Deteriorated bone microarchitecture caused by sympathetic overstimulation in pheochromocytoma and paraganglioma.

PURPOSE: Despite the potentially destructive effect of sympathetic activity on bone metabolism, its impact on bone microarchitecture, a key determinant of bone quality, has not been thoroughly investigated. This study aims to evaluate the impact of sympathetic activity on bone microarchitecture and bone strength in patients with pheochromocytoma and paraganglioma (PPGL). METHODS: A cross-sectional study was conducted in 38 PPGL patients (15 males and 23 females). Bone turnover markers serum procollagen type 1 N-terminal propeptide (P1NP) and ß-carboxy-terminal crosslinked telopeptide of type 1 collagen (ß-CTX) were measured. 24-h urinary adrenaline (24hUE) and 24-h urinary norepinephrine levels (24hUNE) were measured to indicate sympathetic activity. High-resolution peripheral quantitative computed tomography (HR-pQCT) was conducted to evaluate bone microarchitecture in PPGL patients and 76 age-, sex-matched healthy controls (30 males and 46 females). Areal bone mineral density (aBMD) was measured by dual-energy X-ray absorptiometry (DXA) simultaneously. RESULTS: PPGL patients had a higher level of ß-CTX. HR-pQCT assessment revealed that PPGL patients had notably thinner and more sparse trabecular bone (decreased trabecular number and thickness with increased trabecular separation), significantly decreased volume BMD (vBMD), and bone strength at both the radius and tibia compared with healthy controls. The deterioration of Tt.vBMD, Tb.Sp, and Tb.1/N.SD was more pronounced in postmenopausal patients compared with the premenopausal subjects. Moreover, subjects in the highest 24hUNE quartile (Q4) showed markedly lower Tb.N and higher Tb.Sp and Tb.1/N.SD at the tibia than those in the lowest quartile (Q1). Age-related bone loss was also exacerbated in PPGL patients to a certain extent. CONCLUSIONS: PPGL patients had significantly deteriorated bone microarchitecture and strength, especially in the trabecular bone, with an increased bone resorption rate. Our findings provide clinical evidence that sympathetic overstimulation may serve as a secondary cause of osteoporosis, especially in subjects with increased sympathetic activity.

High prevalence of vertebral deformity in tumor-induced osteomalacia associated with impaired bone microstructure.

PURPOSE: Patients with tumor-induced osteomalacia (TIO) often suffer from irreversible height loss due to vertebral deformity. However, the prevalence of vertebral deformity in TIO patients varies among limited studies. In addition, the distribution and type of vertebral deformity, as well as its risk factors, remain unknown. This study aimed to identify the prevalence, distribution, type and risk factors for vertebral deformity in a large cohort of TIO patients. METHODS: A total of 164 TIO patients were enrolled in this retrospective study. Deformity in vertebrae T4-L4 by lateral thoracolumbar spine radiographs was evaluated according to the semiquantitative method of Genant. Bone microstructure was evaluated by trabecular bone score (TBS) and high-resolution peripheral QCT (HR-pQCT). RESULTS: Ninety-nine (99/164, 60.4%) patients had 517 deformed vertebrae with a bimodal pattern of distribution (T7-9 and T11-L1), and biconcave deformity was the most common type (267/517, 51.6%). Compared with patients without vertebral deformity, those with vertebral deformity had a higher male/female ratio, longer disease duration, more height loss, lower serum phosphate, higher bone turnover markers, lower TBS, lower areal bone mineral density (aBMD), lower peripheral volumetric BMD (vBMD) and worse microstructure. Lower trabecular vBMD and worse trabecular microstructure in the peripheral bone and lower spine TBS were associated with an increased risk of vertebral deformity independently of aBMD. After adjusting for the number of deformed vertebrae, we found little difference in clinical indexes among the patients with different types of vertebral deformity. However, we found significant correlations of clinical indexes with the number of deformed vertebrae and the spinal deformity index. CONCLUSION: We reported a high prevalence of vertebral deformity in the largest cohort of TIO patients and described the vertebral deformity in detail for the first time. Risk factors for vertebral deformity included male sex, long disease duration, height loss, abnormal biochemical indexes and bone impairment. Clinical manifestation, biochemical indexes and bone impairment were correlated with the number of deformed vertebrae and degree of deformity, but not the type of deformity.

[Effect of equal temperature bladder irrigation in patients with transurethral resection of prostate: A meta-analysis].

OBJECTIVE: To evaluate the effect of equal temperature bladder irrigation on bladder spasm, postoperative bleeding, vital signs and discomfort of chills in patients of transurethral resection of prostate using meta-analysis. METHODS: Several electronic databases included Cochrane Library, PubMed, Embase, China National Knowledge Infrastructure (CNKI), Wanfang, VIP, China Biology Medicine (CBM) were searched systematically for published randomized controlled trial about equal temperature bladder irrigation in patients with transurethral resection of prostate before November 20, 2019. Two reviewers selected independently the literature in the light of the inclusion and exclusion criteria, assessed the risk of bias by quality assessment and extracted data which were consisted of clinical efficacy indexes, such as incidence of bladder spasm, severity of bladder spasm, incidence of tube plugging, amount of bladder flushing fluid, time of bladder flushing, heart rate, systolic pressure, diastolic pressure, and incidence of chills. Data were pooled using fixed-effects model or random-effects model, and the summary effect measure was calculated by risk ratio (RR) or mean difference (MD) and 95% confidence interval (95%CI). Meta-analysis was performed by Review Manager 5.3 Software. RESULTS: In the study, 13 randomized controlled trails met the requirement with a total of 2 033 patients of transurethral resection of prostate were included, of whom 1 015 were carried out with equal temperature bladder irrigation and 1 018 with room temperature bladder irrigation. The results of meta-analysis showed that incidence of bladder spasm [RR=0.51, 95%CI (0.45, 0.57), P < 0.001], severity of bladder spasm [MD=-1.61, 95%CI (-2.00, -1.23), P < 0.001], incidence of urinary blockage [RR=0.29, 95%CI (0.19, 0.44), P < 0.001], dosage of bladder irrigation [MD=-6.75, 95%CI (-7.33, -6.17), P < 0.001], time of bladder rinse [MD=-7.60, 95%CI (-11.91, -3.29), P < 0.001], heart rate [MD=-13.68, 95%CI (-15.19, -12.17), P < 0.001], systolic pressure [MD=-29.26, 95%CI (-31.92, -26.59), P < 0.001], diastolic pressure [MD=-29.36, 95%CI (-31.75, -26.98), P < 0.001], incidence of chills and discomfort [MD=0.37, 95%CI (0.31, 0.44), P < 0.001] in equal temperature group of the patients with transurethral resection of prostate had significantly statistical difference compared with room temperature group. CONCLUSION: Based on current available evidence, equal temperature bladder irrigation reduced the incidence of bladder spasm and urinary blockage, relieved bladder spasm, reduced dosage and time of bladder irrigation, and hardly affected normal vital signs and increased the patient' s comfort.

Definition of large niche after Cesarean section based on prediction of postmenstrual spotting: Chinese cohort study in non-pregnant women.

OBJECTIVE: A large niche after Cesarean section (CS) is associated with long-term complications, of which postmenstrual spotting is associated positively with the size of the niche. However, the diagnosis of a large niche in the literature is inconsistent and the definition is largely subjective. The aim of this study was to generate a definition for a large niche in non-pregnant women based on the presence of postmenstrual spotting. METHODS: Women who had undergone CS in our hospital between January 2012 and June 2017 were selected randomly from our database, contacted by telephone and subsequently examined between January 2016 and June 2020. Eligible for inclusion were non-pregnant women who had their last CS more than 1 year earlier and agreed to undergo transvaginal sonography (TVS). All participants underwent examination of their CS scar by TVS (two-dimensional color Doppler) during the midfollicular phase. Niche depth, length, width, residual myometrial thickness (RMT), adjacent myometrial thickness (AMT) and ratio of niche depth/AMT were recorded. Women diagnosed with a niche, defined as an indentation at the site of the CS with a depth of at least 2 mm, were classified into two groups (symptomatic or asymptomatic) according to whether they experienced postmenstrual spotting. Logistic regression analysis was used to establish the best cut-off values for the niche parameters to predict postmenstrual spotting. A new definition was generated based on the niche parameters with the highest area under the receiver-operating-characteristics (ROC) curve (AUC) for the prediction of postmenstrual spotting. RESULTS: A total of 727 women who had a CS > 1 year earlier underwent TVS examination, of whom 263 were diagnosed with a niche (prevalence of 36.2%). Of these, 160 women experienced postmenstrual spotting and 103 were asymptomatic. The three variables with the highest AUC for prediction of postmenstrual spotting were niche depth/AMT ratio (AUC, 0.798; 95% CI, 0.745-0.852), niche depth (AUC, 0.731; 95% CI, 0.668-0.795) and RMT (AUC, 0.683; 95% CI, 0.618-0.748). Based on the best cut-offs according to ROC-curve analysis, a large niche was defined as: niche depth ≥ 0.50 cm, RMT ≤ 0.21 cm or niche depth/AMT ratio ≥ 0.56. The prevalence of a large niche according to this definition was 22.4% (163/727). The new definition had a specificity of 61.17% (95% CI, 52.34-70.41%) and sensitivity of 76.87% (95% CI, 70.28-84.16%) for a large niche. CONCLUSION: This study has provided a new definition for a large niche after CS. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

A prospective study on vulvovaginal candidiasis: multicentre molecular epidemiology of pathogenic yeasts in China.

BACKGROUND: Vulvovaginal candidiasis (VVC) is frequent in women of reproductive age, but very limited data are available on the epidemiology in cases of VVC in China. OBJECTIVES: The current study has been conducted to reveal the prevalence, species distribution of yeast causing VVC and molecular genetics of Candida albicans in China. METHODS: Vaginal swabs were collected from 543 VVC outpatients recruited in 12 hospitals in China between September 2017 and March 2018. They were preliminarily incubated on Sabouraud dextrose agar and then positive subjects of which were then transmitted to our institute for further identification. CHROMagar™ was used to isolate Candida species, and all isolates were finally identified by DNA sequencing. Multilocus sequence typing (MLST) was used to analyse phylogenetic relationships of the various C. albicans isolates. RESULTS: Eleven different yeast species were identified in 543 isolates, among which C. albicans (84.7%) was the most frequent, followed by C. glabrata (8.7%). We obtained 117 unique diploid sequence types from 451 clinical C. albicans isolates and 92 isolates (20.4%) belonged to a New Clade. All the strains appearing in the New Clade were from northern China and they were isolated from non-recurrent VVC. CONCLUSIONS: Our findings suggest that C. albicans are still the main cause of VVC in China and the majority of C. albicans isolates belongs to Clade 1 with DST 79 and DST 45 being two most common. Moreover, the New Clade revealed in our study seems to be specific to northern China.

[Long-term efficacy and safety of simultaneous integrated boost radiotherapy in non-operative esophageal squamous cell carcinoma: a multicenter retrospective data analysis (3JECROG R-05)].

Objective: To analyze the survival benefits and treatment related toxic effects of simultaneous integrated boost intensity-modulated radiotherapy (SIB-RT) for non-operative esophageal squamous cell carcinoma patients. Methods: The data of 2 132 ESCC patients who were not suitable for surgery or rejected operation, and underwent radical radiotherapy from 2002 to 2016 in 10 hospitals of Jing-Jin-Ji Esophageal and Esophagogastric Cancer Radiotherapy Oncology Group (3JECROG) were analyzed. Among them, 518 (24.3%) cases underwent SIB (SIB group) and 1 614 (75.7%) cases did not receive SIB (No-SIB group). The two groups were matched with 1∶2 according to propensity score matching (PSM) method (caliper value=0.02). After PSM, 515 patients in SIB group and 977 patients in No-SIB group were enrolled. Prognosis and treatment related adverse effects of these two groups were compared and the independent prognostic factor were analyzed. Results: The median follow-up time was 61.7 months. Prior to PSM, the 1-, 3-, and 5-years overall survival (OS) rates of SIB group were 72.2%, 42.8%, 35.5%, while of No-SIB group were 74.3%, 41.4%, 31.9%, respectively (P=0.549). After PSM, the 1-, 3-, and 5-years OS rates of the two groups were 72.5%, 43.4%, 36.4% and 75.3%, 41.7%, 31.6%, respectively (P=0.690). The univariate survival analysis of samples after PSM showed that the lesion location, length, T stage, N stage, TNM stage, simultaneous chemoradiotherapy, gross tumor volume (GTV) and underwent SIB-RT or not were significantly associated with the prognosis of advanced esophageal carcinoma patients who underwent radical radiotherapy (P<0.05). Cox model multivariate regression analysis showed lesion location, TNM stage, GTV and simultaneous chemoradiotherapy were independent prognostic factors of advanced esophageal carcinoma patients who underwent radical radiotherapy (P<0.05). Stratified analysis showed that, in the patients whose GTV volume≤50 cm(3), the median survival time of SIB and No-SIB group was 34.7 and 30.3 months (P=0.155), respectively. In the patients whose GTV volume>50 cm(3), the median survival time of SIB and No-SIB group was 16.1 and 20.1 months (P=0.218). The incidence of radiation esophagitis and radiation pneumonitis above Grade 3 in SIB group were 4.3% and 2.5%, significantly lower than 13.1% and 11% of No-SIB group (P<0.001). Conclusions: The survival benefit of SIB-RT in patients with locally advanced esophageal carcinoma is not inferior to non-SIB-RT, but without more adverse reactions, and shortens the treatment time. SIB-RT can be used as one option of the radical radiotherapy for locally advanced esophageal cancer.

Impaired bone microarchitecture in distal interphalangeal joints in patients with primary hypertrophic osteoarthropathy assessed by high-resolution peripheral quantitative computed tomography.

This study aimed to investigate the bone impairment in finger joints in PHO patients by HR-pQCT. Results showed distinguished differences in bone architecture and biomechanics parameters at DIPs between PHO patients and healthy controls using HR-pQCT assessment. Besides, serum PGE2, hsCRP and ESR levels were found negatively correlated with total vBMD. INTRODUCTION: This study aimed to investigate the bone impairment in finger joints in primary hypertrophic osteoarthropathy (PHO) patients firstly by high-resolution peripheral quantitative computed tomography (HR-pQCT). METHODS: Fifteen PHO patients and 15 healthy controls were enrolled in this study. Bone erosions in hands at distal interphalangeal joints (DIPs) in both PHO patients and controls were evaluated by X-ray. Bone geometry, vBMD, microstructure parameters, and size of individual bone erosion were also measured at the 3rd DIP by HR-pQCT as well. Blood biochemistry levels between the two groups were also compared. RESULTS: Compared to X-ray, HR-pQCT assessment were more sensitive for detection of bone erosions, with 14 PHO patients by HR-pQCT versus ten PHO patients by X-ray judged at the 3rd DIP. The average depth, width, and volume of erosions size in PHO patients were 1.38 ± 0.80 mm, 0.79 ± 0.27 mm, and 1.71 ± 0.52 mm3, respectively. The bone cross-areas including total area (+ 25.3%, p ≤ 0.05), trabecular area (+ 56.2%, p ≤ 0.05), and cortical perimeter (+ 10.7%, p ≤ 0.05) at the defined region of interest of 3rd DIP was significantly larger than controls. Total vBMD was 11.9% lower in PHO patients compared with the controls (p ≤ 0.05). Biochemical test results showed the increased levels of inflammatory cytokines, bone resorption markers, and joint degeneration markers in PHO patients. Serum prostaglandin PGE2, high-sensitive C-reactive protein (hsCRP) and erythrocyte sedimentation rate (ESR) levels were found negatively correlated with total vBMD. CONCLUSIONS: This study demonstrated higher sensitivity of the HR-pQCT measurement at DIPs by showing the differences in architecture and biomechanics parameters at DIPs between the PHO patients and healthy controls, which would be of interest clinically to investigate bone deterioration in PHO patients.

[Efficacy analysis of the radiotherapy and chemotherapy in patients with stage â £ esophageal squamous carcinoma: a multicenter retrospective study of Jing-Jin-Ji Esophageal and Esophagogastric Cancer Radiotherapy Oncology Group (3JECROG R-01F)].

Objective: To evaluate the survival and prognostic factors of radiotherapy in patient with Ⅳ stage esophageal squamous carcinoma treated with radiation or chemoradiation. Methods: The medical records of 608 patients with stage Ⅳ esophageal squamous cell carcinoma who met the inclusion criteria in 10 medical centers in China from 2002 to 2016 were retrospectively analyzed. The overall survival and prognostic factors of all patients at 1, 3 and 5 years were analyzed. Results: The 1-, 3-, 5- year overall survival (OS) rates was 66.7%, 29.5% and 24.3% in stage ⅣA patients, and 58.8%, 29.0% and 23.5% in stage ⅣB patients. There was no statistical difference between the two groups (P=0.255). Univariate analysis demonstrated that the length of lesion, treatment plan, planned tumor target volume (PGTV) dose, subsequent chemotherapy, and degrees of anemia, radiation esophagitis, radiation pneumonia were related to the prognoses of patients with Ⅳ stage esophageal carcinomas after radiotherapy and chemotherapy (P<0.05). Multivariate analysis demonstrated that PGTV dose (OR=0.693, P=0.004), radiation esophagitis (OR=0.867, P=0.038), and radiation pneumonia (OR=1.181, P=0.004) were independent prognostic factors for OS. Conclusions: For patients with stage Ⅳ esophageal squamous cell carcinoma, chemoradiotherapy followed by sequential chemotherapy is recommended, which can extend the total survival and improve the prognosis of the patients. PGTV dose more than 60 Gy has better efficacy.

[Prognostic analysis of definitive radiotherapy for early esophageal carcinoma(T1-2N0M0): a multi-center retrospective study of Jing-Jin-ji Esophageal and Esophagogastric Cancer Radiotherapy Oncology Group].

Objective: To evaluate the prognostic factors of T1-2N0M0 esophageal squamous cell carcinoma (ESCC) treated with definitive radiotherapy. Methods: The clinical data of 196 patients with T1-2N0M0 ESCC who were treated with definitive radiotherapy in 10 hospitals were retrospectively analyzed. All sites were members of Jing-Jin-Ji Esophageal and Esophagogastric Cancer Radiotherapy Oncology Group (3JECROG). Radiochemotherapy were applied to 78 patients, while the other 118 patients received radiotherapy only. 96 patients were treated with three-dimensional conformal radiotherapy (3DCRT) and 100 treated with intensity-modulated radiotherapy (IMRT). The median dose of plan target volume(PTV) and gross target volume(GTV) were both 60 Gy. The median follow-up time was 59.2 months. Log rank test and Cox regression analysis were used for univariat and multivariate analysis, respectively. Results: The percentage of normal lung receiving at least 20 Gy (V(20)) was (18.65±7.20)%, with average dose of (10.81±42.05) Gy. The percentage of normal heart receiving at least 30 Gy (V(30)) was (14.21±12.28)%. The maximum dose of exposure in spinal cord was (39.65±8.13) Gy. The incidence of radiation pneumonia and radiation esophagitis were 14.80%(29/196) and 65.82%(129/196), respectively. The adverse events were mostly grade 1-2, without grade 4 toxicity. Median overall survival (OS) and progression-free survival (PFS) were 70.1 months and 62.3 months, respectively. The 1-, 3- and 5-year OS rates of all patients were 75.1%、57.4% and 53.2%, respectively. The 1-, 3- and 5-year PFS rates were 75.1%、57.4% and 53.2%, respectively. Multivariate analysis demonstrated that patients'age (HR=1.023, P=0.038) and tumor diameter (HR=1.243, P=0.028)were the independent prognostic factors for OS, while tumor volume were the independent prognostic factor for PFS. Conclusions: Definitive radiotherapy is a promising therapeutic method in patients with T1-2N0M0 ESCC. Patients' age, tumor diameter and tumor volume may impact patients' prognosis.

[Finite element analysis of evaluating the change of the hip joint biomechanics following femoral neck shortening after cannulated screw fixation for osteoporotic femoral neck fracture].

Objective: To evaluate the stress status of femoral head and neck, screws and acetabulum caused by femoral neck shortening after internal fixation of femoral neck fracture with finite element method, and to analyze the stress of proximal femoral neck and acetabulum from the mechanical point of view. Methods: CT scan data of hip of a healthy adult female were collected. Three-dimensional reconstruction MICs and related module function simulation was used to establish the postoperative shortening model of femoral neck fracture with Pauwells angle>50°, which was treated with cannulated screws. The models were divided into four groups: normal femoral neck without shortening, shortening for 2.5 mm, shortening for 7.5 mm and shortening for 12.5 mm. The finite element analysis software MSC. Nastran2012 was used to do the mechanical analysis. The acetabulum surface, femoral head surface, proximal femur and the maximum stress, stress nephogram and other relevant data were collected. Results: The maximum tensile stress and the maximum stress at the fracture site of the femoral neck increased gradually with the increasing of shortening of femoral neck, however, the maximum compressive stress under the femoral neck and the medial cortex decreased gradually; the maximum stress on the surface of the femoral head was 14.9, 15.0, 16.3 and 16.3 MPa, respectively; the maximum stress on the surface of the acetabulum was 10.1, 10.1 and 10.5,11.7 MPa, respectively. Conclusion: The mechanical environment of the hip joint changes with femoral neck shortening. With the increasing of femoral neck shortening, the peak stress of the acetabulum increases continuously. When the femoral neck is shortened seriously, the load distribution is uneven and the complex mobility of hip joint is decreased. In addition, the change of shortening might play a role in the necrosis of femoral head.

Novel SLCO2A1compound heterozygous mutation causing primary hypertrophic osteoarthropathy with Bartter-like hypokalemia in a Chinese family.

PURPOSE: Primary hypertrophic osteoarthropathy (PHO) is an inherited disease characterized by digital clubbing, periostosis and pachydermia with defects in the degradation of prostaglandin E2 (PGE2). Mutations in SLCO2A1 gene-encoding prostaglandin transporter (PGT) resulted in PHO, autosomal recessive 2 (PHOAR2). The spectrum of mutations and variable clinical complications of PHOAR2 has been delineated. In this study, we investigated a Chinese PHO family with a manifestation of Bartter-like hypokalemia. METHODS: Clinical manifestations were collected and genetic analyses were performed in the PHO family. RESULTS: The 33-year-old male proband had severe hypokalemia due to potassium loss from the kidney, while his brother had mild hypokalemia. After being treated with etoricoxib, the serum potassium level of the patient increased rapidly to the normal range which corresponded with the reduction in his serum PGE2 and PE2 metabolite (PGEM) levels. A novel SLCO2A1 compound heterozygous mutation of p.I284V and p.C459R was identified in two PHO patients in this family. CONCLUSIONS: The present findings supported that the Bartter-like hypokalemia is a new complication of PHOAR2 caused by the high level of PGE2. Etoricoxib was demonstrated to be effective for the renal hypokalemia in PHO patients.

Absolute CBV for the differentiation of recurrence and radionecrosis of brain metastases after gamma knife radiotherapy: a comparison with relative CBV.

AIM: To investigate the efficiency of absolute cerebral blood volume (CBV) in the differentiation of tumour recurrence (TR) and radionecrosis (RN) in brain metastases (BM) and to evaluate the performance of absolute CBV compared to relative CBV (rCBV). MATERIALS AND METHODS: Between March 2015 and June 2017, 46 patients with BM underwent quantitative dynamic susceptibility contrast perfusion-weighted imaging (DSC-PWI) because new enhancement had been demonstrated in irradiated lesions after gamma knife radiotherapy. The patients were assigned to either the TR group or RN group on the basis of MR perfusion follow-up or histopathological outcome. Absolute CBV of lesions (CBVlesion) and contralateral normal appearing white matter (CBVNAWM) in both groups were obtained. Mean rCBV were calculated as CBVlesion/CBVNAWM, which was equal to rCBV using traditional DSC-PWI. RESULTS: CBVlesion of TR alone was significantly higher than the other parameters in both groups (p<0.001, separately). CBVlesion had smaller interobserver difference than CBVNAWM and rCBV (p<0.001, separately). Although CBVlesion significantly correlated with rCBV (r=0.914, p<0.001) and both had a similar specificity (96%) in differential diagnosis, CBVlesion had a higher sensitivity (96.9% versus 90.9%) to predict the treatment outcome. The best cut-off value of CBVlesion was 21.8 ml/100 g. CONCLUSION: Quantitative DSC-PWI is a powerful method for the assessment of radiosurgically treated brain metastases. Absolute CBV has higher diagnostic efficiency than rCBV, which enables an absolute quantification of the regional CBV and prediction of tumour response. These advantages promote the intra- and inter-patient quantitative image comparison across different institutions.

miR-133b acts as a tumor suppressor and negatively regulates EMP2 in glioma.

In recent years, the incidence of neuroglioma (glioma) has trended towards a younger age-group. Gene therapy has been widely implemented and a growing number of microRNAs associated with glioma have been identified., Herein, we detected the expression of micro RNA - miR-133b - in glioma by qPCR and also its effect on cell viability, survival and apoptosis of in vitro U87 and A172 cells. The binding effect of miR-133b on epithelial membrane protein-2 (EMP2) was verified and we then investigated the effect of EMP2 on in vitro glioma cells and tested the expression of apoptosis related factors after administration of altered miR-133b and EMP2 expressions. We found that miR-133b was down-regulated in glioma compared to adjacent non-tumorous tissue and also that its over-expression inhibits cell viability and survival and enhances apoptosis in the U87 and A-172 cells. Moreover, miR-133b effectively binds to EMP2, down-regulates its expression and negates its normal function. EMP2 normally promotes cell apoptosis and reduces cell viability and survival while miR-133b over-expression regulates the expression of apoptotic-associated protein and activates the apoptotic pathway, thus counteracting EMP2 regulation of opposite expression effects. Further, miR-133b can be considered a tumor suppressor because of its low expression and effects on cell apoptosis via down-regulating EMP2 expression and activating the apoptotic cell pathway in glioma. EMP2 is a risk factor for glioma, and miR-133b should prove a potential target for glioma clinical prevention and treatment.

[Clinical significance of NS1-BP expression in esophageal squamous cell carcinoma].

Objective: To investigate the clinical significance of NS1-BP expression in patients with esophageal squamous cell carcinoma (ESCC), and to study the roles of NS1-BP in proliferation and apoptosis of ESCC cells. Methods: A total of 98 tumor tissues and 30 adjacent normal tissues from 98 ESCC patients were used as study group and control group, and these samples were collected in Sun Yat-Sen University Cancer Center between 2002 and 2008. In addition, 46 ESCC tissues which were collected in Cancer Institute and Hospital of Tianjin Medical University were used as validation group. Expression of mucosal NS1-BP was detected by immunohistochemistry. Kaplan-Meier curve and log-rank test were used to analyze the survival rate. Multivariate Cox proportional hazard model was used to analyze the prognostic factors. Furthermore, NS1-BP was over expressed or knocked down in ESCC cells by transient transfection. Protein levels of c-Myc were detected by western blot. Cell viability and apoptosis was analyzed by MTT assay and flow cytometry. Results: Among all of tested samples, NS1-BP were down-regulated in 9 out of 30 non-tumorous normal esophageal tissues (30.0%) and 85 out of 144 ESCC tissues (59.0%), respectively, showing a statistically significant difference (P=0.012). In the study group, three-year disease-free survival rate of NS1-BP high expression group (53.2%) was significantly higher than that of NS1-BP low expression group (27.6%; P=0.009). In the validation group, the three-year disease-free survival rates were 57.8% and 25.5% in NS1-BP high and low levels groups, respectively, showing a similar results (P=0.016). Importantly, multivariate analyses showed that low expression of NS1-BP was an independent predictor for chemoradiotherapy sensitivity and shorter disease-free survival time in ESCC patients(P<0.05 for all). Furthermore, overexpressed NS1-BP in TE-1 cells repressed c-Myc expression, inhibited cell proliferation and promoted apoptosis. In contrast, knockdown NS1-BP in KYSE510 cells induced c-Myc expression, increased cell proliferation and repressed apoptosis. Conclusions: NS1-BP is an independent favorable prognostic factor in ESCC. It inhibits cell proliferation and enhances cell apoptosis via repressing c-Myc. Targeting NS1-BP may be a new therapeutic strategy for ESCC patients.

A large common-source outbreak of norovirus gastroenteritis in a hotel in Singapore, 2012.

An outbreak of gastroenteritis affected 453 attendees (attack rate 28·5%) of six separate events held at a hotel in Singapore. Active case detection, case-control studies, hygiene inspections and microbial analysis of food, environmental and stool samples were conducted to determine the aetiology of the outbreak and the modes of transmission. The only commonality was the food, crockery and cutlery provided and/or handled by the hotel's Chinese banquet kitchen. Stool specimens from 34 cases and 15 food handlers were positive for norovirus genogroup II. The putative index case was one of eight norovirus-positive food handlers who had worked while they were symptomatic. Several food samples and remnants tested positive for Escherichia coli or high faecal coliforms, aerobic plate counts and/or total coliforms, indicating poor food hygiene. This large common-source outbreak of norovirus gastroenteritis was caused by the consumption of contaminated food and/or contact with contaminated crockery or cutlery provided or handled by the hotel's Chinese banquet kitchen.

Novel mutations of CLCN7 cause autosomal dominant osteopetrosis type II (ADO-II) and intermediate autosomal recessive osteopetrosis (IARO) in Chinese patients.

SUMMARY: Osteopetrosis is a group of genetic bone disorders. Mutations in the chloride channel 7 gene (CLCN7) lead to chloride channel defect, which results in autosomal dominant osteopetrosis type II (ADO-II), autosomal recessive osteopetrosis (ARO), and intermediate autosomal recessive osteopetrosis (IARO). In the present study, we identified seven novel mutations of the CLCN7 gene and reported the first case of IARO with compound heterozygous mutation in Chinese population. INTRODUCTION: Osteopetrosis is a heritable bone disorder due to the deficiency of or function defect in osteoclasts. Mutations in the CLCN7 lead to chloride channel defects, which result in osteopetrosis with diverse severity ranging from asymptomatic or relatively mild symptoms in ADO-II to the very severe phenotype in ARO. Heterozygous mutations in CLCN7 are associated to ADO-II, while homozygous and compound heterozygous mutations in CLCN7 may result in ARO and IARO. To date, a total of 24 mutations in CLCN7 were identified in ADO-II, and only 3 mutations were identified in IARO. In the present study, we reported seven unrelated ADO-II patients and one IARO patient from Chinese population and elucidated the characteristics of CLCN7 gene mutations in these patients. METHODS: All 25 CLCN7 exons and exon-intron boundaries from genomic DNA were amplified and sequenced in eight affected individuals suffering from ADO-II/IARO. The clinical, biochemical, and radiographic analysis were evaluated to compare the differences between ADO-II and IARO both in genotype and phenotype. RESULTS: The results showed that there were seven novel CLCN7 mutations identified in these ADO-II/IARO patients, including six heterozygous missense mutations (p.L224R, p.S290Y, p.R326G, p.G347R, p.S473N, and p.L564P) and a novel splice mutation (p.K691FS). CONCLUSIONS: The compound heterozygous mutations (p.L224R and p.K691FS) were firstly observed in one IARO patient. The present study would enrich the database of CLCN7 mutations and improve our understanding of this heritable bone disorder.

Clinical research on neuroblastoma based on serum lactate dehydrogenase.

In recent years, more and more scholars tend to study neuroblastoma (NB) since it possesses increasing morbidity, but lack of effective treatment. This paper aims to investigate variation and clinical significance of the neuron-specific enolase (NSE) and lactic dehydrogenase (LDH) level in serum of children with NB before and after Auto Peripheral Blood Stem Cell Transplantation (APBSCT). A total of 90 children with NB from various hospitals were included in this research, and we analyzed the relationship between levels of NSE and LDH and the change of disease by comparing the two levels before and after APBSCT treatment. The results indicated that the positive rate of NSE in serum was high before treatment, and the levels of NSE and LDH were remarkably higher than those when the treatment was valid; after comprehensive treatment of chemotherapy, excision and radiotherapy, there was a significant difference of NSE and LDH levels in serum between children with complete remission (CR) and those with partial remission (PR); however, no significant differences of NSE and LDH levels were found among children in progressive stage compared to before treatment. It is believed that NSE and LDH levels are associated to the recurrence and treatment effect of NB, proving that both can reflect tumor load, therefore they can be taken as the auxiliary indicators for monitoring curative effects of NB treatment.

Physiological evaluation of the responses of Larix olgensis families to drought stress and proteomic analysis of the superior family.

The conifer Larix olgensis has been analyzed to delineate physiological and proteomic changes that occur under drought stress. Studies of the deleterious effects of drought in the larch families have mainly focused on photosynthesis. In the present study, when the intensity of drought was increased, plant height was inhibited as both POD and MDA levels increased, which indicates oxidative stress. Two-dimensional gel electrophoresis analysis detected 23 significantly differentially expressed proteins, of which 18 were analyzed by peptide mass fingerprinting by using MALDI-TOF/TOF. Eight spots were found to be up-regulated, while the other 10 spots were down-regulated during drought stress. The proteins that were induced by drought treatment have been implicated in the physiological changes that occurred. These results could provide additional information that could lead to a better understanding of the molecular basis of drought-sensitivity in larch plants.

A unique disulfide bridge of the thermophilic xylanase SyXyn11 plays a key role in its thermostability.

Based on the hyperthermostable family 11 xylanase (EvXyn11(TS)) gene sequence (EU591743), the gene Syxyn11 encoding a thermophilic xylanase SyXyn11 was synthesized with synonymous codons biasing towards Pichia pastoris. The homology alignment of primary structures among family 11 xylanases revealed that, at their N-termini, only SyXyn11 contains a disulfide bridge (Cys5-Cys32). This to some extent implied the significance of the disulfide bridge of SyXyn11 to its thermostability. To confirm the correlation between the N-terminal disulfide bridge and thermostability, a SyXyn11(C5T)-encoding gene, Syxyn11(C5T), was constructed by mutating the Cys5 codon of Syxyn11 to Thr5. Then, the genes for the recombinant xylanases, reSyXyn11 and reSyXyn11(C5T), were expressed in P. pastoris GS115, yielding xylanase activity of about 35 U per ml cell culture. Both xylanases were purified to homogeneity with specific activities of 363 and 344 U/mg, respectively. The temperature optimum and stability of reSyXyn11(C5T) decreased to 70 and 50°C from 85 and 80°C of reSyXyn11, respectively. There was no obvious change in pH characteristics.

The safety and efficacy of balanced crystalloid vs. normal saline in non-cardiac surgeries - A systematic review and meta-analysis.

OBJECTIVE: Balanced crystalloid and normal saline are routinely used in clinical anesthesia, but their safety and efficacy in non-cardiac surgeries are still unclear. MATERIALS AND METHODS: PubMed, Embase, Web of Science, Cochrane Library, Wanfang, and CNKI, from January 1980 to March 2023, were searched. Studies comparing balanced crystalloid (BC) with normal saline (NS) during non-cardiac surgeries were included. The primary outcomes were clinical outcomes (acidosis, renal insufficiency, and mortality), and the secondary outcomes were pH value, Na+, Cl- and creatinine levels, and vasopressor requirement. RESULTS: Forty-three RCTs were included in this meta-analysis. Low evidence revealed that the development of acidosis was lower in the BC group than in the NS group (OR: 0.05, 95% CI: 0.01-0.43, I2=80.8%, p=0.00), and no between-group difference exists in renal insufficiency and mortality. At the end of surgery and on postoperative day 1 (POD 1), the pH value was higher, and the levels of Na+ and Cl- were lower in the BC group. No between-group difference exists in creatinine level and vasopressor requirement. CONCLUSIONS: Perioperative balanced crystalloids can maintain the stability of acid-base and electrolyte balance and reduce acidosis compared with saline, but they cannot reduce postoperative renal insufficiency and mortality.