Influencing factors of anastomotic leakage after laparoscopic intersphincter resection for extremely low rectal cancer and construction of nomogram prediction model / 中华消化外科杂志

Objective:To investigate the influencing factors of anastomotic leakage after laparoscopic intersphincter resection (ISR) for extremely low rectal cancer and construction of nomogram prediction model.Methods:The retrospective case-control study was conducted. The clinicopathological data of 812 patients who underwent laparoscopic ISR for extremely low rectal cancer in the Second Affiliated Hospital of Naval Medical University (Shanghai Changzheng Hospital) from February 2012 to February 2022 were collected. There were 459 males and 353 females, aged (51±11)years. Observation indicators: (1) surgical situations; (2) follow-up; (3) influencing factors of postoperative anastomotic leakage; (4) construction and evaluation of nomogram prediction model for postoperative anastomotic leakage. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M(range). Count data were described as absolute numbers. The COX proportional hazard model was used for univariate and multivariate analyses. The R software(3.5.1 version) was used to construct nomogram prediction model. The receiver operating characteristic (ROC) curve was drawn and the area under curve (AUC) was used to evaluate the efficacy of the nomogram prediction model. The Bootstrap method was used for internal verification and to calculate the average consistency index (C-index). Results:(1) Surgical situations. All 812 patients underwent laparoscopic ISR for extremely low rectal cancer, including 388 cases undergoing partial ISR, 218 cases undergoing subtotal ISR and 206 cases undergoing complete ISR. All 812 patients underwent ileal protective ostomy, and there were 306 cases with double anastomosis and 203 cases with left colic artery preserved, respectively. The operation time and volume of intraoperative blood loss of 812 patients was (179±33)minutes and (33±13)mL, respectively. (2) Follow-up. All 812 patients were followed up for (13.5±0.9)months. Of the 812 patients, there were 62 cases with postoperative anastomotic leakage and the healing time of these cases was (33±6)days. (3) Influencing factors of postoperative anastomotic leakage. Results of multivariate analysis showed that male, neoadjuvant chemoradiotherapy, failure of reser-ving left colic artery were independent risk factors of anastomotic leakage after laparoscopic ISR for extremely low rectal cancer ( hazard ratio=5.98, 4.00, 16.26, 95% confidence interval as 1.66-24.12, 1.30-12.42, 3.00-90.89, P<0.05). (4) Construction and evaluation of nomogram prediction model for postoperative anastomotic leakage. According to the results of multivariate analysis, male, neoadju-vant chemoradiotherapy and failure of reserving left colic artery were used to construct the nomogram prediction model for anastomotic leakage after laparoscopic ISR for extremely low rectal cancer, and the score of these indexes in the nomogram prediction model was 50, 49, 93, respectively. The total score of these index corresponded to the incidence rate of anastomotic leakage. Results of ROC curve showed that the AUC of nomogram prediction model of anastomotic leakage after laparoscopic ISR for extremely low rectal cancer was 0.87 (95% confidence interval as 0.80-0.93, P<0.05), with sensi-tivity and specificity 0.96 and 0.60, respectively. Results of internal verification showed that the C-index of nomogram prediction model was 0.87. Conclusion:Male, neoadjuvant chemoradiotherapy, failure of reserving left colic artery are independent risk factors of anastomotic leakage after laparo-scopic ISR for extremely low rectal cancer, and the nomogram prediction model based on these indexes can predict the incidence rate of postoperative anastomotic leakage.

Clinicopathological analysis of superior mediastinal lymph node metastases in medullary thyroid carcinoma / 中华肿瘤杂志

Objective: To investigate the clinicopathological characteristics of superior mediastinal lymph node metastases (sMLNM) in medullary thyroid carcinoma (MTC). Methods: This retrospective analysis enrolled the patients who were treated for sMLNM of MTC in our hospital from May 2012 to January 2021. All patients were suspected of sMLNM due to preoperative imaging. According to the pathological results, the patients were divided into two groups named sMLNM group and the negative superior-mediastinal-lymph-node group. We collected and analyzed the clinical features, pathological features, pre- and post-operative calcitonin (Ctn), and carcinoembryonic antigen (CEA) levels of the two groups. Logistic regression analysis was used to analyze risk factors, and receiver operation characteristic (ROC) curves were drawn to determine the optimal cut-off values of preoperative Ctn and preoperative CEA for predicting sMLNM. Results: Among the 94 patients, 69 cases were in the sMLNM group and 25 cases were in the non-SMLNM group. Preoperative Ctn level (P=0.003), preoperative CEA level (P=0.010), distant metastasis (P=0.022), extracapsular lymph node invasion (P=0.013), the number of central lymph node metastases (P=0.002) were related to sMLNM, but the multivariate analysis did not find any independent risk factors. The optimal threshold for predicting sMLNM by pre-operative Ctn is 1500 pg/ml and AUC is 0.759 (95% CI: 0.646, 0.872). The sensitivity, specificity, positive predictive value, and negative predictive value of diagnosis are 61.2%, 77.3%, 89.1%, 39.5%, respectively. In patients who underwent mediastinal lymph node dissection through transsternal approach, the metastatic possibility of different levels from high to low were level 2R (82.3%, 28/34), level 2L (58.8%, 20/34), level 4R (58.8%, 20/34), level 3 (23.5%, 8/34), level 4L (11.8%, 4/34). Postoperative complications occurred in 41 cases (43.6%), and there was no perioperative death in all cases. 14.8% (12/81) of the patients achieved biochemical complete response (Ctn≤12 pg/ml) one month after surgery, 5 of these patients were in sMLNM group. Conclusions: For patients who have highly suspicious sMLNM through imaging, combining with preoperative Ctn diagnosis can improve the accuracy of diagnosis, especially for patients with preoperative Ctn over 1 500 pg/ml. The superior mediastinal lymph node dissection for the primary sternotomy should include at least the superior mediastinal levels 2-4 to avoid residual lesions. The strategy of surgery needs to be cautiously performed. Although the probability of biochemical cure in sMLNM cases is low, nearly 40% of patients can still benefit from the operation at the biochemical level.

Cholinergic dysfunction-induced insufficient activation of alpha7 nicotinic acetylcholine receptor drives the development of rheumatoid arthritis through promoting protein citrullination via the SP3/PAD4 pathway

Both cholinergic dysfunction and protein citrullination are the hallmarks of rheumatoid arthritis (RA), but the relationship between the two phenomena remains unclear. We explored whether and how cholinergic dysfunction accelerates protein citrullination and consequently drives the development of RA. Cholinergic function and protein citrullination levels in patients with RA and collagen-induced arthritis (CIA) mice were collected. In both neuron-macrophage coculture system and CIA mice, the effect of cholinergic dysfunction on protein citrullination and expression of peptidylarginine deiminases (PADs) was assessed by immunofluorescence. The key transcription factors for PAD4 expression were predicted and validated. Cholinergic dysfunction in the patients with RA and CIA mice negatively correlated with the degree of protein citrullination in synovial tissues. The cholinergic or alpha7 nicotinic acetylcholine receptor (α7nAChR) deactivation and activation resulted in the promotion and reduction of protein citrullination in vitro and in vivo, respectively. Especially, the activation deficiency of α7nAChR induced the earlier onset and aggravation of CIA. Furthermore, deactivation of α7nAChR increased the expression of PAD4 and specificity protein-3 (SP3) in vitro and in vivo. Our results suggest that cholinergic dysfunction-induced deficient α7nAChR activation, which induces the expression of SP3 and its downstream molecule PAD4, accelerating protein citrullination and the development of RA.

Clinical study of using basement membrane biological products in pelvic floor reconstruction during pelvic exenteration / 中华胃肠外科杂志

Objective: To investigate the value of reconstruction of pelvic floor with biological products to prevent and treat empty pelvic syndrome after pelvic exenteration (PE) for locally advanced or recurrent rectal cancer. Methods: This was a descriptive study of data of 56 patients with locally advanced or locally recurrent rectal cancer without or with limited extra-pelvic metastases who had undergone PE and pelvic floor reconstruction using basement membrane biologic products to separate the abdominal and pelvic cavities in the Department of Anorectal Surgery of the Second Affiliated Hospital of Naval Military Medical University from November 2021 to May 2022. The extent of surgery was divided into two categories: mainly inside the pelvis (41 patients) and including pelvic wall resection (15 patients). In all procedures, basement membrane biologic products were used to reconstruct the pelvic floor and separate the abdominal and pelvic cavities. The procedures included a transperitoneal approach, in which biologic products were used to cover the retroperitoneal defect and the pelvic entrance from the Treitz ligament to the sacral promontory and sutured to the lateral peritoneum, the peritoneal margin of the retained organs in the anterior pelvis, or the pubic arch and pubic symphysis; and a sacrococcygeal approach in which biologic products were used to reconstruct the defect in the pelvic muscle-sacral plane. Variables assessed included patients' baseline information (including sex, age, history of preoperative radiotherapy, recurrence or primary, and extra-pelvic metastases), surgery-related variables (including extent of organ resection, operative time, intraoperative bleeding, and tissue restoration), post-operative recovery (time to recovery of bowel function and time to recovery from empty pelvic syndrome), complications, and findings on follow-up. Postoperative complications were graded using the Clavien-Dindo classification. Results: The median age of the 41 patients whose surgery was mainly inside the pelvis was 57 (31-82) years. The patients comprised 25 men and 16 women. Of these 41 patients, 23 had locally advanced disease and 18 had locally recurrent disease; 32 had a history of chemotherapy/immunotherapy/targeted therapy and 24 of radiation therapy. Among these patients, the median operative time, median intraoperative bleeding, median time to recovery of bowel function, and median time to resolution of empty pelvic syndrome were 440 (240-1020) minutes, 650 (200-4000) ml, 3 (1-9) days, and 14 (5-105) days, respectively. As for postoperative complications, 37 patients had Clavien-Dindo < grade III and four had ≥ grade III complications. One patient died of multiple organ failure 7 days after surgery, two underwent second surgeries because of massive bleeding from their pelvic floor wounds, and one was successfully resuscitated from respiratory failure. In contrast, the median age of the 15 patients whose procedure included combined pelvic and pelvic wall resection was 61 (43-76) years, they comprised eight men and seven women, four had locally advanced disease and 11 had locally recurrent disease. All had a history of chemotherapy/ immunotherapy and 13 had a history of radiation therapy. The median operative time, median intraoperative bleeding, median time to recovery of bowel function, and median time to relief of empty pelvic syndrome were 600 (360-960) minutes, 1600 (400-4000) ml, 3 (2-7) days, and 68 (7-120) days, respectively, in this subgroup of patients. Twelve of these patients had Clavien-Dindo < grade III and three had ≥ grade III postoperative complications. Follow-up was until 31 October 2022 or death; the median follow-up time was 9 (5-12) months. One patient in this group died 3 months after surgery because of rapid tumor progression. The remaining 54 patients have survived to date and no local recurrences have been detected at the surgical site. Conclusion: The use of basement membrane biologic products for pelvic floor reconstruction and separation of the abdominal and pelvic cavities during PE for locally advanced or recurrent rectal cancer is safe, effective, and feasible. It improves the perioperative safety of PE and warrants more implementation.

Surgical skills and precautions of pelvic exenteration combined with pelvic wall resection / 中华胃肠外科杂志

The treatment of locally advanced rectal cancer (LARC) or locally recurrent rectal cancer (LRRC) has been a difficulty and challenge in the field of advanced rectal cancer, while pelvic exenteration (PE), as an important way to potentially achieve radical treatment of LARC and LRRC, has been shown to significantly improve the long-term prognosis of patients. The implementation of PE surgery requires precise assessment of the extent of invasion of LARC or LRRC and adequate preoperative preparation through multidisciplinary consultation before surgery. The lateral pelvis involves numerous tissues, blood vessels, and nerves, and resection is most difficult, and the ureteral and Marcille triangle approaches are recommended; while the supine transabdominal approach combined with intraoperative change to the prone jacket position facilitates adequate exposure of the surgical field and enables precise overall resection of the bony pelvis and pelvic floor muscle groups invaded by the tumor. Empty pelvic syndrome has always been an major problem to be solved during PE. The application of extracellular matrix biological mesh to reconstruct pelvic floor defects and isolate the abdominopelvic cavity is expected to reduce postoperative pelvic floor related complications. Reconstruction of the urinary system and important vessels after PE is essential, and the selection of appropriate reconstruction methods helps to improve the patient's postoperative quality of life, while more new methods are also being continuously explored.

Review of Modern TCM Oncology Academic Thought / 肿瘤防治研究

With the establishment of modern traditional Chinese medicine (TCM) as an oncology discipline, it has made great development and progress in the prevention and treatment of tumors. As a result, a number of academic thoughts and viewpoints have emerged. In the tumor field of TCM, the current representative theories include the theory of strengthening the body and treating cancer, the theory of treating from the membrane, the theory of surviving with tumor, the pathogenesis theory of cancer virus, the theory of consolidating the root and clearing the source, and the theory of regulating qi and detoxing. In TCM oncology, a large number of results have been achieved in the research of the thoughts of famous TCM doctors. However, discussions on these thoughts together are relatively few. This article summarizes and studies the above innovative theories from the aspects of academic connotation and clinical application to provide new ideas for further guiding the clinical practice of TCM oncology.

Comparative application of three methods for testing distance visual acuity among children / 中国学校卫生

Objective@#To understand the differences in the application of three distant vision examination methods in children, so as to provide a reference for developing a unified distant vision examination for this population.@*Methods@#The study involved 98 children aged 4 to 16 years who visited the ophthalmology department of a children s hospital in Anhui Province between August 15 and 25, 2022. Vision was measured using the distant vision test method specified in the 2014 National Student Physical Fitness and Health Survey (V1), the 2019 National Student Physical Fitness and Health Survey (V2), and Specification for Screening of Refractive Error in Primary and Secondary School Students (WS/T 663-2020) (V3). The paired samples McNemar s test and Wilcoxon test were performed to compare the detection rate of poor vision and the difference between the visual acuity test results of the three methods.@*Results@#The results of the 98 children examined according to V1, V2, and V3 showed that the M (P25, P 75 ) of the right eye were 4.8（4.6，5.0），4.8（4.7，5.0），and 4.8（4.7，5.0）while the left eye visual acuity M ( P 25 , P 75 ) were 4.8 （4.6，5.0），4.9（ 4.7 ，5.0），and 4.9（4.7，5.0），respectively. The rates of poor visual acuity detection for the right eye were 63.3%, 58.2% and 58.2 % for V1, V2, and V3, respectively, while for the left eye, they were 58.2%, 54.1% and 53.1%, respectively. McNemar test results showed that there were no statistically significant differences in the rates of poor visual acuity detection between the right and left eyes for V1 vs. V2, V1 vs. V3, and V2 vs. V3 (left eyes： χ 2=2.25，2.29，0.00，right eyes： χ 2=3.20，3.20，0.00， P >0.05).Wilcoxon test results indicated that there were statistically significant differences between the right and left eye visual acuity groups for V1 vs. V2 and V1 vs. V3 (left eyes： Z =-4.15，-4.60, right eyes： Z = -4.70，-4.99, P <0.01).@*Conclusion@#Irrespective of whether the starting visual standard starts at row 4.0 or 5.0, different standards of visual standard passage have an impact on the visual acuity results. It is recommended that existing methods of screening for distance vision are standardized.

Comparison of PBL and CBL combined with PCMC in standardized training of nurses in department of respiratory medicine / 中华医学教育探索杂志

Objective:To observe and compare the teaching effects of problem-based learning (PBL) and case-based learning (CBL) combined with problem-originated clinical medicine curriculum (PCMC) on standardized training of nurses in the department of respiratory medicine.Methods:Thirty-one standardized training nurses from the Department of Respiratory Medicine, Nanjing Hospital Affiliated to Nanjing Medical University/Nanjing First Hospital during April 2019 to March 2020 were taken as the control group, and CBL combined with PCMC was used for teaching. Another 31 nurses from April 2020 to March 2021 were taken as the observation group, using PBL combined with PCMC teaching. Both teaching period lasted for 3 months. The examination results, their work ability before and after training and their recognition of teaching methods were compared between the two groups. SPSS 25.0 was used for t test and chi-square test. Results:The scores of academic and practical evaluation were significantly higher in the observation group than the control group[(92.58±5.25) vs. (86.80±6.74); (90.05±6.27) vs. (85.64±7.23)]. After the training, the scores of leadership, clinical nursing, education and consultation, interpersonal relationship, legal and ethical practice, and professional development, critical thinking and scientific research and the total scores of working ability were significantly improved than before the training ( P<0.05), and the scores of the above dimensions of the observation group were significantly higher than those of the control group ( P<0.05). In addition, the observation group's recognition scores of teaching methods to clarify the learning focus, mobilize learning enthusiasm, broaden knowledge, enhance group collaboration, improve nurse-patient communication skills, cultivate critical thinking, and promote teacher-student communication were significantly higher than those of the control group ( P<0.05). Conclusion:The application of PCMC combined with PBL in the standardized training of nurses in the department of respiratory medicine not only helps to improve the assessment results, but also enhances their working ability and is recognized by them.

Inhibitory effect of RMT1-10-induced tolerogenic dendritic cells in vitro on high-risk corneal allograft rejection in mice and its mechanism / 中华实验眼科杂志

Objective:To investigate the inhibitory effect of RMT1-10-induced tolerogenic dendritic cells (Tol-DCs) in vitro on high-risk corneal allograft rejection in mice and its mechanism. Methods:One hundred SPF male BALB/c mice and fifty SPF male C57BL/6 mice were selected.Bone marrow-derived immature dendritic cells (imDCs) obtained from C57BL/6 mice were divided into imDCs group, mature dentritic cells (mDCs) group, RMT1-10 group, and IgG isotype control group.The imDCs in the four groups were cultured with no intervention, lipopolysaccharide, RMT1-10 and lipopolysaccharide, or IgG isotype antibody and lipopolysaccharide for 7 days according to grouping.The expression levels of different phenotypes of DCs including CD11c, CD80, CD86, major histocompatibility complex (MHC)-Ⅱ, T cell immunoglobulin and mucin domain containing molecule (Tim)-4 and CD103 in the four groups were detected by flow cytometry.The concentrations of interleukin-10 (IL-10) and transforming growth factor-β (TGF-β) in the DCs supernatants were determined by enzyme-linked immunosorbent assay.A mixed lymphocyte culture system was established, and the stimulation index (SI) of CD4 + T cell proliferation stimulated with DCs was detected by cell counting kit 8 method.Corneal neovascularization was induced by corneal stromal suture in BALB/c mice, and the 80 mice with neovascularization in 4 quadrants growing into the middle and peripheral cornea were used as recipients.The recipient mice were randomized into imDCs group, mDCs group, RMT1-10 group, and IgG isotype control group using the random number table method, with 20 mice in each group.An injection of corresponding DCs (1×10 6 cells/100 μl) was administered to the recipient mice via the tail vein according to grouping.At 7 days following the injection, C57BL/6 mice were used as donors and penetrating keratoplasty was performed.Within one month after the operation, signs of corneal grafts rejection, including opacity, edema and neovascularization, were observed by slit lamp biomicroscopy and scored every day.At 21 days after the operation, 5 recipients selected from each group were subcutaneously injected with naive C57BL/6 splenocytes (1×10 6 cells/100 μl) behind the ear.The delayed type hypersensitivity (DTH) was evaluated by ear swelling at 24 hours after the subcutaneous injection.The use and care of experimental animals complied with the Regulations on the Management of Experimental Animals promulgated by the State Science and Technology Commission.This study protocol was approved by an Ethics Committee of the Affiliated Hospital of Chengde Medical University (No.CYFYLL2020055). Results:Compared with mDCs group, the expressions of CD80, CD86 and MHC-Ⅱ, and the percentage of Tim-4-positive cells in CD11c-positive cells were significantly decreased in RMT1-10 group, showing statistically significant differences (all at P<0.001). The percentage of Tim-4-positive cells were significantly decreased in RMT1-10 group than imDCs group, and the percentage of CD103-positive cells in RMT1-10 group was significantly higher than imDCs group, mDCs group and IgG isotype control group (all at P<0.001). The concentrations of IL-10 and TGF-β in the cell culture supernatant of RMT1-10 group were significantly higher than those of the other three groups, with statistically significant differences (all at P<0.001). There were statistically significant differences in the SI of CD4 + T cell proliferation simulated by DCs ( Fgroup=1 833.00, P<0.001; Fratio=230.40, P<0.001; Finteraction=3.06, P=0.01). The SI of DCs/CD4 + T cells ratio at 1∶5, 1∶10, 1∶20 and 1∶40 were all significantly lower in imDCs group than mDCs group, and were all significantly lower in RMT1-10 group than imDCs group (all at P<0.05). There was a statistically significant difference in corneal graft survival curve among various groups ( χ2=77.69, P<0.001). The survival rate of RMT1-10 group was significantly higher than that of imDCs group ( χ2=9.74, P=0.002), and the survival rate of imDCs group was significantly higher than that of mDCs group ( χ2=31.02, P<0.001). The ear swelling of recipient mice of positive control group, mDCs group, IgG isotype control group, imDCs group and RMT1-10 group was (503.6±17.2), (475.7±17.6), (456.2±18.8), (225.2±39.4), (118.1±12.6), and (106.4±7.4) μm, with a statistically significant difference among them ( F=377.10, P<0.001). The mice ear swelling was more serious in positive control group than mDCs group, more serious in IgG isotype control group than imDCs group, and more serious in imDCs group than RMT1-10 group (all at P<0.05). Conclusions:RMT1-10 can inhibit the rejection of high-risk corneal transplantation in mice, the mechanism of which may be attributed to inducing imDCs to transform into Tol-DCs in vitro and up-regulating the expression of TGF-β and IL-10, which promotes antigen-specific immune tolerance after adoptive transfer, thereby indirectly prolongs the survival of corneal grafts.

Analysis on vaccination willingness and related factors of influenza, pneumonia, and herpes zoster vaccine among people over 50 years old in Minhang district of Shanghai / 中华预防医学杂志

Objective: To determine the knowledge of influenza, pneumonia, herpes zoster and related vaccines, willingness to vaccinate under multiple payment scenarios, and corresponding risk factors among people over 50 years old in Minhang District of Shanghai. Methods: A total of 1 672 respondents aged 50-69 from 13 communities/towns in Minhang district of Shanghai were included in this study using a stratified random sampling strategy on December 2020. The knowledge of influenza, pneumonia, herpes zoster and vaccines was investigated using a questionnaire, and the differences in the willingness under multiple payment scenarios were determined using chi-square test. The consistency in the willingness under multiple payment scenarios was compared using Cohen's Kappa and the risk factors of the willingness was determined using ordinal logistic regression. Results: The average age of 1 672 respondents was (60.48±5.96) years old, including 777 (46.47%) males and 895 (53.53%) females. A total of 1 350 subjects (80.74%) had local household registration in Shanghai. The proportion of the willingness to vaccinate for themselves, spouses, and parents under any payment scenario was determined to be 80.6% (influenza vaccine), 81.5% (pneumonia vaccine), and 74.0% (herpes zoster vaccine). The willingness to vaccinate against influenza and pneumonia under multiple payment scenarios remained stable (Kappa value ≥0.6), while that against herpes zoster infection was inconsistent (Kappa value ≤0.35). Logistic regression analysis showed that respondents who had higher knowledge of influenza and influenza vaccine [OR (95%CI): 1.111 (1.054-1.170), 1.182 (1.126-1.240), respectively], aged 50-59 [1.305 (1.085-1.531)] and local household registration in Shanghai [1.372 (1.079-1.721)] had higher willingness to vaccinate against influenza, while males had lower willingness [0.733 (0.551-0.910)]. Respondents who had higher knowledge of pneumonia and pneumonia vaccine [OR (95%CI): 1.837 (1.152-2.517), 2.217 (1.541-2.893), respectively] had higher willingness to receive pneumonia vaccine. Respondents aged 50-59 [1.327 (1.059-1.537)] and with local household registration in Shanghai [2.497 (1.417-4.400)] were more likely to be vaccinated against herpes zoster, while those with middle school degree or below [0.664 (0.396-0.992)] and high school degree [0.559 (0.324-0.964)] were less likely to be vaccinated. Conclusion: Among people aged over 50 years old in Minhang district of Shanghai, the willingness to vaccinate for themselves, spouses, and parents against influenza, pneumonia and herpes zoster infection is quite different under multiple payment scenarios, especially for herpes zoster vaccine.

Prescription Patterns for Bipolar Disorder in Asian Countries:Findings from Research on Asian Prescription Pattern-Bipolar Disorder

Objective@#Pharmacotherapy including mood stabilizers and antipsychotics are frequently used in bipolar disorder (BD); however, the lack of consensus regarding the definition of polypharmacy hinders conducting comparative studies across different settings and countries. Research on Asian Prescription Pattern (REAP) is the largest and the longest lasting international collaborative research in psychiatry in Asia. The objective of REAP BD was to investigate the prescription patterns of psychotropic medications across Asian countries. The rates of polypharmacy and psychotropic drug load were also analyzed. @*Methods@#The data collection was web-based. Prescription patterns were categorized as (1) mood stabilizer monotherapy: one mood stabilizer; (2) antipsychotic monotherapy: one antipsychotic; (3) simple polypharmacy: one mood stabilizer and one antipsychotic; and (4) complex polypharmacy: ≥ 2 mood stabilizers or/and antipsychotics. The psychotropic drug load in each patient was calculated using the defined daily dose method. @*Results@#Among 2003 patients with BD (52.1% female, 42.4 years) from 12 countries, 1,619 (80.8%) patients received mood stabilizers, 1,644 (82.14%) received antipsychotics, and 424 (21.2%) received antidepressants, with 14.7% mood stabilizer monotherapy, 13.4% antipsychotic monotherapy, 48.9% simple polypharmacy, 20.3% complex polypharmacy, and 2.6% other therapy. The average psychotropic drug load was 2.05 ± 1.40. Results varied widely between countries. @*Conclusion@#Over 70% of psychotropic regimens involved polypharmacy, which accords with the high prevalence of polypharmacy in BD under a permissive criterion (2 or more core psychotropic drugs) worldwide. Notably, ≥ 80% of our sample received antipsychotics, which may indicate an increasing trend in antipsychotic use for BD treatment.

Real-world study on the efficacy and prognostic predictive biomarker of patients with metastatic non-small cell lung cancer treated with programmed death-1/programmed death ligand 1 inhibitors / 中华肿瘤杂志

Objective: To describe the actual efficacy of programmed death-1 (PD-1)/ programmed-death ligand 1 (PD-L1) inhibitors in patients with metastatic non-small cell lung cancer (NSCLC) and explore potential prognostic predictive biomarkers. Methods: Patients with metastatic NSCLC who were treated with PD-1/PD-L1 inhibitors at Cancer Hospital, Chinese Academy of Medical Sciences from January 2016 to December 2019, either as monotherapy or in combination with other agents, were consecutively enrolled into this study. We retrospectively collected the data of demographics, clinical information and pathologic assessment to evaluate the therapeutic efficacy and conduct the survival analysis. Major endpoint of our study is progression-free survival (PFS). Secondary endpoints include objective response rate (ORR), disease control rate (DCR) and overall survival (OS). Results: The ORR of 174 patients who underwent PD-1/PD-L1 inhibitor was 28.7%, and the DCR was 79.3%. Immune-related adverse events (irAEs) occurred in 23 patients (13.2%). Brain metastasis, line of treatment, and treatment patterns were associated with the ORR of metastatic NSCLC patients who underwent immunotherapy (P<0.05). After a median follow-up duration of 18.8 months, the median PFS was 10.5 months (ranged from 1.5 to 40.8 months) while the median OS was not reached. The 2-year survival rate was estimated to be 63.0%. The pathologic type was related with the PFS of metastatic NSCLC patients who underwent immunotherapy (P=0.028). Sex, age, brain metastasis and autoimmune diseases were associated with OS (P<0.05). Analysis of the receptor characteristic curve (ROC) of neutrophil/lymphocyte ratio (NLR) predicting ORR of immunotherapy in metastatic NSCLC showed that the areas under the curve of NLR before immunotherapy (NLR(C0)), NLR after one cycle of immunotherapy (NLR(C1)) and ΔNLR were 0.600, 0.706 and 0.628, respectively. Multivariate logistic regression analysis showed that NLR(C1) was an independent factor of the ORR of metastatic NSCLC patients who underwent immunotherapy (OR=0.161, 95% CI: 0.062-0.422), and the efficacy of combination therapy was better than that of single agent (OR=0.395, 95% CI: 0.174-0.896). The immunotherapy efficacy in patients without brain metastasis was better than those with metastasis (OR=0.291, 95% CI: 0.095-0.887). Multivariate Cox regression analysis showed that NLR(C1) was an independent influencing factor of PFS of metastatic NSCLC patients after immunotherapy (HR=0.480, 95% CI: 0.303-0.759). Sex (HR=0.399, 95% CI: 0.161-0.991, P=0.048), age (HR=0.356, 95% CI: 0.170-0.745, P=0.006) were independent influencing factors of OS of metastatic NSCLC patients after immunotherapy. Conclusions: PD-1/PD-L1 inhibitors are proved to be efficacious and have tolerable toxicities for patients with metastatic NSCLC. Patients at advanced age could still benefit from immunotherapy. Brain metastasis is related to compromised response. Earlier application of immunotherapy in combination with other modalities enhances the efficacy without elevating risk of irAEs. NLR(C1) is an early predictor of clinical outcome. The OS of patients younger than 75 years may be improved when treated with immunotherapy.

The role and mechanism of SIRT1 gene in depression / 生理学报

As a kind of mental illness, depression produces great difficulties in clinical diagnosis and treatment, and has a high disability rate. It is urgent to clarify the mechanism of depression to find potential therapeutic targets and effective clinical treatment methods. As a deacetylase, silent mating type information regulator 2 homolog 1 (SIRT1) is involved in many biological processes such as cell aging, cancer, and cardiovascular disease. In recent years, more and more studies have found that SIRT1 gene plays an important role in the pathogenesis of depression, but the mechanism is still unclear. Therefore, this review mainly summarizes the relevant research progress on the role and mechanism of SIRT1 gene in the hippocampus, prefrontal cortex, amygdala, hypothalamic suprachiasmatic nucleus, and nucleus accumbens in depression, in order to provide new ideas for exploring the mechanism and prevention of depression.

A Call for a Rational Polypharmacy Policy: International Insights From Psychiatrists

Objective@#Recently, rational polypharmacy approaches have been proposed, regardless of the lower risk and cost of monotherapy. Considering monotherapy as first-line treatment and polypharmacy as rational treatment, a balanced attitude toward polypharmacy is recommended. However, the high prevalence of polypharmacy led the Japanese government to establish a polypharmacy reduction policy. Based on this, the association between the policy and psychiatrists’ attitude toward polypharmacy has been under debate. @*Methods@#We developed an original questionnaire about Psychiatrists’ attitudes toward polypharmacy (PAP). We compared the PAP scores with the treatment decision-making in clinical case vignettes. Multiple regression analyses were performed to quantify associations of explanatory variables including policy factors and PAP scores. The anonymous questionnaires were administered to psychiatrists worldwide. @*Results@#The study included 347 psychiatrists from 34 countries. Decision-making toward polypharmacy was associated with high PAP scores. Multiple regression analysis revealed that low PAP scores were associated with the policy factor (β=-0.20, p=0.004). The culture in Korea was associated with high PAP scores (β=0.34, p<0.001), whereas the culture in India and Nepal were associated with low scores (β=-0.15, p=0.01, and β=-0.17, p=0.006, respectively). @*Conclusion@#Policy on polypharmacy may influence psychiatrists’ decision-making. Thus, policies considering rational polypharmacy should be established.

Biological mesh versus primary closure for pelvic floor reconstruction following extralevator abdominoperineal excision: a meta-analysis / 中华胃肠外科杂志

Objective: To compare the morbidity of perineum-related complication between biological mesh and primary closure in closing pelvic floor defects following extralevator abdominoperineal excision (ELAPE). Methods: A literature search was performed in PubMed, Embase, Cochrane Library, Web of Science, Wanfang database, Chinese National Knowledge Infrastructure, VIP database, and China Biological Medicine database for published clinical researches on perineum-related complications following ELAPE between January 2007 and August 2020. Literature inclusion criteria: (1) study subjects: patients undergoing ELAPE with rectal cancers confirmed by colonoscopy pathological biopsy or surgical pathology; (2) study types: randomized controlled studies or observational studies comparing the postoperative perineum-related complications between the two groups (primary perineal closure and reconstruction with a biological mesh) following ELAPE; (3) intervention measures: biological mesh reconstruction used as the treatment group, and primary closure used as the control group; (4) outcome measures: the included literatures should at least include one of the following postoperative perineal complications: overall perineal wound complications, perineal wound infection, perineal wound dehiscence, perineal hernia, chronic sinus, chronic perineal pain (postoperative 12-month), urinary dysfunction and sexual dysfunction. Literature exclusion criteria: (1) data published repeatedly; (2) study with incomplete or wrong original data and unable to obtain original data. Two reviewers independently performed screening, data extraction and assessment on the quality of included studies. Review Manager 5.3 software was used for meta-analysis. The mobidities of perineum-related complications, including overall perineal wound (infection, dehiscence, hernia, chronic sinus) and perineal chronic pain (postoperative 12-month), were compared between the two pelvic floor reconstruction methods. Finally, publication bias was assessed, and sensitivity analysis was used to evaluate the stability of the results. Results: A total of five studies, including two randomized controlled studies and three observational controlled studies, with 650 patients (399 cases in the biological mesh group and 251 cases in primary closure group) were finally included. Compared with primary closure, biological mesh reconstruction had significantly lower ratio of perineal hernia (RR=0.37, 95%CI: 0.21-0.64, P<0.001). No significant differences in ratios of overall perineal wound complication, perineal wound infection, perineal wound dehiscence, perineal chronic sinus and perineal chronic pain (postoperative 12-month) were found between the two groups (all P>0.05). Conclusion: Compared with primary closure, pelvic floor reconstruction following ELAPE with biological mesh has the advantage of a lower incidence of perineal hernia.

Value of amplitude-integrated electroencephalogram combined with quantitative indices of cranial magnetic resonance imaging in predicting short-term neurodevelopment in moderately and late preterm infants: a prospective study / 中国当代儿科杂志

OBJECTIVES@#To study the association of amplitude-integrated electroencephalogram (aEEG) and the quantitative indices biparietal width (BPW) and interhemispheric distance (IHD) of cranial magnetic resonance imaging (cMRI) with short-term neurodevelopment in moderately and late preterm infants.@*METHODS@#A total of 104 moderately and late preterm infants who were admitted to the neonatal intensive care unit from September 2018 to April 2020 were selected as the subjects for this prospective study. The Naqeeb method and sleep-wake cycling (SWC) were used for aEEG assessment within 72 hours after birth. cMRI was performed at the corrected gestational age of 37 weeks. BPW and IHD were measured at the T2 coronal position. At the corrected age of 6 months, the Developmental Screening Test for Child Under Six (DST) was used to follow up neurodevelopment. According to developmental quotient (DQ), the infants were divided into a normal DST group (78 infants with DQ≥85) and an abnormal DST group (26 infants with DQ<85). Related indices were compared between the two groups. The association between aEEG and cMRI was evaluated.@*RESULTS@#Compared with the normal DST group, the abnormal DST group had significantly lower aEEG normal rate and SWC maturation rate (@*CONCLUSIONS@#For moderately and late preterm infants, aEEG within 72 hours after birth and the quantitative indices BPW and IHD of cMRI at the corrected gestational age of 37 weeks may affect their neurodevelopmental outcome at the corrected age of 6 months.

Which risk factors are associated with stomal recurrence after total laryngectomy for laryngeal cancer? A meta-analysis of the last 30 years / Quais fatores de risco estão associados à recorrência estomal após laringectomia total para câncer de laringe? Uma meta-análise dos últimos 30 anos

Abstract Introduction Stomal recurrence is a troublesome complication after total laryngectomy. Despite a large number of studies having been performed, there is still controversy about which risk factors are most significant for the development of stomal recurrence. Objective The objective of the present meta-analysis was to analyze the potential factors leading to stomal recurrence after total laryngectomy. Methods PubMed, Web of Science, Cochrane Library, and Ovid databases were systematically searched using multiple search terms. Eighteen studies with 6462 patients were identified. The quality of evidence was assessed by The National Institute for Health and Clinical Excellence. Results The results showed that, tumor subsite (supraglottic vs. subglottic, RR = 0.292, 95% CI 0.142-0.600, p = 0.001; glottic vs. subglottic, RR = 0.344, 95% CI 0.175-0.676, p = 0.002), T stage (RR = 0.461, 95% CI 0.286-0.742, p = 0.001), preoperative tracheotomy (RR = 1.959, 95% CI 1.500-2.558, p < 0.001) were the high-risk factors associated with the development of stomal recurrence. Conclusion From the results of our study, tumor subsite, T stage and preoperative tracheotomy were the significant risk factors for stomal recurrence. Methodologically high-quality comparative investigations are needed for further evaluation.

Resumo Introdução A recorrência estomal pós-laringectomia total e é uma complicação de difícil manejo. Apesar de um grande número de estudos ter sido feito, ainda há controvérsias sobre quais fatores de risco são mais significativos para o seu desenvolvimento. Objetivo O objetivo da presente meta-análise foi analisar os fatores potenciais para recorrência estomal após a laringectomia total. Método As bases de dados PubMed, Web of Science, Cochrane Library e Ovid foram sistematicamente pesquisadas com vários termos de busca. Dezoito estudos com 6.462 pacientes foram identificados. A qualidade da evidência foi avaliada pelo National Institute for Health and Clinical Excellence. Resultados Os resultados mostraram que o subsítio tumoral (supraglótico vs. subglótico, RR = 0,292, IC 95% 0,142 ± 0,600, p = 0,001; glótico vs. subglótico, RR = 0,344, IC 95% 0,175 ± 0,676, p = 0,002), estágio T (RR = 0,461, IC 95% 0,286 ± 0,742, p = 0,001), traqueotomia pré-operatória (RR = 1,959, IC 95% 1.500 ± 2.558, p < 0,001) foram os fatores de alto risco associados ao desenvolvimento de recorrência estomal. Conclusão Com base nos resultados de nosso estudo, o subsítio do tumor, o estágio T e a traqueotomia pré-operatória foram fatores de risco significativos para recorrência estomal. São necessárias investigações comparativas metodologicamente de alta qualidade para maior avaliação.

Drying temperature affects rice seed vigor via gibberellin, abscisic acid, and antioxidant enzyme metabolism / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Seed vigor is a key factor affecting seed quality. The mechanical drying process exerts a significant influence on rice seed vigor. The initial moisture content (IMC) and drying temperature are considered the main factors affecting rice seed vigor through mechanical drying. This study aimed to determine the optimum drying temperature for rice seeds according to the IMC, and elucidate the mechanisms mediating the effects of drying temperature and IMC on seed vigor. Rice seeds with three different IMCs (20%, 25%, and 30%) were dried to the target moisture content (14%) at four different drying temperatures. The results showed that the drying temperature and IMC had significant effects on the drying performance and vigor of the rice seeds. The upper limits of drying temperature for rice seeds with 20%, 25%, and 30% IMCs were 45, 42, and 38 °C, respectively. The drying rate and seed temperature increased significantly with increasing drying temperature. The drying temperature, drying rate, and seed temperature showed extremely significant negative correlations with germination energy (GE), germination rate, germination index (GI), and vigor index (VI). A high IMC and drying temperature probably induced a massive accumulation of hydrogen peroxide (H2O2) and superoxide anions in the seeds, enhanced superoxide dismutase (SOD) and catalase (CAT) activity, and increased the abscisic acid (ABA) content. In the early stage of seed germination, the IMC and drying temperature regulated seed germination through the metabolism of H2O2, gibberellin acid (GA), ABA, and α-amylase. These results indicate that the metabolism of reactive oxygen species (ROS), antioxidant enzymes, GA, ABA, and α-amylase might be involved in the mediation of the effects of drying temperature on seed vigor. The results of this study provide a theoretical basis and technical guidance for the mechanical drying of rice seeds.

Long-term efficacy of bioprosthetic anal fistula plug in the treatment of transsphincteric anal fistula / 中华胃肠外科杂志

Objective@#To evaluate the long-term healing rate of transsphincteric anal fistula treated with anal fistula plug procedure and the risk factors affecting the healing of anal fistula.@*Methods@#A retrospective case-control study was conducted to analyze the clinical data of 207 patients with transsphincteric anal fistulas who received anal fistula plug procedure at the Department of General Surgery, Beijing Chaoyang Hospital of Capital Medical University from August 2008 to September 2012. Inclusion criteria: (1) consistent with the diagnosis of transsphincteric anal fistula: the anal fistula passed through the internal and external sphincter; (2) complete data; (3) initial treatment with anal fistula plug procedure. Exclusion criteria: (1) acute rectal or perianal infection or poorly controlled focal infection; (2) recent incision and drainage of perianal abscess or spontaneous rupture of abscess; (3) patients with malignant tumor; (4) patients with Crohn′s disease or ulcerative colitis; (5) patients with heart, liver, brain, lung or renal insufficiency; (6) cachexia due to various chronic wasting diseases; (7) patients could not tolerate surgery. Patients were followed up for anal fistula healing. The cumulative healing rate of patients with transsphincteric anal fistula was plotted using the Kaplan-Meier method, and the factors affecting anal fistula healing were explored by univariate and multivariate logistic regression analysis.@*Results@#There were 186 males and 21 females with age of 15 to 69 (mean 38) years. The duration of anal fistula was 3-60 (mean 15) months. Three patients had a history of previous episodes of perianal abscess and underwent incision and drainage of perianal abscess (all more than 3 months). During follow-up ending on October 31, 2018, 72 patients (34.8%) were lost to follow-up. Among 135 patients who were successfully followed up, the average follow-up period was 96 (75-124) months. Seventy-five patients had anal fistula healing, with healing rate of 55.6%. Kaplan-Meier survival curve showed that the healing time of anal fistula was prolonged and finally stabilized at 55.6%. In the patients who failed initial treatment with anal fistula plug packing, there were 6 cases whose anal fistula healed spontaneously without other treatment. Among them, 3 cases healed spontaneously 2 years and 3 cases 3 years after operation without recurrence. From 2008 to 2012, the annual healing rates of anal fistula plug treatment were 3/6, 61.5% (24/39), 42.1% (24/57), 12/15 and 12/18, respectively. Multivariate logistic regression analysis showed that the duration of anal fistula≥6 months (OR=3.187, 95% CI: 1.361-7.466, P=0.008) was an independent risk factor for anal fistula healing after treatment with anal fistula plug.@*Conclusion@#The long-term efficacy of anal fistula plug procedure in the treatment of transsphincteric anal fistula is positive, and this procedure should be implemented as soon as possible.

Techniques enhancement for tissue expander/implant two-stage breast reconstruction / 北京大学学报(医学版)

OBJECTIVE@#To investigate the outcomes of breast reconstruction with employing improved techniques throughout the tissue expander/implant two-stage breast reconstructed process, which involved the tissue expander placement, the saline filling intraoperatively and postoperatively, the implant selection, and the permanent implant replacement.@*METHODS@#In this study, 68 patients who had been provided immediate or delayed tissue expander/implant two-stage breast reconstruction with autologous fat injection post-mastectomy in Peking University Third Hospital from April 2014 to September 2018 were involved, and the relevant information was analyzed retrospectively. The enhancements of the techniques, involving the incision selection, the expander placement, the principle of expansion, the management of capsule, the prosthesis selection, and the assisted reconstruction method were summarized, and the reconstruction outcomes were evaluated objectively through three-dimensional surface imaging.@*RESULTS@#Among the 68 patients in this study, immediate reconstruction was conducted in 25 patients and 43 patients underwent delayed reconstruction. The median time of tissue expansion was 7.0 (3.0, 20.0) months, and the average volume of expansion was (372.8±87.2) mL. The median size of breast implant was 215 (100, 395) mL. The median number of injections for fat grafting was 1 (1, 3), and the average volume of fat grafting was (119.3±34.1) mL. The median follow-up time was 7.0 (4.0, 24.0) months. During the process of breast reconstruction, the tissue expander leakage was observed in two patients, and one of them underwent expander replacement due to the secondary infection. In the immediate reconstruction cases, the volume symmetry of bilateral breasts after reconstruction got even better than that before mastectomy (t=4.465, P<0.01). And in the delayed reconstruction cases, the volume between bilateral breasts also achieved good symmetry after reconstruction (t=0.867, P>0.1).@*CONCLUSION@#Good results of tissue expander/implant two-stage breast reconstruction could be achieved through the techniques enhancement, which involved the preferred transverse incision, the downward placement of expander, the rapid expansion of chest soft tissue, the release of capsule tension, the application of sizer in prosthesis selection, and the assisted autologous fat grafting.