Objective To investigate the mechanism by which lectin-like oxidized low density lipoprotein receptor-1(LOX-1)regulates hyperglycemic-induced myocardial fibroblast(CFs)fibrosis through the glycogen synthase kinase-3β(GSK-3β)/signal transducer and activator of transcription 3(STAT3)pathway.Methods CFs were isolated,cultured and identified.LOX-1 RNAi lentiviral vector was constructed and infected CFs.The experimental groups were as follows:Normal control(NC)group,High glucose(HG)group,LV-LOX-1,LV-Con group,Hypertonic(HPG)group.After LV-LOX-1 and LV-Con were infected with CFs,adding 25 mmol/L glucose to culture CFs for 24 h,they were denoted as HG+LV-LOX-1 group and HG+LV-Con group.Cells in HG+LV-LOX-1 group and HG+LV-Con group were treated with 10 μ mol/L SB216763 and 10 μ mol/L STATTIC for 24 h,respectively,and then they were recorded as HG+LV-LOX-1+SB216763 group,HG+LV-Con+SB216763 group,HG+LV-LOX-1+STATTIC group and HG+LV-Con+STATTIC group.CCK-8 was used to detect the activity of CFs,and the expression levels of mRAN and protein of LOX-1,collagen type I(COL-I),thioredoxin 5(TXNDC5),GSK-3β,STAT3,p-GSK-3β and p-STAT3 were detected by qRT-PCR and Western blot.Results CFs infected with LOX-1 RNAi lentiviral vector were obtained,which showed green under fluorescence microscopy.Compared with HG and HG+LV-Con groups,the mRNA expressions of LOX-1,COL-I and TXNDC5 were decreased in HG+LV-LOX-1 group(P<0.05).Compared with HG+LV-LOX-1 group,mRNA expressions of COL-I and TXNDC5 were decreased in HG+LV-LOX-1+SB216763 and HG+LV-LOX-1+STATTIC groups(P<0.05).Compared with HG and HG+LV-Con groups,p-GSK-3β protein expression was increased in HG+LV-LOX-1 group(P<0.05),while LOX-1,p-STAT3,COL-I,TXNDC5 protein expression was decreased in HG+LV-LOX-1 group(P<0.05).Compared with HG+LV-LOX-1 group,p-GSK-3β protein expression was increased in HG+LV-LOX-1+SB216763 group(P<0.05),while the protein expressions of p-STAT3,COL-I and TXNDC5 were decreased in HG+LV-LOX-1+SB216763 and HG+LV-LOX-1+STATTIC groups(P<0.05).Conclusion LOX-1,GSK-3β,STAT3,TXNDC5,and COL-I are involved in high glucose induced CFs fibrosis.LOX-1 promotes the expression of TXNDC5 and COL-I through GSK-3β/STAT3 pathway,and inhibition of LOX-1 can inhibit high glucose induced CFs fibrosis.

Objective:To investigate the current situation and organizational management policies of government procurement in public hospitals,and to improve the level of standardized management of government procurement.Methods:An electronic questionnaire survey was conducted to investigate the current status of organization and administration of government procurement in different types and levels of public hospitals across the country.The current situation of the organizational structure,management system,working mode,supervision and evaluation,budget establishment,bidding and procurement,contract signing,acceptance process,payment management,and other aspects of government procurement management in public hospitals were analyzed.Results:A total of 216 valid questionnaires were collected from 216 public hospitals in 28 provinces,municipalities and autonomous regions across the country,including 165 general hospitals,37 specialized hospitals and 13 traditional Chinese medicine hospitals,accounting for 76.39％,17.13％and 6.02％respectively;among the hospital levels,there were 202 tertiary hospitals(accounting for 93.52％).Among the surveyed government procurement management institutions of public hospitals,there were 112,103,110 and 112 organizations at the four levels of procurement management committee,procurement management office,procurement center and business and administrative logistics department,accounting for 51.85％,47.69％,50.93％and 51.85％respectively.The quota standards for public bidding for government procurement in all hospitals were in line with the requirements of national laws and regulations.The approval of funds payment must conditions of each hospital complied with relevant requirements.In terms of management effects of risk prevention and control,the hospitals with very good,good,average and inadequate were 48,125,34 and 9 respectively,accounting for 22.22％,57.87％,15.74％and 4.17％.Conclusion:The organizational framework and management system of government procurement in public hospitals are becoming increasingly standardized,and there are certain differences in the work mode and process of government procurement in different hospitals,and the supervision and evaluation are relatively weak,which is worthy of attention and strengthened administration.

Tumor aerobic glycolysis is one of the main features of tumor metabolic reprogramming. This abnormal glycolytic metabolism provides bioenergy and biomaterials for tumor growth and proliferation. It is worth noting that aerobic glycolysis will not only provide biological materials and energy for tumor cells, but also help tumor cells to escape immune surveillance through regulation of immune microenvironment, thereby resisting tumor immunotherapy and promoting tumor progression. Based on the pathogenesis of renal cell carcinoma, this paper describes the characteristics of aerobic glycolysis, the effect of glycolytic metabolism on the immune microenvironment of renal cell carcinoma, the effect of glycolysis inhibitors on the immune microenvironment of renal cell carcinoma, and the prospect of glycolysis inhibitors combined with immune checkpoint inhibitors in the treatment of renal cell carcinoma.
Humans ; Carcinoma, Renal Cell/therapy* ; Immunotherapy ; Glycolysis ; Metabolic Reprogramming ; Kidney Neoplasms/therapy* ; Tumor Microenvironment

Objective:To investigate the clinical characteristics and the efficacy of thrombus aspiration in patients with early intrastent thrombosis (EST) following carotid artery stenting (CAS).Methods:This study is a retrospective case series, collecting clinical data of five patients who developed EST after CAS in the Department of Neurosurgery, Beijing Chaoyang Hospital, Capital Medical University from January 2021 to September 2023.All patients were male, with an age of (64.0±11.9) years (range:48 to 77 years), accounting for 2.0% (5/244) of CAS procedures during the same period.Among them, three patients did not receive standard dual antiplatelet therapy before the procedure, and one had an inadequate ADP inhibition rate (45.6%).Four patients received XACT carotid stents, while one received a Wallstent carotid stent.All five patients showed significant residual stenosis ranging from 43% to 55% after CAS.Emergency thrombus aspiration was performed in all cases, and data regarding perioperative conditions, vascular patency, and clinical outcomes were collected.Results:The interval between CAS and the occurrence of EST ranged from 3 hours to 14 days.The main clinical symptoms included sudden onset of consciousness disorders and contralateral limb weakness.None of the patients received preoperative intravenous thrombolysis, and thrombus aspiration was performed during the procedure to restore vascular patency.Four cases underwent balloon angioplasty during the procedure, and two cases utilized overlapping stents.Two patients experienced intraoperative embolization of thrombus to the C 2 segment.In one case, the embolized thrombus was retrieved using an intracranial thrombectomy stent, while in another case, it was aspirated using a guiding catheter.Postoperatively, all patients had a thrombolysis in cerebral infarction grade of 3, and symptoms improved in four cases.One patient showed no improvement in symptoms, and MRI revealed extensive new infarction in the right frontal and insular regions, adjacent to the right lateral ventricle.Regular follow-up examinations after discharge did not reveal restenosis or embolism within the stent.The follow-up period ranged from 7.6 to 21.2 months, with modified Rankin scale scores of 0 to 1 point in four cases and 2 points in one case, indicating good recovery in all patients. Conclusions:Acute intrastent thrombosis is a rare complication after carotid artery stenting.The combined use of percutaneous thrombus aspiration and endovascular techniques, such as balloon angioplasty and stent overlapping, can rapidly restore vessel patency with favorable outcomes.However, further large-scale clinical studies are needed to confirm the effectiveness of these treatments for acute intrastent thrombosis.

Objective:To investigate the value of systemic inflammatory response syndrome (SIRS), pediatric sequential organ failure assessment (pSOFA) and pediatric critical illness score (PCIS) in predicting mortality of pediatric sepsis in pediatric intensive care units (PICU) from Southwest China.Methods:This was a prospective multicenter observational study. A total of 447 children with sepsis admitted to 12 PICU in Southwest China from April 2022 to March 2023 were enrolled. Based on the prognosis, the patients were divided into survival group and non-survival group. The physiological parameters of SIRS, pSOFA and PCIS were recorded and scored within 24 h after PICU admission. The general clinical data and some laboratory results were recorded. The area under the curve (AUC) of the receiver operating characteristic curve was used to compare the predictive value of SIRS, pSOFA and PCIS in mortality of pediatric sepsis.Results:Amongst 447 children with sepsis, 260 patients were male and 187 patients were female, aged 2.5 (0.8, 7.0) years, 405 patients were in the survival group and 42 patients were in the non-survival group. 418 patients (93.5%) met the criteria of SIRS, and 440 patients (98.4%) met the criteria of pSOFA≥2. There was no significant difference in the number of items meeting the SIRS criteria between the survival group and the non-survival group (3(2, 4) vs. 3(3, 4) points, Z=1.30, P=0.192). The pSOFA score of the non-survival group was significantly higher than that of the survival group (9(6, 12) vs. 4(3, 7) points, Z=6.56, P<0.001), and the PCIS score was significantly lower than that of the survival group (72(68, 81) vs. 82(76, 88) points, Z=5.90, P<0.001). The predictive value of pSOFA (AUC=0.82) and PCIS (AUC=0.78) for sepsis mortality was significantly higher than that of SIRS (AUC=0.56) ( Z=6.59, 4.23, both P<0.001). There was no significant difference between pSOFA and PCIS ( Z=1.35, P=0.176). Platelet count, procalcitonin, lactic acid, albumin, creatinine, total bilirubin, activated partial thromboplastin time, prothrombin time and international normalized ratio were all able to predict mortality of sepsis to a certain degree (AUC=0.64, 0.68, 0.80, 0.64, 0.68, 0.60, 0.77, 0.75, 0.76, all P<0.05). Conclusion:Compared with SIRS, both pSOFA and PCIS had better predictive value in the mortality of pediatric sepsis in PICU.

Objective:To investigate the clinical characteristics and the efficacy of thrombus aspiration in patients with early intrastent thrombosis (EST) following carotid artery stenting (CAS).Methods:This study is a retrospective case series, collecting clinical data of five patients who developed EST after CAS in the Department of Neurosurgery, Beijing Chaoyang Hospital, Capital Medical University from January 2021 to September 2023.All patients were male, with an age of (64.0±11.9) years (range:48 to 77 years), accounting for 2.0% (5/244) of CAS procedures during the same period.Among them, three patients did not receive standard dual antiplatelet therapy before the procedure, and one had an inadequate ADP inhibition rate (45.6%).Four patients received XACT carotid stents, while one received a Wallstent carotid stent.All five patients showed significant residual stenosis ranging from 43% to 55% after CAS.Emergency thrombus aspiration was performed in all cases, and data regarding perioperative conditions, vascular patency, and clinical outcomes were collected.Results:The interval between CAS and the occurrence of EST ranged from 3 hours to 14 days.The main clinical symptoms included sudden onset of consciousness disorders and contralateral limb weakness.None of the patients received preoperative intravenous thrombolysis, and thrombus aspiration was performed during the procedure to restore vascular patency.Four cases underwent balloon angioplasty during the procedure, and two cases utilized overlapping stents.Two patients experienced intraoperative embolization of thrombus to the C 2 segment.In one case, the embolized thrombus was retrieved using an intracranial thrombectomy stent, while in another case, it was aspirated using a guiding catheter.Postoperatively, all patients had a thrombolysis in cerebral infarction grade of 3, and symptoms improved in four cases.One patient showed no improvement in symptoms, and MRI revealed extensive new infarction in the right frontal and insular regions, adjacent to the right lateral ventricle.Regular follow-up examinations after discharge did not reveal restenosis or embolism within the stent.The follow-up period ranged from 7.6 to 21.2 months, with modified Rankin scale scores of 0 to 1 point in four cases and 2 points in one case, indicating good recovery in all patients. Conclusions:Acute intrastent thrombosis is a rare complication after carotid artery stenting.The combined use of percutaneous thrombus aspiration and endovascular techniques, such as balloon angioplasty and stent overlapping, can rapidly restore vessel patency with favorable outcomes.However, further large-scale clinical studies are needed to confirm the effectiveness of these treatments for acute intrastent thrombosis.

OBJECTIVE To evaluate the efficacy and safety of Huoxue Xiaoyi Granule in inhibiting the recurrence of endometrio-sis(EMs)after conservative operation,and to provide evidence for Chinese medicine in inhibiting the recurrence of EMs.METHODS A total of 72 patients with qi-stagnation and blood-stasis after EMs operation were selected as the study objects and randomly divid-ed into the Chinese medicine group and the Western medicine group,36 cases in each group.The Chinese medicine group was treated with Huoxue Xiaoyi Granule,and the Western medicine group was treated with GnRH-α.The postoperative recurrence rate,TCM syn-drome score,carbohydrate antigen 125(CA125),dysmenorrhea score,pelvic pain score,pregnancy rate,serum sex hormones[estra-diol(E2),luteinizing hormone(LH),follicle stimulating hormone(FSH)]and safety indexes of the two groups were observed.RE-SULTS At 9 months and 12 months after surgery,the total TCM syndrome scores of the two groups of patients were significantly re-duced(P<0.05),and the Chinese medicine group was better than the Western medicine group(P<0.05);12 months later,the TCM total clinical curative rate in the Chinese medicine group was better than that in the Western medicine group;after surgery,the serum CA125 levels,dysmenorrhea scores and pelvic pain severity of the two groups of patients were significantly reduced(P<0.05,P<0.01);during treatment,the total incidence of adverse reactions in the Chinese medicine group was lower than that in the Western medicine group(P<0.01);the recurrence rate of the Chinese medicine group was slightly lower than that of the Western medicine group,but there was no statistical difference(P>0.05).CONCLUSION Huoxue Xiaoyi Granule can significantly improve TCM syndromes in patients with qi-stagnation and blood-stasis after EMs surgery.It is safe and has equivalent efficacy to GnRH-α in pre-venting postoperative recurrence of EMs,and worthy of clinical promotion and application.

Objective:To observe the effects of ultrasound intermediate frequency acupoint targeted drug guiding technology on the recovery of gastrointestinal function and serum gastrin levels in elderly patients after lumbar spine surgery under general anesthesia.Methods:This study used prospective research methods.A total of 90 elderly patients undergoing lumbar spine surgery after general anesthesia in the orthopaedic ward of Beijing Geriatrics Hospital from June 2019 to June 2021 were randomly divided into blank control group, drug control group, and drug-guided treatment group, with 30 cases each group. After the operation, no intervention was given to the blank control group, the drug control group received oral mosapride citrate tablets, the drug-guided treatment group used the D patch to guide the medicine at the two acupoints of Zusanli and Zhongwan with ultrasound medium frequency guided medicine instrument for 1 week each. The serum gastrin levels of the patients in each group were detected 1 d before operation, 3 d after operation, and 1 week after operation, and the time of first exhaust and first defecation after operation were recorded.Results:The results showed that the level of serum gastrin preoperativein the three groups was not significantly different ( P>0.05). On the third day after operation, the levelof serum gastrin in the drug guide treatment group, drug control group and blank control group were lower than those at 1 d before operation: (66.51 ± 5.34) ng/L vs. (69.36 ± 6.50) ng/L, (58.34 ± 5.71) ng/L vs. (68.75 ± 5.13) ng/L, (55.76 ± 6.23) ng/L vs. (70.20 ± 6.71) ng/L, the differences were statistically significant ( P<0.05), and showed a decreasing trend in turn. Among them, the level of serum gastrin in the drug guide treatment group was higher than that in the drug control group and blank control group, the difference was statistically significant ( P<0.05). One week after operation, the level of serum gastrin in the three groups increased compared with the third day after operation ( P<0.05), and the drug guiding treatment group was higher than the drug control group and the blank control group: (72.38 ± 6.78) ng/L vs. (67.15 ± 6.27) ng/L, (63.52 ± 5.38) ng/L, the differences were statistically significant ( P<0.05). The time of first exhaust and defecation after the operation of the three groups of patients, the drug-guided treatment group was significantly shorter than the drug control group and the blank control group: (15.25 ± 3.10) h vs. (20.38 ± 4.21) h and (28.52 ± 3.69) h, (24.14 ± 3.53) h vs. (36.15 ± 3.54) h and (49.51 ± 4.37) h, the differences were statistically significant ( P<0.05). Conclusions:Ultrasound intermediate frequency acupoint drug guiding technology can increase the patient′s serum gastrin level and promote the recovery of gastrointestinal function in elderly patients with lumbar spine surgery after general anesthesia.

Objective:To prepare the virus-like particle (VLP) of the GII.3[P12] human norovirus (HuNoV) strain GZ2013-L20 in Guangzhou and its polyclonal antibody, and systematically characterize its immunogenicity and receptor binding ability, which would provide data for prevention and control of HuNoV.Methods:ORF2 gene was amplified from the genome of the GZ2013-L20 strain to construct the recombinant transposon vector, which was further transformed into Escherichia coli DH10 Bac to develop the recombinant baculovirus Bacmid-L20-ORF2. VLP was expressed in the sf9 insect cells and then purified. Transmission electron microscopy, SDS-PAGE, Western blot (WB), and receptor binding experiments were performed to characterize the purified VLP. In addition, the polyclonal antibody from the immunized mice was evaluated by indirect enzyme-linked immunosorbent assay (ELISA) and the blocking test of receptor binding. Results:The recombinant baculovirus plasmid Bacmid-L20-ORF2 was constructed, and the target VLP was successfully obtained. The result by the transmission electron microscope demonstrated that the VLP were about 30 nm in diameter. SDS-PAGE and WB analyses showed that the protein’s relative molecular mass (Mr. ×10 3) was about 58. The result of receptor binding experiments showed that the VLP could bind to the secretory salivary receptors (types of A, B, AB and O), non-secretory salivary receptors (O type) and the porcine gastric mucin. The polyclonal antibody with a titer of 2 × 10 5 was detected in the immunized mice, which showed strong cross-immunoreactivity with capsid proteins of 20 (20/28) HuNoV genotypes. In addition, the result of blocking tests of receptor binding showed that the VLP polyclonal antibody only blocked the viral VLP of the same genotype, but had no neutralizing effects on the VLPs of GII.2, GII.4, GII.8 and GII.17. Conclusions:The VLP of GII.3[P12] HuNoV Guangzhou strain showed strong binding ability to both secretory and non-secretory salivary receptors, and its polyclonal antibody showed a broad spectrum of immunobinding, but its neutralization blocking feature was effective only against the virus of the same genotype. The result provide basic data for rational design of vaccine development.

Tocilizumab has been reported to attenuate the "cytokine storm" in COVID-19 patients. We attempted to verify the effectiveness and safety of tocilizumab therapy in COVID-19 and identify patients most likely to benefit from this treatment. We conducted a randomized, controlled, open-label multicenter trial among COVID-19 patients. The patients were randomly assigned in a 1:1 ratio to receive either tocilizumab in addition to standard care or standard care alone. The cure rate, changes of oxygen saturation and interference, and inflammation biomarkers were observed. Thirty-three patients were randomized to the tocilizumab group, and 32 patients to the control group. The cure rate in the tocilizumab group was higher than that in the control group, but the difference was not statistically significant (94.12% vs. 87.10%, rate difference 95% CI-7.19%-21.23%, P = 0.4133). The improvement in hypoxia for the tocilizumab group was higher from day 4 onward and statistically significant from day 12 (P = 0.0359). In moderate disease patients with bilateral pulmonary lesions, the hypoxia ameliorated earlier after tocilizumab treatment, and less patients (1/12, 8.33%) needed an increase of inhaled oxygen concentration compared with the controls (4/6, 66.67%; rate difference 95% CI-99.17% to-17.50%, P = 0.0217). No severe adverse events occurred. More mild temporary adverse events were recorded in tocilizumab recipients (20/34, 58.82%) than the controls (4/31, 12.90%). Tocilizumab can improve hypoxia without unacceptable side effect profile and significant influences on the time virus load becomes negative. For patients with bilateral pulmonary lesions and elevated IL-6 levels, tocilizumab could be recommended to improve outcome.
Antibodies, Monoclonal, Humanized ; COVID-19/drug therapy* ; Humans ; SARS-CoV-2 ; Treatment Outcome