clearance of hypoimmune mice.It was also found that these pills could make the con- centration of serum-hydrocortisone rise and the Vitamin C content in suprarene lower remarkably.

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