Objective To establish an "human serum - porcine aortic endothelial cells (PAEC) - human platelets" in vitro model and explore the mechanism of xenotransplantation-related coagulation dysfunction mediated by immune complexes - platelet FcγRⅡa (CD32a) receptor. Methods Healthy human serum was co-incubated with PAEC to prepare the supernatant containing immune complexes, which was then used to stimulate healthy human platelets, or directly treated with the serum of xenogeneic liver transplant recipients. Flow cytometry was used to detect platelet activation markers CD62P and surface IgG binding levels, and the platelet adhesion function was evaluated by platelet-PAEC adhesion experiments. CD32a blocking antibody IV.3 and SYK blocker SKYIN 4 were used to clarify the signaling pathways. Results The supernatant from the co-incubation of healthy human serum and PAEC could significantly induce platelet activation and endothelial adhesion. The use of the serum from xenogeneic liver transplant recipients could also significantly induce platelet activation. Antibody IV.3 and SYK blocker SKYIN 4 could significantly inhibit these effects. Conclusions In xenotransplantation, the immune complexes formed by human serum antibodies and porcine endothelial antigens may induce abnormal platelet activation through the platelet CD32a receptor, which is an important mechanism of non-complement-dependent post-transplant coagulation dysfunction, providing a new target for the intervention of coagulation complications in xenotransplantation.

Azvudine and nirmatrelvir/ritonavir (Paxlovid) are recommended for COVID-19 treatment in China, but their safety and efficacy in the elderly population are not fully known. In this multicenter, retrospective, cohort study, we identified 5131 elderly hospitalized COVID-19 patients from 32,864 COVID-19 patients admitted to nine hospitals in Henan Province, China, from December 5, 2022, to January 31, 2023. The primary outcome was all-cause death, and the secondary outcome was composite disease progression. Propensity score matching (PSM) was performed to control for confounding factors, including demographics, vaccination status, comorbidities, and laboratory tests. After 2:1 PSM, 1786 elderly patients receiving azvudine and 893 elderly patients receiving Paxlovid were included. Kaplan-Meier and Cox regression analyses revealed that compared with Paxlovid group, azvudine could significantly reduce the risk of all-cause death (log-rank P = 0.002; HR: 0.71, 95% CI: 0.573-0.883, P = 0.002), but there was no difference in composite disease progression (log-rank P = 0.52; HR: 1.05, 95% CI: 0.877-1.260, P = 0.588). Four sensitivity analyses verified the robustness of above results. Subgroup analysis suggested that a greater benefit of azvudine over Paxlovid was observed in elderly patients with primary malignant tumors (P for interaction = 0.005, HR: 0.32, 95% CI: 0.18-0.57) compared to patients without primary malignant tumors. Safety analysis revealed that azvudine treatment had a lower incidence of adverse events and higher lymphocyte levels than Paxlovid treatment. In conclusion, azvudine treatment is not inferior to Paxlovid treatment in terms of all-cause death, composite disease progression and adverse events in elderly hospitalized COVID-19 patients.

Objective To construct the performance evaluation index system of specialist cooperation alliance in hos-pital-community in order to scientifically evaluate the effect of the construction of the specialist cooperation alliance.Methods By searching literature related to the construction of specialized league,sort out national and local policy documents,and the"structure-process-result"model was adopted to initially construct the index system.The ex-pert letter consultation form of the indicator system was formed through the discussion of the special group,two rounds of Delphi expert consultation were carried out to determine the evaluation indicator system,and the weight coefficient of each indicator was determined by the simultaneous application of analytic hierarchy process.Results The effective recovery rates of the two rounds of questionnaire were 84.62％and 100.00％,respectively.The positive de-gree of experts was high,and the average authority degree of experts was 0.864.The importance,operability,sen-sitivity Kendall's W coefficient and x2 test value of all indexes were P＜0.05.Finally,an evaluation index system covering 9 first-level indicators and 25 second-level indicators was established.Conclusion The constructed perfor-mance evaluation index is scientific and reliable.The practical application shows that it can be used as a tool to evalu-ate the effect of integrated,continuous and collaborative health service delivery in hospital-community.

Objective To analyze the current status of medical services in secondary and tertiary hospitals in Shandong Province based on DRG,and to provide effective support for the implementation strategies of bidirectional referral.Methods The DRG group was used to analyze 42.348 3 million cases from 75 secondary hospitals and 69 tertiary hospitals in Shandong Province from 2019 to 2023.Experts were organized to establish standards for bidirectional referral of diseases.Results(1)35 high-frequency DRG disease groups with diagnosis,treatment ability and medical resources in secondary hospitals were selected,(2)The medical expenses and medical quality in the high-frequency DRG disease groups within secondary hospitals were lower than those in tertiary hospitals,(3)To develop standardized referral standards and programs with esophageal cancer as an example.Conclusion It is urgent to triage patients gradually and accurately through disease classification management,and formulate disease diagnosis and treatment plans and bidirectional referral standards to improve the medical quality of secondary hospitals.

Objective To analyze the current status of medical services in secondary and tertiary hospitals in Shandong Province based on DRG,and to provide effective support for the implementation strategies of bidirectional referral.Methods The DRG group was used to analyze 42.348 3 million cases from 75 secondary hospitals and 69 tertiary hospitals in Shandong Province from 2019 to 2023.Experts were organized to establish standards for bidirectional referral of diseases.Results(1)35 high-frequency DRG disease groups with diagnosis,treatment ability and medical resources in secondary hospitals were selected,(2)The medical expenses and medical quality in the high-frequency DRG disease groups within secondary hospitals were lower than those in tertiary hospitals,(3)To develop standardized referral standards and programs with esophageal cancer as an example.Conclusion It is urgent to triage patients gradually and accurately through disease classification management,and formulate disease diagnosis and treatment plans and bidirectional referral standards to improve the medical quality of secondary hospitals.

Objective To construct the performance evaluation index system of specialist cooperation alliance in hos-pital-community in order to scientifically evaluate the effect of the construction of the specialist cooperation alliance.Methods By searching literature related to the construction of specialized league,sort out national and local policy documents,and the"structure-process-result"model was adopted to initially construct the index system.The ex-pert letter consultation form of the indicator system was formed through the discussion of the special group,two rounds of Delphi expert consultation were carried out to determine the evaluation indicator system,and the weight coefficient of each indicator was determined by the simultaneous application of analytic hierarchy process.Results The effective recovery rates of the two rounds of questionnaire were 84.62％and 100.00％,respectively.The positive de-gree of experts was high,and the average authority degree of experts was 0.864.The importance,operability,sen-sitivity Kendall's W coefficient and x2 test value of all indexes were P＜0.05.Finally,an evaluation index system covering 9 first-level indicators and 25 second-level indicators was established.Conclusion The constructed perfor-mance evaluation index is scientific and reliable.The practical application shows that it can be used as a tool to evalu-ate the effect of integrated,continuous and collaborative health service delivery in hospital-community.

Objective To explore the clinical efficacy of arthroscopy combined with cubital tunnel expansion and plasty in the treatment of patients with elbow osteoarthritis and cubital tunnel syndrome.Methods A total of 101 patients with elbow osteoarthritis and cubital tunnel syndrome who were admitted to the Department of Orthopedics,Cangzhou Hospital of Integrated TCM-WM Hebei from September 2020 to August 2023 were selected as the research subjects.According to different surgical methods,the patients were divided into an observation group(n=51)and a control group(n=50).The surgical method in the observation group was arthroscopy combined with cubital tunnel expansion and plasty,and the surgical method in the control group was conventional cubital tunnel expansion and plasty.The operation time,intraoperative blood loss,length of hospital stay,and complications were observed and recorded for both groups.The mayo elbow performance score(MEPS)was used to assess elbow function,the activities of daily living(ADL)scale was used to evaluate daily living ability,and the visual analogue scale(VAS)was used to assess pain levels preoperatively and at 6 months postoperatively.Elbow range of motion,including pronation,supination,and flexion-extension,was measured using a goniometer.Nerve recovery was evaluated by measuring compound muscle action potential(CMAP)of the abductor digiti minimi,ulnar nerve conduction velocity(NCV),and motor evoked potential latency(MEPLP)using a Keypoint electromyography device.Results The operation time and length of hospital stay in the observation group were significantly shorter than those in the control group,and the intraoperative blood loss and complications were significantly less than those in the control group(P＜0.05).Before operation,there were no statistically significant differences in MEPS scores,ADL scores and VAS scores between the observation group and the control group(P＞0.05);6 months after operation,the MEPS scores and ADL scores of patients in the observation group were signifi-cantly higher than those in the control group,and the VAS scores were significantly lower than those in the control group(P＜0.05).Before operation,there were no statistically significant differences in pronation,supination and flexion-extension between the observation group and the control group(P＞0.05);6 months after operation,the pronation,supination and flexion-extension of patients in the two groups were significantly higher than those before operation(P＜0.05),but there were no statistically significant differences in pronation,supination and flexion-extension between the observation group and the control group(P＞0.05).Before operation,there were no statistically significant differences in CMAP,NCV and MEPLP between the observation group and the control group(P＞0.05);6 months after operation,the CMAP and NCV of patients in the observation group were significantly higher than those in the control group,and the MEPLP ratio was significantly lower than that in the control group(P＜0.05).Conclusion Conventional cubital tunnel expansion and plasty and arthroscopy combined with cubital tunnel expansion and plasty can improve the range of motion of the elbow in patients with elbow osteoar-thritis and cubital tunnel syndrome,but the latter features less damage and faster recovery,is better in improving elbow function and daily living ability,reducing pain,and adjusting electromyographic examination indicators,and has fewer complications.

Objective:To explore clinical features, diagnosis, localization, and therapeutic strategy of migratory pharyngeal and cervical esophageal foreign bodies.Methods:A total 23 cases of pharyngeal and cervical esophageal migratory foreign bodies were admitted between January 2015 and December 2021. There were 14 females and 9 males with the age ranged from 35 to 82 (55.0±12.7)years. In all the cases, esophageal CT was taken to confirm the esophageal foreign body. Multiplanar reconstruction (MPR) was performed to locate the foreign body from the horizontal, coronal and sagittal dimensions as well as the corrected reconstructed MPR. According to the location of the foreign body, appropriate surgical method was selected.The symptoms, complications, types of foreign body, positioning, surgical methods, and relevant information were recorded.Data were analyzed using the descriptive method and SPSS 25.0 software.Results:The clinical symptoms of 23 migrating esophageal foreign bodies included pharyngodynia (20/23), foreign body sensation (6/23), hoarsenss (1/23), difficulty in turning neck(1/23), difficulty in opening mouth (1/23), fever (7/23), poor appetite (1/23), and abdominal pain (1/23). The foreign bodies included 19 fish bones, 2 wires, 1 embroidery needle and 1 chicken bone. There were 9 cases (39.1%) of foreign bodies located in extraluminal cervical esophagus, 2 cases (8.7%) of foreign bodies located in the muscular layer of the cervical esophagus and 12 cases (52.2%) of foreign bodies located in pharynx. Twenty-one cases of foreign bodies were removed by cervical lateral incision, in which 11 were removed by cervical lateral incision directly, 10 by the second lateral cervical incision after the foreign bodies were accurately located by MPR and/or corrected MPR, 1 foreign body was removed by incision of the pharyngeal mucosa under suspension laryngoscope, 1 foreign body was removed by tracheoscopy. Compared with patients with intraluminal foreign bodies ( n=308) treated in the same period, intake of fishbone [19 (19/23) vs. 133 (82.6% (43.2%, 133/308), OR=7.31] and first visit was more than 24 hours [20(87.0%, 20/23) vs. 77(25.0%, 77/308), OR=17.2] were the significant risk factors of migratory esophageal foreign bodies. Conclusions:MPR and the corrected MPR can accurately locate the migrating pharyngeal and cervical esophageal foreign bodies, by providing more intuitive imaging evidence for doctors, which provide imaging basis for formulation of surgical programs. Foreign bodies in pharyngeal and cervical esophagus need to be treated as soon as possible, otherwise they are easy to migrate, leading lead to serious complications.

Objective To observe the impacts of Xingnao Kaiqiao acupuncture(AC)method on synaptic plasticity and intestinal flora in stroke rats.Methods The middle cerebral artery occlusion method was applied to establish a rat model of ischemic stroke,and the rats with Zea Longa score of 1-3 were randomly grouped into model(M)group and AC group,and rats without middle cerebral artery occlusion were regarded as the sham(S)group,with 15 animals per group.After modeling,groups S and M were not intervened,and group AC was intervened with AC,once a day,for 7 consecutive days.The Zea Longa method was applied to assess neurological function;transmission electron microscopy(TEM)and Golgi staining were applied to visualize synaptic structures in the ischemic penumbra(IP);Western blot was applied to detect the protein expression of BDNF,SYN and GAP-43 in the IP cortex tissue;ELISA was applied to detect the content of IL-1β,TNF-α,IL-17 in the IP cortex tissue;16S rDNA amplification and sequencing method was applied to analyze the structure of rat intestinal flora.Results Compared with the S group,the M group had irregular synaptic morphology,blurred boundaries,thinned postsynaptic zona densities,higher neurological function scores,protein levels of BDNF,SYN,GAP-43 and content of IL-1β,TNF-α,IL-17(P<0.05),and lower density of spines(P<0.05).Compared with the M group,AC intervention could improve the synaptic morphology,reduce the neurological function score and content of IL-1β,TNF-α,IL-17(P<0.05),and increase the density of dendritic spines,BDNF,SYN,and GAP-43 protein levels(P<0.05).The intestinal flora analysis showed that compared with the S group,the M group had a reduced diversity and number of bacterial flora,at the phylum level,the M group had a lower relative abundance of Bacteroidetes,and higher F/B ratio(P<0.05);at the genus level,the group M had a higher relative abundances of Bacteroides and Rikenbacteria(P<0.05),and lower relative abundances of Lactobacillus and Lachnospiraceae_UCG-006(P<0.05).Compared with the M group,AC intervention could increase the diversity and quantity of the flora,increase the relative abundance of Bacteroidetes and reduce the F/B ratio at the phylum level(P<0.05),increase the relative abundances of Faecalibacterium and Lactobacillus and reduce the relative abundances of Riken,Escherichia-Shigella,etc.at the genus level(P<0.05).Conclusion Xingnao Kaiqiao acupuncture can restore the relative abundance of beneficial bacteria,reduce the relative abundance of harmful bacteria,attenuate brain inflammation,improve synaptic plasticity,and reduce neurological damage in stroke rats.

RNA modifications affect many biological processes and physiological diseases. The 5-methylcytosine (m⁵C) modification regulates the progression of multiple tumors. However, its characteristics and functions in hepatocellular carcinoma (HCC) remain largely unknown. Here, we found that HCC tissues had a higher m⁵C methylation level than the adjacent normal tissues. Transcriptome analysis revealed that the hypermethylated genes mainly participated in the phosphokinase signaling pathways, such as the Ras and PI3K-Akt pathways. The m⁵C methyltransferase NSUN2 was highly expressed in HCC tissues. Interestingly, the expression of many genes was positively correlated with the expression of NSUN2, including GRB2, RNF115, AATF, ADAM15, RTN3, and HDGF. Real-time PCR assays further revealed that the expression of the mRNAs of GRB2, RNF115, and AATF decreased significantly with the down-regulation of NSUN2 expression in HCC cells. Furthermore, NSUN2 could regulate the cellular sensitivity of HCC cells to sorafenib via modulating the Ras signaling pathway. Moreover, knocking down NSUN2 caused cell cycle arrest. Taken together, our study demonstrates the vital role of NSUN2 in the progression of HCC.
Humans ; ADAM Proteins ; Apoptosis Regulatory Proteins ; Carcinoma, Hepatocellular/metabolism* ; Liver Neoplasms/metabolism* ; Membrane Proteins ; Methyltransferases/metabolism* ; Phosphatidylinositol 3-Kinases/metabolism* ; Repressor Proteins ; RNA, Messenger/metabolism* ; Sorafenib ; RNA Methylation/genetics*