Effect of Xinnao Shutong capsule and its active ingredients on damage of cerebral microvascular endothelial cell barrier integrity caused by oxygen glucose deprivation/reoxygenation and its mechanism / 中国药理学通报

Aim To investigate the effect of XNST and its monomeric components on the barrier structure and tight junction protein expression of brain microvascular endothelial cells damaged by oxygen glucose deprivation/reoxygenation (OGD/R) and the possible mechanism. Methods The mouse brain microvascular endothelial cell line bEnd. 3 was inoculated in the upper layer of the Transwell chamber to establish an OGD/R damage model, and the effect of the drug on the integrity of the endothelial cell barrier was investigated by the transmembrane resistance value and fluorescein-so-dium transmittance. Claudin-5 immunofluorescence staining was used to observe the changes of tight junction structure between endothelial cells. RT-PCR and Western blot were employed to detect mRNA and protein expression levels of tightly linked proteins Claudin-5 , Occludin, ZO-1. Western blot was applied to detect the expression levels of MAPKs (JNK, p38, ERK) , I kappa B a, I kappa B kinase phosphorylated protein expression, and Western blot and immunofluorescence were utilized to detect NF-K.B/p65 nucleation expression. Results XNST and its three monomers could significantly increase endothelial cell resistance and de- crease fluorescein-sodium transmittance. Claudin-5 fluorescence staining showed that the tight junction between cells in the model group was significantly damaged , while XNST and its monomer components could significantly improve its tight structure. RT-PCR and Western blot results showed that it could significantly upregulate the expression of mRNA and protein of Claudin-5, Occludin and ZO-1, and further study on the mechanism showed that XNST and its monomer components could significantly inhibit the phosphoryla-tion of JNK, p38 and ERK, inhibit the phosphorylation of I kappa B a and I kappa B kinases, and significantly inhibit the nuclear translocation of NF-KB/p65. Conclusion Both XNST and its monomeric components can exert cerebroprotective effects by increasing the tight junction structure between cells to promote barrier integrity, and the mechanism may be related to inhibition of NF-kB and MAPKs signaling pathway activation.

Structure-based design of novel heterocycle-substituted ATDP analogs as non-nucleoside reverse transcriptase inhibitors with improved selectivity and solubility

Following on our recently developed biphenyl-ATDP non-nucleoside reverse transcriptase inhibitor ZLM-66 (SI = 2019.80, S = 1.9 μg/mL), a series of novel heterocycle-substituted ATDP derivatives with significantly improved selectivity and solubility were identified by replacement of the biphenyl moiety of ZLM-66 with heterocyclic group with lower lipophilicity. Evidently, the representative analog 7w in this series exhibited dramatically enhanced selectivity and solubility (SI = 12,497.73, S = 4472 μg/mL) in comparison with ZLM-66 (SI = 2019.80, S = 1.9 μg/mL). This new NNRTI conferred low nanomolar inhibition of wild-type HIV-1 strain and tested mutant strains (K103N, L100I, Y181C, E138K, and K103N + Y181C). The analog also demonstrated favorable safety and pharmacokinetic profiles, as evidenced by its insensitivity to CYP and hERG, lack of mortality and pathological damage, and good oral bioavailability in rats (F = 27.1%). Further development of 7w for HIV therapy will be facilitated by this valuable information.

Efficacy and safety of Kangxian Huanji Granule as adjunctive treatment in acute exacerbation of idiopathic pulmonary fibrosis: An exploratory randomized controlled trial / 中西医结合学报

BACKGROUND@#Acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) is an important occurrence in the natural history of idiopathic pulmonary fibrosis (IPF), associated with high hospitalization rates, high mortality and poor prognosis. At present, there is no effective treatment for AE-IPF. Chinese herbal medicine has some advantages in treating IPF, but its utility in AE-IPF is unclear.@*OBJECTIVE@#The treatment of AE-IPF with Kangxian Huanji Granule (KXHJ), a compound Chinese herbal medicine, lacks an evidence-based justification. This study explores the efficacy and safety of KXHJ in patients with AE-IPF.@*DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS@#We designed a randomized, double-blind, placebo-controlled, exploratory clinical trial. A total of 80 participants diagnosed with AE-IPF were randomly assigned to receive KXHJ or a matching placebo; the treatment included a 10 g dose, administered twice daily for 4 weeks, in addition to conventional treatment. Participants were followed up for 12 weeks after the treatment.@*MAIN OUTCOME MEASURES@#The primary endpoints were treatment failure rate and all-cause mortality. Secondary endpoints included the length of hospitalization, overall survival, acute exacerbation rate, intubation rate, the modified British Medical Research Council (mMRC) score, and the St George's Respiratory Questionnaire for IPF (SGRQ-I) score.@*RESULTS@#The rate of treatment failure at 4 weeks was lower in the intervention group compared to the control group (risk ratio [RR]: 0.22; 95% confidence interval [CI]: 0.051 to 0.965, P = 0.023). There was no significant difference in all-cause mortality at 16 weeks (RR: 0.75; 95% CI: 0.179 to 3.138; P > 0.999) or in the acute exacerbation rate during the 12-week follow-up period (RR: 0.69; 95% CI: 0.334 to 1.434; P = 0.317). The intervention group had a shorter length of hospitalization than the control group (mean difference [MD]: -3.30 days; 95% CI, -6.300 to -0.300; P = 0.032). Significant differences in the mean change from baseline in the mMRC (between-group difference: -0.67; 95% CI: -0.89 to -0.44; P < 0.001) and SGRQ-I score (between-group difference: -10.36; 95% CI: -16.483 to -4.228; P = 0.001) were observed after 4 weeks, and also in the mMRC (between-group difference: -0.67; 95% CI: -0.91 to -0.43; P < 0.001) and SGRQ-I (between-group difference: -10.28; 95% CI, -15.838 to -4.718; P < 0.001) at 16 weeks. The difference in the adverse events was not significant.@*CONCLUSION@#KXHJ appears to be effective and safe for AE-IPF and can be considered a complementary treatment in patients with AE-IPF. As a preliminary exploratory study, our results provide a basis for further clinical research.@*TRIAL REGISTRATION@#Chinese Clinical Trial Registry (ChiCTR1900026289). Please cite this article as: Li JS, Zhang HL, Guo W, Wang L, Zhang D, Zhao LM, Zhou M. Efficacy and safety of Kangxian Huanji Granule as adjunctive treatment in acute exacerbation of idiopathic pulmonary fibrosis: an exploratory randomized controlled trial. J Integr Med. 2023; 21(6): 543-549.

Geographic Variations in the Prevalence, Awareness, Treatment, and Control of Dyslipidemia among Chinese Adults in 2018-2019: A Cross-sectional Study / 生物医学与环境科学（英文）

OBJECTIVE@#To investigate the spatial patterns of the prevalence, awareness, treatment, and control rates of dyslipidemia at the provincial level in China.@*METHODS@#A national and provincial representative cross-sectional survey was conducted among 178,558 Chinese adults in 31 provinces in mainland China in 2018-2019, using a multi-stage, stratified, cluster-randomized sampling design. Subjects, as households, were selected, followed by a home visit to collect information. Both descriptive and linear regression procedures were applied in the analyses.@*RESULTS@#The overall prevalence of dyslipidemia was 35.6%, and wide geographic variations of prevalence, treatment, and control rates of dyslipidemia were identified among 178,558 eligible participants with a mean age of 55.1 ± 13.8 years. The highest-lowest difference regarding the provincial level prevalence rates were 19.7% vs. 2.1% for high low-density lipoprotein cholesterol, 16.7% vs. 2.5% for high total cholesterol, 35.9% vs. 5.4% for high triglycerides, and 31.4% vs. 10.5% for low high-density lipoprotein cholesterol. The treatment rate of dyslipidemia was correlated with the socio-demographic index ( P < 0.001), urbanization rate ( P = 0.01), and affordable basic technologies and essential medicines ( P < 0.001).@*CONCLUSION@#Prevailing dyslipidemia among the Chinese population and its wide geographic variations in prevalence, treatment, and control suggest that China needs both integrated and localized public health strategies across provinces to improve lipid management.

Does Early Endoscopy Affect the Clinical Outcomes of Patients with Acute Nonvariceal Upper Gastrointestinal Bleeding? A Systematic Review and Meta-Analysis

Background/Aims@#In patients with acute nonvariceal upper gastrointestinal bleeding (ANVUGIB), the optimal timing of endoscopy is still a matter of dispute. We conducted a systematic review and meta-analysis to determine the clinical benefit of early endoscopy. @*Methods@#A literature search of the MEDLINE, Embase, and Cochrane databases was conducted to identify publications from inception to March 1, 2022. Eligible studies included observational cohort studies and randomized controlled trials that reported clinical outcomes of endoscopy in patients with ANVUGIB. ANVUGIB patients who underwent endoscopy within 24 hours of admission were considered to have had an early endoscopy. The primary outcome was the mortality rate in ANVUGIB patients who had early or nonearly endoscopy. @*Results@#The final analysis included five randomized controlled studies (RCTs) and 20 observational studies from the 1,206 identified articles. The mortality rate was not significantly reduced among patients who received endoscopy performed within 24 hours, whether in cohort studies nor in RCTs. For subgroup analysis, a higher mortality rate was found only among patients who received very early endoscopy within 12 hours (odds ratio, 1.66; p<0.001, I 2 =0) in cohort studies. No significant difference in mortality rates was found among patients at high risk of bleeding who received early versus nonearly endoscopy. @*Conclusions@#Early endoscopy within 24 hours does not appear to significantly reduce the mortality rates of patients with ANVUGIB. Further well-designed studies are warranted to address if very early endoscopy within 12 hours can provide a clinical benefit for patients at high risk of bleeding.

Effect of LncRNA GATA3-AS1 Targeting MiR-515-5p on Cell Proliferation and Apoptosis in Childhood Acute Lymphoblastic Leukemia Cells / 中国实验血液学杂志

OBJECTIVE@#To investigate the effects of long non-coding RNA (lncRNA) GATA3 antisense RNA 1 (GATA3-AS1) targeting miR-515-5p on the proliferation and apoptosis of childhood acute lymphoblastic leukemia (ALL) cells.@*METHODS@#RT-qPCR was used to determine the expression of GATA3-AS1 and miR-515-5p in the plasma of controls and ALL children. Human ALL cells Jurkat were divided into si-GATA3-AS1, si-NC, miR-NC, miR-515-5p, si-GATA3-AS1+anti-miR-NC and si-GATA3-AS1+anti-miR-515-5p groups. CCK-8 assay was used to detect the cell proliferation, and flow cytometry was used to detect the cell apoptosis. The targeting relationship between GATA3-AS1 and miR-515-5p was determined by dual-luciferase reporter assay.@*RESULTS@#The expression level of GATA3-AS1 in the plasma of ALL children was significantly higher than that of controls (P <0.001), while the expression level of miR-515-5p was significantly lower than that of controls (P <0.001). Compared with the si-NC group, the cell inhibition rate, apoptosis rate, and miR-515-5p expression level in si-GATA3-AS1 group were significantly increased (P <0.001). Compared with the miR-NC group, the cell inhibition rate and apoptosis rate in miR-515-5p group were significantly increased (P <0.001). GATA3-AS1 could directly and specifically bind to miR-515-5p. Compared with the si-GATA3-AS1+anti-miR-NC group, the cell inhibition rate and apoptosis rate in si-GATA3-AS1+anti-miR-515-5p group were significantly decreased (P <0.001).@*CONCLUSION@#Down-regulation of GATA3-AS1 can inhibit proliferation and induce apoptosis of childhood ALL cells by targeting up-regulation of miR-515-5p expression.

Analysis of influence of MR signs on Harris score in ARCO stages 2-4 femoral head necrosis / 中国骨伤

OBJECTIVE@#To analysis and determine MR signs of Harris score ARCO stages 2-4 in osteonecrosis of femoral head (ONFH).@*METHODS@#Thirty-four patients with ONFH of ARCO stages 2 to 4 who underwent routine MR, T2 mapping, 3D-SPACE sequence examination and Harris score were retrospectively collected from January 2019 to June 2020, and 3 patients were excluded, and 31 patients were finally included, including 23 males and 8 females, aged from 18 to 62 years old with an average of(40.0±10.8) years old. Among them 21 patients with bilateral femoral head necrosis, totally 52 cases, including 17 with ARCO stage 2 patients, 24 ARCO stage 3, and 11 ARCO stage 4. MR imaging signs (femoral head collapse depth, ONFH index, bone marrow edema, hyperplasia, grade and T2 value of cartilage injury, and joint effusion) were scored and measured on the picture archiving and communication system (PACS) workstation, and the cartilage quantitative parameter T2 value was calculated and measured on Siemens postprocessing workstation. Pearson correlation analysis was used to evaluate the correlation between various MR signs and Harris score, and then multiple linear regression analysis was used to examine impact of MR signs on Harris hip score.@*RESULTS@#Femoral head collapse depth(r=-0.563, P=0.000), grade of cartilage injury(r=-0.500, P=0.000), and joint effusion (r=-0.535, P=0.000) were negatively correlated with Harris score by Pearson correlation analysis. Multiple linear regression analysis showed that joint effusion(β=-6.198, P=0.001) and femoral head collapse depth(β=-4.085, P=0.014) had a significant negative impact on Harris hip score.@*CONCLUSION@#Femoral head collapse depth and joint effusion both had significant negative relationship with Harris hip score. It is recommended to routinely evaluate femoral head collapse depth and joint effusion quantitatively and gradedly, so as to efficiently and accurately assist clinical diagnosis and treatment.

Long-term effectiveness of uncemented allograft-prosthesis composite for reconstruction of bone defects after proximal femur tumor resection / 中国修复重建外科杂志

OBJECTIVE@#To investigate the long-term effectiveness of uncemented allograft-prosthesis composite (APC) for reconstruction of bone defects after proximal femur tumor resection.@*METHODS@#Between June 2007 and March 2014, 21 patients who underwent uncemented APC reconstruction of proximal femur after tumor resection were retrospectively evaluated. There were 9 males and 12 females with an average age of 33.2 years (range, 19-54 years). There were 9 cases of giant cell tumor of bone, 5 cases of osteosarcoma, 4 cases of osteoblastic osteosarcoma, 2 cases of chondrosarcoma, and 1 case of undifferentiated pleomorphic sarcoma. Thirteen cases of benign bone tumors were all classified as stage 3 by Enneking staging; and 8 cases of malignant bone tumors were classified as grade ⅡB in 7 cases and grade ⅡA in 1 case according to the American Joint Committee on Cancer (AJCC) staging system. Among them, 7 patients underwent reoperation after recurrence, and the rest were primary operations; 8 patients presented with pathological fractures. The preoperative Harris hip score (HHS) and American Musculoskeletal Tumor Society (MSTS) score was 40 (30, 49) and 9.1±3.5, respectively. The length of osteotomy was 80-154 mm, with an average of 110 mm. At 1 year after operation and last follow-up, HHS and MSTS scores were utilized to evaluate the function of hip joint; the gluteus medius strength score was used to evaluation of the hip abduction function. Image examinations were taken at 1, 3, 6, 9, and 12 months after operation and every year thereafter to assess the union of allograft-host bone interfaces. Intra- and post-operative complications were also recorded.@*RESULTS@#All patients were followed up 84-163 months (mean, 123.5 months). At 1 year after operation and last follow-up, the HHS and MSTS scores significantly improved when compared with the preoperative scores ( P<0.05). However, there was no significant difference in the HHS score, MSTS score, and gluteus medius strength score between the two time points after operation ( P>0.05). Image examination showed that all allograft-host bone interfaces achieved union after 5-10 months (mean, 7.6 months). At last follow-up, all patients had bone resorption, including 11 severe cases, 4 moderate cases, and 6 mild cases; the bone resorption sites included Gruen 1, 2, and 7 regions. Complications included 10 fractures and 1 prosthetic fracture. Local recurrence occurred in 3 patients and pulmonary metastasis in 3 patients.@*CONCLUSION@#Uncemented APC is a reliable method for the reconstruction of bone defects after proximal femur tumor resection. It has the good long-term effectiveness and possesses obvious advantages in the union at the bone-bone surface.

Three-dimensional-printed hemi-pelvic prosthesis for revision of aseptic loosening or screw fracture of modular hemi-pelvic prosthesis / 中国修复重建外科杂志

OBJECTIVE@#To investigate the effectiveness of three-dimensional (3D)-printed hemi-pelvic prosthesis for revision of aseptic loosening or screw fracture of modular hemi-pelvic prosthesis.@*METHODS@#Between February 2017 and January 2020, 11 patients with aseptic loosening or screw fracture of modular hemi-pelvic prosthesis were revised using 3D-printed hemi-pelvic prostheses. There were 7 males and 4 females with an average age of 44 years (range, 25-60 years). In the first operation, all patients underwent total tumor resection, modular hemi-pelvic prosthesis reconstruction, and autologous femoral head transplantation. According to the Enneking pelvic partition system, 8 cases were resected in zones Ⅰ+Ⅱ and 3 cases in zones Ⅰ+Ⅱ+Ⅲ. The interval from the initial operation to this revision ranged from 14.3-66.2 months, with an average of 35.8 months. The operation time, the amount of intraoperative bleeding, and the occurrence of complications were recorded. At 6 months after the first operation, before revision, and at last follow-up, the American Musculoskeletal Tumor Society (MSTS) score and Harris score were used to evaluate the recovery of lower limb function. The pain-free walking distance of patients without brace assistance was recorded at last follow-up. X-ray films were taken at 1 month after the first operation, before revision, and at 1 month after revision, the acetabulum position was assessed by the differences in weight arm and cup height between bilateral hip joints. At last follow-up, the digital X-ray tomography was taken to evaluate the prosthesis-bone integration and the occurrence of aseptic loosening.@*RESULTS@#The operation time was 182.6-238.0 minutes (mean, 197.4 minutes). The amount of intraoperative bleeding was 400-860 mL (mean, 550.0 mL). All incisions healed by first intention with no infection, hip dislocation, nerve damage, or vascular-related adverse events. The MSTS score and Harris score at last follow-up were significantly higher than those at 6 months after the first operation and before revision ( P<0.05), while the score before revision was significantly lower than that at 6 months after the first operation ( P<0.05). At last follow-up, the patients were able to walk more than 1 000 meters painlessly without brace assistance. Imaging review showed that the difference of cup height at 1 month after revision was significantly lower than that at 1 month after the first operation and before revision, and at 1 month after the first operation than before revision operation, and the differences were significant ( P<0.05). There was no significant difference in the difference of weight arm among three time points ( P>0.05). All prostheses were well integrated, and no aseptic loosening of the prosthesis or screw fracture occurred.@*CONCLUSION@#Revision with 3D-printed hemi-pelvic prostheses benefited in reconstructing stable pelvic ring and natural bodyweight transmission for patients encountering the aseptic loosening or screw fracture of modular hemi-pelvic prosthesis. Early postoperative rehabilitation training can maximize the recovery of patient limb function, reduce pain during walking, and reduce the incidence of complications.

Mid-term effectiveness of hip preservation in the reconstruction of ultrashort bone segments in the proximal femur with three-dimensional printed customized cementless intercalary endoprosthesis with an intra-neck curved stem / 中国修复重建外科杂志

OBJECTIVE@#To explore the design points of a three-dimensional (3D) printed customized cementless intercalary endoprosthesis with an intra-neck curved stem and to evaluate the key points and mid-term effectiveness of its application in the reconstruction of ultrashort bone segments in the proximal femur.@*METHODS@#Between October 2015 and January 2021, 17 patients underwent reconstruction with a 3D printed-customized cementless intercalary endoprosthesis with an intra-neck curved stem. There were 11 males and 6 females, the age ranged from 10 to 76 years, with an average of 30.1 years. There were 9 cases of osteosarcoma, 4 cases of Ewing sarcoma, 2 cases of chondrosarcoma, 1 case of liposarcoma, and 1 case of myofibroblastoma. The disease duration was 5-14 months, with an average of 9.5 months. Enneking staging included 16 cases of stage ⅡB and 1 case of stage ⅢB. The distances from the center of the femoral head to the body midline and the acetabular apex were measured preoperatively on X-ray images. Additionally, the distances from the tip of the intra-neck curved stem to the body midline and the acetabular apex were measured at immediate postoperatively and last follow-up. The neck-shaft angle was also measured preoperatively, at immediate postoperatively, and at last follow-up. The status of osseointegration at the bone-prosthesis interface and bone growth into the prosthesis surface were assessed by X-ray films, CT, and Tomosynthesis-Shimadzu metal artefact reduction technology (T-SMART). The survival status of the patients, presence of local recurrence or distant metastasis, and occurrence of postoperative complications were assessed. The recovery of lower limb function was evaluated pre- and post-operatively using the Musculoskeletal Tumor Society (MSTS) scoring system, and pain relief was evaluated using the visual analogue scale (VAS) scores.@*RESULTS@#The patient's femoral resection length was (163.1±57.5) mm, the remaining proximal femoral length was (69.6±9.3) mm, and the percentage of femoral resection length/total femoral length was 38.7%±14.6%. All 17 patients were followed up 25-86 months with an average of 58.1 months. During the follow-up, 1 patient died of lung metastasis at 46 months postoperatively, and the remaining 16 patients survived tumor-free. There was no complication such as periprosthetic infection, delayed incision healing, aseptic loosening, prosthesis fracture, or periprosthetic fracture. No evidence of micromotion or wear around the implanted stem of the prosthesis was detected in X-ray and T-SMART evaluations. There was no significant radiolucent lines, and radiographic evidence of bone ingrowth into the bone-prosthesis interface was observed in all stems. There was no significant difference in the distance from the tip of the curved stem to the body midline and the apex of the acetabulum at immediate postoperatively and last follow-up compared with the distance from the center of the femoral head to the body midline and the apex of the acetabulum before operation, respectively (P>0.05), and there was no significant difference in the above indexes between immediate postoperatively and last follow-up (P>0.05). The differences in the neck-shaft angle at various time points before and after operation were also not significant (P>0.05). At last follow-up, the MSTS score was 26.1±1.2 and the VAS score was 0.1±0.5, which were significantly improved when compared with those before operation [19.4±2.1 and 5.7±1.0, respectively] (t=14.735, P<0.001; t=21.301, P<0.001). At last follow-up, none of the patients walked with the aid of crutches or other walkers.@*CONCLUSION@#The 3D printed customized cementless intercalary endoprosthesis with an intra-neck curved stem is an effective method for reconstructing ultrashort bone segments in the proximal femur following malignant tumor resection. The operation is reliable, the postoperative lower limb function is satisfactory, and the incidence of complications is low.

Quantitative grading evaluation of the therapeutic efficacy of asymmetric bilateral lateral rectus recession in type Ⅲ Duane retraction syndrome / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To quantitatively evaluate the therapeutic efficacy of the asymmetric recession of bilateral lateral rectus in patients with unilateral type III Duane retraction syndrome.METHOD:Retrospective analysis of clinical data. The clinical data of 12 cases of type III Duane retraction syndrome with unilateral lateral rectus recession were analyzed. All subjects had restricted internal rotation, with narrowing of the palpebral fissure and vertical deviation, and restricted external rotation with widening of the palpebral fissure. All patients had abnormal head positions. The degree of strabismus was measured while maintaining the head in a neutral position. Asymmetric recession of bilateral lateral rectus was selected based on the degree of strabismus of affected eye or 1～3mm longer, with a smaller recession and Y-splitting in the affected eye and a larger recession in the healthy eye.RESULT:The difference in the degree of strabismus in the healthy eyes before and after surgery was statistically significant(Z=-4.158, P&#x003C;0.01), as was the difference in the degree of restricted internal rotation(Z=-2.640, P=0.008). The difference in the degree of restricted external rotation was not statistically significant(Z=-1.732, P=0.083). The difference in abnormal head position was statistically significant(Z=-4.181, P&#x003C;0.01), while the difference in eyeball recession was not statistically significant(Z=-1.414, P=0.157). The difference in vertical deviation was statistically significant(Z=-3.115, P=0.002). A total of 10 patients(83%)had stereoscopic vision before surgery, and 11 patients(92%)had recovered stereoscopic vision after surgery, with a further improvement in stereoacuity in 50% of patients.CONCLUSION:Asymmetric recession of bilateral lateral rectus combined with Y-splitting of the affected lateral rectus can effectively improve the degree of strabismus, abnormal head position, vertical deviation and stereoacuity without aggravating the degree of restriction of external rotation or eyeball recession.

Diurnal differences in acute gout attacks: A clinical study of male gout patients / 北京大学学报(医学版)

OBJECTIVE@#To observe the diurnal difference of acute gout attacks in men, and provide reference for accurate clinical prevention and treatment.@*METHODS@#Using a single-center, cross-sectional study design, the patients diagnosed with gout in the outpatient department of Rheumatology and Immuno-logy of PLA Joint Logistic Support Force No.980 Hospital from October 2021 to April 2022 were selected. The information about the patient's current/last acute gout attacks (less than 2 weeks from visit), date and time of attacks, joint symptoms and signs, medication use, and relevant biochemical tests on the day of visit was recorded. The diurnal time difference of acute gout attacks in male patients was analyzed, and univariate comparison and multivariate Logistic regression analyses were conducted to compare the diurnal difference of acute gout attacks with clinical characteristics and biochemical indicators.@*RESULTS@#A total of 100 male gout patients were included, and 100 acute attacks were recorded. Diurnal distribution of acute gout attacks: morning (6:00~11:59, 18, 18%), afternoon (12:00~17:59, 11, 11%), the first half of the night (18:00~23:59, 22, 22%), the second half of the night (0:00~05:59, 49, 49%); During the day (included morning and afternoon, 29, 29%) and at night (included the first half of the night and the second half of the night, 71, 71%). The rate of acute gout attack was significantly higher at night than in the day (about 2.5 ∶1). No matter the first or recurrent gout, no matter the duration of the disease, the number of acute gout attacks had the difference of less in the day and more in the night. Serum urate (SU) level was higher in the patients with nocturnal attack than in those with daytime attack (P=0.044). Comorbidities were significantly different in the day-night ratio of the number of acute gout attack (P=0.028). Multiple Logistic regression analysis showed that SU level (OR=1.005, 95%CI: 1.001-1.009) and comorbidities (OR=3.812, 95%CI: 1.443-10.144) were the correlative factors of nocturnal acute gout attacks.@*CONCLUSION@#No matter the first or recurrent gout, no matter the duration of the disease, it has a diurnal variation characterized by multiple attacks at night, increased SU level and comorbidities are correlative factors for nocturnal acute attack of gout.

Expression and Clinical Significance of Serum sFas/sFasL in Patients with Secondary Hemophagocytic Lymphohistiocytosis / 中国实验血液学杂志

OBJECTIVE@#To investigate the expression and clinical significance of soluble Fas (sFas) and sFasL in patients with secondary hemophagocytic lymphohistiocytosis (sHLH).@*METHODS@#From September 2015 to December 2020, 86 sHLH patients who met the HLH2004 diagnostic criteria were collected. They were divided into 55 cases in the MAHLH group and 31 cases in the NonMAHLH group according to the etiology. Thirty healthy persons were chosen as the normal control group, and 20 patients with systemic lupus erythematosus (SLE) were chosen as the disease control group. The expression levels of sFas and sFasL in the serum of patients with each group were detected by ELISA, and the clinical data were collected for statistical analysis. The significance of sFas and sFasL in sHLH was analyzed by ROC curve.@*RESULTS@#Serum levels of sFas and sFasL in patients with newly diagnosed sHLH were significantly higher than those in disease control group and normal control group (P<0.01). The levels of sFas and sFasL in MAHLH group were significantly higher than those in nonMAHLH (infection related HLH and autoimmune disease related HLH) group (P<0.01). The serum levels of sFas and sFasL in 17 newly treated patients with sHLH (17/86) after treatment were significantly lower than those before treatment (P<0.01). The serum sFas level in newly diagnosed sHLH patients was positively correlated with SF(r=0.35), sCD25(r=0.79) and sFasL(r=0.73). The serum sFasL level was positively correlated with SF(r=0.39), sCD25(r=0.64) and sFas(r=0.73). Compared with the NonMAHLH group, the area under the ROC curve was 0.707 (95% CI: 0.593-0.821) (P=0.0015). The optimal critical value for diagnosing MAHLH by sFas level was 12 743 pg/ml, and the sensitivity and specificity were 70.9% and 71% respectively. Compared with the NonMAHLH group, the area under the ROC curve was 0.765(95% CI: 0.659-0.87)(P<0.01). The median OS time of sFas high expression group (≥16798.5 pg/ml) and sFasL high expression group (≥4 785 pg/ml) was significantly shorter than that of the low expression group (P<0.001).@*CONCLUSION@#Serum levels of sFas and sFasL can be used for the early diagnosis and differential diagnosis of sHLH disease, and are the factor related to the poor prognosis of sHLH.

Association between semen collection time and semen parameters: an observational study / 亚洲男科学杂志(英文版)

The process of semen collection plays a key role in the quality of semen specimens. However, the association between semen collection time and semen quality is still unclear. In this study, ejaculates by masturbation from 746 subfertile men or healthy men who underwent semen analysis were examined. The median (interquartile range) semen collection time for all participants was 7.0 (5.0-11.0) min, and the median time taken for semen collection was lower in healthy men than that in subfertile men (6.0 min vs 7.0 min). An increase in the time required to produce semen samples was associated with poorer semen quality. Among those undergoing assisted reproductive technology (ART), the miscarriage rate was positively correlated with the semen collection time. After adjusting for confounders, the highest quartile (Q4) of collection time was negatively associated with semen volume and sperm concentration. A longer time to produce semen samples (Q3 and Q4) was negatively correlated with progressive and total sperm motility. In addition, there was a significant negative linear association between the semen collection time and the sperm morphology. Higher risks of asthenozoospermia (adjusted odds ratio [OR] = 2.06, 95% confidence interval [CI]: 1.31-3.25, P = 0.002) and teratozoospermia (adjusted OR = 1.98, 95% CI: 1.10-3.55, P = 0.02) were observed in Q3 than those in Q1. Our results indicate that a higher risk of abnormal semen parameter values was associated with an increase in time for semen collection, which may be related to male fertility through its association with semen quality.

Risk factors of childhood systemic lupus erythematosus with thyroid dysfunction / 中华儿科杂志

Objective: To investigate the risk factors of childhood systemic lupus erythematosus (SLE) with thyroid dysfunction and to explore the relationship between thyroid hormone and kidney injury of lupus nephritis (LN). Methods: In this retrospective study, 253 patients who were diagnosed with childhood SLE and hospitalized in the First Affiliated Hospital of Zhengzhou University from January 2019 to January 2021 were enrolled in the case group, and 70 healthy children were the control cases. The patients in the case group were divided into the normal thyroid group and the thyroid dysfunction group. Independent t-test, χ2 test, and Mann-Whitney U test were used for comparison between the groups, Logistic regression analysis was used for multivariate analysis, and Spearman correlation. Results: A total of 253 patients, there were 44 males and 209 females in the case group, and the age of onset was 14 (12, 16) years; a total of 70 patients, 24 males and 46 females were in the control group, and the age of onset was 13 (10, 13) years. The incidence of thyroid dysfunction in the case group was higher than that in the control group (48.2% (122/253) vs. 8.6% (6/70), χ²=36.03, P<0.05). Of the 131 patients, there were 17 males and 114 females in the normal thyroid group, and the age of onset was 14 (12, 16) years. Of the 122 patients in the thyroid dysfunction group, 28 males and 94 females were in the thyroid dysfunction group, and the age of onset was 14 (12, 16) years. Of the 122 had thyroid dysfunction, including 51 cases (41.8%) with euthyroid sick syndrome, 25 cases (20.5%) with subclinical hypothyroidism, 18 cases (14.8%) patients with sub-hyperthyroidism, 12 cases (9.8%) with hypothyroidism, 10 cases (8.2%) with Hashimoto's thyroiditis, 4 cases (3.3%) with hyperthyroidism, and 2 cases (1.6%) with Graves disease. Compared to patients with normal thyroid function, the serum level of triglyceride, total cholesterol, urine white blood cell, urine red blood cell, 24 h urine protein, D-dimer, and fibrinogen, ferritin and systemic lupus erythematosus disease activity Index-2000 (SLEDAI-2K) score were higher in patients with thyroid dysfunction (Z=3.07, 3.07, 2.48, 3.16, 2.40, 3.99, 2.68, 2.55, 2.80, all P<0.05), while the serum level of free thyroxine and C3 were lower in thyroid disfunction patients (10.6 (9.1, 12.7) vs. 11.3 (10.0, 12.9) pmol/L, and 0.46 (0.27, 0.74) vs. 0.57 (0.37, 0.82) g/L, Z=2.18, 2.42, both P<0.05). The higher level of triglyceride and D-dimer were the independent risk factors for childhood SLE with thyroid dysfunction (OR=1.40 and 1.35, 95%CI 1.03-1.89 and 1.00-1.81, respectively, both P<0.05). There were 161 patients with LN in the case group, all of which were conducted with renal biopsies, including 11 cases (6.8%) with types Ⅰ LN, 11 cases (6.8%) with typesⅡLN, 31 cases (19.3%) with types Ⅲ LN, 92 cases (57.1%) with types Ⅳ LN, and 16 cases (9.9%) with types Ⅴ LN. There were significant differences in the level of free triiodothyronine and thyroid stimulating hormone among different types of kidney pathology (both P<0.05); compared with types I LN, the serum level of free triiodothyronine was lower in types Ⅳ LN (3.4 (2.8, 3.9) vs. 4.3 (3.7, 5.5) pmol/L, Z=3.75, P<0.05). The serum level of free triiodothyronine was negatively correlated with the acute activity index score of lupus nephritis (r=-0.228, P<0.05), while the serum level of thyroid stimulating hormone was positively correlated with the renal pathological acute activity index score of lupus nephritis (r=0.257, P<0.05). Conclusions: There is a high incidence of thyroid dysfunction in childhood SLE patients. The higher SLEDAI and more severe renal damage were found in SLE patients with thyroid dysfunction compared to these with normal thyroid functions. The risk factors of childhood SLE with thyroid dysfunction are the higher level of triglyceride and D-dimer. The serum level of thyroid hormone is possibly related to the kidney injury of LN.

Interpretation of the World Society of Emergency Surgery Guidelines for Diagnosis and Treatment of Acute Left Colonic Diverticulitis in the Elderly (2022 edition) / 中华外科杂志

Acute colonic diverticulitis is one of the most common clinical conditions encountered by surgeons in the acute setting. Acute left colonic diverticulitis in the elderly presents with unique epidemiological features when compared with younger patients. Elderly patients have a lower risk of recurrent episodes, higher in-hospital and postoperative mortality. An international multidisciplinary panel of experts from the World Society of Emergency Surgery (WSES) formulated the guidelines for diagnosis and treatment of acute left colonic diverticulitis in the elderly (2022 edition). This article aims to interpret the guidelines statements on the following topics: diagnosis, management, non-surgical therapy and surgical technique.

Associations between glycated hemoglobin and glucose indicators in adults in areas at different altitude in China / 中华流行病学杂志

Objective: To explore the associations of glycated hemoglobin (HbA1c) with FPG and oral glucose tolerance test 2-hour (OGTT-2 h) in areas at different altitude in China. Methods: Subjects who participated in 2018-2019 China Chronic Disease and Risk Factor Surveillance and had no prior type 2 diabetes diagnosis were included. Subsequently, they were categorized into three groups based on altitude of living area (<2 000, 2 000- and ≥3 000 m). With adjustment for intracluster correlation, multivariable linear regression analysis was performed to evaluate the associations of HbA1c with FPG and OGTT-2 h in the context of HbA1c was normal (<5.7%) or abnormal (≥5.7%). Furthermore, the shape of relationships between HbA1c and glucose indicators was examined using restricted cubic spline. Finally, receiver operating characteristic curve was used to evaluate the diagnostic performance of HbA1c for diabetes. Results: A total of 157 277 subjects were included in the analysis. While FPG and OGTT-2 h levels gradually decreased with increase of altitude, HbA1c level was similar among the three groups. When HbA1c was <5.7%, its association with FPG and OGTT-2 h was weak and no obvious difference was observed among the three groups. When HbA1c was ≥5.7%, the FPG and OGTT-2 h increased by 15.45% (95%CI:14.71%- 16.18%) and 24.54% (95%CI:23.18%-25.91%) respectively per one standard deviation increase in HbA1c in group in area at altitude <2 000 m. However, the FPG and OGTT-2 h increased by 13.08% (95%CI:10.46%-15.76%) and 21.72% (95%CI:16.39%-27.31%), respectively, in group in area at altitude 2 000- m, and increased by 11.41% (95%CI:9.32%-13.53%) and 20.03% (95%CI:15.38%- 24.86%), respectively, in group of altitude ≥3 000 m. The restricted cubic spline indicated that the curve showing the association of HbA1c with FPG and OGTT-2 h was flat when HbA1c was <5.7%, but showed a positive linear relationship when HbA1c was ≥5.7%. The area under curve for detecting diabetes was 0.808 (95%CI:0.803-0.812) in group of altitude <2 000 m and 0.728 (95%CI:0.660-0.796, P=0.022) in group of altitude ≥3 000 m. The relevant optimal cutoff value of HbA1c was 5.7%, with a sensitivity of 65.4% and a specificity of 83.0%, and 6.0%, with a sensitivity of 48.3% and a specificity of 93.7%, respectively. Conclusions: When HbA1c was ≥5.7%, the association between HbA1c and glucose indicators became weaker as the increase of altitude. In the area at altitude ≥3 000 m, it may not be appropriate to use HbA1c in the diagnosis of diabetes.

Monocyte/High-Density Lipoprotein Ratio Is Associated with Atrial High-Rate Episodes within One Year Detected by Cardiac Implantable Electronic Devices

ABSTRACT Objective: To investigate the risk factors for predicting atrial high-rate episodes (AHREs) detected by cardiac implantable electronic devices (CIEDs). Methods: A total of 140 patients with CIED in our hospital from June 2013 to June 2018 were included and were followed up to observe whether they had AHREs. AHRE are defined as atrial rate ≥ 175 times/minute, lasting > 5 minutes, and reviewed by an experienced electrophysiologist with unclear clinical diagnosis. The patients fasted for 12 hours after implantation, and blood samples were collected for biochemical, lipid, and whole blood count detection. Follow-up was regular after discharge to record follow-up data of each patient and conduct statistical analysis. Results: One hundred and forty patients were implanted with dual-chamber pacemakers, their median age was 70 years old, 44.29% were male, 27 patients had AHRE within one year, and AHRE incidence rate was 19.29%. The microcytic to hypochromic (M/H) ratio was calculated for all AHRE patients and compared with the patients without AHRE; the M/H value of AHRE patients was significantly higher. Throughout the entire follow-up period, a total of 44 patients developed AHRE; when adjusted by multivariate analysis, only M/H ratio ≥ 4.5 vs. < 4.5 had statistical significance, and the adjusted hazard ratio value was 4.313 (1.675-11.105). Conclusion: As an indicator, M/H ratio may play an important role in the occurrence and development of atrial fibrillation and can be used as a predictor of AHRE in patients with CIED.

OLIG2 expression level could be used as an independent prognostic factor for patients with cerebellar Glioblastoma (cGBM)

Abstract Objectives: The incidence of cerebellar Glioblastoma Multiforme (cGBM) is rare. Database like TCGA have not distinguish cGBM from GBM, our knowledge on cGBM gene expression characteristics is limited. The expression status of Oligodendrocyte Lineage Transcription factor 2 (OLIG2) and its clinical significance in cGBM is still unclear. Methods: The clinical data and tissue specimens of 73 cGBM patients were retrospectively studied. The association between OLIG2 expression level and the demographic characteristics of cGBM patients was identified by the Chi-Square test. The survival curves were drawn by Kaplan-Meier analysis. The independent prognostic factors was calculated according to Cox regression analysis. Results: The OLIG2 high expression was observed in about 57.5% (42/73) of the cGBM patients. Patients with high OLIG2 expression levels had a higher alive ratio at the end of follow-up (alive ratio: 70.6% vs. 29.4%, p = 0.04). The median survival time was 21 months and 13 months for high and low expression of OLIG2 (p < 0 .05). Univariate analysis and Multivariate analysis indicated that EOR (HR = 3.89, 95% CI 1.23−12.26, p = 0.02), low OLIG2 expression (HR = 5.26, 95% CI 1.13−24.59, p = 0.04), and without adjuvant therapy (HR = 4.95, 95% CI 1.22−20.00, p = 0.03) were independent risk factors for the OS of cGBM patients. Conclusion: High expression level of OLIG2 could be used as an independent favorable prognosis indicator in cGBM patients and be recognized as a characteristic biomarker of cGBM.