Targeting histone deacetylases for cancer therapy: Trends and challenges

Dysregulation of histone deacetylases (HDACs) is closely related to tumor development and progression. As promising anticancer targets, HDACs have gained a great deal of research interests and two decades of effort has led to the approval of five HDAC inhibitors (HDACis). However, currently traditional HDACis, although effective in approved indications, exhibit severe off-target toxicities and low sensitivities against solid tumors, which have urged the development of next-generation of HDACi. This review investigates the biological functions of HDACs, the roles of HDACs in oncogenesis, the structural features of different HDAC isoforms, isoform-selective inhibitors, combination therapies, multitarget agents and HDAC PROTACs. We hope these data could inspire readers with new ideas to develop novel HDACi with good isoform selectivity, efficient anticancer effect, attenuated adverse effect and reduced drug resistance.

Effects and mechanisms of ferroptosis on high glucose-induced retinal pigment epithelial cells injury / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To observe the effects and mechanisms of ferroptosis on high glucose(HG)-induced retinal pigment epithelium(RPE)cells injury, and to provide new ideas for the treatment of diabetic retinopathy(DR).METHODS: The ARPE-19 cell lines cultured in vitro were divided into normal control group(NC group), high glucose group(HG group), and high glucose+Ferrostatin-1 group(Fer-1 group). The cell viability of each group was detected by CCK-8 assay. The expressions of interleukin 6(IL-6), IL-1β and monocyte chemotactic protein-1(MCP-1)were detected using ELISA kits. The levels of malondialdehyde(MDA), glutathione(GSH), glutathione peroxidase 4(GPX4)and iron content were detected using the corresponding assay kits. The mitochondrial changes in ARPE-19 cells were observed by transmission electron microscopy. The expressions of ferroptosis-related proteins including long-chain lipoyl CoA synthase 4(ACSL4)and GPX4, as well as vascular endothelial growth factor(VEGF)were detected by Western blotting and immunofluorescence staining.RESULTS: Compared with NC group, the cell viability of HG group decreased significantly, the expression levels of inflammatory factors in cell supernatant increased, the contents of MDA and iron significantly increased, GSH and GPX4 significantly decreased(all P<0.01), the mitochondria of ARPE-19 cells shrunk, the expression of proteins ACSL4 and VEGF increased, while the expression of GPX4 decreased(all P<0.01). Compared with HG group, the cell viability of Fer-1 group significantly increased, the expression levels of inflammatory factors in cell supernatant decreased, MDA and iron contents significantly decreased, GSH contents and GPX4 viability significantly increased(all P<0.05), the morphology of mitochondria in ARPE-19 cells improved, the expression of ACSL4 and VEGF decreased, while the expression of GPX4 increased(all P<0.05).CONCLUSION: Ferroptosis is involved in the injury of RPE induced by HG. Inhibiting ferroptosis can improve cell viability, reduce inflammation and oxidative stress, and alleviate HG-induced RPE cells injury.

Rational choice of treatment for the female hypospadias / 中华泌尿外科杂志

Objective:To summarize the ideal strategy for the treatment of female hypospadias.Methods:The data of 12 female patients with hypospadias admitted to the Sixth People's Hospital Affiliated to Shanghai Jiaotong University School of Medicine from December 2011 to December 2019 were retrospectively analyzed. The patients was (31.0±16.6) years old (7-67 years old). Among them, 3 cases had a history of pelvic fracture trauma, 3 cases had a history of birth trauma, and the remaining 6 cases had no history of trauma and surgery. Among them, there were 6 cases of congenital hypospadias and 6 cases of acquired hypospadias. The clinical manifestations were urinary incontinence in 6 cases and dysuria in 6 cases. Examination of the normal position of the external opening of the genital urethra did not show the opening of the urethra, but moved down to different parts of the anterior wall of the vagina. All patients underwent urethral lengthening. For congenital hypospadias, the urethral plate is used to cut the coiled tube during the operation to prolong the urethra. For acquired hypospadias, the stenotic urethra was enlarged and lengthened with a labial pedicled flap coil. The subcutaneous fat pad of the labia majora was mobilized and transferred to the outside of the newly constructed urethra to prevent the occurrence of urethro-vaginal fistula and increase the pressure of the urethra. Five patients with significant urinary incontinence underwent bladder neck reconstruction at the same time. Anatomical success of the procedure was defined as the appearance of a normal-shaped external urethral opening beneath the clitoris. Functional success was defined as the absence of moderate to severe urinary incontinence after surgery, and the maximum urinary flow rate was >15ml/s during the 12-month follow-up period.Results:All operations were successfully completed. All patients had no perioperative complications, and were followed up for 18-96 months, with an average of 57.3±32.5 months. All patients were able to urinate spontaneously after operation, 4 cases of urinary incontinence disappeared, and 2 cases improved significantly; 4 cases of patients with strenuous urination urinated smoothly. The remaining 2 cases still complained of dysuria after operation, which was solved by subsequent urethral dilatation. The anatomical repair success rate was 100.0%(12/12) and the functional success rate was 83.3% (10/12).Conclusions:Urethral lengthening is an effective method for female hypospadias. The pedicled fat pad helps to increase urethral pressure and prevent fistulas. For female patients with hypospadias and severe urinary incontinence, bladder neck reconstruction is an ideal method. of the technique.

Safety evaluation of naborphine hydrochloride combined with propofol in painless colonoscopy diagnosis and treatment of hypertensive patients / 中国医师杂志

Objective:To evaluate the safety of naborphine hydrochloride combined with propofol in painless colonoscopy diagnosis and treatment of hypertensive patients.Methods:From October 2018 to September 2020, 900 patients with ASA grade Ⅰ to Ⅲ, aged 18 to 65, who underwent colonoscopy in Zhuhai Hospital Affiliated to Jinan University and Shanghai East Hospital Affiliated to Tongji University were prospectively selected. According to the random number table method, the patients were divided into 3 groups ( n=300): naborphine hydrochloride group 1 (N1 group, intravenous injection of 0.05 mg/kg naborphine hydrochloride); naborphine hydrochloride group 2 (N2 group, intravenous injection of 0.1 mg/kg naborphine hydrochloride); sufentanil group (SF group, intravenous injection of 0.1 μg/kg sufentanil). During anesthesia induction, propofol was combined with sedation, and the dose of propofol was 1.5 mg/kg. The systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), pulse oxygen saturation (SpO 2), respiratory rate (RR), and mean arterial pressure (MAP) of the three groups were compared before anesthesia (T 0), during induction (T 1), 1 min after induction (T 2), 2 min after induction (T 3), 3 min after induction (T 4) and 4 min after induction (T 5), and the bispectral index (BIS) were monitored. At the same time, the examination time, total dosage of propofol, recovery time, postoperative Visual Analogue Scale (VAS) score and perioperative anesthesia related adverse reactions of the three groups were compared. Results:There was no significant difference among the three groups in examination time, total dosage of propofol, recovery time, postoperative VAS score and adverse anesthetic reactions (all P>0.05). There was no significant difference in HR, SpO 2 and RR among the three groups at different time points (all P>0.05). The SBP, DBP and MAP in N1 group at T 1, T 3, T 4 and T 5 were lower than those in SF group (all P<0.05); The SBP, DBP and MAP in N2 group at T 1, T 3 and T 4 were higher than those in N1 group (all P<0.05). The BIS in T 3 and T 4 of N2 group was higher than that of N1 group (all P<0.05). Conclusions:0.1 mg/kg naborphine hydrochloride combined with propofol for painless enteroscopy in patients with hypertension has fine anesthetic effect and safety.

Intraocular pressure fluctuation range and correction after small incision lenticule extraction / 国际眼科杂志(Guoji Yanke Zazhi)

@#AIM:To investigate changes in the normal intraocular pressure(IOP)fluctuation range after the small incision lenticule extraction(SMILE)in patients with low, moderate and high myopia and to explore new methods for postoperative IOP(IOP_post)correction.<p>METHODS: In this prospective case series study, 79 patients(158 eyes)who underwent SMILE at the Affiliated Hospital of Qingdao University from March 2018 to September 2019 were involved, and they were divided into low myopia(A), moderate myopia(B), and high myopia(C)groups. The 24-hour IOP was measured by the non-contact tonometer(NCT)and Goldmann applanation tonometer(GAT). Spherical equivalent(SE), central corneal thickness(CCT), the horizontal corneal diameter(WTW), corneal curvature, corneal volume(CV), ratio of the central 3-mm diameter CV(CCV_3mm)to the total CV, and the ratio of the cutting CV(ΔCV)to the CV were measured 3d preoperatively and 6mo postoperatively. The correlation between the postoperative NCT measurements(NCT_post)and various factors was statistically analysed, and the IOP_post expression model was established by phased multiple linear regression analysis.<p>RESULTS:The differences in IOP measured by NCT and GAT were not statistically significant(<i>P</i>>0.05), but the differences in IOP of the three groups were statistically significant(<i>P</i><0.05). The IOP_post range by NCT were 8-17 mmHg in group A, 7-16.3 mmHg in group B, and 7.7-14.3 mmHg in group C. The IOP_post range by GAT were 8-17 mmHg. The IOP_post fluctuation was <6 mmHg. The IOP_post difference between the right eye and left eye was 0-4 mmHg. A staged multivariate regression model was established: NCT_{post corrected(A)}= 0.349 × NCT_post + 4.137 × CCV_pre3mm - 1.533; NCT_{post corrected(B)}= 0.477 × NCT_post + 3.643 × CCV_post3mm -1.125; NCT_{post corrected(C)}= 0.638 × NCT_post + 3.426 × CCV_post3mm -0.716.<p>CONCLUSION:The IOP measured by NCT and GAT after SMILE was lower than that measured before surgery. For different patients, the greater the rate of change in CV before and after surgery, the lower the IOP_post. CCV_post3mm is an important index for evaluating IOP after SMILE and thus guide postoperative medication administration.

The efficacy and feasibility of free inner prepuce graft combined with Oradi flap urethroplasty for the treatment of the obliterated penile urethral atresic stricture / 中华泌尿外科杂志

Objective:To investigate the efficacy and feasibility of urethroplasty using inner prepuce graft combined with Orandi flap for the treatment of the obliterated penile urethral atresic stricture.Methods:From January 2016 to September 2019, the clinical data of 18 obliterated penile urethral stricture cases were analyzed retrospectively. All the patients were treated using inner prepuce flap combined with Orandi Flap. The average age of the patients was 62.1 years old (range 20-81 years old). Ten cases had suprapubic cystostomy before operation. The maximum flow rate was 1.6-6.2 ml/s, with an average of 4.2ml/s. The intubation general anesthesia and lithotomy position was used. The foreskin of penis was incised longitudinally. The urethra was exposed and the segment of stricture was opened longitudinally. The range of stricture length was measured with soft ruler, ranging from 2.0 to 7.5 cm, with an average of 5.0cm. After the fibrotic tissue was completely removed, the dorsal inner prepuce was incised with needed length and width for harvesting a free skin flap in order to transplant and reconstruct the dorsal urethral. The Orandi flap was used to cover the ventral urethra, and a F14-16 silicone catheter was retained. The length range of the inner prepuce graft was 2.0-7.5 cm, with an average of 5.1cm; the width was 1.2-1.8 cm, with an average of 1.4cm. The length of Orandi flap was 2.2-7.7 cm, with an average of 6.0cm; the width was 1.0-1.5 cm, with an average of 1.3 cm. The catheter was removed 3-4 weeks after operation. The patients were then followed up after 3, 6 and 12 months postoperatively and then with annual assessments for the symptoms, urinary flow rate, and urethrography or soft urethroscopy when necessary.Results:All of the 18 operations were completed successfully. The patients were followed up for 6-36 months, with an average of 22 months. There were 5 patients with terminal dripping, 4 patients with recurrent urinary tract infection within half a year after operation, and antibiotic treatment being effective. The quality of life scores at 3 months and 6 months after operation were 0.8 (0-2) and 0.6 (0-1), respectively, which were statistically significant compared with before operation ( P<0.001). Conclusions:The use of free inner prepuce flap combined with Orandi flap is an effective treatment for the obliterated penile urethral atresic stricture, especially for the patients who are unwilling or unsuitable to harvest the oral mucosa. It has the advantages of convenient harvesting and less complications.

A novel robust nomogram based on peripheral monocyte counts for predicting lymph node metastasis of prostate cancer / 亚洲男科学杂志(英文版)

Accurate methods for identifying pelvic lymph node metastasis (LNM) of prostate cancer (PCa) prior to surgery are still lacking. We aimed to investigate the predictive value of peripheral monocyte count (PMC) for LNM of PCa in this study. Two hundred and ninety-eight patients from three centers were divided into a training set (n = 125) and a validation set (n = 173). In the training set, the independent predictors of LNM were analyzed using univariate and multivariate logistic regression analyses, and the optimal cutoff value was calculated by the receiver operating characteristic (ROC) curve. The sensitivity and specificity of the optimal cutoff were authenticated in the validation cohort. Finally, a nomogram based on the PMC was constructed for predicting LNM. Multivariate analyses of the training cohort demonstrated that clinical T stage, preoperative Gleason score, and PMC were independent risk factors for LNM. The subsequent ROC analysis showed that the optimal cutoff value of PMC for diagnosing LNM was 0.405 × 109 l

Experience for post-adolescent postoperative urethral stricture of hypospadias in a single center (a report of 71 cases) / 中华泌尿外科杂志

Objective:To explore management experience for post-adolescent postoperative urethral stricture of hypospadias in a single center.Methods:The clinical data of 71 cases of postoperative urethral stricture of post-adolescent hypospadias from January 2015 to December 2019 were retrospectively analyzed. The average age was 27.7(12-65) years. The mean duration of urethral stricture was 33.4(1-240) months. The number of prior surgeries was 2.5(1-9). There were 32 cases of ectopic urethral orifice, including 22 on penile, 8 on scrotum and 2 on perineum. There were 17 cases of urethral stricture with penile curvature, 11 with urethra-cutaneous fistula, 9 with urethral diverticulum, 11 with urethral calculus and 25 with urethral infection. Ten patients kept suprapubic tubes; 61 patients were able to urinate on their own, but suffered from dysuria and weak steam. The average maximum uroflow rate of 71 cases was 4.7(0-11.2) ml/s. The primary urethral reconstruction procedures were performed on 33 cases, included 11 penile or scrotal septum flap urethroplasty, 2 urethral diverticulum wall flap urethroplasty, 12 oral mucosal urethroplasty and 8 urethrotomy. Thirty-three cases underwent two-staged surgery. For patients with penile curvature greater than 30 degrees, the penis was straightened with a urethrotomy in first stage. Besides, the dorsal skin of penis or oral mucosal graft were transferred to the ventral side of the penis to the preset urethral plate. In second-stage, Denis Brown urethroplasty was performed on 23 patients, tubularized incised plate (Snodgrass) urethroplasty on 6, and oral mucosa inlay urethral plate (Snodgraft) urethroplasty on 4. In 5 cases, preplacing of oral mucosa was done in the second stage with a third-staged urethroplasty. Penile curvature was relieved by ventral scar resection with the folding the dorsal tunica albuginea of corpus cavernosum when necessary.Results:The mean follow-up time was 30.5(4-59) months. Sixty-one patients got satisfying postoperative urination, with an average maximum uroflow rate of 22.7 ml/s (15.8-37.2 ml/s). Restenosis occurred in 10 cases, and urethral fistula in 7 cases. Re-stricture patients underwent urethrotomy in 5 cases, augmented urethroplasty with flap in 4 cases, and urethroplasty with oral mucosal graft in 1 case. Among the 7 patients with urethral fistula, 5 were cured by one fistula repair, and 1 cured by second repair; the rest one was left untreated. 2 patients still had penile curvature after operation.Conclusions:It is difficult to manage post-adolescent postoperative urethral stricture of hypospadias, especially for patients with residual penile curvature greater than 30 degrees and lack of penile skin. Performing correction of the curvature and reconstruction of the urethral plate in first stage and Denis Brown urethroplasty or Snodgrass urethroplasty in second or third stage could achieve good results.

Mechanism of Dahuang Zhechongwan in Inhibiting Silicosis in Mice via p38 MAPK/NF-κB/TGF-β1 Pathway / 中国实验方剂学杂志

Objective:To explore the effects and mechanism of Chinese classical prescription Dahuang Zhechongwan on silicosis in mice. Method:Thirty-six male Kunming mice of SPF grade were randomized into the normal control group， model control group， tetrandrine （Tet， 0.039 mg·kg^-1） group， as well as high- （1.560 g·kg^-1）， medium- （0.780 g·kg^-1）， and low-dose （0.390 g·kg^-1） Dahuang Zhechongwan groups， with six mice in each group. Mice in all groups except for the normal control group underwent static inhalation of silica （SiO₂） dust for 40 consecutive days to induce fibrosis. After 28 days of intervention with corresponding drugs， the mice were sacrificed to collect the serum and lung tissues， with the former used for detecting tumor necrosis factor-<italic>α</italic> （TNF-<italic>α</italic>）， interleukin-1<italic>β </italic>（IL-1<italic>β</italic>）， IL-6， and hydroxyproline （HYP） levels by enzyme-linked immunosorbent assay （ELISA） and the latter for observing the pathological changes. Meanwhile， the protein and mRNA expression levels of p38 mitogen-activated protein kinase （p38 MAPK）， nuclear transcription factor-<italic>κ</italic>B （NF-<italic>κ</italic>B）， transforming growth factor-<italic>β</italic>₁ （TGF-<italic>β</italic>₁）， <italic>α</italic>-smooth muscle actin （<italic>α</italic>-SMA）， Smad2， Smad3， and Smad7 in the lung tissues were determined by Western blot and real-time polymerase chain reaction （Real-time PCR）. Result:Compared with the normal group， the contents of TNF-<italic>α</italic>， IL-1<italic>β</italic>， IL-6 and HYP in the model group were significantly increased， the difference was statistically significant（<italic>P</italic><0.05，<italic>P</italic><0.01）； compared with the model group， the high-dose group of Dahuang Zhechongwan could significantly reduce the contents of TNF-<italic>α</italic>， IL-6 and HYP in the serum of mice（<italic>P</italic><0.05， <italic>P</italic><0.01）， indicating that Dahuang Zhechongwan could reduce the lung inflammation of silicosis mice. At the same time， compared with the normal group， the protein and mRNA expression levels of p38 MAPK， NF-<italic>κ</italic>B p65， TGF-<italic>β</italic>₁， <italic>α</italic>-SMA， Smad2 and Smad3 in the model group were significantly increased（<italic>P</italic><0.05，<italic>P</italic><0.01）， while the protein and mRNA expression levels of Smad7 were significantly decreased（<italic>P</italic><0.01）； compared with the model group， the protein and mRNA expression levels of p38 MAPK， NF-<italic>κ</italic>B p65， TGF-<italic>β</italic>₁， <italic>α</italic>-SMA， Smad2 and Smad3 in the high-dose Dahuang Zhechongwan group were significantly increased the protein and mRNA expression levels were significantly decreased（<italic>P</italic><0.05，<italic>P</italic><0.01）， while Smad7 protein and mRNA expression levels were significantly increased（<italic>P</italic><0.05，<italic>P</italic><0.01）. Conclusion:Dahuang Zhechongwan ameliorates the alveolar inflammation， extracellular matrix （ECM） deposition， and fibrosis in mice with silicosis possibly by regulating the p38 MAPK/NF-<italic>κ</italic>B/TGF-<italic>β</italic>₁ pathway.

Mechanism of Dahuang Zhechongwan Against Multiple Organ Fibrosis： A Review / 中国实验方剂学杂志

Dahuang Zhechongwan （DHZCW） is a classic prescription from the Jingui Yaolue（《金匮要略》） by ZHANG Zhong-jing，with the effects of tonifying deficiency， relaxing the middle， promoting regeneration， and resolving stasis. It has been widely used in the clinical treatment of various diseases with definite efficacy achieved. The research on multiple organ fibrosis has shown that DHZCW can slow down the development of organ fibrosis in the heart， liver， kidney， lung， etc.， and good results in both clinical practice and experimental research have been obtained. The present study reviewed the previous investigations on the experimental mechanism of DHZCW in the treatment of multiple organ fibrosis and revealed that the pathogenesis was closely related despite different disease sites. From the perspective of traditional Chinese medicine （TCM），these diseases shared a common pathogenesis，which was manifested by deficiency. Long-term diseases led to the formation of "dried blood". From the perspective of modern medicine， the diseases all showed pathological changes in the deposition of extracellular matrix （ECM）， and their occurrence and development were all based on certain effector cells ［such as hepatic stellate cell （HSC） and pancreatic stellate cell （PSC）］， with same cytokines ［such as tumor necrosis factor-α （TNF-α），interleukin-6 （IL-6），IL-1β，and α-smooth muscle actin （α-SMA）］ and some key pathways ［transforming growth factor-β1 （TGF-β1）/Smad， phosphatidylinositol-3-kinase （PI3K）/protein kinase B （Akt）， and lipopolysaccharide （LPS） paracrine and autocrine mechanisms］ involved. As a classic prescription for "deficiency-induced dry blood"， DHZCW was effective in treating fibrosis， which was presumedly related to the inhibition of ECM deposition by intervening in the above-mentioned mechanisms， thereby delaying the disease progression. This study is expected to provide literature support to clarify the scientific connotation of DHZCW in the treatment of multiple organ fibrosis and lay a foundation for further experimental and clinical research.

Urethra rerouted under corpora cavernosus anastomotic urethroplasty for treatment of complex posterior urethral strictures / 中华泌尿外科杂志

Objective:To explore the outcomes of urethra around corpora cavernosus anastomotic urethroplasty for the treatment of complex posterior urethral strictures.Methods:Between June 2008 and June 2020, 35 patients with complex posterior urethral strictures were treated using urethra rerouted under one corpora cavernosus anastomotic urethroplasty. The patients’ age was 3-54 years(mean 23.2 years), the urethral stricture or loss length was 4-7 cm(mean 5.2 cm), and 6 patients associated with urethrorectal fistula. The technique involved: ①The anterior urethra is dissected long more than 5 cm, separation of the proximal corporeal bodies, inferior pubectomy and the dissected proximal urethra.②A channel around the left crus of the penis through the inferior pubectomy is separated and urethra rerouted under left corpora cavernosus to allow a tension-free anastomosis to the proximal urethra.Results:Two patients lost follow-up; the remainder 33 patients were followed-up for 3 to 144 months(mean 37 months). Thirty-two patients could void normally(97%), The examination of maximal urinary flow rates(Q max) were taken in 21 patients, of whom Q max was 13.6-35.5 ml/s (mean 17.5 ml/s) in 7 children and 16.3-77.6 ml/s(mean 27.9 ml/s) in 14 adult patients. All 6 patients associated with urethrorectal fistula successful repaired, of these patients 1 had died of hemorrhage of brain 6 years postop. One patient developed urethral stenosis postoperatively. Continence was achieved in 29 patients, the remaining 3 patients had incontinence from mild to moderate. Conclusions:Urethra rerouted under left corpora cavernosus anastomotic urethroplasty is not only an effective surgical salvage option, with low recurrent rate for patients with complex posterior urethral strictures, but also do not cause curve and affect growth of corpora cavernosus.

Comparative Study of Transrectal Real-time Tissue Elastography and Magnetic Resonance Diffusion-Weighted Imaging in the Diagnosis and Guided Biopsy of Prostate Cancer / 中山大学学报(医学科学版)

@#【Objectives】 To comparatively analyze the diagnostic performance of transrectal real- time elastography（TRTE）and magnetic resonance diffusion- weighted imaging （DWI）in differentiating benign from malignant prostatic lesions，to evaluate the value of the two methods in guided prostate biopsy，and to investigate the correlation between the two methods and Gleason scores. 【Methods】 A total of 126 patients with suspected prostate cancer underwent prostate biopsy. Preoperative tests of TRTE and DWI were performed in all of the included patients. Combined with pathological results，the diagnostic efficacy of TRTE and DWI for prostate cancer and the effects of prostate biopsy guided by the two methods were compared ，and the relationship between the elastography score and ADC value and Gleason scores were also evaluated.【Results】 The sensitivity，specificity，accuracy of diagnosing prostate cancer by TRTE were 78.8% ，78.3% ，78.6% ，the sensitivity，specificity，accuracy of diagnosing prostate cancer by DWI were 87.9% ，90% ，88.9% ， there was no significant difference of sensitivity and specificity between the two groups（P > 0.05），and the accuracy was statistically different（P < 0.05）. The AUC of elastography score and ADC value were 0.859 and 0.906，the accuracy of the diagnosis of benign and malignant prostate lesions by ADC value method was higher than elastography score ，but there was no statistically significant difference （P > 0.05）. A significant positive correlation was found between elastography score and Gleason scores，while a significant negative correlation was found between ADC value and Gleason scores.【Conclusions】TRTE and DWI is valuable in diagnosis of prostatic lesions. Biopsy guided by the two methods can improve the detection rate of prostate cancer and can provide indicative evidence for tumor differentiation analysis.

Prediction and analysis of death of children under 5 years old in Lanzhou based on time series model / 中华疾病控制杂志

Objective To analyze the death trend of children under 5 years old in Lanzhou and establish the time series model to predict the mortality and incidence of children under 5 years old in Lanzhou in 2019. Methods Descriptive epidemiological method was used to analyze the mortality of children under 5 years old in Lanzhou from January 2010 to December 2018. SPSS 21.0 software was used to construct time series analysis model, selecting the best model and predict the mortality of children under 5 years old in Lanzhou in 2019. Results A total of 1 650 deaths of children under 5 years old were reported in Lanzhou from 2010 to 2018. The number of deaths reported by boys and girls was 871 and 774 respectively, with an average annual mortality rate of 6.23‰. In recent years, the overall mortality rate of children under 5 years old in Lanzhou had declined. The majority of deaths among children under 5 years old were neonates, accounting for 65.27%. Simple seasonal model was the best model by comparing different models. The model could well fit the monthly death cases of children under 5 years old in Lanzhou from 2010 to 2018. It is predicted that the total number of deaths of children under 5 years old in Lanzhou will be 140 in 2019, which is similar to the number of deaths in 2018. Conclusions The mortality rate of children under 5 years old in Lanzhou is decreasing year by year. Simple seasonal model can better reflect the mortality trend of children under 5 years old in Lanzhou and make short-term prediction.

Contributions of the medical alliance of northwest Guangxi hospitals in the health anti-poverty campaign / 中华医院管理杂志

To implement the task of health anti-poverty campaign,the medical alliance of northwest Guangxi hospitals made full use of its synergy strengths to achieve remarkable progress in constructing a telemedicine cooperation network, nurturing medical discipline of primary hospitals in the alliance, promoting regional medical resources sharing, and improving the humanities connection mechanism.To further develop health anti-poverty via medical alliances,relevant institutions are recommended to probe into such problems as telemedicine compensation mechanism,precision-based disciplinary support,breakdown of resource sharing barriers and profit distribution mechanisms.

Six-minute walk distance and its influencing factors in patients underwent cardiac surgery before discharge / 中华护理杂志

Objective To investigate six-minute walk distancc (6MWD) of inpatients underwent cardiac surgery before discharge and to identify its influencing factors,and to provide references for further studies of hospital rehabilitation.Methods Using convenience sampling,from August 2016 to June 2017,167 eligible patients underwent cardiac surgery were recruited from a cardiovascular hospital in Beijing.General and disease-related intormation were collected.According to requirements of six-minute walk tcst (6MWT) from American Thoracic Society,patients' rehabilitation was evaluated using 6MWD.Results After discharge from intensive care unit(ICU),6MWD of patients increased along with hospital stays.On the day before discharge,mean 6MWD of patients was (213.86±75.87).The influencing factors of 6MWD included types of surgery (P=0.019),cardiopulmonary bypass (P=0.004),postoperative left ventdcular ejection fraction (LVEF)(P=0.015),and hospital stays after discharge from ICU (P=0.003).Conclusion During hospitalization,6MWD of patients underwent cardiac surgery increased along with hospital stays.On the day before discharge,6MWD of patients tended to be stable,and ready for further rehabilitation process.Patients could have different rehabilitation differences in types of surgery,using cardiopulmonary bypass,LVEF and hospital stays after discharge from ICU.

Current status and influencing factors of application of the Confusion assessment method for the Intensive Care Unit (CAM-ICU) / 中华护理杂志

Objective To investigate the current status of application of the Confusion assessment method for the Intensive Care Unit (Cam-ICU),and to explore its influencing factors.Methods A total of 300 patients admitted to were enrolled.The researchers and nurses used Cam-ICU to assess patients' delirium,respectively,and the differences in deliriun assessment were analyzed.Results For delirium assessment,the Kappa value was 0.546 between the researchers and nurses.The consensus rate was 17.6％ for hypoactive delirium,and 77.8％ for hyperactive delirium in 44 delirium patients.Logistic regression analysis showed that APACHE Ⅱ score,RASS score and delirium type were influencing factors of accurate assessment of delirium.Conclusion The consistence of assessment of delirium by ICU nurses is generally good,but the accuracy of assessment of hypoactive delirium is the worst.

Study on cardiovascular injury of anesthesia rat induced by chronic intermittent hypoxia / 局解手术学杂志

Objective To investigate the effect of chronic intermittent hypoxia(CIH)on the cardiovascular system in anesthetized rats. Methods A totally of 72 male SD rats were randomly divided into three groups(n=24),namely the ormoxia control group(control group), the normoxia anesthesia group(model group)and the chronic intermittent hypoxia group(CIH group).Rats of the control group breathe nor-mally.The model group was given intraperitoneal injection of 10%hydration with 0.3 mL/kg,and the CIH group was given chronic intermit-tent hypoxic stimulation with 8 h/d in addtion to the model group.The difference of ultrasonic echocardiography data,blood pressure,endothe-lin type-1,and endothelial nitric oxide synthase(eNOS)in rats of the three groups were compared.After 28 days,these rats were sacrificed to observe the changes of myocardial cell structure.Results In the control group,the myocardial morphology was normal,the cells arranged e-venly,and there was no swelling and inflammation.In the model group,the myocardial cells were evenly arranged without hypertrophy and in-flammatory changes.In the CIH group,the myocardial cells in the hypoxic group were not evenly arranged,and hypertrophy,swelling,deform-ation,hyperchromia,and obvious inflammatory changes of the myocardial tissue were observed.In the control group,myocardial cell nucleus and cytoplasm were uniformly arranged,and there was no obvious changes in the model group.On the contrary,myocardial cell morphology changed obviously in the CIH group,with the cell morphology and size of the inhomogeneity increased, and the color of the apoptosis cells changes from light to dark.The tail artery systolic pressure of rats in CIH group was significantly higher than that of the control group and the model group,and the LVEF of CIH group was significantly lower than that of the other two groups(P<0.05).Ultrasound detection value sug-gests that the LVID and left ventricular of rats in the CIH group were slightly larger,and the diastolic function was normal.The LVDs of the model group and the CIH group were both higher than that of the control group with statistically significant difference(P<0.05).The RBC, HCT,dp/dtmax,and -dp/dtmax in the CIH group were significantly higher than those of the control group and the model group(P<0.05). Serum levels of endothelin-1 in CIH group were significantly higher than that of control group and model group,while the summation of serum NO2-/NO3-and eNOS in CIH group were significantly lower than those of the control group and the model group(P<0.05).Conclusion Chronic intermittent hypoxia can cause cardiac dysfunction in anesthetized rats,which may lead to the imbalance of serum endothelin-1 and NO levels,leading to endothelial dysfunction and myocardial injury.

The "Internet + Medical" Mode Promotes the Implementation of Tiered Diagnosis and Treatment / 医学信息学杂志

By taking the People's Hospital of Hechi as an example,the paper analyzes the implementation situation and causes of difficulty in China's tiered medical service,introduces the way by which implementation of tiered diagnosis and treatment is promoted through "internet + medical".It points out that the mode is effective in promoting the smooth development of tiered diagnosis and treatment and enhancing medical efficiency of quality medical resources.

Cytoplasmic translocation of Cx32 mediates cisplatin resistance in ovarian cancer cells / 中国药理学与毒理学杂志

OBJECTIVE To investigate the underlying mechanism of drug resistance to cisplatin and increasing the sensitivity to therapeutic drugs are key steps towards the improved treatment of patients with ovarian cancer. Gap junction (GJ) and connexin (Cx) are closely related to tumor formation, but the relationship between cisplatin resistance and GJ or Cx are undetermined. METHODS We established the cisplatin-resistant human ovarian cancer cell line A2780-CDDP over an 11-month period, with the concentration of cisplatin gradually increasing from 0.5 g·L-1 to 16 g·L-1. To explore the effect of GJ in the process of cisplatin resistance, we investigated GJ using a parachute dyecoupling assay in A2780- RI(1.2), A2780- RI(1.7), A2780- RI(2.9), A2780- RI(4.3) and A2780- CDDP cells. We further explored whether the Cxs responsible for GJ were related to cisplatin resistance. In A2780- RI(1.2), A2780-RI(1.7), A2780-RI(2.9), A2780-RI(4.3) and A2780-CDDP, we used q-PCR to analyze the levels of Cx43, Cx40, Cx37, and Cx32. To confirm the effect of Cx32 on cisplatin resistance, we knocked down Cx32 in A2780-CDDP cells with siRNA-Cx32. As GJ was decreased whereas Cx32 expression was elevated during the cisplatin resistance process, it drove us to explore the underlying mechanism. To resolve this issue, we extracted membrane-bound and cytoplasmic proteins from A2780 and A2780-CDDP cells. RESULTS Here we showed that cisplatin resistance was correlated to the loss of GJ and the upregulation of Cx32 expression. Enhancing GJ in A2780-CDDP cells could increase the apoptotic response to cisplatin treatment. Furthermore, although Cx32 expression was increased in A2780-CDDP cells, it was more localized to the cytoplasm rather than in the membrane, and knockdown of Cx32 in A2780-CDDP cells sensitized them to cisplatin treatment. CONCLUSION In summary, Cx32 is involved in cisplatin resistance, and cytoplasmic Cx32 plays an important role in chemoresistance.

Gap junctions enhance the antiproliferative effect by transfer of microRNAs in glioma cells / 中国药理学与毒理学杂志

OBJECTIVE To investigate the permeability of gap junction composed of connexin 43 (Cx43) for microRNAs (miRNAs) and the impact of gap junction-mediated transfer of miRNAs in glioma U87 cells. METHODS Co-culture assay demonstrated the transmission of miRNAs through gap junction channel into adjacent cells. U87 cells were labeled with green fluorescein protein (GFP) as receivers and cells were transfected miRNAs as donors. Receiver cells and donor cells were mixed together in a ratio of 1:1. After 12 h co-culture, cells were separated using a BD influx flow cytometer based on the GFP labeled. Quantitative real-time polymerase chain reaction (qRT-PCR) was applied detect to the expressions of miRNAs and Cx43 mRNA. Western blotting was performed to detect the protein expressions of Cx43 and GFP in U87 cells. CCK-8 assay is used to detect cell growth. RESULTS Co-culture assays demonstrated miR-34a could transfer between U87 cells. The role of the contact independent could also transfer of miR-34a. Gap junctions inhibitor (CBX and 18-α-GA) showed lower miR-34a expression than co-culture group, whereas gap junctions enhancer (RA and Galanglin) enhanced miR-34a expression. Knockdown of Cx43 could significantly decrease the transferring of miR-34a between U87 cells. Different length of miRNAs (miR-1827, miR-144, miR-203a and miR-1183) were similar to the expression of miR-34a between U87 cells. Additionally, we demonstrated that gap junctions mediate the effect of antiproliferation mediated by miR- 34a in U87 cells. The functional inhibition of gap junctions using either siRNA or inhibition eliminated the miR- 34a mediated antiproliferation, whereas the enhancement of gap junctions treatment augmented this miR34a-mediated antiproliferation. CONCLUSION Our study demonstrates that gap junction composed of Cx43-mediated transfer miRNAs in different length of nucleotides and gap junction-mediated transfer of miR-34a enhance the antiproliferative effect in glioma U87 cells.