Age-related decline in melatonin contributes to enhanced osteoclastogenesis via disruption of redox homeostasis.

BACKGROUND: Increased oxidative stress contributes to enhanced osteoclastogenesis and age-related bone loss. Melatonin (MT) is an endogenous antioxidant and declines with aging. However, it was unclear whether the decline of MT was involved in the enhanced osteoclastogenesis during the aging process. METHODS: The plasma level of MT, oxidative stress status, bone mass, the number of bone marrow-derived monocytes (BMMs) and its osteoclastogenesis were analyzed in young (3-month old) and old (18-month old) mice (n = 6 per group). In vitro, BMMs isolated from aged mice were treated with or without MT, followed by detecting the change of osteoclastogenesis and intracellular reactive oxygen species (ROS) level. Furthermore, old mice were treated with MT for 2 months to investigate the therapeutic effect. RESULTS: The plasma level of MT was markedly lower in aged mice compared with young mice. Age-related decline in MT was accompanied by enhanced oxidative stress, osteoclastogenic potential and bone loss. MT intervention significantly suppressed the receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclastogenesis, decreased intracellular ROS and enhanced antioxidant capacity of BMMs from aged mice. MT supplementation significantly attenuated oxidative stress, osteoclastogenesis, bone loss and deterioration of bone microstructure in aged mice. CONCLUSIONS: These results suggest that age-related decline of MT enhanced osteoclastogenesis via disruption of redox homeostasis. MT may serve as a key regulator in osteoclastogenesis and bone homeostasis, thereby highlighting its potential as a preventive agent for age-related bone loss.

Tanshinone IIA attenuates osteoarthritis via inhibiting aberrant angiogenesis in subchondral bone.

Excessive angiogenesis in subchondral bone is a pathological feature of osteoarthritis (OA). Tanshinone IIA (TIIA), an active compound found in Salvia miltiorrhiza, demonstrates significant anti-angiogenic properties. However, the effect of TIIA on abnormal subchondral angiogenesis in OA is still unclear. This study aims to investigate the mechanism of TIIA in modulating subchondral bone angiogenesis during OA and assess its therapeutic potential in OA. Our findings demonstrate that TIIA attenuated articular cartilage degeneration, normalized subchondral bone remodeling, and effectively suppressed aberrant angiogenesis within subchondral bone in monosodium iodoacetate (MIA)-induced OA mice. Additionally, the angiogenesis capacity of primary CD31hiEmcnhi endothelial cells was observed to be significantly reduced after treatment with TIIA in vitro. Mechanically, TIIA diminished the proportion of hypertrophic chondrocytes, ultimately leading to a substantial reduction in the secretion of vascular endothelial growth factor A (VEGFA). The supernatant of hypertrophic chondrocytes promoted the tube formation of CD31hiEMCNhi endothelial cells, whereas TIIA inhibited this process. Furthermore, TIIA effectively suppressed the expression of vascular endothelial growth factor receptor 2 (VEGFR2) along with its downstream MAPK pathway in CD31hiEmcnhi endothelial cells. In conclusion, our data indicated that TIIA could effectively inhibit the abnormal angiogenesis in subchondral bone during the progression of OA by suppressing the VEGFA/VEFGR2/MAPK pathway. These findings significantly contribute to our understanding of the abnormal angiogenesis in OA and offer a promising therapeutic target for OA treatment.

TEDC2 plays an oncogenic role and serves as a therapeutic target of hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common malignancies and tends to have a poor prognosis due to its insidious onset, difficulty in early diagnosis, and limited treatment options. Tubulin epsilon and delta complex 2 (TEDC2), also known as C16orf59, is implicated in maintaining centriole stability, but the involvement of TEDC2 in HCC remains unknown. This study aimed to investigate the expression profile and potential mechanisms of TEDC2 in HCC. METHODS: Multiple RNA sequencing datasets were screened for differentially expressed genes in HCC, and the prognosis-related gene, TEDC2, was further screened as a target gene in this study. The expression of TEDC2 in public datasets and clinical specimens was analyzed, and the involvement of TEDC2 in HCC was investigated by bioinformatic analysis and in vitro experiments. RESULTS: TEDC2 levels were elevated in HCC compared to healthy livers. Overexpression of TEDC2 was positively correlated with pathologic stage and histologic grade. In addition, TEDC2 was found to be an independent prognostic predictor. An excellent prognostic model of HCC was successfully constructed with TEDC2 in combination with the TNM stage. Bioinformatic analysis revealed that overexpression of TEDC2 might be associated with impaired tumor immunity in HCC, as evidenced by increased infiltration of T helper 2 (Th2) cells and reduced infiltration of cytotoxic cells. Further studies showed that TP53 mutations regulated TEDC2 expression, and TEDC2 was significantly associated with drug sensitivity. Moreover, overexpression of TEDC2 promoted cell metastasis and proliferation in vitro. CONCLUSION: These findings initially suggested a crucial effect of TEDC2 overexpression on HCC tumor progression, suggesting its potential as a novel prognostic and therapeutic target in HCC.

Theoretical derivation and clinical validation of the resolution limit of human eye to spherical lens change: a self-controlled study.

PURPOSE: The aim of this study was to deduce theoretically and verify the resolution limit of human eye to spherical lens change for more reasonable design of the trial lenses. METHODS: A total of 119 normal subjects with different myopia (not more than - 6D) were included. First, the resolution limit of discernible change in spherical power was derived based on the optical model. Then, the subjects were observed to see if they could perceive the changes in spherical power as per the resolution limit and compare the difference in the best-corrected visual acuity obtained with the resolution limit and interval of 0.25D. RESULTS: Assuming that the cone cell diameter is 3 µm and the pupil diameter of 4 mm, the theoretically resolution limit was 0.05D. When the diopter of spherical power was increased, the ratios of ability to perceive 0.05D spherical lens change were 98.3% and 96.7% in right and left eyes. When the diopter of spherical power was decreased, the ratios of ability to perceive 0.05D spherical lens change were 78.9% and 83.2% in right and left eyes. The best-corrected visual acuity obtained with the 0.05 D interval trial lens was significantly better than in the 0.25 D interval on both eyes (Right eye - 0.04 ± 0.07 vs - 0.02 ± 0.06, p < 0.001; Left eye - 0.07 ± 0.06 vs - 0.04 ± 0.06, t = 8.825, p < 0.001). CONCLUSION: The resolution limit of human eye to spherical lens change was about 0.05D and the better corrected visual acuity can be obtained by adjusting the spherical power at an interval of 0.05D. TRIAL REGISTRATION NUMBER: ChiCTR2100047074. Date of registration: 2021/6/7.

Small molecule inhibitors of RORγt for Th17 regulation in inflammatory and autoimmune diseases / 药物分析学报

As a ligand-dependent transcription factor,retinoid-associated orphan receptor γt(RORyt)that controls T helper(Th)17 cell differentiation and interleukin(IL)-17 expression plays a critical role in the pro-gression of several inflammatory and autoimmune conditions.An emerging novel approach to the therapy of these diseases thus involves controlling the transcriptional capacity of RORyt to decrease Th17 cell development and IL-17 production.Several RORyt inhibitors including both antagonists and inverse agonists have been discovered to regulate the transcriptional activity of RORyt by binding to orthosteric-or allosteric-binding sites in the ligand-binding domain.Some of small-molecule inhibitors have entered clinical evaluations.Therefore,in current review,the role of RORyt in Th17 regulation and Th17-related inflammatory and autoimmune diseases was highlighted.Notably,the recently developed RORyt inhibitors were summarized,with an emphasis on their optimization from lead compounds,ef-ficacy,toxicity,mechanisms of action,and clinical trials.The limitations of current development in this area were also discussed to facilitate future research.

Erythropoietin promotes myocardial infarction repair in mice by improving the function of Sca-1+ stem cells / 生理学报

Myocardial infarction (MI) is one of the leading causes of death in the world. With the improvement of clinical therapy, the mortality of acute MI has been significantly reduced. However, as for the long-term impact of MI on cardiac remodeling and cardiac function, there is no effective prevention and treatment measures. Erythropoietin (EPO), a glycoprotein cytokine essential to hematopoiesis, has anti-apoptotic and pro-angiogenetic effects. Studies have shown that EPO plays a protective role in cardiomyocytes in cardiovascular diseases, such as cardiac ischemia injury and heart failure. EPO has been demonstrated to protect ischemic myocardium and improve MI repair by promoting the activation of cardiac progenitor cells (CPCs). This study aimed to investigate whether EPO can promote MI repair by enhancing the activity of stem cell antigen 1 positive stem cells (Sca-1+ SCs). Darbepoetin alpha (a long-acting EPO analog, EPOanlg) was injected into the border zone of MI in adult mice. Infarct size, cardiac remodeling and performance, cardiomyocyte apoptosis and microvessel density were measured. Lin- Sca-1+ SCs were isolated from neonatal and adult mouse hearts by magnetic sorting technology, and were used to identify the colony forming ability and the effect of EPO, respectively. The results showed that, compared to MI alone, EPOanlg reduced the infarct percentage, cardiomyocyte apoptosis ratio and left ventricular (LV) chamber dilatation, improved cardiac performance, and increased the numbers of coronary microvessels in vivo. In vitro, EPO increased the proliferation, migration and clone formation of Lin- Sca-1+ SCs likely via the EPO receptor and downstream STAT-5/p38 MAPK signaling pathways. These results suggest that EPO participates in the repair process of MI by activating Sca-1+ SCs.

Association between sarcopenia and metabolic syndrome in middle-aged and elderly people in Urumqi， Xinjiang / 上海预防医学

ObjectiveTo obtain the prevalence of sarcopenia in middle-aged and elderly people in Urumqi based on the 2020 updated based on the 2020 updated Consensus Report 2019 of Asian Working Group for Sarcopenia （AWGS2019）， and to further explore the association between sarcopenia and metabolic syndrome （MS）. MethodsA total of 1 438 middle-aged and elderly people （aged≥50 years） in Urumqi from July 2018 to January 2019 were selected as the research subjects. Data were collected by questionnaire survey， physical examination and laboratory test. Skeletal muscle mass，grip strength and 4 m walking speed were used to represent muscle mass， muscle strength and body function， respectively. Bioelectrical impedance analysis （BIA） was used to measure human body components. Based on the diagnostic criteria of sarcopenia recommended by AWGS2019， the prevalence of sarcopenia in people over 50 years old was obtained. Multivariate logistic regression model was used to explore the correlation between sarcopenia and MS in middle-aged and elderly people of different genders. ResultsThere were 194 patients with sarcopenia， with a prevalence of 13.49%. The prevalence was 15.56% in males and 12.12% in females. There was no significant difference in the prevalence of MS between male sarcopenia group （40.45%） and non-sarcopenia group （38.92%）， while the prevalence of MS in female sarcopenia group （39.04%） was higher than that in non-sarcopenia group （27.56%）. Multivariate logistic regression analysis showed that sarcopenia was a related factor of MS. Compared with non-sarcopenia， the risk of MS in male sarcopenia group was higher （OR=2.11，95%CI： 1.15‒3.88 ）. ConclusionSarcopenia increases the risk of MS in middle-aged and elderly people， with a greater risk in men. Fully understanding of sarcopenia is helpful to early identify high-risk groups of MS and prevent the occurrence of MS.

Chinese herbal medicines for treating ulcerative colitis via regulating gut microbiota-intestinal immunity axis / 中草药·英文版

Ulcerative colitis (UC) is one of types of inflammatory bowel disease with high recurrence. Recent studies have highlighted that microbial dysbiosis as well as abnormal gut immunity are crucial factors that initiate a series of inflammatory responses in the UC. Modulating the gut microbiota-intestinal immunity loop has been suggested as one of key strategies for relieving UC. Many Chinese herbal medicines including some of single herb, herbal formulas and the derived constituents have been reported with protective effect against UC through modulating gut microbiome and intestinal immunity. Some clinical trials have shown promising results. This review thus focused on the current knowledge on using Chinese herbal medicines for treating UC from the mechanism aspects of regulating intestinal homeostasis involving microbiota and gut immunity. The existing clinical trials are also summarized.

Effect of posture on total hip arthroplasty through direct anterior approach / 中国骨伤

OBJECTIVE@#To investigate the effect of different postures on direct anterior approach(DAA) total hip arthroplasty.@*METHODS@#Total of 94 patients who underwent DAA total hip arthroplasty from July 2016 to June 2020 were retrospectively analyzed. They were divided into two groups according to different positions during the operation, including 45 cases in lateral position and 49 cases in supine position (with the aid of stent). The general data such as gender, affected limb, body mass index(BMI), incision length, operation time, intraoperative bleeding volume, drainage volume 24 hours after operation, hemoglobin difference before and after operation, first landing time after operation, postoperative hospitalization time, postoperative complications, visual analogue scale(VAS) at 1 day, 1, 2 weeks, 1, 3 and 6 months after operation, Harris score at 1, 2 weeks, 1, 3 and 6 months after operation were observed and compared between the two groups.@*RESULTS@#Patients in both groups were followed up for 6 to 12 months with an average of (8.31±2.22) months. There was no significant difference between two groups in gender, affected limb, age, height, weight, body mass index(BMI), preoperative VAS score and preoperative Harris score(P>0.05). The incision length, operation time, intraoperative bleeding volume, 24-hour drainage volume, hemoglobin difference before and after operation, first time to the ground and postoperative hospitalization time of patients in supine position (assisted by stent) group were all better than those in lateral position group(P<0.05);There was no significant difference in the number of blood transfusions during and after operation(P=0.550). There was no significant difference in anteversion angle and abduction angle in the supine position(with the aid of stent) group during and after operation (P=0.825, P=0.066);There was significant difference in anteversion angle and abduction angle in the lateral position group during and after operation(P<0.05). VAS of patients in supine position (assisted by stent) group were lower than those in lateral position group at 1 day, 1, 2 weeks and 1 month after operation(P<0.05), and there was no statistical difference between two groups at 3 and 6 months after operation(P>0.05). Harris scores of patients in supine position(assisted by stent) group were higher than those in lateral position group at 1 week, 1 month and 3 months after operation(P<0.05), and there was no significant difference between two groups at 6 months after operation(P>0.05).@*CONCLUSION@#Compared with the lateral position, the supine position DAA total hip arthroplasty has the advantages of small incision, short operation time, less bleeding, early landing time, short hospitalization time, and small intraoperative acetabular cup position judgment error. It has the advantage of fast postoperative recovery, but the recovery of hip joint function is the same after 6 months.

Cross-sectional associations between reproductive lifespan duration and urinary albumin-creatinine ratio / 中华内科杂志

Objective:To investigate the association between reproductive lifespan duration (RLD) and urinary albumin-creatinine ratio (UACR) in a Chinese postmenopausal population.Methods:This cross-sectional study included 11 055 naturally postmenopausal women from seven regions of China from May to December 2011. RLD was divided into four groups. Propensity score matching was performed to reduce bias, and logistic regressions and stratifications were conducted to investigate the association between RLD and increased UACR (≥30 mg/g). Mediation effect analysis was performed to quantify the effect of RLD on cardiovascular disease (CVD) induced by elevated UACR.Results:There were 2 373 participants with a RLD of 18-31 years, 2 888 participants with a RLD of 32-34 years, 2 472 participants with a RLD of 35-36 years, and 3 322 participants with a RLD of 37-50 years. The shortest RLD (18-31 years) group was characterized with older age ( P<0.001), a higher incidence of CVD ( P=0.025), and the highest level of UACR ( P<0.001). After adjusting for confounders, women with a longer RLD (37-50 years group) exhibited a lower risk of UACR elevation compared with those with the shortest RLD (18-31 years group) ( OR=0.72, 95% CI 0.64-0.82, P<0.001). Every 1-year extension in RLD was linked to a 2% reduction in the risk of UACR elevation ( OR=0.98, 95% CI 0.97-0.99, P<0.001). Stratified analysis revealed a more significant association between RLD and UACR in women who were a normal weight ( P=0.003) or overweight ( P=0.001), in those without CVD history ( P=0.001), and in those with impaired estimated glomerular filtration rate ( P=0.004). The mediation casual analysis showed that 3.0% of proteinuria inducing CVD events was mediated by RLD ( P=0.048). Conclusion:A longer RLD (37-50 years) is associated with a lower UACR in Chinese postmenopausal women.

Correlation between hemoglobin level and diabetic retinopathy in patients with type 2 diabetes mellitus / 中华内分泌代谢杂志

Objective:To evaluate the relationship between hemoglobin(Hb) level and the risk of diabetic retinopathy(DR) in patients with type 2 diabetes mellitus(T2DM).Methods:This study was a prospective cohort study. A total of 1 730 T2DM patients without DR, who received regular management at the Li′s Clinic in Taiwan, China starting from 2002, were selected as the study population. All patients underwent annual dilated fundus examination by professional ophthalmologists. General patient information and laboratory results were collected and analyzed. Based on the occurrence of DR during patient follow-up, patients were divided into the DR group and the non-DR(NDR) group. The impact of Hb levels on DR was explored using a generalized linear mixed model, and the relationship between Hb levels and DR was studied using Cox proportional hazards regression model.Results:After an average follow-up of 9.79 years, 481 patients with DR were detected. Compared with NDR group, DR group displayed a longer course of diabetes, higher rates of cataract, insulin use, and anemia, and higher systolic blood pressure, HbA 1C, and UACR as well as lower Hb. The results of the generalized linear mixed model showed a negative correlation between Hb and the occurrence of DR( β=-0.015, P<0.001). The Cox proportional hazards regression model showed that, after adjusting for confounding variables and based on quartiles of average Hb levels during follow-up, the risk of developing DR increased by 56.9% in the Q1 group(Hb≤127 g/L) compared to the Q4 group(Hb≥142 g/L). The cumulative risk plot showed that, after adjusting for confounding variables, the Q1 group had the highest cumulative risk of developing DR, and the difference was statistically significant( P<0.05). Conclusion:Hb was negatively correlated with DR, and the lower Hb levels were associated with the occurrence of DR, independent of other influencing factors.

Evaluation of Orthokeratology Lens Fitting Assisted by Sagittal Height Simulation Software.

OBJECTIVES: To evaluate a novel sagittal height fitting algorithm for estimation of alignment curve (AC) radius during Euclid orthokeratology lens trial. METHODS: Chinese myopic children were recruited in this study and were randomly divided into two groups. The AC radius of one group was calculated by the novel fitting algorithm. The AC radius of the other group was decided by the optometrist using flat K readings and eccentricity values. The number of lens trials was recorded for each patient, and the consistencies of AC radius between the first trial lenses and the final ordered lenses were tested by Pearson correlations and Bland-Altman plots. RESULTS: One hundred three adolescent patients (103 eyes) were enrolled, including 57 boys and 46 girls. The numbers of trials for the novel algorithm and traditional method were 1.2±0.4 times versus 1.4±0.5 times, respectively, and the difference between the two methods was significant (t=2.404, P=0.018). The difference of AC value between the first trial lens and the lens to be produced for the novel algorithm and traditional method 0.000±0.020 mm and 0.003±0.028 mm separately. There was no statistical difference between the two methods (t=0.748, P=0.456). CONCLUSIONS: The new sagittal height simulation software can accurately calculate the AC value of the orthokeratology lens suitable for the Chinese patients.

The Relationship between MicroRNA Expression Profiling in Imatinib-Resistant Cell Line K562/G and Potential Mechanism through FOXO3/Bcl-6 Signaling Pathway / 中国实验血液学杂志

OBJECTIVE@#To investigate the drug resistant related FOXO3/Bcl-6 signaling pathway in K562/G cell line and its related microRNA(miRNA) mechanisms.@*METHODS@#The drug resistance potency of imatinib on K562/G was detected by MTT assay. The expression of FOXO3 and Bcl-6 proteins in K562 and K562/G cells was detected by Western blot. Real-time PCR (RT-PCR) was used to detect the expression of FOXO3 and Bcl-6 mRNA. The miRNA expression profiling in K562 and K562/G cells was analyzed by microarray technique, and the miRNA targeted to FOXO/Bcl-6 signaling pathway was identified.@*RESULTS@#The expression of FOXO3 and Bcl-6 protein was significantly increased in K562/G cells as compared with that in K562 cells (P<0.01), the expression level of Bcl-6 mRNA showed no increase in K562/G cells. However, FOXO3 mRNA was up-regulated in K562/G cells (P<0.05). MiRNA microarray results showed that 109 miRNAs were expressed differentially in K562 and K562/G cells. The expression of 81 miRNAs were up-regulated while 28 miRNAs were down-regulated. Through reverse prediction by bioinformatics, miR-6718-5p, miR-5195-5p, miR-4711-3p, miR-4763-5p, miR-4664-5p and miR-3176 were related to FOXO/Bcl-6 signaling pathway.@*CONCLUSION@#The FOXO3/Bcl-6 signaling pathway contributes to imatinib resistance in K562/G cell line, and the miRNA expression profiles showed significant differences between K562/G and K562 cells.

Risk of developing second malignant neoplasms in patients with neuroblastoma: a population study of the US SEER database.

BACKGROUND: Neuroblastoma is a common extracranial malignant tumor in children. Its main treatment modality is a combination of chemotherapy, radiotherapy, and surgery. Given the advances in chemotherapy regimens and the widespread use of bone marrow transplantation over the decades, there has been improvement in treatment efficacy, which has led to prolonged patient survival. Accordingly, long-term complications have become a growing concern among physicians and patients. This study aimed to analyze the survival rate of patients with neuroblastoma and the risk factors for developing second malignant neoplasms (SMNs). METHODS: The SEER 18 Regs (1973-2015) and SEER 9 Regs (1973-2015) data of the surveillance, epidemiology, and end results (SEER) database of the US National Cancer Institute were adopted for survival and SMN analysis. RESULTS: The 5-, 10-, and 20-year overall survival rates of patients with neuroblastoma were 67%, 65%, and 62%, respectively. Among 38 patients with neuroblastoma who presented with SMNs, those with abdomen as the primary site accounted for the majority (63.2%), followed by those with thorax (26.3%) and other sites (10.5%). SMNs occurred more commonly in non-specific neuroblastoma (incidence: 0.87%) than ganglioneuroblastoma (incidence: 0.3%). Compared with the general population, the risk of SMN is significantly higher (SIR = 4.36). The risk of developing SMNs was significantly higher in the digestive system (SIR = 7.29), bones and joints (SIR = 12.91), urinary system (SIR = 23.48), brain and other nervous systems (SIR = 5.70), and endocrine system (SIR = 5.84). Multivariate analysis revealed that the year of diagnosis (OR = 2.138, 95% CI = 1.634-2.797, p < 0.001) was the only independent risk factor for developing SMNs. CONCLUSION: This study identifies the risk factor for developing SMNs in patients with neuroblastoma, which could facilitate individualized screening for high-risk patients, to allow early diagnosis and treatment of SMNs.

Is anterior decompression and fusion superior to laminoplasty for cervical myelopathy due to ossification of posterior longitudinal ligament? A systematic review and meta-analysis.

Context: Considerable controversy exists over surgical procedures for ossification of the posterior longitudinal ligament (OPLL).Objective: The purpose of the meta-analysis was to compare the clinical outcome of anterior decompression and fusion (ADF) with laminoplasty (LAMP) in treatment of cervical myelopathy due to OPLL.Methods: PubMed, EMBASE and the Cochrane Register of Controlled Trials database were searched to identify potential clinical studies compared ADF with LAMP for cervical myelopathy owing to OPLL. We also manually searched the reference lists of articles and reviews for possible relevant studies. Thirteen studies with 1120 patients were included in our analysis. Subgroup analyses were performed by the canal occupying ratio of OPLL.Results: Overall, the mean preoperative Japanese Orthopaedic Association (JOA) score was similar between two groups. Compared with LAMP group, ADF group was higher at the mean postoperative JOA scores and mean recovery rate, reoperation rate, and longer at mean operation time. There was not significantly different in mean blood loss and complication rate between two groups. In subgroup analysis, ADF had a higher mean postoperative JOA score and recovery rate than LAMP in cases of OPLL with occupying ratios ≥ 50%, while those difference were not found in cases of OPLL with occupying ratios < 50%.Conclusion: ADF achieves better neurological improvement compared with LAMP in treatment of cervical myelopathy due to OPLL, especially in cases of OPLL with occupying ratios ≥ 50%. Complication rate is similar between two groups, but ADF can increase the risk of reoperation.

Role of p38 MAPK/CREB signaling pathway in tetramethylpyrazine-induced reduction of hippocampal inflammatory responses in mice with sepsis-associated encephalopathy / 中华麻醉学杂志

Objective:To evaluate the role of p38 mitogen-activated protein kinase (MAPK)/cyclic adenosine monophosphate response element-binding protein (CREB) signaling pathway in tetramethylpyrazine-induced reduction of hippocampal inflammatory responses in mice with sepsis-associated encephalopathy (SAE).Methods:Sixty healthy male C57BL6 mice, weighing 24-27 g, were divided into 4 groups ( n=15 each) using a random number table method: sham operation group (group Sham), sepsis group (group Sep), tetramethylpyrazine group (group TMP) and p38 MAPK inhibitor SB203580 group (group SB). The model of SAE was established by cecal ligation and puncture in anesthetized mice.Tetramethylpyrazine 10 mg/kg was injected intraperitoneally once a day at 3 days before the establishment of the model in TMP group, and SB203580 2.0 mg/kg was intraperitoneally injected at 30 min after the establishment of the model in SB group.The equal volume of normal saline was given intraperitoneally in Sham and Sep groups.At 1 day after operation, cognitive function was assessed by Morris water maze, and the escape latency and ratio of time spent in the target quadrant were recorded.The animals were sacrificed after the test, and hippocampal tissues were taken for determination of the contents of interleukin-1beta (IL-1β), tumor necrosis factor-alpha (TNF-α) and IL-6 (by enzyme-linked immunosorbent assay) and for detection of the expression of phosphorylation of p38 MAPK, GSK3 and CREB and expression of brain-derived neurotrophic factor (BDNF) (by Western blot). Results:Compared with group Sham, the escape latency was significantly prolonged, the ratios of time spent in the target quadrant were decreased, the contents of IL-1β, TNF-α and IL-6 were increased, the phosphorylation of hippocampus p38 MAPK was increased, the phosphorylation of GSK3 and CREB were decreased, and the expression of BDNF was down-regulated in Sep, TMP and SB groups ( P<0.05). Compared with group Sep, the escape latency was significantly shortened, the ratios of time spent in the target quadrant were increased, the contents of IL-1β, TNF-α and IL-6 were decreased, the phosphorylation of hippocampus p38 MAPK was decreased, the phosphorylation of GSK3 and CREB were increased, and the expression of BDNF was up-regulated in TMP and SB groups ( P<0.05). Compared with group TMP, no significant change was found in the parameters mentioned above in group SB ( P>0.05). Conclusion:p38 MAPK/CREB signaling pathway is involved in the process of tetramethylpyrazine-induced reduction of hippocampal inflammatory responses in mice with SAE.

Surgical methods and clinical efficacy of different types of cesarean scar pregnancy / 中国基层医药

Objective:To compare surgical methods and clinical efficacy among different types of cesarean scar pregnancy (CSP).Methods:A total of 158 patients with CSP who received treatment in Yuncheng Central Hospital from January 2016 to June 2019 were included in this study. According to Expert Consensus on Diagnosis and Treatment of Cesarean Scar Pregnancy (2016 version), type I CSP was found in 55 patients, type II in 86 patients and type III in 17 patients. These patients were divided into groups A (ultrasound-guided suction curettage), B (uterine artery chemoembolization + ultrasound-guided suction curettage) and C (laparoscopic scar pregnancy lesion resection + scar repair) according to different surgical methods. The amount of intraoperative blood loss, the difference in human chorionic gonadotropin (HCG) level between before and after surgery, the time to postoperative HCG level returning to normal level, menstruation recovery, and re-pregnancy were compared between groups.Results:The amount of intraoperative blood loss in the groups A, B and C was (43.33 ± 72.31) mL, (34.41 ± 17.16) mL, (65.71 ± 70.52) mL, respectively. There was significant difference between groups ( F = 8.51, P = 0.014]. The difference in HCG level between before and after surgery in groups A, B and C was (0.64 ± 0.18), (0.79 ± 0.10), (0.76 ± 0.19), respectively. There was significant difference in the difference in HCG level between groups ( F = 19.21, P < 0.001). There was significant difference in the incidence of postoperative menstrual volume reduction between group B and the other two groups ( χ2 = 6.73, P = 0.003). After surgery, intrauterine pregnancy occurred in 12 patients, including 8 patients in group A (type I CSP in 2 patients, type II CSP in 3 patients, type III CSP in 3 patients), 4 patients in group B (type I CSP in 3 patients, type II CSP in 1 patient). Finally, full-term fetus delivery by cesarean section was performed in 6 patients (4 patients in group A and 2 patients in group B). Conclusion:Uterine artery chemoembolization combined with uterine curettage had less blood loss, during surgery and leads to an obvious decrease in HCG level, but it can result in reduction of menstrual volume. Ultrasound-guided suction curettage is preferred for type I and type II CSP. Balloon compression can be used to stop bleeding if massive bleeding occurs. Laparoscopic scar pregnancy lesion resection plus scar repair is recommended for type III CSP.

Relationship of serum homocysteine, folic acid and genetic polymorphism of methyltetrahydrofolate reductase in patients with type 2 diabetic nephropathy / 中华核医学与分子影像杂志

Objective:To investigate the relationship between serum homocysteine (HCY), folate (FOL) and methylenetetrahydrofolate reductase (MTHFR) C677T, A1298C gene polymorphism in patients with type 2 diabetic nephropathy (DN).Methods:A total of 161 patients with type 2 diabetes diagnosed in Jiangsu Shengze Hospital between January 2017 and December 2018, including 81 DN (41 males, 40 females; age: (61.5±14.2) years), 80 diabetic mellitus without nephropathy (DM; 42 males, 38 females, age: (57.7±10.8) years), and 77 normal controls (NC; 39 males, 38 females, age: (58.2±16.3) years) were retrospectively analyzed. The serum levels of HCY and FOL were detected by enzyme circulation and electrochemiluminescence respectively. TaqMan genotyping technique was used to detect MTHFR 677T&A1298 gene polymorphism. The serum levels of HCY and FOL were compared with one-way analysis of variance (the least significant difference t test), and the distribution differences of MTHFR gene were analyzed by χ2 test. Results:The difference of HCY level among DN, DM and NC groups was significantly different ((19.76±7.81), (15.62±5.01) and (8.09±3.74) μmol/L; F=81.738, P<0.001). The FOL level among the 3 groups was also significantly different ((12.18±3.01), (13.50±2.71) and (15.43±2.95) μg/L; F=26.978, P<0.001). The frequencies of 677T allele (51.2%, 83/162), 677TT/1298AA genotype (25.9%, 21/81) in DN group were significantly higher than those in DM (33.1%, 53/160; 11.2%, 9/80) and NC (33.8%, 52/154; 10.4%, 8/77) groups ( χ2 values: 10.821, 9.099, both P<0.05), but the 1298C allele frequency was not significantly different among the 3 groups (21.6%(35/162, DN) vs 16.9%(27/160, DM) vs 18.2%(28/154, NC); χ2=1.269, P>0.05). The levels of HCY and FOL in individuals with 677TT/1298AA genotype were significantly higher than those in individuals with other genotypes ( F values: 12.955, 15.504, all P<0.05). Conclusion:The abnormal metabolism of HCY and FOL caused by MTHFR C677T&A1298C gene polymorphism may be the genetic risk factor of DN.

Research progress in pachychoroid spectrum disease / 国际眼科杂志(Guoji Yanke Zazhi)

@#Choroidal thickening spectrum diseases include pachychoroid pigment epitheliopathy(PPE)central serous chorioretinopathy(CSC), pachychoroid neovascularization(PNV)and polypoidal choroidal-vasculopathy(PCV). PPE refers to permanent abnormal increase in choroidal thickness. It is manifested as dilatation of large choroidal vessels(Haller layer)oppressing the surrounding middle vascular layer(Sattler layer)and capillary layer(Choriocapillaris layer), resulting in insufficient blood supply to the retinal pigment epithelium and causing a series of retinitis pigmentosa. The other three diseases can progress from the pachychoroid pigment epitheliopathy. The study of the pathogenic characteristics and imaging changes of choroidal thickening spectrum diseases will help to explore the diseases' pathogenesis, providing reference for early clinical diagnosis, prevention and treatment.

Oxidative Stress Contributes to Hyperalgesia in Osteoporotic Mice.

PURPOSE: Chronic pain is one of the most common complications of postmenopausal osteoporosis. Since oxidative stress is involved in the pathogenesis of postmenopausal osteoporosis, we explored whether oxidative stress contributes to postmenopausal osteoporotic pain. METHODS: Osteoporosis was induced in mice by ovariectomy (OVX). Pain-related behaviours were assessed by measuring sensitivity to mechanical, thermal and cold stimulation. The expression of pain-related transcripts, such acid-sensing ion channel 3 (ASIC3), transient receptor potential vanilloid 1 (TRPV1) and calcitonin gene-related peptide (CGRP), was evaluated. Plasma markers of oxidative stress were also measured. In addition, the effects of the reactive oxygen species scavenger phenyl N-tert-butylnitrone (PBN) on these parameters were assessed. RESULTS: The OVX mice presented hyperalgesia, as demonstrated by decreased paw withdrawal thresholds to mechanical stimulation and withdrawal latencies to thermal and cold stimulation, along with upregulated expression of ASIC3, TRPV1 and CGRP in the dorsal root ganglia, spinal cord and thalamus tissue. OVX elevated the plasma levels of malondialdehyde (MDA) and advanced oxidation protein products (AOPPs). However, the administration of PBN alleviated these effects. CONCLUSION: Our results indicated that oxidative stress contributes to hyperalgesia in OVX mice. Enhanced oxidative stress may be associated with osteoporotic pain. Antioxidant treatment could help alleviate chronic pain in postmenopausal osteoporotic patients.