Objective To evaluate tolerability,safety and pharmacokinetics of JS026 and JS026-JS016 single dose intravenous infusion in healthy adults.Methods This phase 1,randomized,double-blind,placebo-controlled,dose-escalation study totally included 48 participants:32 healthy subjects were enrolled in JS026 single intravenous infusion groups and 16 healthy subjects were enrolled in JS026-JS016 groups.JS026 was sequentially administered from low dose to high dose(30-1 000 mg),with intravenous infusion of JS026 or placebo in JS026 single-dose groups,and intravenous infusion of JS026-JS016 or placebo in the combination drug groups.Blood was collected according to the time point designed for trial.Serum concentrations of JS026 and JS016 were determined by enzyme linked immunosorbnent assay(ELISA),and pharmacokinetics parameters were calculated by WinNonlin 8.2.The power model method was used to evaluate the linear analysis of dose and drug exposure.Results 47 subjects completed trial and 1 subject lost to follow-up.After a single intravenous injection of JS026 of 30 mg,100 mg,300 mg,600 mg,and 1 000 mg,mean Cmax were(9.47±1.53),(33.20±4.95),(96.10±13.70),(177.00±22.20)and(353.00±56.70)μg·mL-1,respectively;mean AUC0-∞ were(4 225.00±607.00),(1.78 × 104±3 268.00),(5.83 × 104±1 038.00),(1.07 × 105±152.00),(1.66 × 105±327.00)μg·h·mL-1,respectively;mean t1/2 of JS026 were 563-709 h.The Cmax and AUC0-∞ of JS026 were basically similar alone or in combination with JS016.The results of Power model showed that Cmax and AUC0-∞ increased approximately linearly with the increasing dose of JS026.Treatment emergent adverse event was not increasing when dose increased and most of adverse event associated with drugs were abnormal on laboratory tests and haematuria,thus JS026 and JS016 was well tolerated in all groups.Conclusion The single intravenous infusion of JS026 can almost be thought to be a linear relationship between the doses and drug serum exposure.JS016 had no significant effect on serum concentration of JS026 and JS026 was well tolerated and safe in healthy subjects within 30-1 000 mg.

Objective To explore the current situation of the clean operating rooms in Guangdong provincial hospitals of traditional Chinese medicine or integrated Chinese and western medicine to provide references for standardizing the construc-tion of the clean operating room.Methods A questionnaire was designed according to GB 50333-2013 Architectural technical code for hospital clean operating department and WS/T 368-2012 Management specification of air cleaning technique in hospitals,and a questionnaire survey and field investigation were conducted from March to October 2021 on the operating rooms of 64 secondary and above hospitals of traditional Chinese medicine or integrated Chinese and western medicine in Guangdong province,which involved in the basic situation of the operating rooms,general requirements for constructing clean operating rooms,requirements for the layout of clean operating rooms and architectural decorations of the clean operating rooms.Results Of the 64 hospitals surveyed there were 51 ones(79.7％)with clean operating rooms.Tertiary hospitals were mainly equipped with Class Ⅲ clean operating rooms(45.8％),secondary hospitals were provided with general operating rooms(35.0％)and Class Ⅲ clean operating rooms(29.2％),and the differences in the types and classes of the operating rooms in levels of hospitals were statistically significant(P＜0.001).The proportions of tertiary hospitals configured with clean operating rooms and the highest configuration of Class I clean operating rooms were also significantly higher than those of secondary hospitals(94.3％vs 62.1％and 88.6％vs 44.8％,respectively),with statistically significant differences(P＜0.05).There were 66.7％hospitals equipped with negative pressure operating rooms;more than 1/2(56.9％)of the hospitals had the service time of their clean operating rooms longer than 10 years.All the tertiary hospitals did not have air shower rooms in their walkways,while 16.7％secondary hospitals did,with the difference being statistically significant(P＜0.05).Most of the building decorations of clean operating rooms in all the hospitals complied with the specifications(compliance rate＞80.0％),and the difference was not statistically significant between the secondary and tertiary hospitals(P＞0.05);the compliance rate of the decrations of the tertiary hospitals was 78.8％for the requirements of general principle,which was obviously lower than that of the secondary hospitals(100％),with the differences being statistically significant(P＜0.05).Conclusion The clean operating rooms in Guangdong provincial hospitals of traditional Chinese medicine or integrated Chinese and western medicine behave well in configuration,while have some defficiencies in general requirements,layout and building,and necessary guidance,supervision and management have to be involved in to standardize the construction of clean operating rooms.[Chinese Medical Equipment Journal,2024,45(10):77-83]

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

Objective To explore the relationship between the status of infarct related artery(IRA)occlusion and thrombus types in patients with non-ST-segment elevation myocardial infarction(NSTEMI)using optical coherence tomography(OCT).Methods A total of 170 NSTEMI patients who underwent emergency percutaneous coronary intervention at Henan Provincial People1s Hospital from October 2021 to August 2023 and underwent OCT examination were included in the study.Among them,83 cases were in the total occlusion group and 87 cases were in the non-total occlusion group.The baseline characteristics,coronary angiography findings,and OCT results of the patients were compared and analyzed.Results Compared with the non-total occlusion group,the patients in the total occlusion group were more younger(P=0.013),the proportion of male was higher(P=0.026),and the proportion of patients with hypertension(P=0.010)and diabetes(P=0.033)was lower.In the total occlusion group,left circumflex artery(LCX)served as the main IRA,whereas in the non-total occlusion group,left anterior descending(LAD)was the predominant IRA(P=0.012);In addition,there was a significantly higher occurrence of rentrop grade Ⅱ～Ⅲ in the total occlusion group compared to the non-total occlusion group(P=0.022).The OCT results showed that in most cases,the total occlusion group was caused by plaque rupture events(P=0.014),mainly red/mixed thrombus(P＜0.001);The non-total occlusion group was more commonly associated with plaque erosion events(P=0.014),with white thrombus being the main cause(P＜0.001).Conclusions Total occlusion of infarct-related artery in NSTEMI patients often occurs in the LCX,and the patient is more younger,the thrombus type is mainly red/mixed thrombus,while non-total occlusion lesions are mainly white thrombus.

The effect of porcine SIRT5 on replication of foot and mouth disease virus type O(FMDV-O)and the underlying regulatory mechanism were investigated.Western blot and RT-qPCR analyses were employed to monitor expression of endoge-nous SIRT5 in PK-15 cells infected with FMDV-O.Three pairs of SIRT5-specific siRNAs were synthesized.Changes to SIRT5 and FMDV-O protein and transcript levels,in addition to virus copy numbers,were measured by western blot and RT-qPCR analyses.PK-15 cells were transfected with a eukaryotic SIRT5 expression plasmid.Western blot and RT-qPCR analyses were used to explore the impact of SIRT5 overexpression on FMDV-O replication.Meanwhile,RT-qPCR analysis was used to detect the effect of SIRT5 overexpression on the mRNA expression levels of type I interferon-stimulated genes induced by SeV and FMDV-O.The results showed that expression of SIRT5 was up-regulated in PK-15 cells infected with FMDV-O and siRNA interfered with SIRT5 to inhibit FMDV-O replication.SIRT5 overexpression promoted FMDV-O replication.SIRT5 over-expression decreased mRNA expression levels of interferon-stimulated genes induced by SeV and FMDV-O.These results suggest that FMDV-O infection stimulated expression of SIRT5 in PK-15 cells,while SIRT5 promoted FMDV-O rep-lication by inhibiting production of type I interferon-stimula-ted genes.These findings provide a reference to further ex-plore the mechanism underlying the ability of porcine SIRT5 to promote FMDV-O replication.

Objective To construct trajectory models of care-seeking patterns for type 2 diabetes mellitus(T2DM)patients,analyze the influencing factors of different trajectories,and explore the fasting blood glucose control levels of T2DM patients with different trajectories.Methods A retrospective cohort study was carried out on 18088 T2DM patients who had health records and been involved in the diabetic management in Community Health Service Center of Minhang District,Shanghai from 2006 to 2009.Starting from Jan 1,2010,participants were followed up until Dec 31,2019,with complete follow-up information.Group-based trajectory modelling(GBTM)was employed to identify and construct the fluctuation trajectory of fasting blood glucose in the patients.Bayesian information criterion(BIC),average posterior probability(AvePP)and other evaluation indicators were used to select the optimum subgroup number model.Then the differences in demographic characteristics,health status,family history,fasting blood glucose,BMI,etc were compared among different categories.Multinational logistic regression model was constructed to explore the influencing factors of different fluctuation trajectories.Cox regression analysis was used to examine the relationship between the long-term trajectories of care-seeking patterns and fasting blood glucose control level.Results Using GBTM analysis,we constructed the optimal Model 4 to categorize 18088 T2DM patients with community health records into five distinct trajectory subgroups:continuous non-attendance group(22.29%),low-level increasing group(15.09%),high-level slowly decreasing group(14.18%),high-level rapidly decreasing group(14.90%),and continuous regular attendance group(33.54%).With the continuous regular attendance group serving as the reference,gender,age,place of residence,baseline comorbidity of hypertension,baseline fasting plasma glucose level,and BMI were found to influence the community attendance trajectories of T2DM patients(P<0.05).After adjusting for confounding factors,Cox regression analysis revealed that compared to the continuous non-attendance group,the low-level increasing group,high-level slowly decreasing group,and continuous regular attendance group had better glycemic control,with HRs of 0.37(95%CI:0.34-0.39),0.72(95%CI:0.67-0.78),and 0.78(95%CI:0.73-0.84),respectively.The glycemic control level in the high-level rapidly decreasing group was comparable,with an HR of 1.06(95%CI:0.99-1.12).Conclusion Based on the optimal model,the community medical treatment trajectories of T2DM patients showed different dynamic characteristics.Factors such as gender,residence,hypertension,and weight loss may influence these varying trajectories.Regular community visits and follow-up may help control blood glucose levels.

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.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objective: To examine the application value of 3D Slicer software assisted domestic frameless stereotactic robot in biopsy of intracranial lesions. Methods: A retrospective analysis was performed on 80 patients who admitted consecutively and underwent intracerebral lesions biopsy with the domestic frameless stereotactic robot at Department of Neurosurgery, Aerospace Central Hospital from January 2019 to December 2021. There were 36 males and 44 females, with a mean age of (38.5±18.0) years (range: 6 to 71 years). Before surgery only enhanced T1-weighted three-dimensional magnetization prepared gradient echo sequences and diffusion tensor imaging scans were performed. Self-reconstruction of intracranial lesions, cerebral cortex and blood vessels was carried out using 3D Slicer software system after the DICOM format imaging data of 80 patients were collected. These imaging data were merged to the workstation of the domestic frameless stereotactic robot for preoperative surgical planning and the surgical puncture path was designed to avoid blood vessels in the brain functional area, cerebral cortex and sulcus. Results: All frameless stereotactic biopsy were successfully performed. Postoperative pathological diagnosis included 50 cases of diffuse astrocytic and oligodendroglioma, 15 cases of lymphoma, 5 cases of metastatic tumors, 5 cases of inflammatory demyelinating disease, 2 cases of inflammatory granuloma, 1 case of hemangioma, 1 case of acute lymphoblastic leukemia intracranial invasion and 1 case of seminoma. The positive diagnosis rate was 100% (80/80). Postoperative imaging confirmed that the puncture path and target were accurately implemented according to the preoperative planning, and the target error was (1.32±0.44) mm (range: 0.55 to 1.99 mm). One case of puncture-related bleeding occurred at the target after surgery and improved after treatment. Conclusion: The three-dimensional multimodal images reconstructed by the 3D Slicer software before operation could help the surgeons make the preoperative planning and reduce the risk of stereotactic brain biopsy.
Male ; Female ; Humans ; Child ; Adolescent ; Young Adult ; Adult ; Middle Aged ; Aged ; Brain Neoplasms/pathology* ; Diffusion Tensor Imaging ; Retrospective Studies ; Robotics ; Biopsy ; Software ; Stereotaxic Techniques

Abstract: Objective　To investigate the clustered regularly interspaced short palindromic repeats (CRISPR) genotypes and regional distribution of Yersinia pestis strains in the natural plague foci of Hainan Tibetan Autonomous Prefecture of Qinghai Province (referred to as "Hainan prefecture") and provide a scientific basis for plague prevention and control in this area. Methods　A total of 36 representative Yersinia pestis strains, which were isolated from different host animals and insect vectors from 1954 to 2009 in Hainan Prefecture, were selected as experimental subjects. The DNAs were extracted using the traditional sodium dodecyl sulfate decomposition and phenol-chloroform method. Three pairs of CRISPR primers (YPa, Ypb, YPc) were used for PCR amplification, sequencing and analysis of the DNA of the tested strains, respectively, as a means to identify the CRISPR genotypes of Yersinia pestis in Hainan Prefecture. Results　A total of 17 spacers were observed among 36 strains of Yersinia pestis, including 9 of YPa, 5 of YPb and 3 of YPc. All strains were divided into 5 CRISPR gene clusters (Cb2, Cb4 ', Ca7, Ca7 ', Ca35 ') and 6 genotypes (G1, G9, G22, G22-A1 ', G26-A1 ', G26-A1 'A4 -). The G26-a1 ' was the main genotype, which was distributed in Gonghe, Guide and Xinghai County, and the G22 is the second type, which was distributed in Gonghe and Guide County. Conclusions　The genetic polymorphism of CRISPR loci of Yersinia pestis strains in Hainan was high, and the regional distribution characteristics of Yersinia pestis strains with different genotypes were significant.