Balanced medial-lateral wall vs selective 3-wall orbital decompression for sight-threatening Graves's orbitopathy: a clinical retrospective cohort study from 2016 to 2022.

PURPOSE: Although urgent orbital decompression surgery for sight-threatening Graves' orbitopathy unresponsive to available medical treatments continues to evolve, post-operative new-onset or worsened pre-operative strabismus or diplopia remains a significant complication. At present, the optimal surgical technique remains debatable. Here, we sought to compare long-term outcomes after balanced medial-lateral wall versus selective 3-wall decompression as an urgent treatment for unresponsive sight-threatening GO. METHODS: This retrospective study examined the post-operative outcome of 102 eyes (57 patients) that underwent urgent orbital decompression for sight-threatening GO. Treatment effectiveness was measured by visual acuity, proptosis, perimetry, and strabismus/diplopia, while fundus findings were detected by fundus color photography and optical coherence tomography and followed up for more than 12 months. RESULTS: Fifty-seven patients (102 orbits) with an average age of 52.7 ± 10.2 years were evaluated. Balanced medial-lateral wall (BMLW-OD) or selective 3-wall decompression(S3W-OD) were performed in 54 and 48 eyes, respectively. Twelve months after orbital decompression, all parameters significantly improved in both groups, including best-corrected visual acuity (BCVA), mean defect of visual field (VF-MD), pattern standard deviation of visual field (VF-PSD), and proptosis (all P < 0.01). However, new-onset esotropia occurred in 25.8% and 3.8% of patients who underwent BMLW-OD surgery or S3W-OD, respectively. Moreover, 6.5% and 38.5% of patients improved after decompression in the medial-lateral wall decompression group and the selective 3-wall decompression group, respectively. CONCLUSIONS: We demonstrated that S3W-OD provides a lower rate of new-onset strabismus/diplopia as compared with BMLW-OD surgery, while still allowing for satisfactory visual outcomes. TRIAL REGISTRATION NUMBER:  : NCT05627401. Date of registration: November 25, 2022.

Prediction and validation of common targets in atherosclerosis and non-small cell lung cancer influenced by atorvastatin.

BACKGROUND: Cardiovascular disease and cancer are the main causes of morbidity and mortality worldwide. Studies have shown that these two diseases may have some common risk factors. Atorvastatin is mainly used for the treatment of atherosclerosis in clinic. A large number of studies show that atorvastatin may produce anti-tumor activities. This study aimed to predict the common targets of atorvastatin against atherosclerosis and non-small cell lung cancer (NSCLC) based on network pharmacology. METHODS: The target genes of atherosclerosis and NSCLC were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. The disease-target-component model map and the core network were obtained using Cytoscape 3.7.1. The MTS and wound healing assay were used to detect the effect of atorvastatin on cell viability and migration of A549 cells. The expression of potential common target genes of atorvastatin against atherosclerosis and NSCLC were confirmed in A549 cells and lung cancer tissues of patients. RESULTS: We identified 15 identical pathogenic genes, and four of which (MMP9, MMP12, CD36, and FABP4) were considered as the key target genes of atorvastatin in anti-atherosclerosis and NSCLC. The MTS and wound healing assays revealed that atorvastatin decreased A549 cells migration significantly. Atorvastatin markedly decreased the expression of MMP9, MMP12, CD36, and FABP4 in A549 cells and patients were treated with atorvastatin. CONCLUSIONS: This study demonstrated 15 common pathogenic genes in both atherosclerosis and NSCLC. And verified that MMP 9, MMP 12, CD 36 and FABP 4 might be the common target genes of atorvastatin in anti-atherosclerosis and NSCLC.

Sex- and reproductive status-specific relationships between body composition and non-alcoholic fatty liver disease.

BACKGROUND: Sex and reproductive status differences exist in both non-alcoholic fatty liver disease (NAFLD) and body composition. Our purpose was to investigate the relationship between body composition and the severity of liver steatosis and fibrosis in NAFLD in different sex and reproductive status populations. METHODS: This cross-sectional study included 880 patients (355 men, 417 pre-menopausal women, 108 post-menopausal women). Liver steatosis and fibrosis and body composition data were measured using FibroScan and a bioelectrical impedance body composition analyzer (BIA), respectively, and the following parameters were obtained: liver stiffness measurement (LSM), controlled attenuation parameter (CAP), waist circumference (WC), body mass index (BMI), percent body fat (PBF), visceral fat area (VFA), appendicular skeletal muscle mass (ASM), appendicular skeletal muscle mass index (ASMI), fat mass (FM), fat free mass (FFM), and FFM to FM ratio (FFM/FM). Multiple ordinal logistic regression (MOLR) was used to analyze the independent correlation between body composition indicators and liver steatosis grade and fibrosis stage in different sex and menopausal status populations. RESULTS: Men had higher WC, ASM, ASMI, FFM, and FFM/FM than pre- or post-menopausal women, while pre-menopausal women had higher PBF, VFA, and FM than the other two groups (p < 0.001). Besides, men had greater CAP and LSM values (p < 0.001). For MOLR, after adjusting for confounding factors, WC (OR, 1.07; 95% CI, 1.02-1.12; P = 0.011) and FFM/FM (OR, 0.52; 95% CI, 0.31-0.89; P = 0.017) in men and visceral obesity (OR, 4.16; 95% CI, 1.09-15.90; P = 0.037) in post-menopausal women were independently associated with liver steatosis grade. WC and visceral obesity were independently associated with liver fibrosis stage in men (OR, 1.05; 95% CI, 1.01-1.09, P = 0.013; OR, 3.92; 95% CI, 1.97-7.81; P < 0.001, respectively). CONCLUSIONS: Increased WC and low FFM/FM in men and visceral obesity in post-menopausal women were independent correlates of more severe liver steatosis. In addition, increased WC and visceral obesity were independent correlates of worse liver fibrosis in men. These data support the sex- and reproductive status-specific management of NAFLD.

Retrospective analysis of 217 fatal intoxication autopsy cases from 2009 to 2021: temporal trends in fatal intoxication at Tongji center for medicolegal expertise, Hubei, China.

This retrospective analysis of fatal intoxication case autopsies was performed at Tongji Center for Medicolegal Expertise in Hubei (TCMEH) from 2009 to 2021 to obtain up-to-date information on intoxication cases. The objective was to describe important data about evolving patterns in intoxication occurrences, enhance public safety policies, and assist forensic examiners and police in more efficient handling of such cases. Analyses based on sex, age, topical exposure routes, toxic agents, and mode of death were performed using 217 records of intoxication cases collected from TCMEH as a sample, and the results were compared with reports previously published (from 1999 to 2008) from this institution. Deaths from intoxications occurred at a higher rate in males than in females and were most common among individuals aged 30-39 years. The most frequent method of exposure was oral ingestion. The causative agents of deadly intoxications have changed when compared to the data from the previous 10 years. For instance, deaths from amphetamine overdoses are becoming more prevalent gradually, whereas deaths due to carbon monoxide and rodenticide intoxication have declined dramatically. In 72 cases, pesticides continued to be the most frequent intoxication cause. A total of 60.4% of the deaths were accidental exposure. Men died from accidents at a higher rate than women, although women were more likely to commit suicide. Particular focus is needed on the use of succinylcholine, cyanide, and paraquat in homicides.

Curcumol inhibits breast cancer growth via NCL/ERα36 and the PI3K/AKT pathway.

Background: Breast cancer (BC) is the most common malignancy worldwide. ERα36 (ERα66 variant) is expressed in many breast cancer cells, especially highly expressed in tamoxifen (TAM)-resistant cell lines and triple-negative breast cancer, and our previous work revealed that nucleolin (NCL) is a protein target of curcumol. This study is aimed at investigating the effect and mechanism of curcumol on ERα36 positive breast cancer cells, and the relationship between curcumol's target protein NCL and ERα36. Study design: Application of in vivo and in vitro studies to reveal the mechanism of curcumol in inhibiting BC growth and the relationship between curcumol's target protein NCL and ERα36. Methods: The anti-tumor effect of curcumol was quantified via an MTT assay, colony formation and cycle arrest, respectively. The expressions of ERα36, NCL and the proteins involved in PI3K/AKT signaling were evaluated by western blotting. The interaction between two proteins was detected using co-immunoprecipitation (Co-IP) and an immunofluorescence assay. A mouse xenograft model was established to verify the role of ERα36 in breast cancer cells and curcumol's effect on ERα36 positive cancer cells. Results: Curcumol inhibited the cell growth, caused cell cycle arrest, decreased cell cycle related proteins and inactivated the PI3K/AKT pathway in ERα36 positive breast cancer cells. There is a positive correlation between NCL and ERα36 in breast cancer cells. In addition, ERα36 bound to NCL; the two proteins were distributed in the nucleus, cytoplasm and plasma membrane, where their expression was obviously decreased by curcumol. Moreover, NCL silenced by NCL siRNA blocked the cell cycle progress and inhibited the activation of PI3K/AKT in MDA-MB-231 cells, while overexpressed ERα36 increased the expression of NCL, promoted the cell cycle progress and enhanced the activity of PI3K/AKT in MCF-7 cells. NCL knockdown or ERα36 overexpression attenuated the effect of curcumol on breast cancer cells. Conclusion: Curcumol reduced the proliferation of breast cancer cells by targeting NCL/ERα36 and inactivating the PI3K/AKT pathway.

Comprehensive transcriptomic profiling and mutational landscape of primary gastric linitis plastica.

BACKGROUND: Primary gastric linitis plastica (GLP) is a distinct phenotype of gastric cancer with poor survival. Comprehensive molecular profiles and putative therapeutic targets of GLP remain undetermined. METHODS: We subjected 10 tumor-normal tissue pairs to whole exome sequencing (WES) and whole transcriptome sequencing (WTS). 10 tumor samples were all GLP which involves 100% of the gastric wall macroscopically. TCGA data were compared to generate the top mutated genes and the overexpressed genes in GLP. RESULTS: Our results reveal that GLP has distinctive genomic and transcriptomic features, dysfunction in the Hippo pathway is likely to be a key step during GLP development. 6 genes were identified as significantly highly mutated genes in GLP, including AOX1, ANKRD36C, CPXM1, PTPN14, RPAP1, and DCDC1). MUC6, as a previously identified gastric cancer driver gene, has a high mutation rate (20%) in GLP. 20% of patients in our GLP cohort had CDH1 mutations, while none had RHOA mutations. GLP exhibits high immunodeficiency and low AMPK pathway activity. Our WTS results showed that 3 PI3K-AKT pathway-related genes (PIK3R2, AKT3, and IGF1) were significantly up-regulated in GLP. Two genes were identified using immunohistochemistry (IHC), IGF2BP3 and MUC16, which specifically expressed in diffuse-type-related gastric cancer cell lines, and its knockdown inhibits PI3K-AKT pathway activity. CONCLUSIONS: We provide the first integrative genomic and transcriptomic profiles of GLP, which may facilitate its diagnosis, prognosis, and treatment.

Exploring the Mechanism of Yi-Jing Decoction in Treating Polycystic Ovary Syndrome by Using Network Pharmacology.

BACKGROUND: Yi-Jing decoction (YJD), a traditional Chinese medicine prescription, has been reported to be effective in the treatment of polycystic ovary syndrome (PCOS). However, the underlying mechanisms of YJD in treating PCOS are still unclear. OBJECTIVE: In the present work, the effective ingredients of YJD and their treatment mechanisms on PCOS were systematically analyzed. METHODS: The effective ingredients of YJD and targets of PCOS were selected from public databases. The network pharmacology method was used to analyze the ingredients, potential targets, and pathways of YJD for the treatment of PCOS. RESULTS: One hundred and three active ingredients were identified from YJD, of which 82 were hit by 65 targets associated with PCOS. By constructing the disease-common targetcompound network, five ingredients (quercetin, arachidonate, beta-sitosterol, betacarotene, and cholesterol) were selected out as the key ingredients of YJD, which can interact with the 10 hub genes (VEGFA, AKT1, TP53, ALB, TNF, PIK3CA, IGF1, INS, IL1B, PTEN) against PCOS. These genes are mainly involved in prostate cancer, steroid hormone biosynthesis, and EGFR tyrosine kinase inhibitor resistance pathways. In addition, the results of molecular docking showed that the ingredients of YJD have a good binding affinity with the hub genes. CONCLUSION: These results demonstrate that the treatment of PCOS by YJD is through regulating the levels of androgen and insulin and improving the inflammatory microenvironment.

Analysis of death attributable to smoking and drinking and the influence on life expectancy among residents ≥ 30 years old in Chengdu / 现代预防医学

@#Objective To understand the prevalence of smoking and drinking among residents ≥ 30 years old in Chengdu, and to investigate the death attributable to smoking and drinking and its effect on life expectancy. Methods The data sources were data of the causes of death of residents in the 2018 Sichuan Health Statistical Yearbook, the health survey data of Chengdu residents in the natural population cohort in southwest China, and the data of smoking and drinking related diseases and their relative risk in the global disease burden of the World Health Organization. The counterfactual attribution method was used to calculate the number of attributable deaths and life expectancy loss caused by smoking and drinking. Results The life expectancy of 30-year-old residents in Chengdu was 53.91 years (51.52 years for males and 56.48 years for females). The total number of deaths attributed to smoking was 14 370, with chronic obstructive pulmonary disease (4 926), lung cancer (4 234), and esophageal cancer (1 578) ranking the top three. The total number of deaths attributed to drinking was 2 185, among which cerebrovascular disease, esophageal cancer, and liver cirrhosis were the three leading causes of death attributable to drinking. The loss of life expectancy caused by smoking was 2.03 years (3.47 years for males and 0.39 years for females), and the loss caused by drinking was 0.28 years (0.48 years for males and 0.04 years for females). Conclusion Smoking and drinking cause a great loss of life expectancy of Chengdu residents and impose a huge disease burden on the death from respiratory system, digestive system, cardiovascular and cerebrovascular diseases.

Efficacy of routine exposure versus neuromonitoring of superior laryngeal nerve in thyroid cancer surgery / 中国基层医药

Objective:To investigate the efficacy of routine exposure versus neuromonitoring of the external branch of the superior laryngeal nerve (EBSLN) in thyroid cancer surgery. Methods:The clinical data of 500 patients who underwent open thyroid cancer surgery in the Department of Breast and Thyroid Surgery, People's Hospital of Quzhou from July 2017 to June 2020 were retrospectively analyzed. These patients were divided into a monitoring group ( n = 300) and an unmonitored group (control group) ( n = 200) according to whether neuromonitoring was performed during surgery. In the control group, the EBSLN was routinely exposed during the surgery for naked observation. In the monitoring group, the EBSLN was monitored. The Voice Handicap Index score, vocal cord function, and serum levels of parathyroid hormone and calcium ion were compared between the two groups before and after surgery. All patients were followed up for 1 year to observe injury to the EBSLN, parathyroid gland injury, and hypocalcemia. Results:In the monitoring group, operative time (112.32 ± 10.42) minutes, intraoperative blood loss (10.58 ± 5.04) mL, time to extubation (2.07 ± 0.54) days, postoperative drainage flow (10.55 ± 3.58) mL, and postoperative hospital stay (3.03 ± 1.03) days were significantly shorter and less compared with the control group ( t = 18.68, 15.09, 15.24, 32.98, 27.37, all P < 0.001). Compared with before surgery, normalized noise energy, amplitude perturbation, fundamental frequency perturbation, and fundamental frequency value in each group were significantly decreased after surgery, harmonic to noise ratio and the Voice Handicap Index were significantly increased after surgery. These indices were more obviously improved in the monitoring group compared with the control group ( t = 43.31, 27.10, 46.45, 37.11, 8.97, all P < 0.001). Compared with before surgery, serum levels of parathyroid hormone and calcium ion in each group were significantly decreased after surgery. After surgery, serum levels of parathyroid hormone and calcium ion in the control group were significantly lower than those in the monitoring group ( t = 41.14, 5.99, both P < 0.001). The incidence of complications in the monitoring group [4 cases of hypocalcemia (1.33%), 0 cases of parathyroid injury (0.00%), 8 cases of injury to the EBSLN] was significantly lower than that in the control group ( χ2 = 73.41, 74.17, 76.29, all P < 0.001). Conclusion:Neuromonitoring of the EBSLN during open thyroid cancer surgery can effectively improve patient voice and vocal cord function, reduce the rate of injury to the EBSLN, and has a clinical application value.

Exploring biological connotation of blood stasis syndrome of rheumatoid arthritis and establishment of improved animal models based on syndrome-symptom mapping / 药学学报

Blood stasis syndrome is one of the core clinical syndrome of rheumatoid arthritis (RA), but the biological connotation of this syndrome is not clear, and there is a lack of disease improved animal models that match the characteristics of this disease and syndrome. The aim of this study was to screen the candidate biomarker gene set of blood stasis syndrome of RA, reveal the biological connotation of this syndrome, and explore and evaluate the preparation method of the improved animal model based on the characteristics of "disease-syndrome-symptom". The study was approved by the ethics committee of Guang'anmen Hospital, Chinese Academy of Traditional Chinese Medicine (No. 2019-073-KY-01) and the First Affiliated Hospital of Tianjin University of Traditional Chinese Medicine (No. TYLL2021[K]018), and the study subjects gave their informed consent. Animal welfare and experimental procedures followed the regulations of the Experimental Animal Ethics Committee of the Chinese Academy of Traditional Chinese Medicine (No. IBTCMCACMS21-2207-01). The whole blood samples were collected clinically from RA patients with blood stasis syndrome (3 cases) or other syndromes (7 types, 3 cases/type), and healthy volunteers (4 cases), and then transcriptome sequencing, KEGG, gene set enrichment analysis (GSEA) and weighted correlation network analysis (WGCNA) analysis were performed. 126 pivotal genes were screened, and their functional annotation results were significantly enriched in "immune-inflammation" related pathways and lipid metabolism regulation (sphingolipids, ether lipid metabolism and steroid biosynthesis). Syndrome-symptom mapping of hub gene set to the TCM primary and secondary symptoms, Western phenotypic symptoms and pathological links showed that joint tingling, abnormal joint morphology, petechiae and abnormal blood circulation are representative of blood stasis syndrome of RA. The results of the improved animal model showed that the rats in the collagen-induced arthritis + adrenaline hydrochloride (CIA+Adr) 3 model group had increased blood rheology, coagulation, platelet function and endothelial function abnormalities compared with the CIA-alone model group, suggesting that the rats with blood stasis syndrome of RA may be in a state of "blood stasis". The results of the study can help to advance the objective study of the evidence of blood stasis syndrome in RA, and provide new ideas for the establishment of an animal model that reflects the clinical characteristics of the disease and syndrome.

Effects of fat suction combined with bipolar radiofrequency on facial and neck rejuvenation / 中华医学美学美容杂志

Objective:To investigate the efficacy and safety of fat suction combined with bipolar radiofrequency on face and neck rejuvenation.Methods:A total of 115 patients with face and neck fat deposits and skin laxity underwent fat suction combined with bipolar radiofrequency between December 2021 and October 2022 by the same surgeon in Changsha My Like Medical Cosmetology Hospital. There were 3 men and 112 women in this research. The mean age was 36.1 years (range, 26-55 years) and the mean body mass index was 21.4 (range, 16.8-27.7 kg/cm 2). Postoperative patient satisfaction surveys were conducted and 2 independent doctors evaluated clinical effect with preoperative and postoperative photographs at 3-6 months postoperatively. Results:The mean amount of fat aspirated was 44.5 ml (range, 10-92 ml) and the mean energy delivered was 4.5 kJ (range, 2.1-8.9 ml). 88.7% of patients were satisfied with their postoperative effect (102/115 patients). 92.2% of doctors were satisfied with the postoperative effect (106/115 patients). Four out of 115 patients (3.5%) developed irregularity by fat suction.Conclusions:Fat suction combined with bipolar radiofrequency can effectively reduce the fat accumulation of facial and neck and significantly improve skin relaxation. It is an effective method to rejuvenate facial and neck.

Role of Nrf2/HO-1 signaling pathway in edaravone-induced attenuation of long-term cognitive impairment caused by long-time sedation with propofol in neonatal rats / 中华麻醉学杂志

Objective:To evaluate the role of nuclear factor E2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling pathway in edaravone-induced attenuation of long-term cognitive impairment caused by long-time sedation with propofol in the neonatal rats.Methods:Eighty SPF healthy newborn Sprague-Dawley rats of both sexes, aged 7 days, weighing 15-20 g, were divided into 4 groups ( n=20 each) using a random number table method: control group (group C), propofol group (group P), edaravone+ propofol group (group EP) and Nrf2 inhibitor ML385+ edaravone+ propofol group (group MEP). Propofol 75 mg/kg was intraperitoneally injected once a day for 7 consecutive days in P group, EP group and MEP group, respectively, while the equal volume of medium/long chain fat emulsion injection was intraperitoneally injected in C group. Edaravone 3 mg/kg was intraperitoneally injected at 30 min before each propofol injection in EP and MEP groups, and ML385 15 mg/kg was intraperitoneally injected simultaneously in group MEP. The spontaneous activity was evaluated by the open field test on day 29 after birth, and the cognitive function was assessed by Morris water maze test on days 30-34 after birth. The rats were sacrificed after the end of water maze test, and brains were removed and hippocampal tissues were obtained for determination of reactive oxygen species (ROS) levels (by flow cytometry), superoxide dismutase (SOD) and malondialdehyde (MDA) levels (by enzyme-linked immunosorbent assay) and expression of Nrf2 and HO-1 (by Western blot) and for microscopic examination of the pathological changes in the hippocampal CA1 area (using HE staining). Results:There was no significant difference in the speed, distance and time of stay at the center of the open field among the four groups ( P>0.05). Compared with C group, the escape latency was significantly prolonged, the number of crossing the original platform quadrant was reduced, the levels of MDA and ROS were increased, the activity of SOD was decreased, the expression of Nrf2 and HO-1 was down-regulated ( P<0.05), and the pathological injury was observed in the hippocampal CA1 region in group P. Compared with P group, the escape latency was significantly shortened, the number of crossing the original platform quadrant was increased, the levels of MDA and ROS in the hippocampus were decreased, the activity of SOD was increased, the expression of Nrf2 and HO-1 was up-regulated ( P<0.05), and the pathological injury in the hippocampal CA1 region was significantly alleviated in EP group. Compared with EP group, the escape latency was significantly prolonged, the number of crossing the original platform quadrant was reduced, the levels of MDA and ROS were increased, the activity of SOD was decreased, the expression of Nrf2 and HO-1 was down-regulated ( P<0.05), and the pathological injury was aggravated in the hippocampal CA1 region in MEP group. Conclusions:The mechanism by which edaravone attenuates long-term cognitive impairment caused by long-time sedation with propofol is related to activation of Nrf2/HO-1 signaling pathway and inhibition of oxidative stress in the neonatal rats.

Role of TLR4/NF-κB signaling pathway in long-term cognitive impairment induced by multiple exposures to sevoflurane anesthesia in neonatal rats / 中华麻醉学杂志

Objective:To evaluate the role of Toll-like receptor 4 (TLR4)/nuclear transcription factor κB (NF-κB) signaling pathway in long-term cognitive impairment induced by multiple exposures to sevoflurane anesthesia in neonatal rats.Methods:Seventy-five SPF healthy newborn Sprague-Dawley rats of either sex, aged 6 days, weighing 12-20 g, were divided into 3 groups ( n=25 each) using a random number table method: control group (group C), multiple exposures to sevoflurane anesthesia group (group S) and TLR4 inhibitor plus multiple exposures to sevoflurane anesthesia group (group I+ S). The rats in group S and group I inhaled 3% sevoflurane for 2 h at 6, 7 and 8 days after birth. TLR4 inhibitor TAK-242 10 mg/kg was intraperitoneally injected before each exposure to sevoflurane in group I, and the equal volume of normal saline was given instead in the other two groups. The spontaneous activity was evaluated by open field test on day 29 after birth, and the cognitive function was assessed by Morris water maze test on days 30-34 after birth. After the behavioral test, the blood samples from the abdominal aorta were collected, and then the rats were sacrificed under deep anesthesia to isolate the hippocampal tissues for measurement of the levels of S100β and neuron-specific enolase (NSE) in serum and hippocampal interleukin-1β (IL-1β), IL-6 and tumor necrosis factor α (TNF-α) (by enzyme-linked immunosorbent assay), expression of TLR4, NF-κB p65 and phosphorylated NF-κB p65 (p-NF-κB p65) (by Western blot) and for microscopic examination of the pathological changes of hippocampal CA1 region after HE staining. Results:Compared with group C, the escape latency was significantly prolonged, the number of crossing the original platform was reduced, the TLR4 expression was up-regulated, the ratio of p-NF-κB p65/NF-κB p65 was increased, the levels of serum S100β protein and NSE and hippocampal IL-1β, IL-6 and TNF-α were increased ( P<0.05), and the pathological changes in the hippocampal CA1 region were aggravated in group S. Compared with group S, the escape latency was significantly shortened, the number of crossing the original platform was increased, TLR4 expression was down-regulated, the ratio of p-NF-κB p65/NF-κB p65 was decreased, the levels of S100β and NSE in serum and hippocampal IL-1β, IL-6 and TNF-α were decreased ( P<0.05), and the pathological changes in hippocampal CA1 area were significantly attenuated in group P. Conclusions:The mechanism by which multiple exposures to sevoflurane anesthesia induces long-term cognitive impairment is related to activation of TLR4/NF-κB signaling pathway and increase in hippocampal inflammatory responses in neonatal rats.

Research progress of familial hereditary prostate cancer / 中华泌尿外科杂志

Hereditary prostate cancer has the highest hereditary rate in men cancers. Genes associated with hereditary prostate cancer susceptibility include mismatch repair genes (MLH1, MSH2, MSH6 and PMS2) and homologous recombination genes (BRCA1/2, ATM, PALB2, CHEK2), and single nucleotide polymorphisms and copy number variants also play a role in genetic mutations. Early onset, rapid disease progression and locally advanced stage are the main features of hereditary prostate cancer. Patients with potentially hereditary prostate cancer would benefit from undergoing genetic testing or counseling. This article reviews the current status of the prevalence, incidence characteristics, and etiology of familial hereditary prostate cancer and other research advances.

Efficacy comparison between pneumovesicoscopic Cohen and Politano-Leadbetter technique in transvesicoscopic ureteral reimplantation in children / 中华实用儿科临床杂志

Objective:To compare the efficacy of pneumovesicoscopic Cohen and Politano-Leadbetter procedures in the treatment of vesicoureteral junction obstruction (VUJO) in children.Methods:The data of 48 children with VUJO who underwent operations in the Department of Urology, Anhui Provincial Children′s Hospital from January 2017 to December 2021 were retrospectively analyzed.According to the operation time, the patients were divided into the pneumovesicoscopic Cohen group(group C) (28 cases) and pneumovesicoscopic Politano-Leadbetter group(group P) (20 cases). The operation time, postoperative urinary catheterization duration, hematuria duration, hospitalization time, and the improvement of hydronephrosis, ureteral dilatation, and renal function after surgery were compared between the 2 groups.The enumeration data were compared by the χ2 test or Fisher′ s exact probability method.The measurement data were compared by the t-test. Results:All the 48 children were successfully operated on by the same surgeon, without conversion to open surgery.Six cases in the group C had a megaureter and underwent ureter tailoring.Two cases in the group P had calyceal and ureteral calculi, which were all removed after operation.There was a statistically significant difference in the operation time between group C and group P[(136.5±35.4) min vs.(165.8±33.2) min, t=-3.154, P=0.002]. The patients were followed up for (10.3±2.6) months after operation.There were 8 cases and 6 cases of urinary tract infection in group C and group P within 2 months after the operation, respectively.They all improved after conservative anti-infection treatment, and the infection was well controlled after removal of the D-J tube.Besides, their intravenous pyelography 6 months after operation showed that the ureter was unobstructed.In group C, 6 months after the operation, the anterior and posterior diameters of the renal pelvis [(1.62±0.54) cm vs.(2.55±1.24) cm, t=-5.027, P=0.001] and the largest diameter of the ureter [(0.95±0.27) cm vs.(1.51±0.52) cm, t=-8.495, P<0.001] were significantly decreased, compared with those before operation.However, the renal cortex thickness was increased significantly [(1.47±0.25) cm vs.(0.86±0.46) cm, t=2.028, P=0.004], and the renal function (as indicated by the diuretic nephrogram) was notably improved [(46.27±2.16)% vs.(41.83±3.04)%, t=1.647, P=0.030]. In group P, 6 months after operation, the anterior and posterior diameters of the renal pelvis[(1.48±0.82) cm vs.(2.68±1.41) cm, t=-2.740, P=0.003] and the maximum diameter of the ureter [(1.05±0.46) cm vs.(1.36±0.27) cm, t=-1.635, P=0.040] were significantly smaller than those before operation.However, the renal cortical thickness was increased [(1.38±0.33) cm vs.(0.74±0.39) cm, t=9.073, P<0.001], and the renal function (as indicated by the diuretic nephrogram) was significantly improved [(45.18±3.35)% vs.(39.55±2.49)%, t=1.277, P=0.030]. Politano-Leadbetter surgery outperformed Cohen surgery in promoting the recovery of the anterior and posterior diameters of the renal pelvis [(1.48±0.82) cm vs.(1.62±0.54) cm, t=-1.748, P=0.030]. Conclusions:Pneumovesicoscopic Politano-Leadbetter operation can establish a longer submucosal tunnel without changing the ureteral shape and opening position, having good effects in treating VUJO combined with calyceal and ureteral calculi.Pneumovesicoscopic Politano-Leadbetter operation can also better improve postoperative recovery from hydronephrosis than Cohen operation.However, the pneumovesicoscopic Politano-Leadbetter operation is more difficult and requires longer time.The surgeon should choose a reasonable operation based on his/her own experience.

Safety and efficacy of the early administration of levosimendan in patients with acute non-ST-segment elevation myocardial infarction and elevated NT-proBNP levels: An Early Management Strategy of Acute Heart Failure (EMS-AHF) / 中华内科杂志

Objectives: To investigated the safety and efficacy of treating patients with acute non-ST-segment elevation myocardial infarction (NSTEMI) and elevated levels of N-terminal pro-hormone B-type natriuretic peptide (NT-proBNP) with levosimendan within 24 hours of first medical contact (FMC). Methods: This multicenter, open-label, block-randomized controlled trial (NCT03189901) investigated the safety and efficacy of levosimendan as an early management strategy of acute heart failure (EMS-AHF) for patients with NSTEMI and high NT-proBNP levels. This study included 255 patients with NSTEMI and elevated NT-proBNP levels, including 142 males and 113 females with a median age of 65 (58-70) years, and were admitted in the emergency or outpatient departments at 14 medical centers in China between October 2017 and October 2021. The patients were randomly divided into a levosimendan group (n=129) and a control group (n=126). The primary outcome measure was NT-proBNP levels on day 3 of treatment and changes in the NT-proBNP levels from baseline on day 5 after randomization. The secondary outcome measures included the proportion of patients with more than 30% reduction in NT-proBNP levels from baseline, major adverse cardiovascular events (MACE) during hospitalization and at 6 months after hospitalization, safety during the treatment, and health economics indices. The measurement data parameters between groups were compared using the t-test or the non-parametric test. The count data parameters were compared between groups using the χ² test. Results: On day 3, the NT-proBNP levels in the levosimendan group were lower than the control group but were statistically insignificant [866 (455, 1 960) vs. 1 118 (459, 2 417) ng/L, Z=-1.25,P=0.21]. However, on day 5, changes in the NT-proBNP levels from baseline in the levosimendan group were significantly higher than the control group [67.6% (33.8%,82.5%)vs.54.8% (7.3%,77.9%), Z=-2.14, P=0.03]. There were no significant differences in the proportion of patients with more than 30% reduction in the NT-proBNP levels on day 5 between the levosimendan and the control groups [77.5% (100/129) vs. 69.0% (87/126), χ²=2.34, P=0.13]. Furthermore, incidences of MACE did not show any significant differences between the two groups during hospitalization [4.7% (6/129) vs. 7.1% (9/126), χ²=0.72, P=0.40] and at 6 months [14.7% (19/129) vs. 12.7% (16/126), χ²=0.22, P=0.64]. Four cardiac deaths were reported in the control group during hospitalization [0 (0/129) vs. 3.2% (4/126), P=0.06]. However, 6-month survival rates were comparable between the two groups (log-rank test, P=0.18). Moreover, adverse events or serious adverse events such as shock, ventricular fibrillation, and ventricular tachycardia were not reported in both the groups during levosimendan treatment (days 0-1). The total cost of hospitalization [34 591.00(15 527.46,59 324.80) vs. 37 144.65(16 066.90,63 919.00)yuan, Z=-0.26, P=0.80] and the total length of hospitalization [9 (8, 12) vs. 10 (7, 13) days, Z=0.72, P=0.72] were lower for patients in the levosimendan group compared to those in the control group, but did not show statistically significant differences. Conclusions: Early administration of levosimendan reduced NT-proBNP levels in NSTEMI patients with elevated NT-proBNP and did not increase the total cost and length of hospitalization, but did not significantly improve MACE during hospitalization or at 6 months.

Immunogenicity and safety of revaccination of 23-valent pneumococcal polysaccharide vaccine in people aged 60 years and above / 中华流行病学杂志

Objective: To evaluate the immunogenicity and safety of revaccination of 23-valent pneumococcal polysaccharide vaccine (PPV23) in elderly people aged ≥60 years. Methods: The elderly aged ≥60 years with 1 dose of PPV23 vaccination were selected as revaccination group and those without history of pneumococcal vaccine immunization were selected as the first vaccination group. One dose of PPV23 was administered to both groups, and the first blood samples were collected before vaccination while the second blood samples were collected on day 28-40 after vaccination. ELISA was used to detect the concentrations of anti-specific serotype Streptococcus pneumoniae podocyte polysaccharide immunoglobulin G, and the safety of the vaccination was evaluated after 30 days. Results: The geometric mean concentration (GMC) of antibody to 23 serotypes before the vaccination (0.73-13.73 μg/ml) was higher in revaccination group than in the first vaccination group (0.39-7.53 μg/ml), the GMC after the vaccination (1.42-31.65 μg/ml) was higher than that before the vaccination (0.73-13.73 μg/ml) in the revaccination group, and the GMC after the vaccination (1.62-43.76 μg/ml) was higher than that before the vaccination (0.39-7.53 μg/ml) in the first vaccination group; the geometric mean growth multiple in revaccination group (2.16-3.60) was lower than that in the first vaccination group (3.86-16.13); The mean 2-fold antibody growth rate was lower in revaccination group (53.68%, 95%CI: 52.30%-55.06%) than in the first vaccination group (93.16%, 95%CI: 92.18%- 94.15%), all differences were significant (P<0.001). After the vaccination, 13 serotypes of GMC were higher in the first vaccination group than in revaccination group (P<0.001), the differences were not significant for 10 serotypes of GMC (P>0.05). The incidence of local adverse reaction was 19.20% and 13.27% in revaccination group and the first vaccination group, respectively (P=0.174). Conclusions: The antibody level in ≥60 years people who received one dose of PPV23 after a 5-year interval was still higher than that in unvaccinated people. The antibody level decreased after 5 years of the first vaccination, and the antibody level could be rapidly increased by one more dose vaccination, but the overall immune response was lower than that of the first vaccination; revaccination with PPV23 has a good safety.

Fontan-associated liver disease current status and transplantation consideration / 中华肝脏病杂志

Fontan-associated liver disease (FALD) is one of the main complications after the Fontan procedure, manifesting mostly as liver fibrosis and even cirrhosis, with a high incidence rate and a lack of typical clinical symptoms that seriously affect patient prognosis. The specific cause is unknown, although it is considered to be associated with long-term elevated central venous pressure, impaired hepatic artery blood flow, and other relevant factors. The absence of association between laboratory tests, imaging data, and the severity of liver fibrosis makes clinical diagnosis and monitoring difficult. A liver biopsy is the gold standard for diagnosing and staging liver fibrosis. The most important risk factor for FALD is time following the Fontan procedure; therefore, it is recommended to do a liver biopsy 10 years after the Fontan procedure and to be cautious for the presence of hepatocellular carcinoma. Combined heart-liver transplantation is a recommended choice with favorable outcomes for patients with Fontan circulatory failure and severe hepatic fibrosis.

Diagnostic value of novel hepatic fibrosis markers in assessing cirrhosis in patients with chronic hepatitis C / 中华肝脏病杂志

Objective: To investigate the efficacy of chitinase-3-like protein 1 (CHI3L1) and Golgi protein 73 (GP73) in the diagnosis of cirrhosis and the dynamic changes of CHI3L1 and GP73 after HCV clearance in patients with chronic hepatitis C (CHC) treated with direct-acting antiviral drugs (DAAs). The comparison of continuous variables of normal distribution were statistically analyzed by ANOVA and t-test. The comparison of continuous variables of non-normal distribution were statistically analyzed by rank sum test. The categorical variables were statistically analyzed by Fisher's exact test and χ(2) test. Correlation analysis was performed using Spearman correlation analysis. Methods: Data of 105 patients with CHC diagnosed from January 2017 to December 2019 were collected. The receiver operating characteristic curve (ROC curve) was plotted to study the efficacy of serum CHI3L1 and GP73 for the diagnosis of cirrhosis. Friedman test was used to compare CHI3L1 and GP73 change characteristics. Results: The areas under the ROC curve for CHI3L1 and GP73 in the diagnosis of cirrhosis at baseline were 0.939 and 0.839, respectively. Serum levels of CHI3L1 and GP73 in the DAAs group decreased significantly at the end of treatment compared with baseline [123.79 (60.25, 178.80) ng/ml vs. 118.20 (47.68, 151.36) ng/ml, P = 0.001; 105.73 (85.05, 130.69) ng/ml vs. 95.52 (69.52, 118.97) ng/ml, P = 0.001]. Serum CHI3L1 and GP73 in the pegylated interferon combined with ribavirin (PR) group were significantly lower at the end of 24 weeks of treatment than the baseline [89.15 (39.15, 149.74) ng/ml vs. 69.98 (20.52, 71.96) ng/ml, P < 0.05; 85.07 (60.07, 121) ng/ml vs. 54.17 (29.17, 78.65) ng/ml, P < 0.05]. Conclusion: CHI3L1 and GP73 are sensitive serological markers that can be used to monitor the fibrosis prognosis in CHC patients during treatment and after obtaining a sustained virological response. Serum CHI3L1 and GP73 levels in the DAAs group decreased earlier than those in the PR group, and the serum CHI3L1 levels in the untreated group increased compared with the baseline at about two years of follow-up.