ObjectiveTo investigate the therapeutic effects and mechanisms of Qinlian Hongqutang （QLHQT） on nonalcoholic steatohepatitis （NASH）. MethodsC57BL/6J mice were randomly divided into normal and modeling groups. The NASH model was established by feeding a high-fat diet for 12 weeks. After successful modeling， mice were randomly assigned to the model group， low-， medium-， and high-dose QLHQT groups （0.51， 1.02， and 2.04 g·kg^-1）， and a positive control metformin group， with six mice in each group. The mice were treated for 8 weeks. Body weight was recorded before and after treatment. Serum levels of total cholesterol （TC）， triglycerides （TG）， and low-density lipoprotein cholesterol （LDL-C）， as well as hepatic TC， TG， and LDL-C contents， were determined by biochemical assays. Hematoxylin-eosin （HE） staining and oil red O staining were used to evaluate liver histopathology and lipid deposition， respectively. Flow cytometry， enzyme-linked immunosorbent assay （ELISA）， and Real-time polymerase chain reaction （Real-time PCR） were used to assess hepatic macrophage expression and related markers. Western blot and immunofluorescence were used to investigate the potential mechanisms of QLHQT in regulating macrophage polarization. ResultsCompared with the normal group， body weight and serum and hepatic levels of TC， TG， and LDL-C were significantly increased in the model group （P<0.01）. Liver histopathology showed unevenly distributed round lipid droplets in the hepatocyte cytoplasm， accompanied by inflammatory cell aggregation. Flow cytometry showed that the proportion of CD86-positive cells was significantly increased， whereas the proportion of CD206-positive cells was markedly decreased （P<0.05）. Hepatic inducible nitric oxide synthase （iNOS） levels and tumor necrosis factor-α （TNF-α） mRNA expression were significantly increased， while hepatic IL-10 levels and IL-4 mRNA expression were significantly decreased （P<0.01）. The protein expression levels of Toll-like receptor 4 （TLR4）， tumor necrosis factor receptor-associated factor 6 （TRAF6）， and myeloid differentiation factor 88 （MyD88） in the liver were significantly increased （P<0.01）. Compared with the model group， body weight was reduced in the high-， medium-， and low-dose QLHQT groups and in the metformin group. Serum and hepatic TC， TG， and LDL-C levels were significantly decreased （P<0.01）. Liver histopathology showed alleviated hepatic lipid deposition， with markedly reduced lipid droplets and inflammation. Immunofluorescence and flow cytometry showed that the proportions of CD86-positive cells were significantly decreased， whereas the proportions of CD206-positive cells were significantly increased in the high-， medium-， and low-dose QLHQT groups （P<0.05）. Hepatic iNOS levels and TNF-α mRNA expression were significantly decreased （P<0.01）， whereas hepatic IL-10 levels and IL-4 mRNA expression were significantly increased （P<0.01）. The hepatic protein expression levels of TLR4， TRAF6， and MyD88 were significantly decreased， while signal transducer and activator of transcription 6 （STAT6） phosphorylation was significantly increased （P<0.05， P<0.01）. There was no statistically significant difference in total STAT6 protein expression. ConclusionQLHQT effectively ameliorates hepatic inflammation in NASH mice， and the mechanism may involve STAT6- and TLR4-mediated signaling pathways driving polarization of M1 macrophages toward the M2 phenotype.

ObjectiveTo investigate the therapeutic effects and mechanisms of Qinlian Hongqutang （QLHQT） on nonalcoholic steatohepatitis （NASH）. MethodsC57BL/6J mice were randomly divided into normal and modeling groups. The NASH model was established by feeding a high-fat diet for 12 weeks. After successful modeling， mice were randomly assigned to the model group， low-， medium-， and high-dose QLHQT groups （0.51， 1.02， and 2.04 g·kg^-1）， and a positive control metformin group， with six mice in each group. The mice were treated for 8 weeks. Body weight was recorded before and after treatment. Serum levels of total cholesterol （TC）， triglycerides （TG）， and low-density lipoprotein cholesterol （LDL-C）， as well as hepatic TC， TG， and LDL-C contents， were determined by biochemical assays. Hematoxylin-eosin （HE） staining and oil red O staining were used to evaluate liver histopathology and lipid deposition， respectively. Flow cytometry， enzyme-linked immunosorbent assay （ELISA）， and Real-time polymerase chain reaction （Real-time PCR） were used to assess hepatic macrophage expression and related markers. Western blot and immunofluorescence were used to investigate the potential mechanisms of QLHQT in regulating macrophage polarization. ResultsCompared with the normal group， body weight and serum and hepatic levels of TC， TG， and LDL-C were significantly increased in the model group （P<0.01）. Liver histopathology showed unevenly distributed round lipid droplets in the hepatocyte cytoplasm， accompanied by inflammatory cell aggregation. Flow cytometry showed that the proportion of CD86-positive cells was significantly increased， whereas the proportion of CD206-positive cells was markedly decreased （P<0.05）. Hepatic inducible nitric oxide synthase （iNOS） levels and tumor necrosis factor-α （TNF-α） mRNA expression were significantly increased， while hepatic IL-10 levels and IL-4 mRNA expression were significantly decreased （P<0.01）. The protein expression levels of Toll-like receptor 4 （TLR4）， tumor necrosis factor receptor-associated factor 6 （TRAF6）， and myeloid differentiation factor 88 （MyD88） in the liver were significantly increased （P<0.01）. Compared with the model group， body weight was reduced in the high-， medium-， and low-dose QLHQT groups and in the metformin group. Serum and hepatic TC， TG， and LDL-C levels were significantly decreased （P<0.01）. Liver histopathology showed alleviated hepatic lipid deposition， with markedly reduced lipid droplets and inflammation. Immunofluorescence and flow cytometry showed that the proportions of CD86-positive cells were significantly decreased， whereas the proportions of CD206-positive cells were significantly increased in the high-， medium-， and low-dose QLHQT groups （P<0.05）. Hepatic iNOS levels and TNF-α mRNA expression were significantly decreased （P<0.01）， whereas hepatic IL-10 levels and IL-4 mRNA expression were significantly increased （P<0.01）. The hepatic protein expression levels of TLR4， TRAF6， and MyD88 were significantly decreased， while signal transducer and activator of transcription 6 （STAT6） phosphorylation was significantly increased （P<0.05， P<0.01）. There was no statistically significant difference in total STAT6 protein expression. ConclusionQLHQT effectively ameliorates hepatic inflammation in NASH mice， and the mechanism may involve STAT6- and TLR4-mediated signaling pathways driving polarization of M1 macrophages toward the M2 phenotype.

BACKGROUND: The primary limitation to kidney transplantation is organ shortage. Recent progress in gene editing and immunosuppressive regimens has made xenotransplantation with porcine organs a possibility. However, evidence in pig-to-human xenotransplantation remains scarce, and antibody-mediated rejection (AMR) is a major obstacle to clinical applications of xenotransplantation. METHODS: We conducted a kidney xenotransplantation in a brain-dead human recipient using a porcine kidney with five gene edits (5GE) on March 25, 2024 at Xijing Hospital, China. Clinical-grade immunosuppressive regimens were employed, and the observation period lasted 22 days. We collected and analyzed the xenograft function, ultrasound findings, sequential protocol biopsies, and immune surveillance of the recipient during the observation. RESULTS: The combination of 5GE in the porcine kidney and clinical-grade immunosuppressive regimens prevented hyperacute rejection. The xenograft kidney underwent delayed graft function in the first week, but urine output increased later and the single xenograft kidney maintained electrolyte and pH homeostasis from postoperative day (POD) 12 to 19. We observed AMR at 24 h post-transplantation, due to the presence of pre-existing anti-porcine antibodies and cytotoxicity before transplantation; this AMR persisted throughout the observation period. Plasma exchange and intravenous immunoglobulin treatment mitigated the AMR. We observed activation of latent porcine cytomegalovirus toward the end of the study, which might have contributed to coagulation disorder in the recipient. CONCLUSIONS 5GE and clinical-grade immunosuppressive regimens were sufficient to prevent hyperacute rejection during pig-to-human kidney xenotransplantation. Pre-existing anti-porcine antibodies predisposed the xenograft to AMR. Plasma exchange and intravenous immunoglobulin were safe and effective in the treatment of AMR after kidney xenotransplantation.
Transplantation, Heterologous/methods* ; Kidney Transplantation/methods* ; Heterografts/pathology* ; Immunoglobulins, Intravenous/administration & dosage* ; Graft Survival/immunology* ; Humans ; Animals ; Sus scrofa ; Graft Rejection/prevention & control* ; Kidney/pathology* ; Gene Editing ; Species Specificity ; Immunosuppression Therapy/methods* ; Plasma Exchange ; Brain Death ; Biopsy ; Male ; Aged

Objective:To clarify the changes in incidence and mortality of various cancers based on analysis on registration data of malignant tumor incidence and mortality from Dehui City and Yanji City in Jilin Province.Methods:The incidence and mortality data of malignant tumors from 2009 to 2016 in Dehui City and Yanji City in Jilin Province,were collected from the Chinese Cancer Registry Annual Report published by the National Cancer Center.The number of cases,deaths,crude incidence rate,crude mortality rate,age-standardized incidence rate(ASIR),age-standardized mortality rate(ASMR),and annual percentage change(APC)of the malignant tumors were analyzed by cancer sites and genders.Results:From 2009 to 2016,the CIR of malignant tumors in Dehui City(APC=1.2%,P=0.019)and Yanji City(APC=3.6%,P=0.058)showed an increasing trend.After standard population age adjustment,the ASIR in males in Dehui City showed a significant decline(APC=-5.7%,P=0.021),while the ASIR in females exhibited an overall downward trend,but the difference was not significant(APC=-2.2%,P=0.111).In Yanji City,the ASIR in males(APC=-1.4%,P=0.535)and females(APC=0.0%,P=0.988)showed no significant changes.The CMR of malignant tumors in Dehui City(APC=1.9%,P=0.001)and Yanji City(APC=5.9%,P=0.001)showed a continuous upward trend.After age-standardization,the ASMR in males(APC=-3.1%,P=0.100)and females(APC=-4.2%,P=0.053)in Dehui City,as well as in males(APC=-1.3%,P=0.438)in Yanji City,showed a slight downward trend.Although the ASMR in females in Yanji City showed a slight increase,the difference was not statistically significant(APC=0.5%,P=0.838).In 2016,the most common malignant tumor in terms of both incidence and mortality in Dehui City was lung cancer,with a CIR of 60.76/100 000 and a CMR of 46.96/100 000.In Yanji City,the most common malignant tumor was liver cancer,with a CIR of 49.04/100 000 and a CMR of 51.09/100 000.Conclusion:Lung cancer,liver cancer,and gastric cancer are the major malignant tumors threatening residents in Dehui City,Yanji City,and even the entire Jilin Province,and should be prioritized in cancer prevention and control efforts.Early diagnosis and treatment should be strengthened.

Objective:To explore the influence of static mechanical strain(SMS)on the osteoclastogenic gene expression of healthy periodontal ligment stem cells(HPDLSCs)and periodontitis periodontal ligment stem cells(PPDLSCs).Methods:HPDLSCs and PP-DLSCs were respectively isolated and cultured by low density in vitro.The expression of mesenchymal stem cell markers were detected by flow cytometry.Then,6％,8％,10％,12％and 14％SMS were respectively loaded to the HPDLSCs and PPDLSCs by Flexcell Tension Unit,and the expression of RANKL and C-fos was detected by real time RT-PCR.Results:Both HPDLSCs and PPDLSCs strongly expressed the mesenchymal stem cell markers STRO-1,CD146,CD90 and CD29,and higher expression of the above markers was found in HPDLSCs compared with PPDLSCs(P＜0.05).The expression of RANKL and C-fos in PPDLSCs was more obvious than that in HPDLSCs without SMS loading(P＜0.05).For HPDLSCs,the SMS of 14％induced significant up-regulation of RANKL and C-fos(P＜0.05),while no alteration was confirmed for the above osteoclastogenic genes when the SMS≤ 12％(P＞O.05).In addition,the expression of RANKL and C-fos was up-regulated significantly in PPDLSCs when the SMS≥ 10％(P＜0.05),and the expression of the above genes was not activated when the SMS ≤8％.Conclusion:HPDLSCs and PPDLSCs response differently to SMS,and ex-cessive SMS may lead to enhanced expression of osteoclastogenic genes in PPDLSCs.

Objective:To comprehensively search the relevant literature on prone position-cardiopulmonary resuscitation (PP-CPR) in adults at home and abroad, analyze the content, summarize the evidence, and provide reference for clinical health care professionals.Methods:Systematic search of CNKI, China Biomedical Literature Service System (SinoMed), Wanfang Data, VIP database, PubMed, Embase, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Cochran Library, Web of Science, Scopus literature database and other Chinese and English databases was conducted. The search period was from inception to June 15 in 2024. The contents of PP-CPR from randomized controlled trial (RCT), non-RCT (prospective or retrospective), cohort studies and case reports were extracted and systematically analyzed. The search results were standardized by the method of scoping review.Results:A total of 523 articles were obtained through preliminary search, and 14 references and gray literature were retrieved, totaling 537 articles. After strict screening by two researchers, a total of 26 literatures were included, 3 were non-RCT and 23 were case reports, involving 12 countries, including 3 in Chinese, 19 in English, 2 in French, 1 in German, and 1 in Korean. Three non-RCT demonstrated that compared with standard cardiopulmonary resuscitation (CPR), PP-CPR could produce higher pressure, and provide good respiratory and circulatory support. A total of 25 adult patients were included in the 23 case reports, of which 17 reported total recovery time and 13 reported PP-CPR time ≤ 5 minutes, all of which recovered spontaneous circulation, indicating the effectiveness of PP-CPR technology. In terms of final outcome, 4 patients (16.0%) died and 21 patients (84.0%) survived, indicating that PP-CPR technology could provide timely blood circulation and improve clinical outcomes for prone cardiac arrest patients. Among the 11 patients who reported complications after resuscitation, no neurological damage was found in the short-term outcomes, indicating that PP-CPR technology had a certain level of safety.Conclusions:PP-CPR can provide timely blood circulation for patients with cardiac arrest who are unable to lie supine quickly, and win "golden time" for defibrillation and further treatment. In clinical practice, medical staff need to evaluate the emergency environment, the number of rescuers and the specific condition of the patient, and implement first aid as soon as possible, so as to reduce the time of no blood flow in the vital organs of patients with cardiac arrest in prone position, and improve the clinical prognosis.

Objective: To observe the effects of Chinese herbalprescription Tizhi-Pingtiao Powder (TP) based on Five-Yun Six-Qi theory to treat hyperlipidemia (HLP). Methods: This study included 641 HLP patients from Constitution medicine clinic in Dongzhimen hospital from January 2015 to November 2017. The embryonic period’s (ten months) Five-Yun Six-Qi endowments of the enrolled patients were analyzed and TP were prescribedaccordingly, in the absent of lipid-lowering drugs. The curative effect was observed after three months’ TP treatment and reviewed ofeach 3 months, and long-term effects will be observed for 1 year,either take the priscription or not. Curative effect is based on blood lipids maintain normal as well as constitution improved while stopped lipid-lowering drugs. Results: Among the 641 patients who met the inclusion criteria, 379 patients take on complete, and 300 patients (79.2%) were clinically cured (with blood lipid decreased to normal, overall constitution and complication condition improved), 375 patients (99.0%) were completely cured. Among 262 patients without dietary restriction, 143 patients (54.6%) were clinically cured, 240 patients (91.6%) were completely cured. Long-term effects showed that 210 patients stopped the TP after 3 months' treatment, the recurrence rate at the end of the 3rd month, 6th month and 12th month in the patients who were on complete dietary restriction were 4.1%, 48.8% and 76.9%, while the recurrence rate in the patients who had not implemented dietary restriction were 37.1%, 70.8%, 89.9%. A total of 115 patients continued the TP for the other 12 months, the recurrence rate at the end of 3rd month, 6th month and 12th month in the patients who were on complete dietary restriction were 2.5%, 4.8% and 6.0%, while the recurrence rate in the patients who had not implemented dietary restriction were 6.5%, 16.1%, 29.0%. The difference between the four groups was significant. All recrudescent patients could gain recovery in a month after re-taking the herbs. Conclusions Chinese herbal priscription TP combined with dietary modification showed long term effect for HLP and improve the constitution comprehensively.

Objective To observe the effects of dexmedetomidine hydrochloride on the cisatracurium-induced neuromuscular blockade in geriatric, young and middle-aged patients. Methods Forty elderly patients and forty young and middle-aged patients undergoing elective abdominal surgery under general anesthesia were randomly divided into 4 groups ( n=20 each):elderly dexmedetomidine hydrochloride group (group DE),elderly control group (group CE),young and middle-aged dexmedetomidine group (group DY) and young and middle-aged control group (group CY).In groups DE and DY,a loading dose of 0.5 μg?kg-1 dexmedetomidine was intravenously infused over 10 min before induction of anesthesia,respectively,followed by infusion at a rate of 0.4μg?kg-1?h-1 until the end of surgery.Equal volume of 0.9% sodium chloride was given in groups CE and CY.Anesthesia was induced with midazolam,fentanyl,propofol and cisatracurium 0.15 mg?kg-1.Four groups were maintained with infusion of propofol and remifentanil. Neuromuscular blockade was maintained with continuous cisatracurium infusion in the four groups and was monitored with TOF-Watch SX acceleromyography at the adductor pollicis.The onset time,TOF no reaction period,duration of action,the amount of cisatracurium consumption,and the spontaneous recovery index ( T1 25% to 75%) were recorded. Results The four groups were comparable in the demographic data.Intubation conditions,the onset time and recovery index were not significantly different among the four groups. The duration of blockade action in groups DE and DY was ( 61. 1 ± 8.9) min and (53.6±9.3) min,which was significantly longer than that in group CE [(49.9±5.8) min] and group CY [(44.8± 6.4) min] (P<0.01).The duration of blockade action was significantly longer in groups DE and CE than in groups DY and CY (P<0.05).The amount of cisatracurium consumption in groups CE and CY was significantly higher than that in groups DE and DY (P<0.05). Conclusion The neuromuscular blockade is longer and the requirement of cisatracurium is less in elderly patients than in young and middle-aged patients.Continuous infusion of dexmedetomidine hydrochloride can't accelerate the onset time of cisatracurium.But duration of action is prolonged and the amount of cisatracurium consumption is lower in patients with infusion of dexmedetomidine hydrochloride.

Objective To investigate the condition of exercise, medicine compliance and the rehabilitation of patients with arteriosclerosis obliterans (ASO) in lower extremity after the surgery, and also to study the influence of self-efficiency and social support to their rehabilitation. Methods The questionnaire survey was performed in 102 patients who had surgical or interventional therapy of arteriosclerosis obliterans in the lower extremity in our hospital, investigated the general information of the patients, their knowledge of postoperative rehabilitation, medicine compliance, exercise condition, general self-efficiency and social support. Results The postoperative time for the patients with arteriosclerosis obliterans was 2 to 22months, the knowledge rate for postoperative rehabilitation was 7.8%-46.1%.The Morisky score for the patients of taking medicine for the treatment of vascular disease was 2.0,and there was only 6 patients(5.9%)with good medicine compliance. There were 22 patients(21.0%) had completed the ambulation training according to the guidelines, and there were 25 patients(24.5%) had completed the Buerger training. The self-efficiency score of the patients was 2.78 ± 0.76, and the gross score of social support was 32.38 ± 7.89. Spearman correlation analysis shows that the Morisky score for the patients of taking medicine for the treatment of vascular disease was in positive correlation with self-efficiency (r=0.289, P=0.003), but in negative correlation with social support (r=–0.286, P=0.006). Conclusions Most of the patients with arteriosclerosis obliterans have poor medicine compliance, and do not do exercise as required by the guidelines. Patients with high self-efficiency demonstrates medicine noncompliance, however the enhancement of social support will help patients improve their medicine compliance.

Anaplasma capra, an emerged tick?borne agent, maintained its natural cycles via ticks and host reserviors. To survey for A. capra infection in Haemaphysalis longicornis in North China, a total of 311 H. longicornis ( 95 adults, 156 nymphs, 60 larvae) were collected in Beijing during May to Sept. in 2012 and 2015. A. capra was identified from 3 adults (3?2%) when amplified by PCR targeting gltA gene and rrs (16S rRNA). No infection was found in the nymphs and larvae. Phylogenetic analyses revealed that the partial gltA and 16S rRNA sequences obtained in the ticks are identical to A. capra harvseted from Mudanjiang′s patients in 2014. The finding of A. capra in ticks in North China indicates the natural foci may exist in North China and it is urgent and necessary to prevent and control the emerged tick borne disease in this area.