Objective To investigate expression level of endoplasmic reticulum stressmarker GRP78 in the testicular tissue in rats with different phases of morphine-dependence. To explore the role of ERS in morphine-de-pendence. Methods SD rats were divided into 6 groups: morphine (mor) -withdrawal group, mor-extinct group, mor-kindling group and their control groups, normal saline (NS)-withdrawal group, NS-extinct group, NS-kindling group. The experimental rats were injected with morphine subcutaneously on increasing dosage to establish the con-ditioned place preference (CPP) model. The rats in control groups were injected NS. Then the rats were suffered from withdrawal for 48 h, extinction and kindling by morphine, separately. The GRP78 expression level in testicular tissues of rats in the time point mentioned above were measured using Western Blot. Results The time of rats in the paired-box was (528.0 ± 81.0) s, which was significantly higher than that in the NS control group (P<0.001). It was (396.8 ± 116.9) s after extinctive phase, which was significantly higher than that the withdrawal phase of rats (P < 0.001). Also it was (396.8 ± 116.9) s after kindling with morphine which was significantly higher than that the extinctive phase of rats (P < 0.001). These changes of the time indicated that the animal models of extinction and kindling were established in the study. The GRP78 levels were down-regulated in 48 h after withdrawal (P <0.05), and increased a bit afterextinctive phase, but up-regulated highly after kindling with morphine (P < 0.01). Conclusion ERS may be related in the morphine dependence and it might play an important role of testicular dys-function in male drugabuser.

Objective:To investigate the perioperative risk factors in contribution of hyperbilirubinemia following cardiopulmonary bypass(CPB) assisted cardiovascular surgery, of which cutoff values of key factors are defined.Methods:1 286 patients received cardiac surgery assisted by CPB from January 2017 to March 2019 were included in the study. The perioperative data and the peak serum total bilirubin at selected timepoints were recorded. Logistic regression of multi-factor analysis was used to define risk factors and then broken-line analysis was applied to predict the risky threshold. Results:312(24.26%)patients developed hyperbilirubinemia after surgery, with the in-hospital mortality rate up to 34.62%(108 cases). In those patients, valve surgery(45.51%, 142/312), great vessel open surgery(37.82%, 118/312) and heart transplantation(7.69%, 24/312) were mostly performed. The duration of postoperative ICU stay and the use of ventilation were 6 days and 68 hours, which were significantly higher than those in non-hyperbilirubinemia group( P<0.01). Multivariate logistic regression showed that the postoperative ventilation time>49 h, the cardiopulmonary bypass(CPB) time>181 min and the abnormal preoperative liver function, use of intra-aortic balloon pump and extracorporeal membrane oxygen, unplanned re-exploration for bleeding were the risk factors for postoperative hyperbilirubinemia( P<0.01). The cutoff duration of postoperative mechanical ventilation and CPB affecting the incidence of hyperbilirubinemia, ICU days and in-hospital mortality were 120.21 h and 143.26 min, 248.20 h and 239.51 min, 259.50 h and 190.60 min, respectively. Conclusion:Preoperative abnormal liver function, intraoperative CPB time, postoperative mechanical ventilation time, postoperative use of IABP or ECMO assistance, and unplanned secondary thoracotomy were high-risk factors for hyperbilirubinemia after CPB-assisted cardiovascular surgery.

Objective:To explore the postoperative hyperbilirubinemia after heart transplantation(HT)and examine its related in-hospital mortality and long-term survival status.And the relationships between preoperative pulmonary hypertension or postoperative right heart dysfunction and hyperbilirubinemia are also elucidated.Methods:From 2014 to 2021, the relevant perioperative data are retrospectively reviewed for 142 HT recipients at Tongji Hospital of Tongji Medical College of Huazhong University of Science & Technology.Based upon the presence or absence of postoperative bilirubin, they were divided into two groups of hyperbilirubinemia(group A, 73 cases) and non-hyperbilirubinemia(group B, 69 cases). And the correlation between preoperative pulmonary hypertension, postoperative right ventricular dysfunction and postoperative hyperbilirubinemia is examined by contingency table; Kaplan-Meier survival curve of postoperative hyperbilirubinemia is plotted.Results:This cohort is composed of 109 males(76.76%)and 33 females(23.24%)with an average age of(47.01±15.31)years.Hyperbilirubinemia occurred in 51.41% of recipients.Logistic analysis revealed in-patient mortality become markedly elevated in hyperbilirubinemia group (OR: 3.855; 95% CI: 1.202~12.367). However, no significant difference existed in 8-year survival curve post-transplant( P=0.09). For group A, 24 cases(32.87%)have pulmonary hypertension pre-operation and duration of CPB was(188.15±63.18)min, 37 and 30 cases(50.68%, 1.67%)have either right or left ventricular dysfunction post-operation.Intra-aortic balloon pump(IABP, 17cases, 23.29%)and extracorporeal membrane oxygenation(ECMO, 11 cases, 15.07%)are employed.The above parameters are all higher in group A than those in group B. Conclusions:The incidence of postoperative hyperbilirubinemia and related in-hospital mortality remains high after HT.However, no significant difference exists in medium/long-term survival rate after adequate treatment.Preoperative pulmonary hypertension and postoperative right heart dysfuncion are associated with hyperbilirubinemia postoperatively.Clinical interventions for risk factors of hyperbilirubinemia are required during perioperative period.

Objective:To investigate the efficacy of the biopsy strategy combining 6-core systematic and 3-core MRI-targeted biopsy on prostate cancer (PCa) detection in biopsy-na?ve patients.Methods:The clinical data of 121 biopsy-na?ve patients who underwent transperineal prostate biopsy in West China Hospital of Sichuan University from July 2018 to January 2020 were retrospectively analyzed. The average age was (64.7±9.1) years old. Pre-biopsy prostate-specific antigen (PSA) was (12.4±7.5)ng/ml, f/t PSA was 0.13±0.05. Prostate volume was (43.1±26.1) ml and PASD was (0.35±0.27) ng/ml 2. The prostate-imaging and data system (PI-RADS) score of MRI before biopsy was reported to be 3 for 29 patients (24.0%), 4 for 54 patients (44.6%) and 5 for 38 patients (31.8%). All 121 patients underwent 12-core systematic biopsy combined with a 3-core or 5-core MRI-targeted biopsy, of which 61 patients underwent 3-core targeted biopsy and 60 underwent 5-core targeted biopsy. There was no significant difference in the pre-biopsy clinical data between the two groups ( P>0.05). A 6-core systematic biopsy was redefined as the results of 6 cores among the 12-core systematic biopsy. We compared the detection rates among the single 12-core systematic biopsy, 6-core systematic biopsy, MRI-targeted biopsy (3-core or 5-core), and different systematic biopsy combing with targeted biopsy for any PCa and clinically significant PCa, and we also analyzed the cumulative cancer detection rates for MRI-targeted biopsy of different cores. Results:Of the 121 patients in this study, the biopsy results were negative for 43 patients (35.5%) and positive for 78 (64.5%). The detection rate of clinically significant PCa was 55.4% (67/121). The detection rate of the 6-core systematic biopsy combined with MRI-targeted biopsy was 62.0% (75/121) for PCa and 55.4% (67/121) for clinically significant PCa, which was of no difference compared with that for the 12-core systematic biopsy combined with MRI-targeted biopsy ( P>0.05), but the 6-core systematic biopsy combined with MRI-targeted biopsy avoided the overdiagnosis of 3 patients with Gleason score 3+ 3. The detection rate of PCa for MRI-targeted biopsy was 57.9% (70/121), including 42.1% (51/121) for the first core, 55.4% (67/121) for the first two cores, and 57.9% (70/121) for the first three cores. Compared with the single-core targeted biopsy for suspicious lesions, the first 2-core targeted biopsy ( OR=1.7, 95% CI 1.0-2.8) and 3-core targeted biopsy ( OR=1.9, 95% CI 1.1-3.1) can significantly increase the detection rate of PCa, while the fourth or fifth core of targeted biopsy can not increase the detection rate additionally (60%, 36/60). Conclusion:For patients with suspected PCa, the prostate biopsy strategy combing 6-core systematic and 3-core MRI-targeted biopsy performs no inferior than the current 12-core systematic biopsy combined with MRI-targeted biopsy.

The cyclic dinucleotide c-di-GMP is known as an important second messenger in bacteria, which controls various important cellular processes, such as cell differentiation, biofilm formation and virulence factors production. It is extremely vital for the development of new antibacterial agents by virtue of blocking c-di-GMP signal conduction. Current research indicates that there are three potential targets for discovering new antibacterial agents based on c-di-GMP regulated signal pathway, which are c-di-GMP synthases, c-di-GMP degrading enzymes and c-di-GMP receptors. Herein, we review small molecules that have been developed to inhibit c-di-GMP related enzymes and indicate perspectives of c-di-GMP inhibitors.

Biofilm is a bacterial lifestyle ubiquitously in natural environments. Bacterial biofilm leads to drug resistance, a main reason why many infectious diseases are difficult to control. Due to the prominent points of biofilms implicated in infectious disease and the spread of multi-drug resistance, it is urgent to discover new antibacterial agents that can regulate biofilm formation and development. This review introduces chemical agents that could modulate bacterial biofilm formation and development.

Objective:To clarify the infection and epidemic characteristics of the human metapneumovirus (HMPV) in Chinese patients with febrile respiratory syndrome (FRS), and to provide important baseline data for clinical diagnosis, treatment, prevention and control of HMPV-induced respiratory tract diseases in China.Methods:FRS cases from January 2009 to June 2021 in 9 provinces in China, including Beijing, Hebei, Jilin, Shandong, Shaanxi, Xinjiang, Anhui, Guangdong, Hunan were retrospectively analyzed for their respiratory samples, clinical and epidemic data.The respiratory samples were detected for HMPV by quantitative real-time PCR.Results:A total of 11 660 cases were tested for HMPV, involving 296 (2.54%) HMPV-positive cases.Among 296 HMPV-positive cases, 218 were single HMPV infection, and 78/296 (26.35%) were co-infected with one or more respiratory viruses.HMPV mainly affected children under 5 years of age (3.10%), and in this population, the proportion of pneumonia in HMPV co-infection cases was significantly higher than that of single HMPV infection.HMPV could be detected all year round, which was more popular in winter and spring, with the peak of HMPV epidemic in March.Conclusions:HMPV is one of the important pathogens causing acute respiratory infection in children, showing a clear seasonal epidemic.HMPV can be infected alone or in combination with other respiratory viruses, which may increase the risk of pneumonia in children.

OBJECTIVE To investigate and analyze the use of acetaminophen in primary medical institutions of Shaanxi province， and to provide evidence for promoting the standardized and rational use of acetaminophen. METHODS According to the method of cluster stratified random sampling， all prescriptions of acetaminophen issued by primary medical institutions in one district and one county （or two districts） were randomly selected from 10 provincial cities of Shaanxi province from 2020 to 2023； the existing clinical diagnoses were classified by using the International Classification of Diseases （ICD） code， and the drug information of collected prescriptions was analyzed descriptively. SPSS 25.0 software was used for single-factor analysis and Logistic regression analysis to find out the key factors affecting the duration of medication ＞10 d. RESULTS A total of 7 375 valid prescriptions for acetaminophen were collected in this study. The patients who used acetaminophen were mainly female （52.11%） and aged 19-64 （66.73%）. Based on the ICD code， the disease categories most involved in the use of acetaminophen were musculoskeletal system， connective tissue diseases or symptoms and signs （43.48%）； the top 3 clinical diagnoses were joint disease （25.59%）， fracture （9.95%）， and toothache （8.58%）. Among the 7 175 prescriptions with clear drug usage and dosage， 3 366 were in line with the recommendation of acetaminophen instruction， and 5.63% of the prescriptions exceeded the maximum dose limit of acetaminophen 2.0 g/d. There were 4 051 prescriptions exceeding the conventional limit of treatment duration （7 d）， and 1 336 prescriptions exceeding the limit of treatment duration （10 d）. The main factors affecting the duration of drug treatment ＞10 d were the region and type of medical institutions， the gender and age of patients， and the phenomenon of the duration of drug treatment ＞10 d was common in the primary medical institutions from southern Shaanxi， township health centers， the elderly and female patients. CONCLUSIONS There are some unreasonable clinical applications of acetaminophen in primary medical institutions of Shaanxi province， which are mainly manifested in inappropriate usage and dosage， unsuitable clinical diagnosis and drug duration. The region， type of medical institution， age and gender of patients will affect the duration of this drug prescription.

Objective: To better understand the evolution and epidemiology of human adenovirus-55 (HAdV-55) and provide a scientific basis for the prevention and control of the epidemic of HAdV-55 in China. Methods: HAdV-55 isolates from 5 provinces in China included Beijing, Hebei, Shandong, Hunan and Yunnan were collected during 2011-2014. The hexon, fiber and penton base gene were sequenced, and compared with other strains of HAdV-55 sequences downloaded from GenBank for homology and evolution analysis. Results: During the past decade, HAdV-55 was found in 15 provinces throughout China. Genetic and phylogenetic analysis showed that the HAdV-55 virus is highly conservative in evolution due to aggregation in a branch in the evolutionary tree. However, bayesian phylogenetic tree shows a certain time evolution trend. The evolution rate of hexon and fiber gene of HAdV-55 are 5.228×10^-5 and 1.238×10^-4 substitutions/site/year respectively, and the latest coevolutionary ancestor tMRCA of hexon gene can be traced back to 1963. Conclusions HAdV-55 has been widely spread and continued circulating in China. Establishing effective monitoring system and conducting vaccine related research is very important for its control and prevention.

Objective: To establish a real-time fluorescence recombinase acid amplification (RAA) method for the detection of adenovirus type 3(HAdV-3)without extraction nucleic acid. Methods: According to the conserved sequence of adenovirus type 3 gene, a pair of primers and a probe were designed, and a real-time fluorescence RAA without extracting nucleic acid was established and optimizing the condition of DNA-free extraction. The sensitivity of the method was analyzed by a series of dilution and the specificity of the method was evaluated by detecting the original samples of other respiratory viruses. The clinical samples of HAdV-3 were detected and compared with the traditional real-time fluorescence quantitative PCR method for nucleic acid extraction. Results: The sensitivity of the real-time fluorescence RAA method was as high as that of qPCR in the detection of 10 series diluted HAdV-3 strains. The highest corresponding CT value of qPCR was 36.87. The sensitivity of the real-time fluorescence RAA method was similar to that of the real-time fluorescence quantitative PCR method . There was no cross-reaction to other common types of respiratory viruses. The two method were used to detect 56 clinical samples at the same time, and the result were completely consistent. Conclusions We provide the first report of the real-time fluorescent RAA assays for the detection of HAdV-3 without extracting nucleic acid and it has high sensitivity and specificity. Is suitable for rapid detection of HAdV-3 in clinical laboratories and on-site unite.