Objective:To explore the causal relationship between human immune cells and hypertrophic scar (HS) using two-sample bidirectional Mendelian randomization (MR) method.Methods:This study was based on two-sample MR method, and the datasets of 731 immune cells and HS were obtained from the genome-wide association study (GWAS) catalog database and Finngen database, respectively. A significance threshold was established to discern single nucleotide polymorphism (SNP) significantly correlated with immune cells or HS, thereby eliminating the impact of weak instrumental variable bias. The inverse variance weighted (IVW) method (meanwhile, the Benjamini-Hochberg (BH) procedure of false discovery rate (FDR) to adjust P values) was used for preliminary detection of the causal relationship between immune cells and HS and screen the immune cells that had a significant causal relationship with HS. Further, the causal relationship between the selected immune cells and HS was detected through five two-sample MR methods: IVW method, weighted median method, simple mode method, weighted mode method, and MR-Egger method, and the scatter plot was drawn. SNPs conformed to the hypothesis were subjected to Cochran Q test for heterogeneity assessment, MR-Egger regression coupled with MR-PRESSO to eliminate horizontal pleiotropic effects, and a leave-one-out analysis was also conducted to determine if significant results were driven by individual SNP. Finally, the IVW method contained in the two-sample MR analysis was utilized to inversely examine the causal relationship between HS and immune cells. Results:The number of SNPs in 731 immune cells reaching the significance threshold varied from 7 to 1 786, while in HS, 119 SNPs met the significance threshold, with the F values of all SNPs being greater than 10, suggesting a low likelihood of bias from weak instrumental variables. The IVW method revealed that 60 types of immune cells potentially had a causal relationship with HS (with all P values <0.05), and after adjustment using the BH method, only CD45RA and CD39 positive regulatory T cell (Treg) maintained a potentially strong causal relationship with HS ( PFDR<0.05). The IVW method (with odds ratio of 1.16 and 95% confidence interval of 1.08-1.24, P<0.05, PFDR<0.05), weighted median method (with odds ratio of 1.16 and 95% confidence interval of 1.05-1.28, P<0.05), weighted mode method (with odds ratio of 1.14 and 95% confidence interval of 1.02-1.27, P<0.05), and MR-Egger method (with odds ratio of 1.18 and 95% confidence interval of 1.07-1.30, P<0.05) of scatter plot all suggested a causal relationship between the 14 SNPs of CD45RA and CD39 positive Treg and risk of HS, only simple mode method of scatter plot suggested a not obvious relationship between the 14 SNPs of CD45RA and CD39 positive Treg and risk of HS ( P>0.05). Cochran Q test indicated no heterogeneity in the causal relationship between CD45RA on CD39 positive Treg and HS ( P>0.05). MR-Egger regression and MR-PRESSO analyses showed that there was no horizontal pleiotropy in the significant causal relationship between CD45RA and CD39 positive Treg and HS ( P>0.05). Leave-one-out analysis confirmed that the significant causal relationship between CD45RA and CD39 positive Treg and HS remained stable after sequentially removing individual SNP. Reverse two-sample MR analysis showed that HS had no potential causal relationship with any of the 731 types of immune cells ( P>0.05). Conclusions:From the perspective of genetics, it is revealed that immune cells CD45RA and CD39 positive Treg may increase the risk of HS.

Objective To analyze the immunological effect and its influencing factors of HAART on HIV/AIDS with a baseline CD4 of less than 350 cells/mm³ in Hubei Province during 2011-2020. Methods The treatment information of people living with HIV/AIDS (PLWH) was collected through China Disease Control and Prevention Information System, and the change of CD4 mean value was analyzed by Wilcoxon sign rank sum test. Chi square test and multivariate logistic regression were used to analyze the factors influencing the immunological effect. Results The mean value of CD4 cell count at baseline was (172.78±107.65) cells/mm3 before treatment and (398.85±206.71) cells/mm³ in the fifth year after treatment. Patients with baseline CD4<50 /mm3 had the largest increase in CD4 mean value after treatment (P<0.05). Multivariate logistic regression analysis showed that Age ≥35 years, heterosexual transmission, time interval from diagnosis to treatment≥1 month, baseline CD4<50 /mm3, treatment time 7-<18 months, and drug failure were the risk factors for the success of antiviral therapy(P<0.05). Conclusion The immunological effect of HIV/AIDS antiviral therapy in Hubei Province is affected by many factors. It is necessary to strengthen the implementation of early detection and early treatment strategy and promote treatment compliance education for patients aged ≥35 years.

Pancreatic cancer remains one of the most lethal malignancies worldwide. The combination of the first-line standard agent gemcitabine (GEM) with the molecular-targeted drug erlotinib (Er) has emerged as a promising strategy for pancreatic cancer treatment. However, the clinical benefit from this combination is still far from satisfactory due to the unfavorable drug antagonism and the fibrotic tumor microenvironment. Herein, we propose a membrane-camouflaged dual stimuli-responsive delivery system for the co-delivery of GEM and Er into pancreatic cancer cells and tissues to block the antagonism, as well as reshapes profibrotic tumor microenvironment via simultaneous delivery of small interference RNA (siRNA) for synergistic pancreatic cancer treatment. This "all-in-one" delivery system exhibits sensitive GSH and pH-dependent drug release profiles and enhances the inhibitory effects on the proliferation and migration of tumor cells in vitro. Excitingly, the systemic injection of such a biomimetic drug co-delivery system not only resulted in superior inhibitory effects against orthotopic pancreatic tumor and patient-derived tumor (PDX), but also greatly extended the survival rate of tumor-bearing mice. Our findings provide a promising therapeutic strategy against pancreatic cancer through the enhanced synergistic effect of target therapy, chemotherapy and anti-fibrotic therapy, which represents an appealing way for pancreatic cancer treatment.

Osteoporotic vertebral compression fracture (OVCF) can lead to lower back pain and may be even accompanied by scoliosis, neurological dysfunction and other complications, which will affect the daily activities and life quality of patients. Vertebral augmentation is an effective treatment method for OVCF, but it cannot correct unbalance of bone metabolism or improve the osteoporotic status, causing complications like lower back pain, limited spinal activities and vertebral refracture. The post-operative systematic and standardized rehabilitation treatments can improve curative effect and therapeutic efficacy of anti-osteoporosis, reduce risk of vertebral refracture, increase patient compliance and improve quality of life. Since there still lack relevant clinical treatment guidelines for postoperative rehabilitation treatments following vertebral augmentation for OVCF, the current treatments are varied with uneven therapeutic effect. In order to standardize the postoperative rehabilitation treatment, the Spine Trauma Group of the Orthopedic Branch of Chinese Medical Doctor Association organized relevant experts to refer to relevant literature and develop the "Guideline for postoperative rehabilitation treatment following vertebral augmentation for osteoporotic vertebral compression fracture (2022 version)" based on the clinical guidelines published by the American Academy of Orthopedic Surgeons (AAOS) as well as on the principles of scientificity, practicality and advancement. The guideline provided evidence-based recommendations on 10 important issues related to postoperative rehabilitation treatments of OVCF.

Objective:To investigate the clinical efficacy of microsurgical resection in primary jugular foramen schwannomas (JFSs).Methods:A retrospective analysis was performed; the clinical data of 58 patients with JFSs treated by microsurgery in Department of Neurosurgery, First Affiliated Hospital of Sun Yat-sen University from May 2012 to June 2021 were collected. Seven patients accepted microsurgery via suboccipital retrosigmoid approach, and 51 patients accepted microsurgery via jugular foramen approach. Fifty-three patients were followed up for 4.5 years (ranged from 0.5-8.5 years); follow-ups included Karnofsky performance status (KPS) scores, postoperative complications, and imaging reexaminations. Results:Fifty patients (86.2%) achieved total tumor resection and 8 (13.8%) subtotal resection. The KPS scores at discharge were 68.6±14.9, which were significantly lower than the preoperative KPS scores (77.6±13.5, t=2.452, P=0.017). During the follow-up, 5 patients(9.4%) had tumor recurrence, and 39 patients (73.6%) had improved symptoms after surgery. One patient (1.9%, modified Samii D type) died of cerebellar hemorrhage and swelling after surgery. The main complications included new/aggravated hoarseness (11/53), cerebrospinal fluid leakage (7/53), new/aggravated dysphagia (5/53), and new facial paralysis (4/53). Conclusion:In microsurgical resection of JFSs, short-term symptoms of the lower cranial nerves may be exacerbated, but long-term results are good.

Objective To evaluate 3.0T high resolution magnetic resonance (HRMRI) scanner for determining the carotid plaque vulnerability.Method Fifteen inpatients with carotid plaque stenosis were enrolled.The stenosis rate confirmed by Doppler ultrasound was 50％-99％ (excluding those with 100％ occlusion of the carotid artery).Head and neck coil 24 (HNC 24) was used for extracranial carotid artery plaque scan.Results There was no statistically significant difference between pathology and 3.0T HRMRI in the detemination of carotid plaque composition (P =0.546)and carotid artery stenosis rate (P =0.289).HRMRI showed good consistency with pathology in detecting intraplaque hemorrhage (Kappa =0.816) and lipid necrosis core (Kappa =0.771),and normal consistency with pathology in detecting calcification (Kappa =0.674).The highest sensitivity (87.23％) and the highest specificity (97.77％) of intraplaque hemorrhage were detected for the core of lipid necrosis.Conclusion The 3.0T high resolution magnetic resonance detailed analysis of extracranial carotid plaque composition,morphology,luminal stenosis,plaque lumen and wall area data for assessment.

Objective To explore the application value of telepathological consultation in helping grassroots hospitals.Methods 578 cases of intraoperative telepathology consultation were reviewed,and the accuracy and the timely rate of diagnosis were calculated.The systematic distribution,benign and malignant distribution,and the distribution difference in different primary hospitals were analyzed,so as to evaluate the popularization value of the intraoperative telepathology consultation.Results The accuracy rate of 578 cases of intraoperative telepathology consultation was 99.83％.The timely rate of consultation in 30min was 96.02％,and most reports could be diagnosed in 2 to 5 mins.The source of tissues involved in consultation were thyroid,breast,ovary/fallopian tube and lung.In all cases,24.39％ of the malignant tumors were found.Among the diseases of different systems,the proportion of malignant tumors is the highest in breast diseases,followed by lung,thyroid and ovary.Among the four hospitals with most of the consultations,the rate of malignant tumor in Renmin Hospital of Jianli County was the highest,followed by Renmin Hospital of Yingshan County,Renmin Hospital of Xiaochang County,and Fifth Division Hospital of Xinjiang.Conclusion Intraoperative telepathology consultation can provide accurate and timely expert consultation for grassmots hospitals,avoid the "second operations" of the patients,improve the access of medical treatment for people living in relatively remote areas,solve the shortage of pathologists at the grassroots hospitals,and improve the level of doctors' diagnosis and treatment at the grassroots hospitals,which is worth popularizing and applying in Pathology Department of the grassroots hospitals.

Objective To investigate the effect of vacuum-assisted closure(VAC)on the circulating number of endothelia progenitor cell(EPCs)in diabetic patients with mild to moderate degrees of ischemic foot ulcer and their related factors. Methods A total of 84 diabetic patients with foot ulcer duration for at least 4 weeks and ankle brachial index(ABI)0.5~0.9 were selected and divided into and assigned to two groups according to 2: 1 randomization:vacuum-assisted closure(VAC)treatment group(n=56)and Non-VAC treatment group(n=28). The control group (NC) was composed of 18 patients who had normal glucose tolerance and lower extremity ulcer without arteriovenous disease. VAC was performed on the ulcer wound after debridement for 1 week in both VAC group and NC group,and the patients in Non-VAC group received conventional treatment process. The circulating number of EPCs was measured before and after various treatments and the influencing factors of their changes were analyzed. Results After VAC treatment,the circulating number of EPCs significantly increased in both VAC group and NC group[(85.3 ± 18.1)vs(34.1 ± 12.5)/106cells,(119.9 ± 14.4)vs(66.1 ± 10.6)/106cells,both P<0.05]. By contrast,the circulating number of EPCs had no significant change in Non-VAC group[(45.2 ± 19.4)vs(34.7 ± 16.8)/106cells, P>0.05]. In addition,the circulating levels of vascular endothelial growth factor(VEGF)and the protein expressions of VEGF and stromal cell-derived factor-1α(SDF-1α)in the granulation tissue also significantly increased after VAC treatment in both VAC group and NC group,but no significant change in Non-VAC group. Compared with Non-VAC group,the changes of VEGF and SDF-1α levels in the sera and granulation tissue were all significantly higher in both VAC group and NC group(P<0.05 or P<0.01). There were no significant differences in changes of the circulating number of EPCs, and VEGF and SDF-1α in the sera and granulation tissue between VAC group and NC group. Correlation analysis showed that the change of the circulating number of EPCs was correlated with the changes of VEGF and SDF-1α levels in the sera and granulation tissue of VAC group and NC group(P<0.05). Conclusion VAC treatment may increase the circulating number of EPCs in diabetic patients with mild to moderate ischemic foot ulcer as in non-diabetic controls,which may be attributed to the upregulation of systemic and local VEGF and SDF-1α levels.

Aim To observe the cytochrome 450 effect of ginsenoside Re on H9c2 cells, in order to clarify the molecular mechanism of ginsenoside Re. Methods H 9 c 2 cells were separately treated with ginsenoside Re for 1, 5, 10, 50, 100 μmol·L-1 or 6, 24, 36, 48, 60 h. CYP2C11, 2J3, 4A1, 4A3, 4F4 and ANP mR-NA expressions were analyzed by Real time PCR, and CYP4 A1 , 2 J3 protein expressions were detected by Western blot. Results Compared with control group, ginsenoside Re could effectively upregulate CYP2 C11 , CYP2 J3 , ANP mRNA expression to 1. 6 , 1. 8 , 3. 2 fold, and downregulate CYP4A1, CYP4A3, CYP4F4 mRNA expression to 0. 4, 0. 15, 0. 3 fold. Ginsen-oside Re could decrease CYP4 A1 protein expression in a concentration-dependent manner, while ginsenoside Re could increase CYP2 J3 protein expression in a con-centration-dependent manner. Conclusion Ginsen-oside could regulate CYP450 enzyme and change ANP gene expression, which might be the molecular mecha-nism of ginsenoside Re.

Objective To establish a CVS-11 pseudovirus particles ( pp)-based assay for detec-tion of neutralizing antibody against rabies virus. Methods An improved rapid fluorescence focus inhibition test ( RFFIT) for detection of neutralizing antibody against rabies virus ( RVNA) was established based on the CVS-11 pseudovirus expressing a luciferase reporter gene. Forty-six human serum samples were analyzed with the improved RFFIT and the results were compared with those by using standard RFFIT. Moreover, the improved RFFIT was used to detect the titers of RVNA in 91 serum samples collected from pet dogs and pet-breeders in Beijing. Results The coincidence rate of the improved RFFIT and the standard RFFIT was 100% regarding to the analysis of 46 human serum samples and 5 negative reference serum samples. Moreo-ver, the RVNA titers of all serum samples obtained with CVS-11 pseudovirus-based assay showed a signifi-cant high correlation with those obtained with standard RFFIT (n=46, r=0. 94, P<0. 000 1). All of the 91 serum samples collected from pet dogs and pet-breeders in Beijing were positive for RVNA as indicated by the improved RFFIT with a mean titer of 33. 01 IU/ml. Conclusion We established an improved RFFIT based on the CVS-11 pp expressing luciferase reporter gene, which might be used as a reliable alternative RFFIT for measuring RVNA titer. Analysis of the 91 serum samples collected in Beijing with the improved RFFIT showed that all samples were positive for RVNA.