Risk factors for diabetic foot ulcers: A systematic review and meta-analysis.

OBJECTIVE: To systematically evaluate the risk factors for developing diabetic foot ulcers (DFU). METHODS: The Cochrane Library, PubMed, Web of Science, SinoMed, CNKI, VIP, and Wanfang Data were searched for relevant studies on DFU risk factors, and the search time frame was from database creation to March 2022. Meta-analysis was performed using RevMan 5.3. RESULTS: A total of 26 publications were included, including 3 cohort studies, 22 case-control studies, and one cross-sectional study. Meta-analysis showed that advanced age [MD = 6.04, 95% CI (3.92, 8.16)], male [OR = 1.84, 95% CI (1.48, 2.29)], elevated body mass index [MD = 1.58, 95% CI (0.47, 2.69)], prolonged duration of diabetes [MD = 2.72, 95% CI (2.33, 3.11)], comorbid nephropathy [OR = 3.15, 95% CI (2.68, 4.60)], comorbid neuropathy [OR = 4.80, 95% CI (2.79, 8.27)], comorbid retinopathy [OR = 3.37, 95% CI (2.26, 5.02)], elevated systolic blood pressure [OR = 8.19, 95% CI (6.33, 10.05)], elevated fasting glucose [MD = 1.60, 95% CI (0.21, 3.00)], elevated glycated hemoglobin [MD = 1.24, 95% CI (0.94, 1.54)], elevated triglycerides [MD = 0.44 (95% CI (0.15, 0.73)], elevated fibrinogen [MD = 1.35, 95% CI (0.62, 2.08)], elevated white blood cell count [MD = 2.56, 95% CI (2.24, 2.88)], elevated C-reactive protein [MD = 15.08, 95% CI (8.03, 22.13)], decreased ankle-brachial ratio [MD = -0.26, 95% CI (-0.36, -0.16)], and decreased total protein levels [MD = -4.58, 95% CI (-6.91, -2.25)] were risk factors for developing DFU (p < 0.05), and increased HDL cholesterol levels [MD = -0.22, 95% CI (-0.36, -0.08)] were protective factor for developing DFU (p < 0.05). CONCLUSION: There are many risk factors for developing of ulcers in the diabetic feet, and early prevention and intervention should be performed as early as possible to assess the risk of developing diabetic foot patients.

iTRAQ-based quantitative proteomics reveals biomarkers/pathways in psoriasis that can predict the efficacy of methotrexate.

BACKGROUND: Methotrexate (MTX) is the first-line medicine to treat psoriasis. So far, there has been less research on protein biomarkers to predict its efficacy by the proteomic technique. OBJECTIVES: To evaluate differentially expressed proteins in peripheral mononuclear cells (PBMCs) between good responders (GRs) and non-responders (NRs) after MTX treatment, compared with normal controls (NCs). METHODS: We quantified protein expression of PBMCs with four GRs and four NRs to MTX and four NCs by isobaric tags for relative and absolute quantification (iTRAQ), analysing and identifying proteins related to efficacy of MTX in 18 psoriatic patients. RESULTS: A total of 3177 proteins had quantitative information, and 403 differentially expressed proteins (fold change ≥1.2, P < 0.05) were identified. Compared to NCs, upregulated proteins (ANXA6, RPS27A, EZR, XRCC6), participating in the activation of NF-κB, the JAK-STAT pathway and neutrophil degranulation were detected in GRs. The proteins (GPV, FN1, STOM), involving platelet activation, signalling and aggregation as well as neutrophil degranulation were significantly downregulated in GRs. These proteins returned to normal levels after MTX treatment. Furthermore, Western blotting identified the expression of ANXA6 and STAT1 in PBMCs, which were significantly downregulated in GRs, but not in NRs. CONCLUSIONS: We identified seven differentially expressed and regulated proteins (ANXA6, GPV, FN1, XRCC6, STOM, RPS27A and EZR) as biomarkers to predict MTX efficacy in NF-κB signalling, JAK-STAT pathways, neutrophil degranulation, platelet activation, signalling and aggregation.

[Analysis of the effect of spread through air spaces on postoperative recurrence-free survival in patients with stage pT1N0M0 lung adenocarcinoma of different tumor size].

Objective: To investigate the effect of spread through air spaces (STAS) on the postoperative prognosis of patients with stage pT1N0M0 lung adenocarcinoma according to different tumor sizes. Methods: The clinicopathological and follow-up data of 511 patients with pT1N0M0 lung adenocarcinoma treated surgically in the Department of Thoracic Surgery, Cancer Hospital, Chinese Academy of Medical Sciences from January 2014 to June 2018 were retrospectively analyzed. There were 285 males and 226 females, aged 60 (53, 66) years. Those patients were divided into two groups according to STAS status, including STAS (-) group (342 cases) and STAS (+) group (169 cases). And the stratified analysis was performed according to the American Cancer Consortium (AJCC) 8th edition postoperative pathological tumor size T-stage (pT) of lung cancer, which was divided into pT1a (pT≤1 cm, 93 cases), pT1b (1 cm0.05]. Before and after IPTW adjustment, statistically significant differences were found in RFS between STAS (+) group and STAS (-) group [(72.50±2.23) vs (85.12±0.72) months, (77.74±1.12) vs (84.59±0.64) months, all P<0.001]. In addition, the risks of both local and distant recurrence were higher in STAS (+) group compared to STAS (-) group (6.7% vs 1.2% and 8.2% vs 3.6%, respectively; both P<0.05). Conclusion: For lung adenocarcinoma patients with pT1bN0M0 and pT1cN0M0, those patients with STAS (+) had a higher incidence of both local and distant recurrence and with poor RFS.

[Role of microbial-derived antioxidants on diquat-induced oxidative stress, endoplasmic reticulum stress and function in mice].

Objective: To study the role of microbial-derived antioxidants (MA) based on the model of diquat-induced oxidative stress, endoplasmic reticulum stress, apoptosis and function in mice. Methods: 18 female C57BL/6 mice with body mass of 16~18 g were selected and randomly divided into 3 groups with 6 mice in each group. After 22 days of feeding, model and antioxidant group mice were intraperitoneally injected with diquat solution and control group were injected with same amount of isotonic saline. The content of free radical, MDA, antioxidant enzyme activity, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activity were detected according to the instructions of the kit. QRT-PCR was used to detect the expression of endoplasmic reticulum stress and apoptosis-related genes. One-way analysis of variance was used for data comparison between groups. Results: Hydrogen peroxide (H(2)O(2)) in the control group, model group and antioxidant group was (8.74 ± 1.38), (11.44 ± 1.01), (9.81 ± 0.98) mmol/g prot, respectively, and the difference between the groups was statistically significant (F = 7.640, P < 0.05). MDA content in the control, model and antioxidant group were (0.65 ± 0.07), (0.86 ± 0.18), (0.70 ± 0.05) nmol/mg prot, respectively, and the difference between the groups was statistically significant (F = 5.406, P <0.05). Aspartate aminotransferase (AST) activity in the model group (146.68 ± 4.29) U/gprot was significantly higher than control group (125.64 ± 15.69) U/gprot and antioxidant group (126.57 ± 1.82) U/gprot, F = 6.192, P < 0.05. Real-time quantitative PCR result showed that the relative expression of protein kinase R-like endoplasmic reticulum kinase (PERK) and activated transcription factor 6 (ATF6) genes in the model group was significantly higher than control group, which were 1.880 ± 0.442 and 1.800 ± 0.380, F = 7.702 and 10.815, and P < 0.05, respectively. Apoptosis-related gene expression results showed that the relative expression levels of caspase3 and caspase8 genes in the antioxidant group (1.136 ± 0.381 and 1.593 ± 0.407) was significantly lower than model group (1.572 ± 0.127 and 2.843 ± 0.973), (F = 12.800, 7.657, P < 0.05). Conclusion: Microbial-derived antioxidants can reduce diquat-induced liver oxidative stress, endoplasmic reticulum stress and hepatocyte apoptosis in mice, and thus improves liver function.

[Analysis of risk factors for acute lung injury/acute respiratory distress syndrome after esophagectomy].

OBJECTIVE: To explore the incidence and risk factors for the acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) after resection of esophageal carcinoma. METHODS: We retrospectively analyzed 422 consecutive patients admitted to the Department of Critical Care Medicine with esophageal carcinoma undergoing esophagectomy from January 2010 to December 2016 in Peking University Cancer Hospital. ALI/ARDS were diagnosed, the patients were divided into ALI/ARDS group and control group without ALI/ARDS, the differences of clinical features were contrasted between the two groups, and the multivariate Logistic regression modeling was used to identify the independent risk factors for ALI/ARDS. RESULTS: In the study, 41 ALI/ARDS cases were diagnosed, making up 9.7% (41/422) of all the enrolled patients undergoing esophagectomy. Comparisons of the ALI/ARDS group and the control group indicated significant statistical differences in the average length of their hospital stay [(18.9±9.7) d vs. (14.8±3.6) d, P=0.011], the proportion of the patients who needed mechanical ventilation support [51.2% (21/41) vs. 9.4% (36/381), P<0.001] and in-hospital mortality [31.7% (13/41) vs. 5.0% (19/381), P<0.001]. Univariate analysis showed significant differences between the patients with ALI/ARDS and without ALI/ARDS in smoking history (P=0.064), preoperative forced expiratory volume in one second/forced vital capacity (FEV1/FVC) (P=0.020), diffusing capacity of the lung for carbon monoxide (DLCO) (P=0.011), body weight index (BMI) (P=0.044), American Society of Anesthesiologists (ASA) physical status classification (P=0.049) and one lung ventilation duration (P=0.008), while multivariate Logistic regression analysis indicated that preoperative FEV1/FVC (OR=1.053, P=0.016, 95%CI 1.010-1.098), ASA physical status classification (OR=2.392, P=0.033, 95%CI 1.073-5.335) and one lung ventilation duration (OR=0.994, P=0.028, 95%CI 0.989-0.999) were the independent risk factors for ALI/ARDS after esophagectomy. CONCLUSION: ALI/ARDS was a serious complication in patients undergoing esophagectomy associated with increment in length of hospital stay and in-hospital mortality. Multivariate Logistic regression analysis indicated that preoperative FEV1/FVC, ASA classification and one lung ventilation duration were the independent risk factors for ALI/ARDS after esophagectomy. Carefully assessing the patient before operation, shortening one lung ventilation duration were the key points in preventing ALI/ARDS after esophagectomy.

[The study of growth differentiation factor-15 in chronic thromboembolic pulmonary hypertension following acute pulmonary thromboembolism].

Objective: To evaluate the incidence of chronic thromboembolic pulmonary hypertension (CTEPH) secondary to acute pulmonary thromboembolism (PTE) and the serum level of growth differentiation factor-15(GDF-15). Methods: Ninety-six acute PTE patients were recruited in the study. Clinical data, Wells score, blood gas analysis, D-dimmer level, GDF-15 level, atrial and ventricular sizes, pulmonary arterial systolic pressure (PASP) and pulmonary artery CT (CTPA) data were collected. Patients were followed up to evaluate the cardiac function (WHO class), ultrasonic cardiogram and CTPA to confirm the incidence of CTEPH. Results: Eighty-fivepatients were followed for 5 months to 58 months (average 26.5±14.7 months). The incidence of CTEPH was 12.9% (11/85). Between CTEPH patients and non-CTEPH patients, PASP, right atrial and ventricular sizes, and GDF-15in the acute stage were significantly different(P<0.05). According to binary logistic regression analysis, the incidence of CTEPH was correlated positively with acute PASP and the serum level of GDF-15. Conclusions: The incidence of CTEPH in acute PTE patients was 12.9% in this study. Acute PASP and higher level of GDF-15 are predictive factors for CTEPH secondary to acute PTE.

Protection from vascular endothelial dysfunction in acute glycemic load-induced primary hypertension by vitamin C and E.

This study aimed to investigate the influence of acute glycemic load on vascular endothelial function in patients with hypertension and to evaluate the protective effect of vitamins C and E during the acute glycemic phase. We randomly selected 39 hypertensive patients and 21 normal subjects and divided them into 3 groups: 75 g oral glucose (glycemic load group), 75 g glucose+0.9 g vitamin C (VC group), 75 g glucose+2 g vitamin C+0.8 g vitamin E (VC+VE group). Extravascular color Doppler ultrasound was used to detect brachial artery flow-mediated vasodilation at 0, 1, 2, and 3 h, and, at the same time, serum anti-oxidant products were measured. Basic endothelial functions in patients with hypertension were decreased in the glycemic load group (9.48±3.33 versus 13.09±6.78%, P<0.05), and was even more depressed in the hypertensive group (9.48±3.33 versus 14.20±6.48%, P<0.05). Antioxidant vitamins played a dose-dependent protective role on acute damage of endothelial function due to glycemic load. Acute high blood sugar damaged vascular endothelial functions, especially in hypertensive patients, but this effect can be reversed by large doses of vitamin C and E.

[Epidemiological characteristics of mpox epidemic in Guangzhou].

Objective: To understand the epidemiological characteristics of mpox epidemic in Guangzhou and provide scientific evidence for the prevention and control of the disease. Methods: Based on the mpox surveillance system in Guangzhou, suspected mpox cases with fever and rash were reported by local hospitals at all levels to centers for disease control and prevention in Guangzhou for sampling, investigation and diagnosis. Descriptive epidemiological analysis was conducted on the clinical characteristics and treatment of the mpox cases and positive detection rate reported in Guangzhou as of 24:00 on June 23. Whole genome sequencing of the virus isolates was performed using Illumina Miniseq high-throughput sequencing platform. Results: The first mpox case in Guangzhou was reported on June 10 in 2023. As of 24:00 on June 23, a total of 25 confirmed mpox cases were reported. All the mpox cases were men with a M(Q1,Q3) of 32 (26, 36) years, the majority of the cases were MSM (96.0%). The main clinical features were rash (100.0%, 25/25), lymphadenectasis (100.0%, 25/25) and fever (52.0%, 13/25). Rash usually occurred near the genitals (88.0%, 22/25). The close contacts, mainly family members (40.4%, 23/57), showed no similar symptoms, such as fever or rash. The positive rate of mpox virus in household environment samples was 30.5%. The analyses on 3 complete gene sequences of mpox virus indicated that the strains belonged to West African type Ⅱb clade, B.1.3 lineage. Conclusions: Hidden transmission of mpox virus had occurred in MSM in Guangzhou. However, the size of affected population is relatively limited, and the possibility of wide spread of the virus is low.

[New discovery and short-term effect analysis of tensor tympani muscle tenotomy for Meniere's disease under otoscope].

Objective: To explore the feasibility and short-term effect of tensor tympani muscle Tenotomy in the treatment of Meniere's disease under otoscope. The possible pathogenesis was discussed and our views were put forward. Methods: The clinical data of 9 cases of Meniere's disease treated by otoscopic Tenotomy were analyzed retrospectively, including 2 males, 7 females, 5 right ones, 2 left ones and 2 bilateral ones. The average age was (56.33± 10.56) years, ranging from 38 to 75 years. We evaluated intraoperative findings and short-term postoperative efficacy, respectively evaluated postoperative aural fullness, tinnitus and hearing recovery, and evaluated postoperative vertigo attack in a short time. Results: Nine patients were completed the operation under general anaesthesia and otoscopy, and no serious complications occurred. We found new pathological changes in tympanic cavity in some cases during operation. There were rupture of round window membrane in 1 case, severe fibrous hyperplasia near the round window membrane and vestibular window and adhesion with ossicular chain in 1 case, fibrous cord and membranous hyperplasia near vestibular window and round window membrane in 1 case, fibrous hyperplasia and adhesion near the round window membrane in 2 cases, membranous hyperplasia and adhesion around vestibular window in 1 case. No fibrous hyperplasia was found in 3 cases in the tympanic cavity. The round window membrane can be exposed in 4 cases and failed in 5 cases. After 3 months of follow-up, we found that we found that 5/5 cases of aural fullness disappeared, 2/2 cases of earache disappeared, 3/8 cases of tinnitus improved, 5/8 cases presented with improvement and no aggravation, 3/3 cases of hearing allergy improved, 4/9 cases of hearing improved, and 5/9 cases showed no improvement or decrease. 9 patients were followed up for 3 months, of whom 8 patients had no vertigo, one patient suffered from vertigo twice within 3 months after operation, and the patient suffered from rupture of round window membrane. Conclusions: Endoscopic Tenotomy for Meniere's disease has obvious curative effect and quick recovery after operation. During the operation, we find that most of Meniere's patients have fibrous cord hyperplasia near the inner ear window membrane, which may be the pathological manifestation after repeated rupture and repair of the inner ear window membrane. The vertigo of Meniere's disease may be related to the destruction and repair of inner ear membrane structure caused by improper contraction or spasm of tympanic tensor muscle.

MicroRNA-99b inhibits NSCLC cell invasion and migration by directly targeting NIPBL.

OBJECTIVE: Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related death worldwide. microRNAs (miRNAs) have been confirmed as vital regulators of multiple tumors, including NSCLC. The aim of the current study was to explore the biological mechanisms of miR-99b in NSCLC progression. PATIENTS AND METHODS: NSCLC tissues and adjacent matched human non-neoplastic lung tissues used in this study were collected from 50 cases of NSCLC patients. The expression of miR-99b and NIPBL in NSCLC tissues and cell lines (A549, NCI-H460, NCI-H1299 and SPC-A1) were determined by real-time-polymerase chain reaction (qRT-PCR). The NIPBL protein level was measured by Western blot. Dual-Luciferase reporter, Western blotting and qRT-PCR were carried out to verify the potential target of miR-99b. Transwell assay was used for investigating miR-99b effect on cell migration and invasion in NSCLC cells. RESULTS: The results of qRT-PCR indicated that the expression of miR-99b was downregulated in the NSCLC tissues and cell lines. Overexpression of miR-99b could significantly inhibit the invasion and migration capacities in NSCLC cells. Furthermore, we also determined that NIPBL was a direct target of miR-99b. Additionally, we found NIPBL was implicated in the suppressive effects on NSCLC cell invasion and migration mediated by miR-99b. CONCLUSIONS: In summary, miR-99b exerted anti-tumor functions in NSCLC via regulation of NIPBL, suggesting that miR-99b/NIPBL axis may be novel biomarkers for NSCLC treatments.

[A challenge for colorectal surgeons: pathogenesis, progression and management of the secondary tumors of the ovary].

A common clinical problem encountered by colorectal surgeons is the secondary tumors of the ovary (STO), particularly in young female patients. Most STO are from the digestive tract, and the known possible metastatic mechanisms include lymphatic, hematogenous, and intraperitoneal spreading. The molecular and histopathological characteristics of STO from different sites are diverse. It is particularly important to correctly identify the origin and feature of STO, which should be clarified by combining medical history, histopathology, immunohistochemistry, molecular biology, imaging and other means. The prognosis of patients with STO is poor in general. Comprehensive therapies based on surgical resection can benefit some patients. There is no specific treatment for STO at present, but not giving up easily on these patients is the right choice that every surgeon should understand.

[Comparative analysis on seroprevalence of hepatitis B in Guangzhou in 2008 and 2018].

Objective: To compare the seroprevalence of hepatitis B in Guangzhou in 2008 and 2018. Methods: According to the proportion of Guangzhou population size, two-stage cluster sampling was used to select the residents aged 1-59 years in the two surveys. Results: 4 989 and 3 980 people aged 1-59 years were involved in 2008 and 2018, respectively. HBsAg prevalence was 9.50% (95%CI:7.34%-11.66%) in 2018 and 12.45% (95%CI:10.58%-14.33%) in 2008 among the people aged 1-59 years, with no significant difference statistically (χ2=18.302, P=0.075). The decrease of HBsAg prevalence was mainly in the population aged 7-16 years. For the people aged 7-16 years, the HBsAg prevalence was 0.88% (95%CI: 0.35%-1.42%) in 2018 and decreased by 80.62% as compared with the rate 4.54% (95%CI:2.71%-6.36%) in 2008, with statistically significant difference (χ2=34.144,P=0.000). Anti-HBs prevalence was 72.30% (95%CI:69.56%-75.04%) in 2018 and ascended by 11.35% as compared with the rate of 64.93% (95%CI:61.65 %-68.22%) in 2008 among the people aged 1-59 years, with statistically significant difference (χ2=51.618, P=0.001). The rise of anti-HBs prevalence was mainly in the population aged 17-59 years. For the people aged 17-59 years, the anti-HBs prevalence was 71.93% (95%CI: 68.90%-74.96%) and risen by 12.80% as compared with the rate of 63.77% (95%CI: 60.16%-67.37%) in 2008, with a statistically significant difference (χ2=28.422, P=0.001). HBV infection rate was 48.10% (95%CI: 43.20%-53.00%) in 2018 and decreased by 22.76% as compared with the rate of 62.27% (95%CI: 59.11%-65.44%) in 2008, with statistically significant difference (χ2=167.138, P=0.000). The HBV infection rates in the population aged 1-6 years, 7-16 years, and 17-59 years were 4.58%, 5.13%, and 56.56% (a decrease of 81.83%, 85.91%, and 18.47%), respectively. The infection rate of HBV was 48.87% (a decrease of 24.70%) in high epidemic areas and 28.81% (a decrease of 38.75%) in people with a history of hepatitis B immunization. Conclusion: The prevention and control of hepatitis B in Guangzhou have achieved remarkable results it already reached the national goal of reducing HBsAg prevalence to less than 1% among children under five years since 2008. However, the target goal of reducing the hepatitis B mortality rate is quite demanding. The neonatal hepatitis B vaccination and monitoring and screening in adults are still needed.

A radiomics method based on MR FS-T2WI sequence for diagnosing of autosomal dominant polycystic kidney disease progression.

OBJECTIVE: We aimed to construct/validate a radiomics method based on MR FS-T2WI sequence for the evaluation of kidney function in patients with autosomal dominant polycystic kidney disease (ADPKD). PATIENTS AND METHODS: The clinical data and MRI images of 114 patients with ADPKD were retrospectively analyzed. With a glomerular filtration rate of 60 mL/min per 1.73 m2 as the cutoff value, patients were divided into two groups, where there were 59 patients with GFR ≥60 mL/min per 1.73 m2 (including CKD1 and CKD2 phase) and 55 patients with GFR <60 mL/min per 1.73 m2 (including CKD3 phase and higher). All patients underwent the 3.0T MR scan of the kidney. Then, the kidney were delineated layer by layer based on the FS-T2WI sequence to obtain the volume of interest (VOI) for radiomics features extraction. The optimal radiomics features were selected by least absolute shrinkage and selection operator (LASSO). Three kinds of data modality including the pure clinical data, the pure image data and the clinical-image fused data were utilized to establish three types of models (clinical, image and with their combination) separately by five machine learning classifiers: k-nearest-neighbors (KNN), support vector machine (SVM), logistic regression (LR), random forests (RF) and multi-layer perception (MLP). Receiver operating characteristic (ROC) curve, areas under the curve (AUC), sensitivity, specificity and precision were employed to evaluate the model's effectiveness to diagnosis the glomerular filtration rate of patients with ADPKD based on different models. Besides, Delong test was applied to compare ROCs between models. RESULTS: 960 radiomics features were extracted from each VOIs, and clinical information included the gender and age of each patient. After feature selection, 23 and 21 features based on pure image data and clinical-image fused data were independently used to construct models for the kidney function evaluation. The clinical-image fused model (AUC=0.89) has better performance than the pure image model (p=0.046) and pure clinical model (p<0.001). Clinical-image fused model based on LR classifier showed the best diagnostic efficiency, with AUC=0.89, sensitivity=0.8867 and specificity=0.7959. CONCLUSIONS: The MR FS-T2WI radiomics analysis based on clinical-image fused model is instrumental in evaluating and predicting the kidney function of patients with polycystic kidney disease.

MicroRNA-29b promotes cell sensitivity to Temozolomide by targeting STAT3 in glioma.

OBJECTIVE: This study aimed to explore the effects of microRNA-29b (miR-29b) on chemoresistance of glioma and to examine the underlying mechanisms. MATERIALS AND METHODS: MiR-29b expression in glioma tissues and cell lines was analyzed by quantitative real time-polymerase chain reaction (qRT-PCR). The cell viability was determined by Cell Counting Kit-8 (CCK-8) assay. Cell apoptosis was analyzed by Annexin V-Fluorescein isothiocyanate (FITC) assay. The relationship between miR-29b and signal transducer and activator of transcription 3 (STAT3) was examined by the Dual-Luciferase reporter gene assay. The levels of cleaved caspase-3, Bax, Bcl-2, and STAT3 were detected by Western blotting assay. RESULTS: The expression of miR-29b was downregulated in glioma tissues compared to normal brain tissue. In addition, the expression level of miR-29b was lower in glioma tissues from patients at late stages (III and IV) compared with early stages (I and II). Besides, miR-29b expression was significantly lower in LN229, U87MG, and U251 cells compared to normal human astrocytes (NHA) cells. Moreover, our results showed that miR-29b expression in Temozolomide (TMZ)-resistance cell lines U251/TMZ and U87MG/TMZ was markedly lower than that of TMZ-sensitivity cell lines U251 and U87MG. The protein levels of STAT3 and the phosphorylation of STAT3 were increased in U251/TMZ and U87MG/TMZ compared to U251 and U87MG. When the expression of miR-29b was repressed, cell viability was increased. Meanwhile, cell apoptosis was reduced, the protein levels of cleaved caspase-3 and (Bcl-2 Associated X Protein) Bax were decreased, whereas the protein level of B-cell lymphoma 2 (Bcl-2) was increased. Moreover, the effects of miR-29b knockdown on the cell growth and apoptosis in U251 and U87MG cells were markedly attenuated by knockdown of STAT3. In TMZ-resistant U251/TMZ and U87MG/TMZ cells, transfection with miR-29b decreased cell growth, promoted apoptotic cell death, elevated the protein levels of cleaved caspase-3, and Bax protein, while downregulated Bcl-2 protein. As expected, the effect of miR-29b upregulation on cell growth and apoptosis of TMZ-resistant glioma cells was reversed by STAT3 overexpression. The results from the Luciferase assay demonstrated miR-29b modulated STAT3 expression by directly bound with 3'-Untranslated Region (3'-UTR). CONCLUSIONS: MiR-29b enhances the cell sensitivity to TMZ by inhibiting STAT3 in glioma. Our study might provide a novel target for treating TMZ-resistant glioma.

Pregnancies conceived using assisted reproductive technologies (ART) have low levels of pregnancy-associated plasma protein-A (PAPP-A) leading to a high rate of false-positive results in first trimester screening for Down syndrome.

BACKGROUND: First trimester screening (FTS) for Down syndrome combines measurement of nuchal translucency, free beta-human chorionic gonadotrophin and pregnancy-associated plasma protein-A (PAPP-A). The aim of this study was to undertake a detailed analysis of FTS results in singleton pregnancies conceived using assisted reproductive technologies (ART) and non-ART pregnancies. METHODS: A record linkage study compared outcomes in 1739 ART-conceived and 50 253 naturally conceived pregnancies. RESULTS: Overall, significantly lower PAPP-A levels were detected in ART pregnancies (0.83 multiples of median, MoM) than in controls (1.00 MoM) (t-test P < 0.001). This difference remained after excluding complicated pregnancies. Analysis of factors affecting PAPP-A levels suggested fresh compared with frozen embryo transfers and use of artificial cycles compared with natural cycles for frozen transfers were associated with lower values. The adjusted odds ratio (AdjOR) for receiving a false-positive result was 1.71 (95% CI 1.44-2.04; P < 0.001) for ART pregnancies compared with non-ART pregnancies, and this leads to a higher AdjOR (1.24, 95% CI 1.03-1.49; P = 0.02) for having a chorionic villous sampling (CVS) or amniocentesis. CONCLUSIONS: ART pregnancies have reduced FTS PAPP-A levels leading to an increased likelihood of receiving a false-positive result and having a CVS/amniocentesis. Lower PAPP-A may reflect impairment of early implantation with some forms of ART.

Perilipin, C/EBPα, and C/EBPß mRNA abundance in longissimus muscle and different adipose tissues of Holstein and Charolais cattle.

Possible regulators of intramuscular fat deposition were investigated in longissimus muscle (LM) and adipose tissues of 18months old Holstein and Charolais bulls. The mRNA abundance of perilipin and transcription factors C/EBPα and C/EBPß was analyzed by real-time RT-PCR. Carcass traits and marbling traits were recorded and relationships among adipogenic genes and tissue traits were determined. Charolais cattle were heavier (P<0.001) and had less body fat (P<0.001). Holstein bulls accumulated more fat in the LM (P=0.02), but the number and size of marbling flecks did not differ (P>0.7) between breeds. Perilipin, C/EBPα, and C/EBPß mRNA abundance was influenced by tissue but not by breed. Relationships between mRNA abundance and marbling traits could not be confirmed, however relationships among adipogenic genes. The transcriptional activity of adipogenic genes in LM suggests that intramuscular adipose tissue is still developing and differentiation still occurs.

[Practice guideline of peroral endoscopic myotomy of achalasia: Zhongshan experience].

Peroral endoscopic myotomy (POEM) is a novel clinical technique developed in 2010, and has been widely accepted for treating achalasia and esophageal motility disorders, because of its minimal invasiveness and good efficacy. Zhongshan Hospital has published the practice guideline (the "Zhongshan experience") of peroral endoscopic myotomy of achalasia (v1.2018) based on experience combined with literatures. (1) Preoperative evaluation includes clinical symptom assessment, gastroscopy, high-resolution manometry and upper gastrointestinal radiography. (2) Absolute indication is idiopathic achalasia, and age is no longer a contraindication. (3) The criteria include the medical centers with legal qualifications and the operators with over 5 years of clinical experience in gastroenterological surgery or gastroenterology and more than 30 cases of esophageal endoscopic submucosal dissection (ESD). (4) The length of the myotomy is 8 to 10 cm. The recommended location of the myotomy is the anterior or posterior wall. Whether a full-thickness or circular muscle myotomy is chosen is based on patient's condition. (5) If pleural effusion, atelectasis or pneumothorax occurs, CT examination is recommended during the postoperative period. If patients presents with symptoms such as vomiting and high fever, endoscopic examination and upper gastrointestinal radiography should be performed. (6) Major adverse events include mucosal injury, perforation, bleeding, pneumothorax and pleural effusion. (7) The Eckardt score system and endoscopic examination are used for evaluating the effectiveness after POEM.

The effect of SOX9 on islet ß cells in high glucose environment through regulation of ERK/P38 signaling pathway.

OBJECTIVE: Islet beta cells are involved in insulin secretion. SRY-related high mobility group 9 (SX-S9) is involved in the progression of various diseases, but the role of SOX9 in islet ß cells remains unclear. PATIENTS AND METHODS: The islet ß cell MIN6 cells were cultured in vitro and randomly divided into control group, high glucose group, and SOX9 siRNA group followed by analysis of SOX9 mRNA and protein expression by real-time PCR and Western blot, respectively, cell proliferation by MTT assay, cell apoptosis by flow cytometry, secretion of inflammatory factors TNF-α and IL-2 by ELISA, insulin secretion levels by spectrophotometer, myeloperoxidase (MPO), and superoxide dismutase (SOD) activities, as well as ERK/P38 signaling protein expression by Western blot. RESULTS: Under high glucose environment, SOX9 mRNA and protein expression were significantly increased, MIN6 cell proliferation was inhibited, apoptosis rate and secretion of TNF-α and IL-2 were increased, along with decreased insulin secretion, increased MPO content, decreased SOD activity and phosphorylation of ERK/P38, compared with control group (p < 0.05). However, transfection of SOX9 siRNA reduced SOX9 expression, promoted proliferation of MIN6 cells, decreased apoptotic rate and secretion of TNF-α and IL-2, increased insulin secretion, decreased MPO content, increased SOD and ERK/P38 protein phosphorylation. Compared with high glucose group, the differences were statistically significant (p < 0.05). CONCLUSIONS: The expression of SOX9 is increased under high glucose environment. Down-regulation of SOX9 expression can inhibit islet cell apoptosis, oxidative stress and inflammation, and promote islet cell proliferation and insulin secretion by regulating ERK/P38 signaling pathway.