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.

Small cell lung cancer(SCLC)is a type of lung cancer with high malignant degree,rapid transformation,rapid invasion and metastasis,which is prone to early metastasis and poor prognosis.Bone metastases of SCLC occur in three stages:cancer cells proliferate at the primary site,break through local tissues,enter the blood circulation to form circulating tumor cells(CTCs),reach bone tissue through blood circulation,and take root and germinate to form new tumor sites with the support of the bone microenvironment.However,traditional imaging and pathology examinations have disadvantages such as low sensitivity,high cost and difficulty in implementation.Exploratory studies based on blood marker detection as screening and efficacy evaluation of SCLC bone metastases have been reported in recent years.By reviewing the molecular biological mechanism of SCLC bone metastasis formation,this paper found that conventional diagnostic methods such as imaging and pathological biopsy were inadequate in SCLC bone metastasis.The changes in hyaluronic acid,protein biomarkers,non-coding RNA,and biomarkers in liquid biopsy were earlier than the changes in imaging,which had the advantages of simple operation and good repeatability.It provides a new idea and method for the early diagnosis of SCLC bone metastasis,which is worthy of clinical application.

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 application effects of a novel framework: the external septal retention bionic framework in East Asian rhinoplasty.Methods:A retrospective analysis was performed based on the clinical data of the patients who received treatments in Department of Plastic and Aesthetic ( Burn) Surgery, the Second Xiangya Hospital, Central South University from January 2022 to July 2023 using an external septal retention bionic framework with autologous costal cartilage rhinoplasty. The patients were all treated with a V-shaped incision at the nasal columella, which continued to both sides of the nose to form a bird-shaped incision. During the operation, the sixth or seventh costal cartilage was sculpted to form the nasal columella support grafts (sturt), external nasal septal graft, cap grafts, and shield grafts, in which the nasal column support graft and external nasal septal graft were implanted in a mortise-and-tenon joint structure to form a septum bionic retained external stent in order to lengthen the nasal columellar column and strengthen the septum. A capsular graft was used to shape the tip of the nose and the rectus abdominis fascia was covered to soften the tip of the nose, and the shield grafts were used to fill out the subnasal lobules. A bulb was sculpted, shaped and implanted in the dorsal space to elevate the nasal dorsum. To observe the postoperative results and complications, a postoperative satisfaction survey was completed using the rhinoplasty outcome evaluation (ROE) and the visual analogue scale (VAS) with regular follow-up. Comparison of preoperative and postoperative scale scores was performed using paired samples t-test. Nasal stent stability was assessed by measuring the patients’ preoperative and postoperative nasolabial angle and nasal tip protrusion. The comparison of preoperative and postoperative nasolabial angle was performed using the paired-sample t-test, and the comparison of nasal tip protrusion was performed using the Wilcoxon signed rank-sum test, P<0.05 considered a statistically significant difference. Results:A total of 33 patients were enrolled, including 4 males and 29 females, with average age of 23.8 years(15-42 years). The follow-up period is (14.52 ± 4.72) months (3 to 21 months). Thirty-three patients recovered well after surgery, and no short-term complications such as infection or bleeding occurred. The patients' nasal aesthetic problems such as saddle nose, deviated nasal columella, bilateral asymmetry of the nose, bilateral nasal base depression, and rounded shield of the nasal tip were improved after surgery. Satisfaction survey results: ROE and VAS scores were significantly higher than those before surgery, which were [(17.92±2.56) vs.(12.78±3.14)] and [(8.08±1.66)vs(5.15±1.99)], ( P<0.05), 87.9% (27/33)of the patients were satisfied with the aesthetic and functional outcomes of the nose. Comparisons of nasolabial angle [(87.28±2.58)° vs. (97.64±1.95)°] and tip protrusion [1.88 (1.78, 1.95) cm vs. 2.16(2.01, 2.32) cm] measurements between preoperative and postoperative period of the 33 patients, the differences were statistically significant ( P<0.05). Conclusion:Rhinoplasty for East Asians employs an external septal retention bionic framework to retain the nasal septum. This technique can avoid septal cartilage resorption caused by compression of grafts transplanted in the future, and cause less damage to the anatomy and physiology of the nose. The framework is relatively easy to construct, with a stable and strong stent, and good patient satisfaction. It can achieve a more desirable aesthetic effect of the nose.

Objective:To investigate the application effects of a novel framework: the external septal retention bionic framework in East Asian rhinoplasty.Methods:A retrospective analysis was performed based on the clinical data of the patients who received treatments in Department of Plastic and Aesthetic ( Burn) Surgery, the Second Xiangya Hospital, Central South University from January 2022 to July 2023 using an external septal retention bionic framework with autologous costal cartilage rhinoplasty. The patients were all treated with a V-shaped incision at the nasal columella, which continued to both sides of the nose to form a bird-shaped incision. During the operation, the sixth or seventh costal cartilage was sculpted to form the nasal columella support grafts (sturt), external nasal septal graft, cap grafts, and shield grafts, in which the nasal column support graft and external nasal septal graft were implanted in a mortise-and-tenon joint structure to form a septum bionic retained external stent in order to lengthen the nasal columellar column and strengthen the septum. A capsular graft was used to shape the tip of the nose and the rectus abdominis fascia was covered to soften the tip of the nose, and the shield grafts were used to fill out the subnasal lobules. A bulb was sculpted, shaped and implanted in the dorsal space to elevate the nasal dorsum. To observe the postoperative results and complications, a postoperative satisfaction survey was completed using the rhinoplasty outcome evaluation (ROE) and the visual analogue scale (VAS) with regular follow-up. Comparison of preoperative and postoperative scale scores was performed using paired samples t-test. Nasal stent stability was assessed by measuring the patients’ preoperative and postoperative nasolabial angle and nasal tip protrusion. The comparison of preoperative and postoperative nasolabial angle was performed using the paired-sample t-test, and the comparison of nasal tip protrusion was performed using the Wilcoxon signed rank-sum test, P<0.05 considered a statistically significant difference. Results:A total of 33 patients were enrolled, including 4 males and 29 females, with average age of 23.8 years(15-42 years). The follow-up period is (14.52 ± 4.72) months (3 to 21 months). Thirty-three patients recovered well after surgery, and no short-term complications such as infection or bleeding occurred. The patients' nasal aesthetic problems such as saddle nose, deviated nasal columella, bilateral asymmetry of the nose, bilateral nasal base depression, and rounded shield of the nasal tip were improved after surgery. Satisfaction survey results: ROE and VAS scores were significantly higher than those before surgery, which were [(17.92±2.56) vs.(12.78±3.14)] and [(8.08±1.66)vs(5.15±1.99)], ( P<0.05), 87.9% (27/33)of the patients were satisfied with the aesthetic and functional outcomes of the nose. Comparisons of nasolabial angle [(87.28±2.58)° vs. (97.64±1.95)°] and tip protrusion [1.88 (1.78, 1.95) cm vs. 2.16(2.01, 2.32) cm] measurements between preoperative and postoperative period of the 33 patients, the differences were statistically significant ( P<0.05). Conclusion:Rhinoplasty for East Asians employs an external septal retention bionic framework to retain the nasal septum. This technique can avoid septal cartilage resorption caused by compression of grafts transplanted in the future, and cause less damage to the anatomy and physiology of the nose. The framework is relatively easy to construct, with a stable and strong stent, and good patient satisfaction. It can achieve a more desirable aesthetic effect of the nose.

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.