AIM:To explore the effect of long-term (6 months) endogenous testosterone deprivation by orchidectomy on the function of voltage-dependent potassium channels of vascular smooth muscle cells in rats. METHODS:Wistar rats were raised for 6 months after castration. Isometric tension measurement of aortic rings,whole-cell patch-clamp technique and Western blotting analysis were employed to examine the functional and posttranscriptional alterations of voltage-dependent potassium channels. RESULTS:Voltage-dependent potassium channel blocker,4-aminopyridine,significantly decreased the constriction of aortic artery rings from male rats after 6-month castration. In castrated rats the amplitude of voltage-dependent potassium currents of aortic artery smooth muscle cells was significantly decreased compared with that in control rats. Meanwhile,the expression of Kv 1.5 channel protein,which plays an essential role in mediating vasomotor function,was also reduced. The functional and molecular alterations of voltage-dependent potassium channels were both restored when the rats were concomitant applied with physiological level of testosterone after castration. CONCLUSION:Long-term deprivation of endogenous testosterone in rats significantly attenuates the function of voltage-dependent potassium channels,and the decreases in expression of Kv1.5 channel protein accounts for this alteration. Long-term application of physiological concentration of testosterone,which recovered the impaired function of voltage-dependent channels,may be beneficial for male gender with hypotestosteronaemia.

Objective To evaluate the hemodynamic changes in patients with middle cerebral artery (MCA) stenosis pre- and post-stenting by transcranial color-coded and pulsed-Doppler sonography.Methods Thirty patients with middle cerebral artery stenosis were included.Two-dimensional,color-coded and pulsed-Doppler sonography were used to monitor the morphologic and hemodynamic changes of the MCA before,in the middle of,and after the endovascular stenting operation.All patients were verified by digital substract angiography.Results The hyper-echoic stent grafts and also the size and location of the stent were clearly shown by two-dimensional ultrasonography in 28 patients.The systolic,diastolic and the timeaveraged maximal flow velocities significantly decreased both instantly and 3 - 7 d after the stenting.Specifically,the systolic peak flow velocity of the MCA dramatically decreased immediately after the stenting [(151.43 ± 25.14) cm/s vs (286.13 ± 57.38)cm/s,P ＜0.05],and showed a further decrease after 3 - 7 d [(108.80 ± 9.95) cm/s vs (151.43 ± 25.14) cm/s,P ＜0.05].Conclusions Transcranial color-coded and pulsed-Doppler sonography could be used to evaluate the hemodynamic changes after MCA stenting,and could be considered as the first choice of method for evaluating the therapeutic outcome of stenting.

Objective To analyze the risk factors of gastrointestinal dysfunction in critically ill patients and provide reference for the prevention and treatment of gastrointestinal dysfunction. Methods A retrospective study was conducted, and the data of patients admitted to intensive care unit (ICU) of Jinghai District Hospital from September 2018 to March 2019 were collected. The data including sex, age, sequential organ failure score (SOFA), acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ), diagnosis in ICU, application of special drugs, hemoglobin (Hb), blood glucose, albumin (Alb) levels and presence or absence of bacteremia were collected. The patients were divided into gastrointestinal dysfunction group and non-gastrointestinal dysfunction group according to whether gastrointestinal dysfunction occurred or not. The general data, related final outcome and prognosis were compared between the two groups. Logistic regression analysis was used to analyze the risk factors affecting gastrointestinal dysfunction in critical ill patients, and the possible existing complications were recorded. The receiver operating characteristic curve (ROC) was drawn to evaluate the predictive values of risk factors. Results One hundred and thirty-eight patients were enrolled in this study, and 86 patients had gastrointestinal dysfunction. The SOFA score and proportions of using catecholamine and bacteremia in the gastrointestinal dysfunction group were significantly higher than those in the non-gastrointestinal dysfunction group [SOFA score: 7.2±3.8 vs. 5.8±3.6, the proportion of using catecholamine: 57.0% (49/86) vs. 38.5% (20/52), the proportion of bacteremia: 32.6%(28/86) vs.17.3%(9/52), all P < 0.05], Alb level was significantly lower than that in the non-gastrointestinal dysfunction group (g/L: 24.15±5.75 vs. 26.55±5.68, P < 0.05). Logistic regression analysis showed that the use of catecholamine, Alb level, bacteremia and SOFA score in ICU were the risk factors for occurrence of gastrointestinal dysfunction in ICU patients [odd ratios (OR) were 1.128, 0.547, 1.645, 1.958, 95% confidence intervals (95% CI) were 1.052-1.219, 0.384-0.765, 1.143-2.597, 1.925-1.993, P values were 0.011, 0.017, 0.021, 0.016, respectively]. Compared with the non-gastrointestinal dysfunction group, the incidence of bedsore, the proportion of energy intake unable to reach the target, the length of stay in ICU and the mortality in gastrointestinal dysfunction group were significantly increased [the incidence of bedsore: 53.5% (46/86) vs. 30.8% (16/52), the proportion of intake unable to reach the target: 27.9% (24/86) vs. 5.8% (3/52), the length of stay in ICU (days): 22.5±17.8 vs. 16.0±11.5, mortality rate: 51.2% (44/86) vs. 34.6% (18/52), all P < 0.05]. ROC curve analysis showed that the use of catecholamine, bacteremia present or not, Alb level and SOFA score showed certain extents of predictive values for the occurrence of gastrointestinal dysfunction in critically ill patients the area under ROC curve (AUC) were 0.794, 0.712, 0.705 and 0.882, respectively, 95% confidence interval (95% CI) were 0.708-0.880, 0.609-0.816, 0.579-0.830, 0.801-0.962, sensitivity were 58.8%, 42.5%, 76.3%, 75.0%, specificity were 100%, 60%, 100%, 85%, all P < 0.05. Conclusions The use of catecholamine, Alb level, bacteremia and high SOFA score are the risk factors of gastrointestinal dysfunction in critically ill patients. Prevention of gastrointestinal motility disorder can improve the treatment success rate of critical patients.

Objective To obtain the data of radiological diagnosis and treatment resource distribution at medical institutions of different levels and in various cities, understand the status of resource allocation, provide policy-making basis and suggestions for optimizing the allocation of radiological diagnosis and treatment resources within the province, and offer data and references for related research. Methods A basic situation questionnaire survey was conducted on radiological diagnosis and treatment institutions in Hunan Province. Data were reviewed, analyzed, and statistically processed using Excel software to understand the allocation situation of radiological diagnosis and treatment resources in Hunan Province. Results As of 2022, there were 3031 radiological diagnosis and treatment institutions, 19770 radiation workers, and 6617 pieces of radiological diagnostic and treatment equipment. There were 80 radiation treatment institutions, 49 nuclear medicine institutions, 178 interventional radiology institutions, and 3028 X-ray imaging diagnosis institutions. There were 1077 radiation workers in radiation treatment, 461 radiation workers in nuclear medicine, 3369 radiation workers in interventional radiology, and 14,863 radiation workers in X-ray imaging diagnosis. There were 135 pieces of radiation treatment equipment, 56 pieces of nuclear medicine equipment, 262 pieces of interventional radiology equipment, and 6164 pieces of X-ray imaging diagnosis equipment. Conclusion Primary and lower grade medical institutions in Hunan Province account for a relatively high proportion of the total number of medical institutions, whereas radiological diagnostic and treatment resources are predominantly concentrated in tertiary medical institutions, demonstrating a unbalanced allocation of radiological diagnosis and treatment resources in various cities. In terms of the overall allocation of radiological diagnosis and treatment resources, interventional radiology is superior to the national average, nuclear medicine and X-ray imaging diagnosis are comparable to the national averages, and radiation treatment is lower than the national average. The total GDP is not the decisive factor in determining the development of local medical levels. It is suggested that relevant authorities should improve the rationality of the planning for the allocation of radiological diagnosis and treatment resources, promote the allocation of radiological diagnosis and treatment resources to the grassroots and underdeveloped areas through various measures, and thus achieve the goal of balanced resource allocation.

Humans ; Severe Acute Respiratory Syndrome ; diagnosis ; therapy

Radiotherapy is widely used in the management of advanced colorectal cancer (CRC). However, the clinical efficacy is limited by the safe irradiated dose. Sensitizing tumor cells to radiotherapy via interrupting DNA repair is a promising approach to conquering the limitation. The BRCA1-BARD1 complex has been demonstrated to play a critical role in homologous recombination (HR) DSB repair, and its functions may be affected by HERC2 or BAP1. Accumulated evidence illustrates that the ubiquitination-deubiquitination balance is involved in these processes; however, the precise mechanism for the cross-talk among these proteins in HR repair following radiation hasn't been defined. Through activity-based profiling, we identified PT33 as an active entity for HR repair suppression. Subsequently, we revealed that BAP1 serves as a novel molecular target of PT33 via a CRISPR-based deubiquitinase screen. Mechanistically, pharmacological covalent inhibition of BAP1 with PT33 recruits HERC2 to compete with BARD1 for BRCA1 interaction, interrupting HR repair. Consequently, PT33 treatment can substantially enhance the sensitivity of CRC cells to radiotherapy in vitro and in vivo. Overall, these findings provide a mechanistic basis for PT33-induced HR suppression and may guide an effective strategy to improve therapeutic gain.