OBJECTIVE To systematically evaluate the efficacy and safety of the sedative effect of remimazolam in endoscopy and to compare it with propofol and midazolam. METHODS Search PubMed, Embase, Cochrane Library, Wanfang database, CNKI and other databases to collect the literature of randomized controlled trials of remimazolam for sedation in endoscopy. The search period was from 2018 onwards when remimazolam was approved for clinical trials until April 2022. The search strategy included the following variable keywords: remimazolam, gastroscopy, bronchoscopy, and colonoscopy. The quality of the included literature was assessed and the collected data were subjected to meta-analysis by RevMan 5.4 software. RESULTS Ten relevant RCTs involving midazolam and propofol, involving a total of 2 076 patients were included in the analysis. The results showed that the sedative effect of remimazolam was significantly higher than that of midazolam [OR=0.03, 95%CI(0.02, 0.05), I2=0%, P<0.000 01]; but lower than that of propofol [OR=11.32, 95%CI(2.12, 60.56), I2=0%, P=0.005]. The onset time of remimazolam was longer than that of propofol, but shorter than that of midazolam; the recovery time was faster than that of propofol and midazolam. Compared with midazolam, there was no significant difference in the incidence of adverse reactions. Compared with propofol, remimazolam was associated with lower rates of hypotension, slowed heart rate, hypoxemia, and injection pain, but higher risk ratio of nausea, with no difference invomiting. CONCLUSION The sedative effect and onset of action of remimazolam are better than midazolam but less than propofol when used for endoscopy. Wake-up time is faster than that of propofol and midazolam. The incidence of respiratory and circulatory depression is lower with remimazolam than with propofol, and there are no significant differences in adverse effects compared with midazolam.

Objective:To investigate the effect of KRT5 knockdown in keratinocytes on melanin content in co-cultured melanocytes, and to explain mechanisms underlying formation of hyperpigmented lesions in reticulate pigmented anomaly of the flexures (Dowling-Degos disease, DDD) .Methods:HaCaT cells with heterozygous mutations in the KRT5 gene were obtained by using clustered regularly interspaced short palindromic repeats (CRISPR) -CRISPR-associated protein 9 (Cas9) technology (experimental group) , and HaCaT cells transfected with non-targeting single guide RNA:Cas9 protein complex served as control group, both of which were in vitro co-cultured with primary human melanocyte cells (HEMn) separately. Immunofluorescence study was conducted to determine the expression of cytokeratin and melanosomes in co-cultured cells; melanin content was detected in melanocytes in different co-culture groups, which were obtained by differential trypsinization. Immunohistochemical study was performed to determine the expression of melanocyte-specific premelanosome protein 17 (Pmel17) in skin lesions in a patient with DDD carrying a KRT5 mutation and normal skin tissues in a healthy control. Results:Sanger sequencing showed a heterozygous mutation (c.1delA) at the initiation codon of exon 1 of the KRT5 gene in HaCaT cells in the experimental group, but no mutation in the KRT5 gene in the control group. Western blot analysis showed that the KRT5 protein expression was significantly lower in the experimental group (0.60 ± 0.05) than in the control group (1.00 ± 0.00, t = 32.38, P = 0.001) . Compared with the co-culture system in the control group, the number of Pmel17-labeled melanosomes markedly increased with the melanin content elevated by 52.5% ( t = -3.48, P = 0.025) in the HEMn cells co-cultured with HaCaT cells in the experimental group. Immunohistochemical study showed that the Pmel17 expression increased in the skin lesions in the DDD patient with KRT5 mutation compared with the normal skin tissues in the healthy control. Conclusion:The effect of HaCaT cells with CRISPR-Cas9-induced KRT5 mutation on the co-cultured HEMn melanocytes was verified by the successfully established in vitro co-culture system, which provides a primary cell model for further studies on interaction mechanisms between keratinocytes and melanocytes, and on pathogenesis of skin pigmentation abnormalities.

Objective To explore the application scope of small splint in the treatment of type-C distal radius fractures. Methods According to CT scan data from the right forearm of a healthy male volunteer, the three-dimensional model of normal distal radius was established. According to AO classification, the fracture line based on normal model was divided to establish nine kinds of high-order tetrahedral mesh models of the upper forearm with C-type fracture. Finite element analysis on nine kinds of fracture models was conducted in ANSYS 15.0 software to obtain the corresponding stress values, and then the stress distribution contours were generated. Results As soft tissues of the wrist were thin with more fracture blocks, after the splint was fixed, the stress on the wrist under 100 N maximum physiological axial load was significantly larger compared with that on the other parts, and the compressive stress was mainly concentrated on the wrist joint. The fixed effect of C2.2, C2.3, C3.2, C3.3-type fracture by small splint was relatively poor, as such comminuted fracture would cause too many and too small fracture blocks, while the fixed effect of C1.1, C1.2, C1.3, C2.1 and C3.1-type fracture was better. Conclusions Through the related finite element study on the treatment of C-type fracture distal radius with small splint, the application scope of small splint was preliminarily determined, which could provide some reference for clinical work.

Objective: To investigate the prevalence of liver depression and spleen deficiency syndrome in sub-health status and the demographic data of liver depression and spleen deficiency syndrome in sub-health status. Methods: The clinical epidemiological survey was conducted in the routine physical examination population using the "Sub-health State TCM Syndrome Questionnaire (3 Edition)". Descriptive analysis was used to analyze the relevant data of sub-health status of liver depression and spleen deficiency syndrome. Results: The incidence of sub-health state of liver depression and spleen deficiency syndrome was 7.16％. The sub-health state of liver depression and spleen deficiency syndrome was characterized by a higher proportion of females than males. The incidence of liver depression and spleen deficiency syndrome was higher in all groups over 19 years of age. The highest proportion occurred in colleges and universities, and the highest proportion occurred in divorced persons in marital status. The occupational status was the highest among persons in charge of enterprises and institutions, administrative personnel, professional technicians, and teachers with administrative personnel.

Objective: To observe the changes of Notch signaling pathway related molecule expression in hippocampus of rats with stagnation of liver qi and spleen deficiency syndrome and to explore the regulatory effect of Xiaoyaosan. Methods: Male SD rats were randomly divided into four groups: normal group, model group, model+xiayaosan group and model+fluoxetine group, each group had 12 rats. The stagnation of liver qi and spleen deficiency model was established by chronic immobilization stress for 21 days. Detection of Nissl bodies by Nissl staining, expression of NICD, Hes1, Hes5 and Jad1 were detected by Fluorescent quantitative PCR and Western-blot method. Results: Compared with the normal group, the number of Nissl bodies in the model group decreased significantly (P ＜ 0.01), which showed that Xiaoyaosan and fluoxetine could reverse it (P ＜ 0.01). The expression of Notch signaling pathway-related protein in model group was significantly lower than that in normal group (P ＜ 0.01), which showed that Xiaoyaosan and fluoxetine could reverse the expression of NICD, Hes5 and Jag1 protein (P ＜ 0.05, P ＜ 0.01). Compared with the normal group, the expression of each gene in the model group decreased (P ＜ 0.01), which showed that Xiaoyaosan and fluoxetine could reverse the expression of NICD, Hes1 and Hes5 mRNA (P ＜ 0.05, P ＜ 0.01). Conclusion: The hippocampal neurons of rats with stagnation of liver qi and spleen deficiency syndrome were damaged and the Nissl bodies were reduced, the expression of each protein and gene in Notch signaling pathway decreased. Xiaoyaosan may play a therapeutic role by regulating the expression level of hippocampal related molecules to protect neurons.

To examine levels of M-type phospholipase A2 receptor (PLA2R) and its antibody in the patients with hepatitis B virus-associated membranous nephropathy (HBV-MN), and to explore the correlation of PLA2R with laboratory parameters and pathological characteristics.
 Methods: A total of 49 adult patients with biopsy-proved HBV-MN were enrolled in this study. Levels of anti-PLA2R antibody in serum and PLA2R in renal tissue were detected. Patients were assigned into two groups: a positive PLA2R group and a negative PLA2R group. Differences in laboratory parameters and pathological characteristics were compared between the two groups.
 Results: Of 49 patients with HBV-MN, 17 had positive PLA2R expression in renal tissues. In the positive PLA2R group, 10 patients were positive for serum anti-PLA2R antibody. Patients with positive PLA2R expression in renal tissues showed higher levels of 24 hour urinary protein [(4.6±3.9) g/d], serum HbsAg (70.5%) and renal HbsAg expression (71%), while lower level of serum albumin [(24.1±7.5) g/L] than those of the negative group.
 Conclusion: PLA2R is expressed in the renal tissues and serum anti-PLA2R antibody can be detected in some HBV-MN patients. Positive PLA2R expression in renal tissue might be related to HbsAg deposition in serum and renal tissues. Patients with positive PLA2R expression in renal tissue have more severe glomerular sclerosis.
Adult ; Antibodies ; Autoantibodies ; genetics ; physiology ; Biopsy ; Glomerulonephritis, Membranous ; complications ; etiology ; genetics ; Hepatitis B ; complications ; Hepatitis B Surface Antigens ; adverse effects ; Hepatitis B virus ; Humans ; Kidney ; blood supply ; chemistry ; physiopathology ; Kidney Diseases ; etiology ; genetics ; physiopathology ; Male ; Prognosis ; Proteinuria ; epidemiology ; genetics ; Receptors, Phospholipase A2 ; blood ; physiology ; Serum Albumin ; genetics

Objective To explore the application value of detection of Mycoplasma,Chlamydia and anti-sperm antibodies for male infertility.Methods Culture method,immune chromatography,and enzyme linked immunosorbent assay were adopted for the detection of Mycoplasma,Chlamydia,and anti-sperm antibodies respectively in 102 cases of infertile males and 42 cases fertile males.And the routine semen analysis was proceed as well.All the subjects were divided into 4 groups according to the detection re-sults:simple Mycoplasma or/and Chlamydia positive group(71 cases),simple anti-sperm antibodies positive group(21 cases),My-coplasma and Chlamydia or/and anti-sperm antibodies positive group(8 cases),Mycoplasma,Chlamydia and anti-sperm antibodies negative group(44 cases).The main indexes of semen routine were compared among 4 groups.Results The positive rates of Myco-plasma,Chlamydia and anti-sperm antibodies in infertile males were significantly higher than those of fertile males (P <0.05).The sperm densities,activity rates,activity of simple Mycoplasma or/and Chlamydia positive group,simple anti-sperm antibodies posi-tive group,and Mycoplasma and Chlamydia or /and anti-sperm antibodies positive group were significantly lower than the nega-tive group,while the sperm malformation rates,liquefaction times,white blood cell counts of the three groups were significantly higher than the negative group(P <0.05 ).Conclusion Mycoplasma,Chlamydia infection and anti-sperm antibodies production have significant effect on the indexes of semen,which cause decline in semen quality and the occurrence of male infertility.

Objective To assess the efficacy and safety of premedicaton with pronase before upper gastrointestinal endoscopy (UGI).Methods A total of 440 outpatients from 5 centers were randomly assigned to receive endoscopy with one of three premedications as follows:dimethylpolysiloxane (DMPS) and pronase (group A,n =170) ; DMPS and sodium bicarbonate (group B,n =170) ; DMPS,pronase and sodium bicarbonate (group C,n =100).Six endoscopists,who were unaware of the premedication types,calculated the visibility scores (range,1 to 4) of the antrum,gastric body,and fundus.The sum of the scores from the three locations was defined as the total visibility score.Results With regards to routine white light endoscopy,the total visibility score of group C was significantly higher than that of group A (P =0.0001),and the score of group A was significantly higher than that of group B (P =0.0019).Concerning chromoendoscopy,the total visibility score of group C was significantly higher than that of group A (P =0.0054),and the score of group A was also significantly higher than that of group B (P ＜ 0.0001).Conclusion Combined application of pronase,dimethylpolysiloxane,and sodium bicarbonate before UGI endoscopy significantly improves endoscopic visualization.

Objective To examine the expression of IgA1 and B1a positive cells in palatine tonsils of IgA nephropathy (IgAN) patients, and to analyze the association between B1a cells and clinicopathological changes. Methods Eight patients diagnosed as IgAN by renal biopsy and 8 chronic tonsillitis patients without nephritis as control were enrolled in the study.Immunofluorescence and laser scanning confocal microscope (LSCM) were applied to observe the localization and quantitative calculation of Bla and IgA1 positive cells. Statistic analysis of the association of B1a cells with proteinuria and pathological Lee's grading was performed. Results Bla cells were mainly localized in germinal center of tonsil, and IgA1 positive cells were mainly localized in subepithelium of tonsil. Compared to control group, the percent of B1a cells and IgA1 positive cells was significantly higher in IgAN (P＜0.01). There was a positive correlation between Bla cells and IgA1 cells (P＜0.05). In IgAN, the percent of B1a cells in patients with hematuria and proteinuria was obviously higher than that of patients with hematuria only (P＜0.05). The number of Bla cells in IgAN patients with≥Lee's grade Ⅲ was significantly higher than that of those ＜ grade Ⅲ (P＜0.05). Conclusions IgA1 may be secreted by Bla cells in the tonsil of IgAN patients. The number of B1a cells is correlated with exacerbation of proteinuria and pathological severity, which may play an important role in pathogenesis of IgAN.

Objective To examine the correlation of urinary podocyte number and giomerular podocalyxin expression with clinicopathology in IgA nephropathy(IgAN)patients. Methods Morning urinary specimens(100 ml)3 days before renal biopsy from 50 patients with IgAN diagnosed by renal biopsy and from 20 healthy volunteers as control were collected. After centrifugation, 300 μI sediment was used for smear. Immunohistochemical staining with monoclonal anti-podocalyxin antibody was performed to detect urinary podocytes and the number of podocyte was counted under optical microscope. Computer image analysis system was used to examine glomerular PCX expression. Renal pathology and classification were investigated based on Lee's grading and Katafuchi semi-quantitative integration method. Relevance analysis was carried out on urinary podocyte number, glomerular PCX expression with pathological score and clinical data. Results The amount of urinary podocytes in IgAN was obviously higher than that in healthy controls(P<0.01). Significant differences were found in multiple comparison of the median of urinary podocytes among Lee's grade groups. I - II group was lower as compared to Ⅲ , Ⅳ, Ⅴ groups(all P<0.05). Ⅲ group was lower as compared to V group(P<0.05). The positive rate of urinary podocyte was the highest in Ⅳ and V groups(100%), while the lowest in Ⅰ - Ⅱ group(55%). Glomerular PCX expression in IgAN decreased with the aggravation of renal pathology. Significant differences were found in multiple comparison of the glomerular PCX expression with the pathological score. Lee's Ⅰ - Ⅱ group was higher as compared to Ⅲ, Ⅳ, Ⅴ groups(all P<0.05). Ⅳ and Ⅳ groups were higher as compared to V group(P<0.05). In IgAN, urinary podocyte excretion was negatively correlated with glomerular PCX expression(r=-0.702, P<0.01), positively correlated with 24-hour urinary protein(r=0.465, P<0.01)and positively correlated with glomerular and tubular scores(r=0.233, 0.307, P<0.05). Glomerular PCX expression was negatively correlated with 24-hour urinary protein(r=-0.367,P<0.05)and negatively correlated with glomerular and tubular scores(r =-0.560, -0.377, P <0.05). Conclusions Injury and desquamation of glomerular podocytes may involve in the development of IgAN. The number of urinary podocyte can reflect the loss of podocytes in renal tissue, which may be used as a marker of disease progression of IgAN.