Artesunate alleviates Sjögren's Syndrome by inhibiting the interferon-α signaling in plasmacytoid dendritic cells via TLR-MyD88-IRF7.

Sjögren's syndrome (SS) is an autoimmune disease in which the salivary glands (SGs) and the lacrimal glands (LGs) are affected by lymphocytic infiltration and inflammation. It has been reported that interferon-α (IFN-α) released by plasmacytoid dendritic cells (pDCs) contribute to the pathology of SS, and ART has been shown to effectively ameliorates SS. Despite the current research endeavors, the mechanism of how ART works in the treatment of SS remains to be fully elucidated. Whether ART can treat SS by inhibiting IFN-α remains unclear. This hypothesis was tested both in vivo and in vitro settings during the study. The SS model mice, which were treated with ART, showed amelioration in symptoms related to dryness. RNA-seq analysis revealed strong anti-IFN-α signaling response upon ART treatment. Additional in vitro studies provided further confirmation that the application of ART inhibits the MyD88 protein expression and the nuclear translocation of IRF7. This suggests that the intervention of ART in the TLR-MyD88-IRF7 pathway plays a role in the therapeutic approach for SS. In summary, this study highlighted the therapeutic potential of ART in SS and ART inhibited the IFN-α signaling in pDCs via the TLR-MyD88-IRF7 pathway.

Intra-bone marrow mesenchymal stem cell transplantation modulates myeloid bias tendency of hematopoietic stem and progenitor cells in severe MRL/lpr lupus mice.

The hematopoietic homeostasis in the bone marrow is inextricably intertwined with the immune milieu in peripheral circulation. Researches investigating the pathogenesis of systemic lupus erythematosus (SLE) have defined considerable secretion of inflammatory mediators and activation of pro-inflammatory cells. However, the impacts of "extrinsic" factors on hematopoietic stem and progenitor cells (HSPCs) remain unclear, and it is uncertain whether treatments can help coordinate the biased differentiation. In this study, we showed differences in the proportions of common myeloid progenitors (CMP) and myeloid output in the bone marrow of premorbid and morbid MRL/lpr mice using flow cytometry. RNA-seq analysis of lineage-affiliated transcriptional factors and dysregulated genes within lin- HSPCs revealed inflammation potentiation during disease progression. Further, intra-bone marrow mesenchymal stem cells transplantation (IBM-MSCT) partially coordinated myeloid generation and counteracted lupus-associated inflammation gene alterations, compared to intravenous injection. Additionally, co-culturing with umbilical cord mesenchymal stem cells (UC-MSCs) intervened in myeloid lineage tendency, as detected by RT-qPCR of myeloid-related genes. Our research demonstrated enhanced tendency toward myeloid differentiation and highlighted the feasibility of IBM-MSCT for lineage-biased HSPCs in MRL/lpr lupus model, providing novel insight into hematopoiesis and MSC-related treatments for SLE.

Neuroplasticity of visual brain network induced by hypoxia.

The effects of hypoxia on brain function remain largely unknown. This study aimed to clarify this issue by visual-stimulated functional magnetic resonance imaging design. Twenty-three college students with a 30-d high-altitude exposure were tested before, 1 week and 3 months after returning to sea level. Brain functional magnetic resonance imaging and retinal electroretinogram were acquired. One week after returning to sea level, decreased blood oxygenation level dependent in the right lingual gyrus accompanied with increased blood oxygenation level dependent in the frontal cortex and insular cortex, and decreased amplitude of electroretinogram a-wave in right eye; moreover, the bilateral lingual gyri showed increased functional connectivity within the dorsal visual stream pathway, and the blood oxygenation level dependent signals in the right lingual gyrus showed positive correlation with right retinal electroretinogram a-wave. Three months after returning to sea level, the blood oxygenation level dependent signals recovered to normal level, while intensively increased blood oxygenation level dependent signals in a broad of brain regions and decreased retinal electroretinogram were also existed. In conclusion, hypoxic exposure has long-term effects on visual cortex, and the impaired retinal electroretinogram may contribute to it. The increased functional connectivity of dorsal stream may compensate for the decreased function of retinal photoreceptor cells to maintain normal visual function.

CFL1 restores the migratory capacity of bone marrow mesenchymal stem cells in primary Sjögren's syndrome by regulating CCR1 expression.

BACKGROUND: Primary Sjögren's syndrome (pSS) is a chronic systemic autoimmune disease. There is no relevant research on whether the migratory ability of bone marrow mesenchymal stem cells (BM-MSC) is impaired in patients with pSS (pSS-BMMSC). METHODS: Trajectories and velocities of BM-MSC were analyzed. Transwell migration assay and wound healing assay were used to investigate the migratory capacity of BM-MSC. The proliferative capacity of BM-MSC was evaluated by EDU and CCK8 assay. RNA-seq analysis was then performed to identify the underlying mechanism of lentivirus-mediated cofilin-1 overexpression BM-MSC (BMMSCCFL1). The therapeutic efficacy of BMMSCCFL1 was evaluated in NOD mice. RESULTS: The migratory capacity of pSS-BMMSC was significantly reduced compared to normal volunteers (HC-BMMSC). The expression of the motility-related gene CFL1 was decreased in pSS-BMMSC. Lentivirus-mediated CFL1 overexpression of pSS-BMMSC promoted the migration capacity of pSS-BMMSC. Furthermore, RNA-seq revealed that CCR1 was the downstream target gene of CFL1. To further elucidate the mechanism of CFL1 in regulating BM-MSC migration and proliferation via the CCL5/CCR1 axis, we performed a rescue experiment using BX431 (a CCR1-specific inhibitor) to inhibit CCR1. The results showed that CCR1 inhibitors suppressed the migration and proliferation capacity of MSC induced by CFL1. CONCLUSION: The pSS-BMMSC leads to impaired migration and proliferation, and overexpression of CFL1 can rescue the functional deficiency and alleviate disease symptoms in NOD mice. Mechanically, CFL1 can regulate the expression level of the downstream CCL5/CCR1 axis to enhance the migration and proliferation of BM-MSC.

Application of metagenomic next-generation sequencing in prevention and control of infection in solid organ transplantation / 器官移植

Organ transplantation has become an effective treatment for multiple end-stage diseases. However, the recipients of organ transplantation need to take immunosuppressive drugs for a long time after operation, which leads to low immune function and relatively high incidence of bacterial, viral and fungal infections. Traditional microbial detection methods, such as pathogen culture, immunological detection and polymerase chain reaction, have been widely applied in infection detection, whereas these methods may cause problems, such as long detection time and presumed pathogens. Metagenomic next-generation sequencing has been widely adopted in infection prevention and control in organ transplantation in recent years due to high detection rate and comprehensive detection of pathogen spectrum. In this article, the application of metagenomic next-generation sequencing in the prevention and control of infection in solid organ transplantation was reviewed, aiming to provide reference for the diagnosis and treatment of transplantation-related infection.

Influencing factors of survival of patients with airway stenosis requiring clinical interventions after lung transplantation / 器官移植

Objective To analyze the influencing factors of survival of patients with airway stenosis requiring clinical interventions after lung transplantation. Methods Clinical data of 66 patients with airway stenosis requiring clinical interventions after lung transplantation were retrospectively analyzed. Univariate and multivariate Cox’s regression models were adopted to analyze the influencing factors of survival of all patients with airway stenosis and those with early airway stenosis. Kaplan-Meier method was used to calculate the overall survival and delineate the survival curve. Results For 66 patients with airway stenosis, the median airway stenosis-free time was 72 (52,102) d, 27% (18/66) for central airway stenosis and 73% (48/66) for distal airway stenosis. Postoperative mechanical ventilation time [hazard ratio (HR) 1.037, 95% confidence interval (CI) 1.005-1.070, P=0.024] and type of surgery (HR 0.400, 95%CI 0.177-0.903, P=0.027) were correlated with the survival of patients with airway stenosis after lung transplantation. The longer the postoperative mechanical ventilation time, the higher the risk of mortality of the recipients. The overall survival of airway stenosis recipients undergoing bilateral lung transplantation was better than that of their counterparts after single lung transplantation. Subgroup analysis showed that grade 3 primary graft dysfunction (PGD) (HR 4.577, 95%CI 1.439-14.555, P=0.010) and immunosuppressive drugs (HR 0.079, 95%CI 0.022-0.287, P<0.001) were associated with the survival of patients with early airway stenosis after lung transplantation. The overall survival of patients with early airway stenosis after lung transplantation without grade 3 PGD was better compared with that of those with grade 3 PGD. The overall survival of patients with early airway stenosis after lung transplantation treated with tacrolimus was superior to that of their counterparts treated with cyclosporine. Conclusions Long postoperative mechanical ventilation time, single lung transplantation, grade 3 PGD and use of cyclosporine may affect the survival of patients with airway stenosis after lung transplantation.

Water-Induced Bandgap Engineering in Nanoribbons of Hexagonal Boron Nitride.

Different from hexagonal boron nitride (hBN) sheets, the bandgap of hBN nanoribbons (BNNRs) can be changed by spatial/electrostatic confinement. It is predicted that a transverse electric field can narrow the bandgap and even cause an insulator-metal transition in BNNRs. However, experimentally introducing an overhigh electric field across the BNNR remains challenging. Here, it is theoretically and experimentally demonstrated that water adsorption greatly reduces the bandgap of zigzag-oriented BNNRs (zBNNRs). Ab initio calculations show that water molecules can be favorably assembled within the trench between two adjacent BNNRs to form a polar ice layer, which induces a transverse equivalent electric field of over 2 V nm-1 accounting for the bandgap reduction. Field-effect transistors are successfully fabricated from zBNNRs with different widths. The conductance of water-adsorbed zBNNRs can be tuned over 3 orders in magnitude via modulation of the equivalent electrical field at room temperature. Furthermore, photocurrent response measurements are taken to determine the optical bandgaps of zBNNRs with water adsorption. The zBNNR with increased width can exhibit a bandgap down to 1.17 eV. This study offers fundamental insights into new routes toward realizing electronic/optoelectronic devices and circuits based on hexagonal boron nitride.

Diagnosis and treatment of primary seminoma of the prostate: A case report and review of literature.

BACKGROUND: Primary seminoma of the prostate (PSP) is a rare type of extragonadal germ cell tumour that is easily misdiagnosed, owing to the lack of specific clinical features. It is therefore necessary for clinicians to work toward improving the accuracy of PSP diagnosis. CASE SUMMARY: A 59-year-old male patient presenting with acute urinary retention was admitted to a local hospital. A misdiagnosis of benign prostatic hyperplasia led to an improper prostatectomy. Histopathology revealed PSP invading the bladder neck and bilateral seminal vesicles. Further radiotherapy treatment for the local lesion was performed, and the patient had a disease-free survival period of 96 mo. This case was analysed along with 13 other cases of PSP identified from the literature. Only four of the cases (28.6%) were initially confirmed by prostate biopsy. In these cases, imaging examinations showed an enlarged prostate (range 6-11 cm) involving the bladder neck (13/14). Of the 14 total cases, 11 (78.6%) presented typical pure seminoma cell features, staining strongly positive for placental alkaline phosphatase, CD117, and OCT4. The median age at diagnosis was 51 (range 27-59) years, and patients had a median progression-free survival time of 48 (range 6-156) mo after treatment by cisplatin-based chemotherapy combined with surgery or radiotherapy. The remaining three were cases of mixed embryonal tumours with focal seminoma, which had clinical features similar to those of pure PSP, in addition that they also had elevated serum alpha-fetoprotein, beta-human chorionic gonadotropin, and lactose dehydrogenase. CONCLUSION: PSP should be considered in patients younger than 60 years with an enlarged prostate invading the bladder neck. Further prostate biopsies may aid in proper PSP diagnosis. Cisplatin-based chemotherapy is still the main primary therapy for PSP.

In the uncharted water: Meaning-making capacity and identity negotiation of Chinese lesbian and bisexual women.

Chinese lesbian and bisexual women (LBW) often face difficulties and challenges on campus due to their multiple, socially-oppressed identities. These students have to navigate through uncharted environments to make meaning of their identities. In this qualitative study, by considering four environmental systems of student life, including the student club (microsystem), the university (mesosystem), families (exosystem), and society (macrosystem), we aim to explore what identity negotiation Chinese LBW students have in them and what their meaning-making capacity influence that identity negotiation. We find students experience identity security in the microsystem, identity differentiation-inclusion or inclusion in the mesosystem, and identity unpredictability-predictability or predictability in the exosystem and macrosystem. Moreover, they employ foundational, transitional (formulaic to foundational or symphonic), or symphonic meaning-making capacity to influence their identity negotiation. Suggestions are made for the university to create an inclusive climate accommodating students with different identities.

Andrographolide protects against atrial fibrillation by alleviating oxidative stress injury and promoting impaired mitochondrial bioenergetics / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Atrial fibrillation (AF) is the most prevalent cardiac arrhythmia seen in clinical settings, which has been associated with substantial rates of mortality and morbidity. However, clinically available drugs have limited efficacy and adverse effects. We aimed to investigate the mechanisms of action of andrographolide (Andr) with respect to AF. We used network pharmacology approaches to investigate the possible therapeutic effect of Andr. To define the role of Andr in AF, HL-1 cells were pro-treated with Andr for 1 h before rapid electronic stimulation (RES) and rabbits were pro-treated for 1 d before rapid atrial pacing (RAP). Apoptosis, myofibril degradation, oxidative stress, and inflammation were determined. RNA sequencing (RNA-seq) was performed to investigate the relevant mechanism. Andr treatment attenuated RAP-induced atrial electrophysiological changes, inflammation, oxidative damage, and apoptosis both in vivo and in vitro. RNA-seq indicated that oxidative phosphorylation played an important role. Transmission electron microscopy and adenosine triphosphate (ATP) content assay respectively validated the morphological and functional changes in mitochondria. The translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) to the nucleus and the molecular docking suggested that Andr might exert a therapeutic effect by influencing the Keap1-Nrf2 complex. In conclusions, this study revealed that Andr is a potential preventive therapeutic drug toward AF via activating the translocation of Nrf2 to the nucleus and the upregulation of heme oxygenase-1 (HO-1) to promote mitochondrial bioenergetics.

Quality of life in patients after minimally invasive coronary artery bypass grafting surgery versus off-pump coronary artery bypass grafting surgery: A propensity score matching study / 中国胸心血管外科临床杂志

@#Objective    To compare and analyze the postoperative quality of life in patients after minimally invasive coronary artery bypass grafting (MICABG) and conventional median thoracotomy off-pump coronary artery bypass grafting surgery (OPCABG). Methods    From November 2015 to January 2018, 94 patients who underwent MICABG in the Peking University Third Hospital were included in the MICABG group. During the same period 441 patients who received OPCABG were included in the OPCABG group. The patients were matched by using propensity score matching method with a ratio of 1∶1. The quality of life was compared between two groups at 1 month, 6 months and 12 months after the surgery using SF-36 scale. Results    A total of 82 patients were matched for each group. In the MICABG group, there were 66 males and 16 females with a mean age of 62.6±8.2 years. In the OPCABG group, there were 67 males and 15 females with a mean age of 63.2±13.2 years. One month after the operation, the physical health assessment (PCS) and mental health assessment (MCS) of the MICABG group were higher than those of the OPCABG group (50.3±10.6 points vs. 46.1±10.3 points, P=0.011; 59.5±9.3 points vs. 54.2±11.0 points, P=0.002). Scores of these following five dimensions: general health, physical functioning (PF), role-physical, social functioning (SF), role-emotion in the MICABG group were higher than those in the OPCABG group, while the score of body pain was inferior to that in the OPCABG group, and the differences were statistically significant (P<0.05). Six months after the surgery, the PCS and MCS of the two groups were not statistically different (80.0±13.1 points vs. 77.8±12.4 points, P=0.271; 81.6±13.5 points vs. 80.4±11.2 points, P=0.537). However, the scores of PF and SF in the MICABG group were still higher than those in the OPCABG group (P<0.05). Twelve months after the surgery, there was no statistical difference in the score of each dimension between the two groups (P>0.05). Conclusion    The improvement of quality of life within 6 months after MICABG is better than that of OPCABG, and it is similar between the two groups at 12 months after the surgery, indicating that MICABG has a certain effect of improving the short-term quality of life after the surgery, and the long-term quality of life is comparable to conventional surgery.

Value of serum chitinase-3-like protein 1 in predicting the risk of decompensation events in patients with liver cirrhosis / 临床肝胆病杂志

Objective To investigate the value of serum chitinase-3-like protein 1 (CHI3L1) in predicting the risk of decompensation events in patients with liver cirrhosis, since prediction of decompensation events and adoption of active preventive measures are the key to improving the survival time of patients with liver cirrhosis. Methods A case-control study was conducted for 305 patients with liver cirrhosis who were diagnosed and treated in Tianjin Second People's Hospital from January 2019 to May 2021, among whom there were 200 patients with compensated liver cirrhosis and 105 patients with decompensated liver cirrhosis at baseline. According to whether decompensation events occurred within 1 year, the 305 patients with liver cirrhosis were divided into decompensation group with 79 patients and non-decompensation group with 226 patients; according to whether decompensation events occurred for the first time within 1 year, the 200 patients with compensated liver cirrhosis were divided into first-time decompensation group with 43 patients and non-first-time decompensation group with 157 patients. The independent samples t -test or the Mann-Whitney U test was used for comparison of normally distributed continuous data between groups, and the Wilcoxon rank-sum test or the chi-square test was used for comparison of categorical data between groups. The binary logistic regression analysis was used to investigate the association between each variable and decompensation events; the receiver operating characteristic (ROC) curve and the area under the ROC curve (AUC) were used to investigate the value of each variable in predicting decompensation events, and the maximum value of Youden index was used to determine the optimal cut-off value. Results The patients who experienced decompensation events within 1 year had a significantly higher baseline serum level of CHI3L1 than those who did not experience such events [243.00 (136.00-372.00) ng/mL vs 117.50 (67.75-205.25) ng/mL, U =4720.500, P < 0.001], and the patients who experienced decompensation events for the first time within 1 year had a significantly higher baseline serum level of CHI3L1 than those who did not experience such events [227.98 (110.00-314.00) ng/mL vs 90.00 (58.00-168.50) ng/mL, U =1 681.500, P < 0.001]. Patients with cirrhosis with higher baseline CHI3L1 levels had an increased risk of decompensation events within 1 year ( OR =1.004, 95% CI : 1.002-1.006, P < 0.001); Patients with compensated cirrhosis with higher baseline serum CHI3L1 levels had an increased risk of first decompensated event within 1 year ( OR =1.006, 95% CI : 1.003-1.008, P < 0.001). The baseline serum level of CHI3L1 had an AUC of 0.751 in predicting the risk of first-time decompensation events, with a sensitivity of 90.7% and a specificity of 55.4% at the optimal cut-off value of 95.5 ng/mL. The predictive model based on the combination of serum CHI3L1 level and Child-Pugh class had an AUC of 0.809, with a sensitivity of 72.1% and a specificity of 77.1% at the maximum value of Youden index. Conclusion Serum CHI3L1 level can be used as an effective predictive factor for the risk of first-time decompensation events in patients with compensated liver cirrhosis, and its combination with Child-Pugh class shows a higher predictive value.

Interaction Between Memory Load and Experimental Design on Brain Connectivity and Network Topology / 神经科学通报·英文版

The conventional approach to investigating functional connectivity in the block-designed study usually concatenates task blocks or employs residuals of task activation. While providing many insights into brain functions, the block design adds more manipulation in functional network analysis that may reduce the purity of the blood oxygenation level-dependent signal. Recent studies utilized one single long run for task trials of the same condition, the so-called continuous design, to investigate functional connectivity based on task functional magnetic resonance imaging. Continuous brain activities associated with the single-task condition can be directly utilized for task-related functional connectivity assessment, which has been examined for working memory, sensory, motor, and semantic task experiments in previous research. But it remains unclear how the block and continuous design influence the assessment of task-related functional connectivity networks. This study aimed to disentangle the separable effects of block/continuous design and working memory load on task-related functional connectivity networks, by using repeated-measures analysis of variance. Across 50 young healthy adults, behavioral results of accuracy and reaction time showed a significant main effect of design as well as interaction between design and load. Imaging results revealed that the cingulo-opercular, fronto-parietal, and default model networks were associated with not only task activation, but significant main effects of design and load as well as their interaction on intra- and inter-network functional connectivity and global network topology. Moreover, a significant behavior-brain association was identified for the continuous design. This work has extended the evidence that continuous design can be used to study task-related functional connectivity and subtle brain-behavioral relationships.

Transluminal repair of iatrogenic bladder fistula: a report of 7 cases / 现代泌尿外科杂志

【Objective】 To explore the technical methods and clinical efficacy of transvaginal or transrectal repair in the treatment of iatrogenic bladder fistula. 【Methods】 The clinical data of 7 cases of iatrogenic bladder fistula patients treated during 2016 and 2019 were retrospectively analyzed, including 6 cases of vesicovaginal fistula (VVF) and 1 case of vesicorectal fistula (VRF). The operation was conducted 3 to 10 months after the diagnosis of urinary fistula, and the vagina or rectum was fully cleaned before operation. Modified Latzko technique was employed to separate the gap between the bladder wall and vaginal or rectal wall along the fistula, the fistula scar was sharply removed, and the fistula, bladder wall, vaginal or intestinal wall, and vaginal or intestinal mucosa were sutured in layers. The urinary catheter was indwelled for 4 weeks. 【Results】 All 7 cases were successfully repaired at one procedure. No urine leakage was found after the urinary catheter was removed. There was no recurrence after 6 to 12 months of follow-up. 【Conclusion】 Selective application of the modified Latzko technique to repair iatrogenic urinary fistula through the natural lumen is an advantageous treatment scheme, which simplifies the operation and reduces trauma.

Effect of antiplatelet treatment on aneurysmal subarachnoid hemorrhage patients after endovascular treatment: a systematic review with meta-analysis.

Antiplatelet treatment (APT) has been reported to be used in some patients with aneurysmal subarachnoid hemorrhage (aSAH) after endovascular treatment, but there is controversy among different studies regarding its clinical effects. This study intends to conduct a meta-analysis to evaluate the impact of APT on aSAH patients after endovascular treatment. The PubMed, EMBASE, and Cochrane Library databases were systematically searched up to January 2022 for eligible English publications. Quality assessment was conducted for the included studies. Publication bias and heterogeneity were assessed by Egger's test and the I2 statistic, respectively. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated by meta-analysis. Robustness was checked by subgroup and sensitivity analyses. In total, 597 and 522 patients with and without APT, respectively, in 5 retrospective studies were retained for the meta-analysis. Pooled analyses showed that the APT group had a lower mortality (41/499 [8%] versus 56/402 [14%]; OR = 0.533; 95% CI, 0.347-0.820; P = 0.004) and a higher proportion of favorable clinical outcomes (400/532 [75%] versus 266/421 [63%]; OR = 1.801; 95% CI, 1.359-2.414; P = 0.000) than the control group. There was no significant difference in the incidence of hemorrhagic complications (39/564 [7%] versus 26/503 [5%]; OR = 1.386; 95% CI, 0.825-2.329; P = 0.218) between groups. Although the incidence of delayed cerebral ischemia (DCI) was significantly lower in the APT group (65/512 [13%] versus 105/447 [23%]; OR = 0.325; 95% CI, 0.107-0.988; P = 0.048), it showed substantial heterogeneity (I2 = 64.7%). Subsequent sensitivity analysis suggested that the meta-analysis was robust. Subgroup analyses revealed that long-term (> 2 weeks) APT (60/479 [13%] versus 103/428 [24%]; OR = 0.212; 95% CI, 0.056-0.806; P = 0.023) significantly reduced the DCI rate and that different grouping methods in the included studies may be a source of heterogeneity. In the absence of randomized controlled trials, a meta-analysis of retrospective studies suggested that APT was associated with reduced mortality and better functional outcomes in aSAH patients after endovascular treatment without an increased incidence of hemorrhagic complications. Long-term APT was also associated with a decrease in the incidence of DCI. Well-designed randomized controlled trials are warranted and updated meta-analyses are needed to verify our findings.

Simultaneous bilateral laparoscopic cortical-sparing adrenalectomy for bilateral pheochromocytomas in multiple endocrine neoplasia type 2.

Purpose: This study aimed to assess the feasibility of synchronous bilateral laparoscopic or open cortical-sparing adrenalectomy (SB-LCSA or SB-OCSA) for bilateral pheochromocytomas (bPHEOs) in multiple endocrine neoplasia type 2 (MEN2). Methods: Altogether, 31 patients (54.8% were women) were diagnosed with MEN2-related bPHEOs, and 29 of them underwent varying specific adrenalectomies. We systematically analyzed and evaluated their clinical profiles, mutation types, tumor histopathological features, and follow-up records. Results: All 31 patients with bPHEOs presented with RET-C634 (90.3%) and RET-M918T (9.7%) mutations, and the median age at initial presentation was 38 years (range, 23-78). bPHEOs were synchronous in 27 patients and metachronous in 4 (12.9%) patients. In total, 29 patients underwent initial cortical-sparing adrenalectomy (CSA) including 23 (79.3%) undergoing synchronous bilateral CSA (18 SB-LCSA and 5 SB-OCSA) and 6 (20.7%) undergoing metachronous CSA. SB-LCSA and synchronous surgery were associated with less bleeding volume and shorter length of hospital stay than SB-OCSA and metachronous surgery (all P's < 0.05). Corticosteroid replacement treatment was necessary for 14 patients (45.2%) after bilateral CSA. During a median follow-up period of 7 years (range, 1.8-23), three of these patients (10.3%) had a recurrent disease that required reoperation. Conclusion: SB-LCSA is feasible for treating synchronous bPHEOs and should be recommended as a prioritized surgical approach.

Risk factors analysis of central airway stenosis after lung transplantation / 器官移植

Objective To investigate the risk factors of central airway stenosis after lung transplantation. Methods Clinical data of 155 recipients undergoing lung transplantation in Wuxi People's Hospital Affiliated to Nanjing Medical University from July 2016 to December 2017 were retrospectively analyzed. According to the incidence of central airway stenosis following lung transplantation, all recipients were divided into the stenosis group (n=36) and control group (n=119). The incidence of central airway stenosis after lung transplantation was summarized. The risk factors of central airway stenosis after lung transplantation were assessed by univariate and multivariate logistic regression analyses. Results Among 155 lung transplant recipients, 36 cases (23.2%) developed central airway stenosis. The average incidence time was (53±13) d after lung transplantation. Univariate analysis demonstrated that bilateral lung transplantation, grade 3 primary graft dysfunction (PGD), airway fungal infection, long cold ischemia time, long mechanical ventilation time and long intensive care unit (ICU) stay were the risk factors for central airway stenosis after lung transplantation (all P < 0.05). Multivariate analysis showed that airway fungal infection, long cold ischemia time and long mechanical ventilation time were the independent risk factors for central airway stenosis after lung transplantation (all P < 0.05). Conclusions Airway fungal infection after lung transplantation, long cold ischemia time and long mechanical ventilation time probably lead to central airway stenosis after lung transplantation. Active preventive measures and intimate monitoring should be taken to improve the quality of life of the recipients after lung transplantation.

Transapical mitral valve repair with LifeClip system: Early outcome of a single center / 中国胸心血管外科临床杂志

@#Objective 　To evaluate the safety and efficacy of transapical mitral valve repair with moderate-to-severe or severe mitral regurgitation (MR) by using LifeClip system. Methods 　We retrospectively analyzed the clinical data of 7 symptomatic patients with moderate-to-severe or severe MR who received transapical mitral valve repair by using the LifeClip system in our hospital from July to November 2021. There were 5 males and 2 females with an average age of 76.0±7.5 years. Results 　There were 2 patients with degenerative MR and 5 patients with functional MR. All of the procedures were successful and 6 patients received 1 LifeClip while the other one patient received 2. The operation time was 135.7±46.9 min, the mechanical ventilation time was 12 (3, 14) h, and the hospital stay time was 18.1±4.1 d. No serious complications or death occurred during the perioperative or follow-up period. MR reduction by ≥ grades was achieved in all the patients at the one-month follow-up. The classification of cardiac function was improved in varying degrees. Conclusion 　Transapical mitral valve repair using the LifeClip system shows good safety and efficacy for severe MR patients, and MR degree is significantly improved at early follow-up. However, the benefit of LifeClip should be validated in a larger sample size of Chinese population and through long-term follow-up.

A combined application of molecular docking technology and indirect ELISA for the serodiagnosis of bovine tuberculosis

Background@#There is an urgent need to find reliable and rapid bovine tuberculosis (bTB) diagnostics in response to the rising prevalence of bTB worldwide. Toll-like receptor 2 (TLR2) recognizes components of bTB and initiates antigen-presenting cells to mediate humoral immunity. Evaluating the affinity of antigens with TLR2 can form the basis of a new method for the diagnosis of bTB based on humoral immunity. @*Objectives@#To develop a reliable and rapid strategy to improve diagnostic tools for bTB. @*Methods@#In this study, we expressed and purified the sixteen bTB-specific recombinant proteins in Escherichia coli. The two antigenic proteins, MPT70 and MPT83, which were most valuable for serological diagnosis of bTB were screened. Molecular docking technology was used to analyze the affinity of MPT70, MPT83, dominant epitope peptide of MPT70 (M1), and dominant epitope peptide MPT83 (M2) with TLR2, combined with the detection results of enzyme-linked immunosorbent assay to evaluate the molecular docking effect. @*Results@#The results showed that interaction surface Cα-atom root mean square deviation of proteins (M1, M2, MPT70, MPT83)-TLR2 protein are less than 2.5 A, showing a high affinity.It is verified by clinical serum samples that MPT70, MPT83, MPT70-MPT83 showed good diagnostic potential for the detection of anti-bTB IgG and M1, M2 can replace the whole protein as the detection antigen. @*Conclusions@#Molecular docking to evaluate the affinity of bTB protein and TLR2 combined with ELISA provides new insights for the diagnosis of bTB.

Effect of effective parts of Dracocephalum moldavica on the necroptosis of HBMECs after OGD/R injury / 药学学报

We investigated the ability of Dracocephalum moldavica (EPDM) flavonoids to protect human brain microvascular endothelial cells (HBMECs) from necroptosis induced by ischemia-reperfusion injury. To mimic the process of cerebral ischemia-reperfusion injury, a necroptosis model was established by treatment with the pan-cysteine aspartic acid protease (caspase) inhibitor Z-VAD-FMK combined with oxygen-glucose deprivation/re-oxygenation (OGD/R) injury using HBMECs. Cell proliferation and cytotoxicity (cell counting kit-8, CCK-8) was used to measure cell viability. A Hoechst33342/PI fluorescent double-staining method was exploited to determine the rate of cell necroptosis. A commercial kit was used to detect lactate dehydrogenase in the cell culture supernate. DCFH-DA probes, calcein AM and JC-1 probes were used to measure changes in ROS production, mitochondrial membrane permeability transformation pore (MPTP) opening and mitochondrial membrane potential (MMP), respectively. Enzyme-linked immunosorbent assay (ELISA) kits were chosen to detect the release of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6). Western blotting was used to detect necroptosis-related proteins. The results show that relative to control group, Z-VAD-FMK combined with OGD/R injury reduced cell viability, increased the necroptosis rate and the levels of LDH and ROS in HBMECs. The MPTP of the model group cells opened and the MMP reduced. TNF-α, IL-1β, and IL-6 levels were significantly elevated. Furthermore, the expression of receptor-interacting protein kinase 3 (RIP3) and mitochondrial phosphoglycerate mutase 5 (PGAM5) was significantly increased, accompanied by an increase of phosphorylated mixed-lineage kinase domain-like protein (p-MLKL)/MLKL. EPDM partially reversed the changes of the above-mentioned factors in HBMECs induced by Z-VAD-FMK plus OGD/R injury. These results indicate that EPDM may protect HBMECs from cerebral ischemia-reperfusion injury by inhibiting the RIP3/MLKL/PGAM5 pathway and MPTP opening to maintain mitochondrial function, thereby providing a scientific basis for the use of EPDM in the treatment of cerebral ischemia-related diseases.