Gastrointestinal manifestations of critical ill heatstroke patients and their associations with outcomes: A multicentre, retrospective, observational study.

BACKGROUND: Extreme heat exposure is a growing health problem, and the effects of heat on the gastrointestinal (GI) tract is unknown. This study aimed to assess the incidence of GI symptoms associated with heatstroke and its impact on outcomes. AIM: To assess the incidence of GI symptoms associated with heatstroke and its impact on outcomes. METHODS: Patients admitted to the intensive care unit (ICU) due to heatstroke were included from 83 centres. Patient history, laboratory results, and clinically relevant outcomes were recorded at ICU admission and daily until up to day 15, ICU discharge, or death. GI symptoms, including nausea/vomiting, diarrhoea, flatulence, and bloody stools, were recorded. The characteristics of patients with heatstroke concomitant with GI symptoms were described. Multivariable regression analyses were performed to determine significant predictors of GI symptoms. RESULTS: A total of 713 patients were included in the final analysis, of whom 132 (18.5%) patients had at least one GI symptom during their ICU stay, while 26 (3.6%) suffered from more than one symptom. Patients with GI symptoms had a significantly higher ICU stay compared with those without. The mortality of patients who had two or more GI symptoms simultaneously was significantly higher than that in those with one GI symptom. Multivariable logistic regression analysis revealed that older patients with a lower GCS score on admission were more likely to experience GI symptoms. CONCLUSION: The GI manifestations of heatstroke are common and appear to impact clinically relevant hospitalization outcomes.

Comprehensive analysis of the transcriptional expressions and prognostic value of S100A family in pancreatic ductal adenocarcinoma.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) remains a treatment-refractory malignancy with poor prognosis. It is urgent to identify novel and valid biomarkers to predict the progress and prognosis of PDAC. The S100A family have been identified as being involved in cell proliferation, migration and differentiation progression of various cancer types. However, the expression patterns and prognostic values of S100As in PDAC remain to be analyzed. METHODS: We investigated the transcriptional expressions, methylation level and prognostic value of S100As in PDAC patients from the Oncomine, GEPIA2, Linkedomics and cBioPortal databases. Real-time PCR was used to detect the expressions of S100A2/4/6/10/14/16 in four pancreatic cancer cell lines and pancreatic cancer tissues from PDAC patients undergoing surgery. To verify the results further, immunohistochemistry was used to measure the expression of S100A2/4/6/10/14/16 in 43 PDAC patients' tissue samples. The drug relations of S100As were analyzed by using the Drugbank database. RESULTS: The results suggested that, the expression levels of S100A2/4/6/10/14/16 were elevated to PDAC tissues than in normal pancreatic tissues, and the promoter methylation levels of S100A S100A2/4/6/10/14/16 in PDAC (n = 10) were lower compared with normal tissue (n = 184) (P < 0.05). In addition, their expressions were negatively correlated with PDAC patient survival. CONCLUSIONS: Taken together, these results suggest that S100A2/4/6/10/14/16 might be served as prognostic biomarkers for survivals of PDAC patients.

TRPM3 channel activation inhibits contraction of the isolated human ureter via CGRP released from sensory nerves.

AIMS: Sensory nerve activation modulates ureteral contractility by releasing neuropeptides including CGRP and neurokinin A (NKA). TRPM3 is a recently discovered thermosensitive channel expressed in nociceptive sensory neurons, and plays a key role in heat nociception and chronic pain. The aim of this study is to examine the role of TRPM3 activation in human ureter motility. MAIN METHOD: Human proximal ureters were obtained from fourteen patients undergoing nephrectomy. Spontaneous or NKA-evoked contractions of longitudinal ureter strips were recorded in an organ bath. Ureteral TRPM3 expression was examined by immunofluorescence. KEY FINDINGS: Spontaneous contractions were observed in 60% of examined strips. TRPM3 activation using pregnenolone sulphate (PS) or CIM0216 (specific TRPM3 agonists) dose-dependently reduced the frequency of spontaneous and NKA-evoked contractions, with IC50s of 241.7 µM and 4.4 µM, respectively. The inhibitory actions of TRPM3 agonists were mimicked by CGRP (10 to 100 nM) or a cAMP analogue (8-Br-cAMP; 1 mM). The inhibitory actions of TRPM3 agonists (300 µM PS or 30 µM CIM0216) were blocked by pretreatment with primidone (TRPM3 antagonist; 30 µM), tetrodotoxin (sodium channel blocker; 1 µM), olcegepant (CGRP receptor antagonist; 10 µM), or H89 (non-specific PKA inhibitor; 30 µM). TRPM3 was co-expressed with CGRP in nerves in the sub-urothelial and intermuscular regions of the ureter. SIGNIFICANCE: TRPM3 channels expressed on sensory terminals of the human ureter involve in inhibitory sensory neurotransmission and modulate ureter motility via the CGRP-cAMP-PKA signal pathway. Targeting TRPM3 may be a pharmacological strategy for promoting the ureter stone passage.

Prevention and treatment system of novel coronavirus infection in medical and health institutions: experience in West China Hospital of Sichuan University.

The novel coronavirus infection broke out in Wuhan, China, in December 2019, and progressed to a global pandemic. We describe the measures taken by West China Hospital of Sichuan University to address the diagnosis, prevention and treatment of the infection.

[Correlation Between the Severity of Lung Ultrasound Score in Non-gravity Dependent Areas and Poor Prognosis of Patients with Shock and on Mechanical Ventilation].

OBJECTIVE: To explore whether ultrasound abnormalities in the non-gravity dependent areas (area 1-2) of the lungs are associated with poor prognosis in patients with shock and on mechanical ventilation. METHODS: We retrospectively analyzed the data of lung ultrasound from 181 patients with shock from Apr. 2016 to Nov. 2017. The patients were divided into the survival group and the non-survival group according to the 28 d outcome. Single factor and multivariate Cox regression were used to analyze the relationship between lung ultrasound score of the overall and each area and the 28 d mortality.Kaplan-Meier curve was used to analyze the relationship between the severity of ultrasound lesions in area 1-2 and the prognosis at 28 d. RESULTS: 169 patients were included.There were 106 males (62.7%) and 63 females (37.3%).There were 90 patients in the survivel group and 79 patients in the non-survival group.Single factor Cox regression analysis found that adjusting the age, acute physiology and chronic health evaluation (APACHE) Ⅱ score, lactate level, urine output per hour, application of vasoactive agent, oxygenation index, lungs ultrasound score of area 1-6, area 1-2 and area 3-4 were associated with 28 d mortality. Multivariate Cox regression revealed that lung ultrasound score of area 1-2 was the independent risk factor of 28 d mortality, as well as APACHE Ⅱ score and lactate level. The Kaplan-Meier curve found that the more severe the lesion in area 1-2, the lower the survival rate at 28 d. CONCLUSION: Lung ultrasound score of area 1-2 in patients with shock and on mechanical ventilation may be a predictor of poor prognosis at 28 d.

Outcomes of health-related quality of life after open, laparoscopic, or robot-assisted radical prostatectomy in China.

PURPOSE: To compare the outcomes of health-related quality of life (HRQOL) in patients undergoing open (ORP), laparoscopic (LRP), or robot-assisted (RARP) radical prostatectomy. PATIENTS AND METHODS: We retrospectively analyzed 347 men with clinically localized prostate cancer treated with ORP (n=97), LRP (n=71), or RARP (n=179) by high-volume surgeons in our institution between January 2014 and December 2016. The primary endpoint was HRQOL including urinary incontinence and erectile dysfunction. RESULTS: One year after surgery, 15.9% of men reported moderate to severe urinary incontinence (ORP 16.5%, LRP 15.4%, and RARP 15.7%), with only 4.6% using pads. There were no statistically significant differences in the ratios of no pad usage and urinary incontinence bother after 12 months postoperatively among the three groups. However, 67.7% of the men reported moderate to severe erectile dysfunction (ORP 66%, LRP 66.1%, and RARP 69.3%) 12 months after surgery. There was no statistically significant difference in the international index of erectile function-5 (IIEF-5) postoperatively among the different surgical groups. In the univariate and multivariate analyses, age at surgery, preoperative IIEF-5, and neurovascular bundle preservation were the risk factors for moderate to severe sexual bother. Interestingly, 16.1% of men with an erection hardness score of grade 3-4 were hesitant to become sexually active postoperatively. CONCLUSION: ORP, LRP, and RARP have similar early HRQOL outcomes with respect to urinary incontinence and erectile dysfunction. In contrast to urinary continence, erectile dysfunction is still a serious concern for patients who undergo radical prostatectomy.

[Microsurgical subinguinal varicocelectomy with delivery of the testis and ligation of gubernacular veins: Evaluation of clinical effects].

OBJECTIVE: To compare the clinical effects and postoperative complications of microsurgical subinguinal varicocelectomy (MSV) with or without delivery of the testis and ligation of gubernacular veins in the treatment of varicocele. METHODS: We retrospectively analyzed the clinical data about 163 varicocele patients treated by MSV, 40 with (group A) and the other 123 without delivery of the testis and ligation of gubernacular veins (group B). We compared the operation time, postoperative complications, rate of recurrence, and semen parameters before and at 3 months after surgery between the two groups of patients. RESULTS: The operation time was significantly longer in group A than in B (ï¼»81.1 ± 20.0ï¼½ vs ï¼»62.3 ± 9.6ï¼½ min, P = 0.041). Sperm concentration, total sperm count per ejaculate, sperm viability, and the percentage of progressively motile sperm were significantly improved in both groups at 3 months after MSV as compared with the baseline (P < 0.05). There were no statistically significant differences in the above semen parameters between the two groups of patients with grade Ⅲ varicocele before and after surgery (P < 0.05). Scrotal edema developed in 5 cases in group A and wound infection in 2 cases in group B after MSV, but no postoperative testicular atrophy or recurrence was observed in either of the two groups. CONCLUSIONS: MSV with delivery of the testis and ligation of gubernacular veins showed no advantages over that without in reducing varicocele recurrence and improving semen parameters, but rather involved longer operation time and a higher incidence rate of postoperative complications.

Zearalenone Delays Rat Leydig Cell Regeneration.

Zearalenone (ZEA), a fungal mycotoxin, is present in a wide range of human foods. By virtual screening, we have identified that ZEA is a potential endocrine disruptor of Leydig cells. The effect of ZEA on Leydig cell development is still unclear. The objective of the present study was to explore whether ZEA affected Leydig cell developmental process and to clarify the underlying mechanism. Adult male Sprague-Dawley rats (60 days old) were randomly divided into three groups and these rats received a single intraperitoneal injection of 75 mg/kg ethane dimethane sulfonate (EDS) to eliminate all Leydig cells. Seven days after EDS treatment, rats intratesticularly received normal saline (control) or 150 or 300 ng/testis/day ZEA for 21 days. Immature Leydig cells isolated from 35-day-old rats were treated with ZEA (0.05-50 µM) for 24 h in vitro. In vivo ZEA exposure lowered serum testosterone levels, reduced Leydig cell number, and decreased Leydig cell-specific gene or protein expression levels possibly via downregulating the steroidogenic factor 1 (Nr5a1) expression. ZEA in vitro inhibited androgen production and steroidogenic enzyme activities in immature Leydig cells by downregulating expression levels of cholesterol side cleavage enzyme (Cyp11a1), 3ß-hydroxysteroid dehydrogenase 1 (Hsd3b1), and steroid 5α-reductase 1 (Srd5a1) at a concentration as low as 50 nM. In conclusion, ZEA exposure disrupts Leydig cell development and steroidogenesis possibly via downregulating Nr5a1.

Prostatic Calculi: Do They Matter?

INTRODUCTION: Prostatic calculi (PC) are frequently detected at computed tomography or ultrasound in men attending the health center or the urology outpatient department. PC have attracted more attention from urologists, but the clinical significance of PC is unknown. AIM: To review the available literature on the effects of PC on prostatic diseases and sexual function in men. METHODS: Relevant clinical trials were identified by searching the PubMed, Embase, and Cochrane Library databases. Results were classified, summarized, and analyzed. MAIN OUTCOME MEASURES: Transabdominal and rectal ultrasonography; urodynamics analysis; International Prostate Symptom Score; pathologic examination of prostatic tissue; prostate-specific antigen; and expressed prostatic secretion. RESULTS: PC can not only prolong the duration of bothersome symptoms but also decrease the cure rate of antibacterial therapy in patients with chronic prostatitis. Patients with PC usually have more severe lower urinary tract symptoms (LUTS), and some studies reported that moderate to marked PC are a predisposing factor for moderate to severe LUTS. Studies also reported that the serum level prostate-specific antigen is not influenced by PC. In addition, the presence of PC is not associated with an increased risk of prostate cancer. However, the correlation between PC in the peripheral zone and prostate cancer is statistically significant. In addition, the association between PC and Gleason scores is controversial. Some novel studies suggested that PC might play an important role in sexual impairment in middle-age men or men with chronic pelvic pain syndrome or chronic prostatitis. Recently, PC were found to increase the incidence of severe LUTS, urinary retention, and hematospermia after transrectal ultrasound-guided prostate biopsy. CONCLUSION: PC can aggravate LUTS, chronic prostatitis, and sexual dysfunction in men, but the association between PC and prostate cancer is still controversial. Cao J-J, Huang W, Wu H-S, et al. Prostatic Calculi: Do They Matter? Sex Med Rev 2018;6:482-491.

[Optimize aqueous extract protocol for Yugubao formula by orthogonal experiment design].

To determine the optimum aqueous extract protocol for Yugubao traditional Chinese medicines formula by using orthogonal experiment design. Through serum pharmacology research, L9(34) orthogonal design with single factor investigation was used to optimize the aqueous extract protocol for Yugubao formula. The effect of water extraction on activity of alkaline phosphatase (ALP) in osteoblast was referred as the evaluation index for investigating four factors: water consumption (A), heating time (B), soaking time (C), and number of decocting (D), analyzing the optimum extraction conditions, and verifying the effectiveness of this process. The optimum aqueous extract protocol for Yugubao was as follows: adding 8 times water into Chinese medical materials, heating for 60 min, soaking for 30 min, and decocting for 1 time. The drug serum of this aqueous extract of Yugubao could significantly up-regulate the osteogenic genes expression. The optimum aqueous extract protocol for Yugubao formula was established in this experiment, providing evidence for the development and utilization of Yugubao traditional Chinese medicines formula.

Risk factors for bladder calculi in patients with benign prostatic hyperplasia.

We aim to find the risk factors that influence the formation of bladder calculi in patients with benign prostate hyperplasia (BPH) and to reduce the surgical intervention related to bladder calculi.Between January 2015 and October 2016, 332 patients with BPH underwent surgical therapy were retrospectively evaluated. Patients with BPH were categorized into 2 groups: 94 patients with bladder calculi in group 1 and 238 patients without bladder calculi in group 2. Medical history, age, body mass index (BMI), total prostate specific antigen, total prostate volume (TPV), International Prostate Symptom Score (IPSS), intravesical prostatic protrusion (IPP), urodynamic parameters, and urine culture were compared between groups.There was no significant difference in the age, BMI, peak flow rate, and total IPSS between groups. TPV, total prostate specific antigen, and duration of BPH were significantly lower in group 1 than those in group 2. In addition, IPP was significantly higher in group 1 than group 2 (P < .001). Besides, after exclusion of patients with urinary retention and indwelling catheter, group 1 associated with a significantly higher preoperative positive rate of urine culture than that of group 2 (P = .046). Multivariate analysis indicated that IPP was a significant independent risk factor for the presence of bladder calculi.The incidence of bladder calculi in patients with BPH was proved to be closely associated with preoperative positive urine culture and longer IPP in our study. Furthermore, the IPP was presented to be an independent risk factor for the formation of bladder calculi. And early antibacterial therapy of urinary tract infection (UTI) may help to prevent the presence of bladder calculi in patients with BPH.

Apoptosis and injuries of heavy ion beam and x-ray radiation on malignant melanoma cell.

This study aims to investigate the influence of high linear energy transfer (LET) heavy ion (12C6+) and low LET X-ray radiation on apoptosis and related proteins of malignant melanoma on tumor-bearing mice under the same physical dosage. C57BL/6 J mice were burdened by tumors and randomized into three groups. These mice received heavy ion (12C6+) and X-ray radiation under the same physical dosage, respectively; their weight and tumor volumes were measured every three days post-radiation. After 30 days, these mice were sacrificed. Then, median survival time was calculated and tumors on mice were proliferated. In addition, immunohistochemistry was carried out for apoptosis-related proteins to reflect the expression level. After tumor-bearing mice were radiated to heavy ion, median survival time improved and tumor volume significantly decreased in conjunction with the upregulated expression of pro-apoptosis factors, Bax and cytochrome C, and the downregulated expression of apoptosis-profilin (Bcl-2, Survivin) and proliferation-related proteins (proliferating cell nuclear antigen). The results indicated that radiation can promote the apoptosis of malignant melanoma cells and inhibit their proliferation. This case was more suitable for heavy ion (12C6+). High LET heavy ion (12C6+) radiation could significantly improve the killing ability for malignant melanoma cells by inducing apoptosis in tumor cells and inhibiting their proliferation. These results demonstrated that heavy ion (12C6+) presented special advantages in terms of treating malignant melanoma. Impact statement Malignant melanoma is a malignant skin tumor derived from melanin cells, which has a high malignant degree and high fatality rate. In this study, proliferating cell nuclear antigen (PCNA) can induce the apoptosis of malignant melanoma cells and inhibit its proliferation, and its induction effect on apoptosis is significantly higher than low LET X-ray; hence, it is expected to overcome its lower sensitivity to radiation. This study can provide theoretical basis for clinical trials, in which malignant melanoma is treated by heavy ion (12C6+), in order to accurately determine the clinical efficacy of heavy ion therapy. Clinical applications has revealed that local tumor control rate is high when heavy ion is used to treat malignant melanoma, indicating that heavy ion is an important direction in treating melanoma in the future.

Ferulic acid induces proliferation and differentiation of rat osteoblasts in vitro through cGMP/PKGII/ENaC signaling.

Ferulic acid (FA) is an active component of the traditional Chinese herb Angelica sinensis. Numerous health benefits have been attributed to FA, but few studies have investigated the effects of FA on osteoblasts (Obs). Our work studied the effects of FA on proliferation, differentiation, and mineralization of rat calvarial Obs and examined the signaling pathways involved. Cell proliferation and differentiation were evaluated by Cell Counting Kit-8 (CCK-8) and alkaline phosphatase (ALP) assay kit, respectively. Cyclic guanosine monophosphate (cGMP)-dependent protein kinase II (PKGII) expression was silenced by small interfering RNA (siRNA). The mRNA expression was investigated by semi-quantitative PCR. FA (40-2560 µM) promoted Ob proliferation and differentiation; at 40-640 µM, FA stimulated calcified nodule formation and increased the expression of osteogenic genes encoding osteopontin and collagen-l. FA (40-2560 µM) increased cGMP levels in Obs and upregulated the expression of PKGII, EnaCα, and ENaCγ mRNAs. Downregulated ENaCα mRNA expression in Obs transfected with the siRNA for PKGII was reversed when FA was introduced into Obs. These results demonstrated that FA promoted proliferation, differentiation, and mineralization of Obs in vitro, and enhanced osteogenic genes expression partly through the cGMP-PKGII-ENaC signaling pathway.

[Role of epithelial sodium channel in rat osteoclast differentiation and bone resorption].

OBJECTIVE: To explore the role of epithelial sodium channel (ENaC) in regulating the functional activity of osteoclasts. METHODS: Multinucleated osteoclasts were obtained by inducing the differentiation of rat bone marrow cells with macrophage colony-stimulating factor (M-CSF) and RANKL. The osteoclasts were exposed to different concentrations of the ENaC inhibitor amiloride, and the expression of ENaC on osteoclasts was examined using immunofluorescence technique. The osteoclasts were identified with tartrate-resistant acid phosphatase (TRAP) staining, and the positive cells were incubated with fresh bovine femoral bone slices and the number of bone absorption pits was counted by computer-aided image processing. RT-PCR was performed to analyze the expression of cathepsin K in the osteoclasts. RESULTS: s Exposure to different concentrations of amiloride significantly inhibited the expression of ENaC and reduced the number of TRAP-positive osteoclasts. Exposure of the osteoclasts to amiloride also reduced the number of bone resorption pits on bone slices and the expression of osteoclast-specific gene cathepsin K. CONCLUSION: s ENaC may participate in the regulation of osteoclast differentiation and bone resorption, suggesting its role in functional regulation of the osteoclasts and a possibly new signaling pathway related with ENaC regulation for modulating bone metabolism.

[Effects of long non-coding RNA-HOTAIR on the cell cycle and invasiveness of prostate cancer].

OBJECTIVE: To investigate the expression of long non-coding RNA-HOTAIR in prostate cancer cells and its effects on the growth and metastasis of the cells. METHODS: Using quantitative reverse-transcription PCR (qRT-PCR), we determined the relative expression of HOTAIR in the normal human prostate epithelial cell line RWPE-I and prostate cancer cell lines PC-3 and DU145. We detected the effects of HOTAIR on the cell cycle and invasiveness of prostate cancer cells by RNA interference, flow cytometry, and Transwell mitration assay. RESULTS: The expressions of HOTAIR in the PC3 and DU145 cells were increased 3.2 and 5.7 times, respectively, as compared with that in the normal RWPE-1 cells. After si-HOTAIR interference, the prostate cancer cells were arrested in the G2 phase and downregulated in the G1 phase. The invasive ability of the prostate cancer cells was evidently inhibited, with the inhibition rates of 32% and 44% of the PC3 cells and 43% and 34% of the DU145 cells for si-HOTAIR1 and si-HOTAIR2, respectively. CONCLUSION: IncRNA HOTAIR is highly expressed in prostate cancer, which is associated with the growth and invasiveness of prostate cancer cells. HOTAIR is potentially a novel marker for the diagnosis and prognosis of prostate cancer.

[[Urodynamic tests contribute to the choice of therapies for type-III B prostatitis].

OBJECTIVE: To analyze the parameters of urodynamic tests for patients with type-III B prostatitis and evaluate the significance of the results of urodynamic tests in the choice of therapies for this disease. METHODS: Urodynamic tests were performed for 87 type-III B prostatitis patients aged 22-45 (30.7 ± 8.5) years, who had moderate or severe lower urinary tract symptoms (LUTS) and failed to respond to routine therapy. Different treatments were administered according to the results of urodynamic tests followed by observation of the therapeutic effects. RESULTS: Urodynamic abnormalities were found in 70 of the 87 patients, bladder outlet obstruction in 28 (32.2%), detrusor overactivity in 25 (28.7%), bladder hyperesthesia in 18 (20.7%), low compliance in 10 (11.5%), detrusor-external urethral sphincter dyssynergia in 1 (1.1%), and impaired detrusor contractile function in 1 (1.1%). Treatments achieved obvious effectiveness in 26 cases (29.9%), effectiveness in 51 (58.6%), and no effectiveness in 10 (11.5%). CONCLUSION: Urodynamic tests contribute significantly to the choice of therapies for type-III B prostatitis patients with moderate or severe LUTS.

[Measurement of peak velocity variation of common carotid artery with bedside ultrasound to estimate preload in surgery ICU].

OBJECTIVE: To investigate the feasibility and accuracy of bedside ultrasound measuring peak velocity variation of common carotid artery to estimate preload of the patients in surgery ICU. METHODS: In this prospective cohort study, SICU patients with sinus rhythm and positive pressure ventilation were included. The peak velocity variation in common carotid artery (delta V peak) during each respiratory circle was measured by ICU resident with short-term training and experienced attending songrapher. Stroke volume before and after the fluid challenge was also measured by the experienced songrapher as the gold standard of fluid responsiveness. Then the ROC, feasibility and accuracy of the diagnosis trial were analyzed. RESULTS: There were 46 patients included. The peak velocity variation of common carotid artery measured by the attending (delta V peak) is highly related with delta SV (r1 = 0.76, P < 0.05). Area under the receiver operating characteristic curve was 0.95 (P < 0.05). The peak velocity variation of common carotid artery (delta V peak) > 12.1% predicted fluid responsiveness with sensitivity of 90.9%, specificity of 83.3%, positive predictive value of 83.3% and negative predictive value of 90.9%. The peak velocity variation of common carotid artery measured by the resident (delta V peak2) were highly related with delta V peak1 (R2 = 0.68, P < 0.05), the AUC was 0.94. CONCLUSION: Measurement of peak velocity variation of common carotid artery with bedside ultrasound can accurately estimate the volume status of the patients in surgery ICU, and it is easy to be performed by the residents of ICU.