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 analyze the atrioventricular synchronization rate after implantation of Micra AV leadless pacemaker,and the impact of postoperative programming optimization on atrioventricular synchronization rate.Methods A prospective cohort study was conducted to select patients with complete atrioventricular block who underwent Micra AV leadless pacemaker implantation at Beijing Anzhen Hospital from August 2022 to June 2023.Programming optimization were performed at 1 week,1 month,and 3 months postoperatively,and atrioventricular synchronization rate,electrical parameters,and echocardiography were recorded.Results A total of 68 patients with complete atrioventricular block implanted with Micra AV were selected,with an average age of(68.2±9.7)years,including 47 males(69.1％).All patients were successfully implanted with Micra AV,and there were no serious postoperative complications;The average threshold,sense,and impedance parameters were stable during 1 week,1 month,and 3 months after the procedure;There was no significant difference in the EF value of postoperative echocardiography(P=0.162);The average atrioventricular synchronization rates at 1 week,1 month,and 3 months postoperatively were(75.2％vs.83.8％vs.91.6％,P=0.001).Conclusions As an mechanical atrial sensing,Micra AV requires personalized adjustment of relevant parameters;Postoperative follow-up programming optimization plays an important role in the atrioventricular synchronization and comfort level in patients with complete atrioventricular block after implantation of Micra AV leadless pacemaker.

ObjectiveTriple-negative breast cancer (TNBC) is the breast cancer subtype with the worst prognosis, and lacks effective therapeutic targets. Colony stimulating factors (CSFs) are cytokines that can regulate the production of blood cells and stimulate the growth and development of immune cells, playing an important role in the malignant progression of TNBC. This article aims to construct a novel prognostic model based on the expression of colony stimulating factors-related genes (CRGs), and analyze the sensitivity of TNBC patients to immunotherapy and drug therapy. MethodsWe downloaded CRGs from public databases and screened for differentially expressed CRGs between normal and TNBC tissues in the TCGA-BRCA database. Through LASSO Cox regression analysis, we constructed a prognostic model and stratified TNBC patients into high-risk and low-risk groups based on the colony stimulating factors-related genes risk score (CRRS). We further analyzed the correlation between CRRS and patient prognosis, clinical features, tumor microenvironment (TME) in both high-risk and low-risk groups, and evaluated the relationship between CRRS and sensitivity to immunotherapy and drug therapy. ResultsWe identified 842 differentially expressed CRGs in breast cancer tissues of TNBC patients and selected 13 CRGs for constructing the prognostic model. Kaplan-Meier survival curves, time-dependent receiver operating characteristic curves, and other analyses confirmed that TNBC patients with high CRRS had shorter overall survival, and the predictive ability of CRRS prognostic model was further validated using the GEO dataset. Nomogram combining clinical features confirmed that CRRS was an independent factor for the prognosis of TNBC patients. Moreover, patients in the high-risk group had lower levels of immune infiltration in the TME and were sensitive to chemotherapeutic drugs such as 5-fluorouracil, ipatasertib, and paclitaxel. ConclusionWe have developed a CRRS-based prognostic model composed of 13 differentially expressed CRGs, which may serve as a useful tool for predicting the prognosis of TNBC patients and guiding clinical treatment. Moreover, the key genes within this model may represent potential molecular targets for future therapies of TNBC.

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.

Aim To investigate the mechanisms of Chaijin JieYu Anshen formula modulating the depres-sive behaviors and the synaptic plasticity of hippocam-pal neurons in insomnia-concomitant depression rats based on the histone deacetylase 5(HDAC5)/myocyte enhancer factor 2C(MEF2C)pathway.Methods A rat model of insomnia-concomitant depression was es-tablished by PCPA injection combined with chronic un-predictable mild stress(CUMS),and the experiment was divided into the control group,the model group,the high,medium and low dose group of Chaijin JieYu Anshen formula,and the positive drug group.The de-pression of rats was evaluated by sugar-water prefer-ence test,open field test and morris water maze.The levels of 5-hydroxytryptamine(5-HT)and dopamine(DA)in serum were measured by enzyme linked im-munosorbent assay(ELISA).The pathological damage of hippocampal neurons was observed by HE staining and Nissl staining.The damage of dendritic spines of hippocampal neurons was observed by Golgi staining,and the levels of HDAC5,MEF2C,postsynaptic densi-ty-95(PSD-95)and synaptophysin 1(SYN1)in hip-pocampus were measured by Western blot,immunohis-tochemistry and immunofluorescence.Results Com-pared with the model group,the Chaijin JieYu Anshen formula could increase the sugar-water preference rate of the model rats,reduce the immobility time in the open field experiment,increase the total activity dis-tance,shorten the evasion latency in the localization navigation experiment,and prolong the residence time in the quadrant where the platform was located in the space exploration experiment(P＜0.05,P＜0.01).Moreover,the Chaijin JieYu Anshen formula improved the hippocampal neuron and dendritic spine damage and increase the dendritic branch length and dendritic spine density of hippocampal neurons(P＜0.01,P＜0.01),restore the serum levels of 5-HT and DA in insomnia-concomitant depression rats(P＜0.05,P＜0.01),down-regulate the HDAC5 protein,and up-regulate the expression of MEF2C,PSD-95,and SYN1 protein(P＜0.05,P＜0.01 or P＜0.001).Conclusions Chaijin JieYu Anshen formula may alle-viate the depression-like behavior of model rats by re-ducing the expression of HDAC5 protein,thus deregu-lating the inhibition of transcription factor MEF2C,promoting the expression of PSD-95 and SNY1 protein,and exerting a protective effect on hippocampal neurons and synapses.

Objective To measure the distance between the lateral compression Ⅱ(LC-Ⅱ)screw guide needle and the surrounding important structures around the anterior inferior iliac spine in pelvic fractures and to locate the needle point,so as to provide anatomical reference for clinical nail placement.Methods Totally 40 adult gross specimens of embalming were implanted with LC-Ⅱ screw guide needle under the surveillance of C-arm machine,and the specimens were dissected.The shortest distance between the insertion point and the lateral femoral cutaneous nerve,femoral nerve,femoral artery,femoral vein,anterior superior iliac spine and inguinal ligament was measured.The triangle was constructed between the insertion point,anterior superior iliac spine and inguinal ligament,and the exact location of the entry point was calculated.Results The average distance between the insertion point of the male needle and the femoral vein was(50.67±7.29)mm＞the anterior superior iliac spine(43.83±7.58)mm＞the femoral artery(38.35±6.63)mm＞the femoral nerve(31.17±1.67)mm=the inguinal ligament(28.69±6.59)mm＞the lateral femoral cutaneous nerve(7.98±3.81)mm.The mean distance between the insertion point of the female needle and the anterior superior iliac spine was(45.28±7.07)mm=femoral vein(43.72±6.89)mm＞femoral artery(33.76±6.33)mm＞femoral nerve(25.66±6.46)mm=inguinal ligament(23.22±5.00)mm＞lateral femoral cutaneous nerve(8.97±4.76)mm.The projection distance of the entry point was 31.77 mm for men and 38.41 mm for women.The Angle b was 42.81°for men and 31.71° for women.Conclusion The lateral femoral cutaneous nerve is most vulnerable to injury when LC-Ⅱ screw is inserted,and the risk of injury has nothing to do with sex.The insertion point positioning method a and b made LC-Ⅱ screw placement quickly,safely and accurately,and reduced fluoroscopy time and frequency.

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.

This study aims to analyze the clinical characteristics and genetic variations of two cases with developmental delay and lactic acidosis in a family, and to explore the relationship between genetic variations and clinical features. A retrospective analysis was conducted on the clinical characteristics of two siblings with developmental delay and lactic acidosis who were treated at the Neonatal Department of Children's Hospital of Chongqing Medical University in May 2019 and December 2021, respectively. Whole-exome sequencing was used to detect genetic variations in the affected children. Homology modeling of the BCS1L protein was performed to analyze the structural and functional changes of the protein. The correlation between genetic variations and clinical phenotypes was analyzed. The results showed that the main clinical features of the two affected children in this family were manifestations of mitochondrial respiratory chain complex Ⅲ deficiency, including prematurity, developmental delay, respiratory failure, lactic acidosis, cholestasis, liver dysfunction, renal tubular lesions, coagulation dysfunction, anemia, hypoglycemia, hypotonia, and early death. Whole-exome sequencing revealed a novel deletion mutation c.486_488delGGA (p.E163del) and a novel missense mutation c.992C>T (p.T331I) in the BCS1L gene. Structural analysis of the homology modeling showed that the compound heterozygous mutation had a significant impact on protein function. In conclusion, the novel mutation site c.992C>T (p.T331I) in the BCS1L gene is a "likely pathogenic" mutation, and the compound heterozygous mutation is closely related to the phenotype of mitochondrial respiratory chain complex Ⅲ deficiency.
Humans ; Acidosis, Lactic/genetics* ; Electron Transport Complex III/genetics* ; Retrospective Studies ; Mutation ; Growth Disorders ; ATPases Associated with Diverse Cellular Activities/genetics*

AIM: To investigate the characteristics of changes in corneal epithelial thickness at the early postoperative stage of femtosecond assisted laser in situ keratomileusis(FS-LASIK)and its related influencing factors.METHOD: Retrospective study. A total of 120 patients(240 eyes)of myopia undergoing FS-LASIK from May 2021 to June 2022 were selected. The corneal epithelium thickness in the central area, inner ring area, and outer ring area of patients before and at 1d, 1wk, 1 and 3mo after operation was recorded. The relationship between the variation of corneal epithelium thickness and spherical equivalent, optical zone diameter, depth of cut and cutting ratio was analyzed by Pearson correlation.RESULTS: There was no statistical significance in corneal epithelial thickness in the central area, inner ring area and outer ring area at 1d after FS-LASIK compared with that before operation(P>0.05). At 1wk, 1 and 3mo after surgery, the corneal epithelial thickness in the central area, inner ring area and outer ring area increased compared with that before surgery, and the corneal epithelial thickness in the central area and inner ring area at 1 and 3mo after surgery was greater than that in the outer ring area(all P<0.05). The corneal epithelial thickness in the central, inner and outer ring areas of high myopia patients was thicker than that of low and moderate myopia patients before operation. The corneal epithelial thickness in the central, inner and outer ring areas of high myopia patients was thinner than that of low and moderate myopia patients at 1wk after operation(P<0.05). At 1 and 3mo after operation, the corneal epithelial thickness in the central, inner and outer ring areas of patients with high myopia was greater than that of patients with low and moderate myopia, and the changes of corneal epithelial thickness in the central, inner and outer ring areas were greater than those of patients with low and moderate myopia(P<0.05). The results of Pearson correlation showed that the changes in corneal epithelial thickness in the central and inner ring area were positively correlated with the corneal curvature, depth of cut and cutting ratio at 3mo after surgery, and they were in negative correlation with the age, spherical equivalent and optical zone diameter(P<0.05).CONCLUSION: The corneal epithelial thickness of patients thickened after the FS-LASIK operation, and it was correlated with age, corneal curvature, preoperative depth of cut, cutting ratio, spherical equivalent and the optic zone diameter.