Pathophysiological roles of thrombospondin-4 in disease development.

Thrombospondin-4 (TSP-4) belongs to the extracellular matrix glycoprotein family of thrombospondins (TSPs). The multidomain, pentameric structure of TSP-4 allows its interactions with numerous extracellular matrix components, proteins and signaling molecules that enable its modulation to various physiological and pathological processes. Characterization of TSP-4 expression under development and pathogenesis of disorders has yielded important insights into mechanisms underlying the unique role of TSP-4 in mediating various processes including cell-cell, cell-extracellular matrix interactions, cell migration, proliferation, tissue remodeling, angiogenesis, and synaptogenesis. Maladaptation of these processes in response to pathological insults and stress can accelerate the development of disorders including skeletal dysplasia, osteoporosis, degenerative joint disease, cardiovascular diseases, tumor progression/metastasis and neurological disorders. Overall, the diverse functions of TSP-4 suggest that it may be a potential marker or therapeutic target for prognosis, diagnosis, and treatment of various pathological conditions upon further investigations. This review article highlights recent findings on the role of TSP-4 in both physiological and pathological conditions with a focus on what sets it apart from other TSPs.

Gabapentin receptor alpha2delta-1 is a neuronal thrombospondin receptor responsible for excitatory CNS synaptogenesis.

Synapses are asymmetric cellular adhesions that are critical for nervous system development and function, but the mechanisms that induce their formation are not well understood. We have previously identified thrombospondin as an astrocyte-secreted protein that promotes central nervous system (CNS) synaptogenesis. Here, we identify the neuronal thrombospondin receptor involved in CNS synapse formation as alpha2delta-1, the receptor for the anti-epileptic and analgesic drug gabapentin. We show that the VWF-A domain of alpha2delta-1 interacts with the epidermal growth factor-like repeats common to all thrombospondins. alpha2delta-1 overexpression increases synaptogenesis in vitro and in vivo and is required postsynaptically for thrombospondin- and astrocyte-induced synapse formation in vitro. Gabapentin antagonizes thrombospondin binding to alpha2delta-1 and powerfully inhibits excitatory synapse formation in vitro and in vivo. These findings identify alpha2delta-1 as a receptor involved in excitatory synapse formation and suggest that gabapentin may function therapeutically by blocking new synapse formation.

Benefits and challenges of 18F-FDG PET/CT in patients with Takayasu arteritis.

AIM: To evaluate the diagnostic performance of 2-[18F]-fluoro-2-deoxy-d-glucose (18F-FDG) positron-emission tomography (PET)/computed tomography (CT) in TA diagnosis and Takayasu arteritis (TA) activity assessment. MATERIALS AND METHODS: This retrospective study included patients with TA diagnosed according to the American College of Rheumatology (ACR) criteria and undergoing 18F-FDG PET/CT imaging from October 2010 to July 2022. TA activity was assessed through 18F-FDG PET/CT (maximum standard uptake value [SUVmax], vascular SUVmax/mean standard uptake value [SUVmean] of liver (SUV ratio), and PET vascular activity score [PETVAS]) using physician global assessment (PGA) as the reference standard, and the results of these assessments were compared against the clinical activity scores (National Institutes of Health [NIH] and Indian Aortitis Disease Activity [ITAS-A] scores), acute-phase reactants (APR), and white blood cell and platelet counts. RESULTS: Twenty 18F-FDG PET/CT examinations from 19 patients were included in the study, nine were performed in the active phase and 11 in the inactive phase. The involved vessels showed segmental and tubular FDG uptake in the active group. The average SUVmax, SUV ratio, and PETVAS was 6.3 ± 2.7 (range 3.4-12), 4.2 ± 1.7 (range 2.1-7.5), and 22.7 ± 11.2 (range 6-39), respectively, in the active group and 1.7 ± 0.9 (0.9-3.1), 1.1 ± 0.6 (range 0.6-2.4), and 3.5 ± 5.5 (range 0-18), respectively, in the inactive group. The sensitivity, specificity of SUVmax, SUV ratio, and PETVAS for TA activity assessment were 100%, 100%; 100%, 90.9%; and 88.9, 90.9%, respectively. After ROC curve analysis, a new SUVmax cut-off was obtained. Based on the new cut-off value, SUVmax 3.3 and SUV ratio 1.9 had a more perfect assessment performance. CONCLUSION: 18F-FDG PET/CT is an alternative imaging technique for TA.

[Initial experience of transcatheter edge-to-edge repair guided by only transesophageal echocardiography in the treatment of tricuspid insufficiency].

Objective: To evaluate the feasibility and safety of transcatheter tricuspid valve edge-to-edge repair guided by only transesophageal echocardiography (TEE). Methods: Patients with severe tricuspid regurgitation in Fuwai Yunnan Cardiovascular Hospital who met the inclusion criteria based on clinical and echocardiographic evaluationand underwent transcatheter tricuspid valve edge-to-edge repair between January 2022 and May 2023 were prospectively enrolled. The procedure was performed under general anesthesia with endotracheal intubation and solely guided by TEE. The patients underwent clinical evaluation, electrocardiogram and transthoracic echocardiography one month after the procedure. Results: A total of 22 patients (12 males and 10 females) were included, with an average age of (71.3±6.7) years. All 22 patients successfully underwent the transcatheter tricuspid valve edge-to-edge repair under TEE guidance, with an average of (1.5±0.6) clips implanted. Immediately after procedure, six patients had no or trace regurgitation, 15 patients had mild regurgitation, and one patient had moderate regurgitation. All 22 patients completed 30-day follow-up, with four patients having trace regurgitation, 17 patients having mild regurgitation, and one patient having moderate regurgitation. Echocardiographic measurements revealed that effective regurgitant orifice area, regurgitant volume, vena contracta width, and proximal isovelocity surface area radius significantly decreased after the procedure (all P<0.05). In addition, inferior vena cava width, right atrial volume, tricuspid annular diameter, and right ventricular end-diastolic diameter significantly improved (all P<0.05), but tricuspid annular plane systolic excursion and right ventricular fractional area change did not show significant differences compared with those before the procedure (both P>0.05). Conclusion: It has been preliminarily confirmed that transcatheter tricuspid valve edge-to-edge repair solely guided by TEE is feasible and safe, but requires more large-scale studies for further validation.

Enhancement of blue and ultraviolet components in PCF-based supercontinuum generation through inter-modal dispersive-wave radiation.

Broadband supercontinuum (SC) light sources generated through nonlinear effects in solid-core photonic crystal fibers (PCFs) have been widely used in spectroscopy, metrology, and microscopy, leading to great application successes. The short-wavelength extension of such SC sources, a longstanding challenge, has been the subject of intensive study over the past two decades. However, the exact mechanism of blue and ultraviolet light generation, especially for some resonance spectral peaks in the short-wavelength regime, is not yet fully understood. Here, we demonstrate that the effect of inter-modal dispersive-wave radiation, which results from phase matching between pump pulses at the fundamental optical mode and packets of linear waves at some higher-order modes (HOMs) propagating in the PCF core, might be one of the critical mechanisms that can result in some resonance spectral components with wavelengths much shorter than that of the pump light. We observed in an experiment that several spectral peaks resided in the blue and ultraviolet regimes of the SC spectrum, whose central wavelengths can be tuned by varying the PCF-core diameter. These experimental results can be interpreted well using the inter-modal phase-matching theory, providing some useful insights into the SC generation process.

First Observation of the ß3αp Decay of

The ß-delayed proton decay of ^{13}O has previously been studied, but the direct observation of ß-delayed 3αp decay has not been reported. Rare 3αp events from the decay of excited states in ^{13}N^{⋆} provide a sensitive probe of cluster configurations in ^{13}N. To measure the low-energy products following ß-delayed 3αp decay, the Texas Active Target (TexAT) time projection chamber was employed using the one-at-a-time ß-delayed charged-particle spectroscopy technique at the Cyclotron Institute, Texas A&M University. A total of 1.9×10^{5} ^{13}O implantations were made inside the TexAT time projection chamber. A total of 149 3αp events were observed, yielding a ß-delayed 3αp branching ratio of 0.078(6)%. Four previously unknown α-decaying excited states were observed in ^{13}N at 11.3, 12.4, 13.1, and 13.7 MeV decaying via the 3α+p channel.

Prevalence and risk factors of erectile dysfunction in COVID-19 patients: a systematic review and meta-analysis.

PURPOSE: Studies have found that erectile dysfunction (ED) may be a short-term or long-term complication in coronavirus disease 2019 (COVID-19) patients, but no relevant studies have completed a pooled analysis of this claim. The purpose of the review was to comprehensively search the relevant literature, summarize the prevalence of ED in COVID-19 patients, assess risk factors for its development, and explore the effect of the COVID-19 infection on erectile function. METHODS: Medline, Embase, and the Cochrane Library was performed from database inception until April 14, 2022. Heterogeneity was analyzed by χ2 tests and I2 was used as a quantitative test of heterogeneity. Subgroup analyses, meta-regression, and sensitivity analyses were used to analyze sources of heterogeneity. RESULTS: Our review included 8 studies, 4 of which functioned as a control group. There were 250,606 COVID-19 patients (mean age: 31-47.1 years, sample size: 23-246,990). The control group consisted of 10,844,200 individuals (mean age: 32.76-42.4 years, sample size 75-10,836,663). The prevalence of ED was 33% (95% CI 18-47%, I2 = 99.48%) in COVID-19 patients. The prevalence of ED based on the international coding of diseases (ICD-10) was 9% (95% CI 2-19%), which was significantly lower than the prevalence of ED diagnosed based on the International Index of Erectile Function (IIEF-5) (46%, 95% CI 22-71%, I2 = 96.72%). The pooling prevalence of ED was 50% (95% CI 34-67%, I2 = 81.54%) for articles published in 2021, significantly higher than that for articles published in 2022 (17%, 95% CI 7-30%, I2 = 99.55%). The relative risk of developing ED was 2.64 times in COVID-19 patients higher than in non-COVID-19 patients (RR: 2.64, 95% CI 1.01-6.88). The GRADE-pro score showed that the mean incidence of ED events in COVID-19 patients was 1,333/50,606 (2.6%) compared with 52,937/844,200 (0.4%) in controls; the absolute impact of COVID-19 on ED was 656/100,000 (ranging from 4/100,000 to 2352/100,000). Anxiety (OR: 1.13, 95% CI 1.03-1.26, I2 = 0.0%) in COVID-19 patients was a risk factor for ED. CONCLUSION: COVID-19 patients have a high risk and prevalence of ED, mainly driven by anxiety. Attention should be paid to patient's erectile functioning when treating COVID-19.

Workplace bullying and suicidal ideation and behaviour: a systematic review and meta-analysis.

OBJECTIVES: Suicidal ideation and behaviour are potential outcomes of workplace bullying. This review aimed to determine the extent of the association between workplace bullying and suicidal ideation and behaviour. STUDY DESIGN: The study incorporated a systematic review and meta-analysis. METHODS: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement was followed to conduct a comprehensive systematic review and meta-analysis. A combination of subject terms and free words was used to search nine electronic databases. Two reviewers independently screened articles and extracted information according to the inclusion criteria. A meta-analysis was performed with averaged weighted correlations across samples using the STATA software (version 16.0) from pooled estimates of the main results from all studies. RESULTS: In total, 25 articles of high or medium quality were included in the systematic review; 15 of these were included in the meta-analysis. The prevalence of suicidal ideation and behaviour was 18% and 4%, respectively. Individuals who experienced workplace bullying had 2.03-times and 2.67-times higher odds of reporting suicidal ideation and behaviour, respectively, after adjustment for confounding factors. Moderating and mediating factors may help reduce the risk of suicidal ideation and behaviour for individuals experiencing workplace bullying. CONCLUSION: This study indicated that exposure to workplace bullying significantly increased the risk of suicidal ideation and behaviour.

[A long-term follow-up study on recurrence and benefit of standardized postoperative chemotherapy of rectal cancer patients with complete pathological response after neoadjuvant chemoradiotherapy].

Objective: To analyze the clinicopathological factors affecting long-term disease-free survival and the characteristics of local recurrence or distance metastasis of rectal cancer patients with complete pathological response after neoadjuvant chemoradiotherapy. Methods: The clinicopathological data and follow-up information of patients with a complete pathological response of rectal cancer after neoadjuvant chemoradiotherapy in the Cancer Hospital of Chinese Academy of Medical Sciences from June 2004 to December 2019 were retrospectively collected. The clinicopathological factors affecting the long-term disease-free survival of patients were analyzed to build a prediction model of local recurrence and distant metastasis and to evaluate the benefits of postoperative chemotherapy. Results: The age of 108 patients was(56.3±11.6) years, of which 68 were males (63.0%); The median follow-up time was 79.9 (61.8, 112.6) months. There were 12 patients (11.1%) who had a local recurrence or distant metastasis. The 5-year disease-free survival rate was 91.1% with 9 patients who experienced recurrence. Multivariate Cox proportional hazards regression analysis showed that the maximum diameter of the residual tumor or scar (HR=8.41, 95%CI: 1.08-65.22, P=0.042) and the distance from the lower edge of the tumor to the anal margin before treatment (HR=4.54, 95%CI: 1.23-16.81, P=0.023) were independent risk factors affecting the prognosis. The prognosis of patients was stratified based on relevant factors. The 5-year cumulative disease-free survival rate of those patients receiving postoperative standardized chemotherapy was 92.0%, while for patients who did not receive or complete standardized chemotherapy, the 5-year cumulative disease-free survival rate was 82.3%. Conclusions: The maximum diameter of the residual tumor or scar and the distance from the lower edge of the tumor to the anal margin before treatment were independent risk factors affecting the prognosis of patients with a complete pathological response. Patients with independent risk factors could benefit from the standardized postoperative chemotherapy.

[Study on the recurrence pattern of rectal cancer patients undergoing radical surgery after neoadjuvant chemoradiotherapy].

Objective: To analyze the recurrence pattern of rectal cancer patients with radical surgery after neoadjuvant chemoradiotherapy. Methods: The clinicopathological characteristics and follow-up information of rectal cancer patients with radical surgery after neoadjuvant chemoradiotherapy in the Cancer Hospital of the Chinese Academy of Medical Sciences from June 2004 to December 2017 were retrospectively collected. The recurrence pattern including the time and site was investigated. Results: The age of 537 patients was (55.5±11.7) years, of whom 361 were male (67.2%). The median follow-up time [M(Q1,Q3)] was 77.9 (64.5, 95.6) months. Moreover, 30.7% (165/537) of patients had distant metastasis or local recurrence; 26.8% (144/537) of patients had distant metastasis; 5.6% (30/537) of patients had local recurrence; 1.7% (9/537) of patients had both distant metastasis and local recurrence. In all the recurrent patients, 23.6% (39/165) were in the first year after surgery, followed by 27.3% (45/165) in the second year, 17.0% (28/165) in the third year, and 15.8% (26/165) after five years. According to the risk curve drawn by the life table, the highest metastasis risk of patients occurred in the second year after surgery, and the metastasis risk peak occurred again after more than five years. The lung was the most common metastatic organ, accounting for 47.9% (69/144), followed by the liver (18.8%, 27/144). The ratios of the recurrent patients in each ypTNM stage were 9.5% (8/84), 12.0% (12/100), 26.5% (41/155), 52.5% (104/198), respectively. The proportion of recurrent patients in tumor regression grade (TRG) 1-2 and TRG 3-5 patients were 19.2% (38/198) and 37.5% (127/339), respectively. Conclusions: The recurrence pattern of patients undergoing radical surgery after neoadjuvant chemoradiotherapy is mainly distant metastasis. The lung is the primary metastatic organ. The risk of distant metastasis and local recurrence is high in the first three years after surgery, and there is still high risk of recurrence after five years. For patients with ypTNM stage 2, 3 and TRG3-5, the postoperative adjuvant chemotherapy and long-term follow-up should be strengthened.

[Analysis on echocardiographic data of fetal heart defects at high altitude in Yunnan province and surrounding high altitude areas].

Objective: To explore the current situation of fetal heart defects in Yunnan Province and surrounding high altitude areas and the social factors affecting pregnancy outcome. Methods: This is a retrospective study. Pregnant woman who underwent fetal echocardiography and diagnosed as fetal cardiac defects in Yunnan Fuwai Cardiovascular Hospital from June 2017 to January 2021 were included. According to the clinical prognostic risk scoring system and grading criteria of fetal cardiac birth defects, the cases were divided into grade Ⅰ to Ⅳ. The disease distribution and proportion of each prognostic grade, pregnancy outcomes were analyzed and compared. The cases were divided into continued pregnancy group and terminated pregnancy group according to pregnancy outcome. The social factors that may affect the selection of pregnancy outcomes were analyzed by multivariate logistic regression analysis. Results: A total of 4 929 fetal echocardiography examination data were collected, and 4 464 cases (90.57%) were from Yunnan Province and surrounding high altitude areas. 2 166 cases of heart defects were finally analyzed, including 998 cases of congenital heart disease (CHD), 93 cases of cardiac tumors, cardiomyopathy and arrhythmia, 1 075 cases of foramen ovale, ductus arteriosus abnormalities and normal variations. The pregnant women were (29.2±5.0) years old with (25.6±3.8) gestational weeks. The number of cases with prognostic grade from Ⅰ to Ⅳ was 1 037 (47.88%), 620 (28.62%), 314 (14.50%), and 44 (2.03%), respectively. And 151 cases (6.97%) were not classified. The cases of normal variation and thin aortic arch development accounted for 42.66% (924/2 166), 5.22% (113/2 166), respectively. The top 3 diseases of grade Ⅱ were ventricular septal defect, coarctation of aorta and mild-moderate pulmonary stenosis, respectively, and their distribution was 11.63% (252/2 166), 3.92% (85/2 166) and 2.35% (51/2 166) respectively in all cases of heart defects, and 25.25% (252/998), 8.52% (85/998) and 5.11% (51/998) respectively in cases of CHD. Among the cases rated as grade Ⅲ and Ⅳ, most of them were complicated congenital heart disease, and the disease types are scattered. The more common cases in grade Ⅲ were complete transposition of great arteries (accounting for 2.40% (52/2 166) of all cases with heart defects, 5.21% (52/998) of all cases with CHD) and pulmonary artery occlusion (type Ⅰ to Ⅲ) with ventricular septal defect (accounting for 2.17% (47/2 166) of all cases with heart defects, and 4.71% (47/998) of all cases with CHD). In grade Ⅳ, single ventricle (0.74% (16/2 166) of all cases with heart defects, 1.60% (16/998) of all cases with CHD) and left ventricular dysplasia syndrome (0.65% (14/2 166) of all cases with heart defects, 1.40% (14/998) of all cases with CHD) are more common. A total of 1 084 cases were successfully followed up, and 675 cases were born, 392 cases were terminated, spontaneous abortion occurred in 17 cases. The proportion of terminated pregnancy cases was significantly increased from grade Ⅰ to Ⅳ, accounting for 5.24% (21/401), 27.78% (70/252), 89.54% (214/239) and 95.56% (43/45), respectively. Among the terminated pregnancy cases, those with grade Ⅲ accounted for the highest proportion (54.59% (214/392)). The distribution of terminated pregnancy cases was mainly complex congenital malformations or diseases with very poor prognosis (pregnancy outcome grade Ⅲ and Ⅳ), and proportion of terminated pregnancy with pregnancy outcome grade Ⅰ and Ⅱ cases (normal variation or good prognosis) accounted for 5.36% (21/392) and 17.86% (70/392), respectively. The results of multivariate logistic regression analysis showed that pregnant women with low education (high school and below: OR=2.73, 95%CI 1.26-5.93, P<0.001; illiteracy: OR=3.27, 95%CI 1.29-7.10, P<0.001) and low family income (Annual income<100 000 yuan: OR=2.47, 95%CI 1.69-5.12, P<0.001) were more likely to choose termination of pregnancy in case of fetal heart defect. Conclusion: In Yunnan province and the surrounding high altitude areas, the disease distribution of fetal heart defect is mainly simple or low-risk disease, but the complex malformation, especially the disease with poor pregnancy outcome, accounts for a relative high proportion. Pregnancy termination also occurs in some cases with good pregnancy outcome. The education level and family income of pregnant women may affect their choice of pregnancy outcome in case of fetal heart defect.

[Comparison on the efficacy of Chinese-made novel-designed mechanical-locked and elastic self-locked transcatheter edge-to-edge repair system in the treatment of patients with functional mitral regurgitation].

Objective: To evaluate and compare the short-term efficacy of domestic mechanical-locked (Clip2Edge) and elastic self-locked (ValveClip) transcranial mitral valve edge-to-edge interventional repair (TEER) devices in the treatment of functional mitral regurgitant valves. Methods: In this retrospective non-randomized comparative study, patients underwent TEER procedure in Fuwai Yunnan Cardiovascular Disease Hospital from May 2022 to April 2023 for heart failure combined with moderate to severe or severe functional mitral valve were divided into Clip2Edge and ValveClip groups based on the TEER system used. Baseline, perioperative, and postoperative 30 d follow-up data were collected and compared between the two groups. The primary outcome was the success rate on the 30 d post operation, while secondary outcomes included immediate postoperative technical success rate and the incidence of all-cause mortality on the 30 d post operation, readmission rate of acute heart failure, cerebral infarction, severe bleeding, and other serious adverse events rates. Results: A total of 60 patients were enrolled, 34 patients were in the Clip2Edge group and 26 in the ValveClip group, mean age was (63.8±9.3) years, and 24 patients (40%) were female. There were no significant differences in baseline data of age, cardiac function, comorbidities, mitral regurgitation 4+(19(73%) vs. 29(85%)), the end-diastolic volume of left ventricle ((220.8±91.2) ml vs. (210.8±71.7) ml) between the two groups (all P>0.05). The technical success rate immediately after the procedure was 100%. There were no readmission of acute heart failure, death, cerebral infarction, severe bleeding, and other serious adverse events up to the 30 d follow-up. Device success rate was similar between the ValveClip group (24 cases (100%)) and the Clip2Edge group (27 cases (96%)) (P>0.05). Conclusion: Both types of novel domestic TEER devices are safe and feasible in treating patients with functional mitral regurgitation.

Single cell transcriptomics in human osteoarthritis synovium and in silico deconvoluted bulk RNA sequencing.

OBJECTIVES: To reveal the heterogeneity of different cell types of osteoarthritis (OA) synovial tissues at a single-cell resolution, and determine by novel methodology whether bulk-RNA-seq data could be deconvoluted to create in silico scRNA-seq data for synovial tissue analyses. METHODS: OA scRNA-seq data (102,077 synoviocytes) were provided by 17 patients undergoing total knee arthroplasty; 9 tissues with matched scRNA-seq and bulk RNA-seq data were used to evaluate six in silico gene deconvolution tools. Predicted and observed cell types and proportions were compared to identify the best deconvolution tool for synovium. RESULTS: We identified seven distinct cell types in OA synovial tissues. Gene deconvolution identified three (of six) platforms as suitable for extrapolating cellular gene expression from bulk RNA-seq data. Using paired scRNA-seq and bulk RNA-seq data, an "arthritis" specific signature matrix was created and validated to have a significantly better predictive performance for synoviocytes than a default signature matrix. Use of the machine learning tool, Cell-type Identification By Estimating Relative Subsets of RNA Transcripts x (CIBERSORTx), to analyze rheumatoid arthritis (RA) and OA bulk RNA-seq data yielded proportions of T cells and fibroblasts that were similar to the gold standard observations from RA and OA scRNA-seq data, respectively. CONCLUSION: This novel study revealed heterogeneity of synovial cell types in OA and the feasibility of gene deconvolution for synovial tissue.

[Seasonal variations influenced the semen quality of the sperm donor in Beijing area].

OBJECTIVE: To investigate the change trends of sperm quality with seasonal variations among the volunteers of sperm donors in Beijing area, as well as the relationship between two parameters. METHODS: Semen data from the volunteers of sperm donors in Human Sperm Bank of Peking University Third Hospital were collected using a retrospective study method. The subjects were divided into 4 seasonal groups based on the lunar solar terms and the time of sperm donation. The data were assessed to find whether there were differences in semen parameters among different seasonal groups, and to analyze the change trends and the influence of seasonal factors on semen parameters. RESULTS: A total of 21 174 semen parameter data were analyzed. Firstly, to analyze all data as a whole, in spring, summer, autumn and winter groups, sperm concentration was (106.04±59.67)×106/mL, (97.61±47.41)×106/mL, (100.18±47.17)×106/mL, (100.59±38.68)×106/mL, respectively, and the spring group was significantly higher than the other 3 seasonal groups (P < 0.001); proportion of progressive motility sperm (PR) was 56.49%±12.76%, 58.02%±13.65%, 58.05%±12.36%, and 57.66%±12.61%, respectively, spring group was lower than the other three seasonal groups, and summer group was better among the latter (P < 0.001). There was no difference in normal rate of sperm morphology among the four seasonal groups. The qualified rate of sperm donors in the winter group was higher than that in the other three seasons groups (P < 0.01), while the qualified rate in the summer group was lower than that in the other three seasons groups. In addition, the semen parameters of the volunteers during the screening period and the official sperm donation period were analyzed respectively, which revealed that sperm concentration of spring group was higher than that of summer and winter groups, and PR was lower than that of summer and autumn groups. On account of the semen parameters of official sperm donation period, multiple linear regression analysis found that season was the main factor affecting sperm concentration, the average sperm concentration in spring group was about 6×106/mL higher than in winter group, but PR was 2.9% lower in spring group compared with autumn group (all P < 0.05). CONCLUSION: Season was the influencing factor of semen quality of sperm donors in Beijing area. We recommend spring and winter may be the preferred seasons for sperm donation.

[The prognostic impact of number-indexes of lymph nodes in stage N1c colorectal cancer patients].

Objective: To evaluate the impact of number-indexes of lymph nodes for prognostic stratification in stage N1c colorectal cancer (CRC) patients. Methods: The clinicopathologic data of CRC patients with stage pTxN1cM0 who initially underwent radical surgery in Cancer Hospital, Chinese Academy of Medical Sciences and the Surveillance, Epidemiology and End Results (SEER) database from January 2010 to December 2015 were retrospectively analyzed. A total of 1 165 patients with stage N1c were included in this study. Among them, 85 patients (including 54 males and 31 females) were from Cancer Hospital, Chinese Academy of Medical Sciences and their median age was 58 (range: 32-80) years; 1 080 patients (including 566 males and 514 females) were from the SEER database and their median age was 66 (range: 24-98) years. The prognostic significance of total number of lymph node (TLN), number of negative lymph node (NLN), and log odds of positive lymph nodes (LODDS) in stage N1c CRC patients were explored. Results: The optimal cut-off value of TLN or NLN was 13, and the optimal cut-off value of LODDS was -1.43. Among the 85 patients of Cancer Hospital, Chinese Academy of Medical Sciences, the 5-year overall survival (OS) rates of stage N1c1 (TLN or NLN≥13, 69 cases) and group LODDS1 patients (LODDS≤-1.43, 69 cases) were both 80.9%, which higher than that of stage N1c2 (TLN or NLN<13, 16 cases) and group LODDS2 (LODDS>-1.43, 16 cases) patients (both 53.3%, P=0.002); In the SEER cohort, the 5-year OS rates of stage N1c1 (837 cases) and group LODDS1 patients (LODDS≤-1.43, 837 cases) were both 64.7%, which higher than that of stage N1c2 (243 cases) and group LODDS2 (LODDS>-1.43, 243 cases) patients (both 52.2%, P<0.001). Both in the NCC cohort and SEER cohort, the results of Cox multivariate analysis all demonstrated that TLN or NLN<13 was the risk factor of OS of CRC patients with stage N1c (HR=3.794, 95%CI: 1.539-9.349, P=0.004; and HR=1.588, 95%CI:1.232-2.048, P<0.001; respectively); LODDS≤-1.43 was the independent protective factor of OS of stage N1c CRC patients (HR=0.264, 95%CI: 0.107-0.650; and HR=0.630, 95%CI: 0.488-0.812; respectively). Conclusions: TLN or NLN and LODDS were all independent prognostic factors of CRC patients with stage N1c. The clinicians could use TLN or NLN and LODDS for prognostic stratification and make the different adjuvant therapeutic schemes for CRC patients with stage N1c.

[Association of extranodal extension and lymph node ratio with radioactive iodine-refractory papillary thyroid cancer].

Objective: To investigate the related factors of radioiodine-refractory thyroid cancer (RAIR-DTC) and the increase of cumulative iodine treatment dose. Methods: The data of patients with papillary thyroid cancer who underwent surgery and iodine treatment for the first time in the Affiliated Cancer Hospital of Zhengzhou University from January 2015 to December 2017 were retrospectively analyzed. The related factors of RAIR-DTC and the increase of cumulative iodine treatment dose were explored. Results: A total of 650 patients were enrolled, including 217 males (33.4%) and 433 females (66.6%), aged 45 (34, 53) years. There were 123 patients (18.9%) over 55 years old, 171 patients (26.3%) with extranodal extension and 18 patients (2.8%) with distant metastasis. The median lymph node ratio was 0.22 (0.11, 0.33). Twenty patients (3.1%) had an accumulated iodine treatment dose>400 mCi and 19 patients (2.9%) had RAIR-DTC. Multivariate logistic regression analysis showed that extranodal extension (OR=19.833, 95%CI: 6.057-73.325, P<0.001) was related factors for the increase of cumulative iodine treatment dose. Age>55 years old (OR=3.322, 95%CI: 1.136-9.466, P=0.024), distant metastasis (OR=10.059, 95%CI: 2.508-38.888, P<0.001), extranodal extension (OR=5.278, 95%CI: 1.707-19.813, P=0.006) and lymph node ratio (OR=34.724, 95%CI: 2.749-384.575, P=0.004) were related factors for RAIR-DTC. Conclusions: Extranodal extension and lymph node ratio are related factors for RAIR-DTC. In clinical practice, more attention should be paid to the influence of different lymph node metastasis characteristics on the occurrence of RAIR-DTC and the cumulative therapeutic dose of iodine.

[Characteristics of the white matter involvement sites on MRI in patients with multiple gliomas].

The retrospective study included 122 cases of multiple glioma and 183 cases of single glioma. Of these, there were 74 males and 48 female with multiple gliomas, aged 18 to 83 (53±13) years, and 104 males and 79 females with single gliomas, aged 10 to 84 (51±14) years. A standard spatial-based lesion analysis method was used for constructing a spatially distributed frequency heatmap of multiple gliomas, to observe the characteristics of their white matter invasion sites. The spatial distribution was more frequent in the subventricular zone, corpus callosum and cingulate gyrus in the multiple glioma group compared to the single glioma group (P<0.001).The white matter areas of multiple gliomas were more extensively involved, with more frequent involvement of the conjoined fibers (corpus callosum, P<0.05) and contact fibers (cingulate, dome, 0.05

[Effect and safety of endobronchial placement of vaseline gauze in the treatment of patients with bronchial fistula].

Objective: To investigate the application of vaseline gauze to occlude the bronchial fistulas and its clinical effectiveness and safety in this retrospective study. Methods: This study retrospectively reviewed the clinical records of 14 patients with bronchial fistulas at Department of Respiratory and Critical Care Medicine, Shanghai Dongfang Hospital affiliated to Tongji University between June 2019 and June 2022. Seven of the 14 patients were female, and the age ranged from 16 to 74 years. We retrieved all the clinical records of all the enrolled patients during the 6 to 12 months follow-up after the operation, including the information for removal of chest drainage pipe, the failure of endobronchial blockage using vaseline gauze, as well as the complications (migration of the vaseline gauze, obstructive pneumonia, pulmonary atelectasis, et. al.) after the operation. Results: Of the 14 patients, 3 patients had fistula located in main or lobar bronchi; 10 patients had fistula located in distal airways; and 1 patient had fistula located both in main bronchi and distal airways. Ten patients were complicated with pneumonia or pleural cavity infections; Five were complicated with pneumothorax or hydropneumothorax. All of the 14 patients achieved successful airway occlusion after the placement of vaseline gauze in the responsible bronchial airways or stumps for the fistulas. Eleven of the 14 patients successfully removed the drainage tube for the residual cavity, 3 of the 14 patients successfully removed the vaseline gauze for the fistula which was healing during the follow up of 6-12 months. No one of the patients had severe complications or treatment failure. Conclusion: Bronchial placement of vaseline gauze might be a feasible and effective technique for treatment of bronchial fistulas.

[Comparison of follow-up treatment regimens for colorectal cancer liver metastases without objective response to neoadjuvant chemotherapy: direct surgery or surgery after second-line chemotherapy].

Objective: To compare the effect of direct surgery or surgery after second-line chemotherapy for colorectal cancer patients with liver metastases who did not achieve objective remission after neoadjuvant chemotherapy. Methods: A retrospective case cohort study was used. The clinical and pathological data of 107 patients with colorectal cancer liver metastases who did not achieve objective response to neoadjuvant chemotherapy at Department of Hepatobiliary Surgery,Cancer Hospital,Chinese Academy of Medical Sciences from December 2008 to December 2016 were retrospectively collected. There were 71 males and 36 females, median age was 57 years (range: 28 to 79 years). According to the different treatment regimens after neoadjuvant chemotherapy,107 cases were divided into a direct surgery group (direct group,n=65) and an operation after receiving second-line chemotherapy group (second-line group,n=42). The propensity score matching(PSM) of the Logistic regression model was used to match the bilobar distribution of liver metastases and the number of first-line chemotherapy cycles in the two groups of patients. The caliper value was set to 0.10 and the matching ratio was 1∶2. T test, Mann-Whitney U test, χ2 test or Fisher's exat test was used to analyzed the data between the tuo groups, respectively. Survival analysis design was used to investigate the difference in prognosis between the two groups of patients. Results: The follow-up time(M(IQR)) was 56.3(34.3) months (range: 2.1 to 95.0 months),and all patients were followed up. After PSM,there were 28 cases in the direct group and 42 cases in the second-line group, there were no significant differences in whether R0 resection was feasible,blood loss,blood transfusion,postoperative complications and postoperative hospital stay between the two groups (all P>0.05). The 1,3,and 5-year progression-free survival(PFS) rates of the direct group were 40.0%,16.5%,and 11.0%,and the 1,3,and 5-year overall survival(OS) rates were 98.5%,61.2%,and 41.4%,respectively, the second-line group 1,3,5 years PFS rates were 35.7%,14.3%,14.3%,1,3,5-year OS rate were 95.2%,55.1%,44.4%,respectively. The median PFS time of the direct group and the second-line group was 8.5 months and 7.5 months,respectively,and the difference was not statistically significant (P=0.826). The median OS time of the direct group and the second-line group were 33.8 months and 46.9 months,respectively. The difference was not statistically significant(P=0.646).The median PFS time of the direct group and second-line chemotherapy complete remission and partial remission group(CR/PR group) was 10.2 months and 9.1 months,respectively,and the difference was not statistically significant(P=0.669). The median OS time of the direct group and the second-line CR/PR group was 51.0 months and 46.9 months,respectively,and the difference was not statistically significant(P=0.427). The results of survival analysis suggested that major liver resection was an independent prognosis factor for PFS (HR=1.809,95%CI: 1.067 to 3.067,P=0.028) and OS(HR=2.751,95%CI: 1.317 to 5.747,P=0.007). Second-line chemotherapy was not an independent prognostic factor for PFS (HR=0.945, 95%CI:0.570 to 1.567,P=0.828) and OS (HR=0.866,95%CI: 0.468 to 1.602,P=0.646). Conclusions: There is no significant difference in the short-term outcome and long-term prognosis between direct surgery patients and second-line chemotherapy followed by surgery. Second-line chemotherapy is not an independent prognostic factor for colorectal cancer liver metastases patients who fail to achieve objective response after neoadjuvant chemotherapy.

Alpha defensin-1 attenuates surgically induced osteoarthritis in association with promoting M1 to M2 macrophage polarization.

OBJECTIVE: Macrophages play an important part in the pathogenesis of osteoarthritis (OA). Our objective was to determine the effects of α-defensin-1 on macrophage polarization and consequently OA. METHODS: OA synovial tissue and synovial fluid were assessed for the presence of M1 (CD68+CD16+CD206-) and M2 (CD68+CD206+CD16-) macrophages by flow cytometry. M0, M1, and M2 macrophages were co-cultured with OA chondrocytes to determine their influence on chondrogenic phenotype. Polarization of THP-1 activated monocytes from M1 to M2 in response to α-defensin-1 was evaluated by flow cytometry, RT-PCR and RNA sequencing. Effects of intra-articular α-defensin-1 in vivo were evaluated in a rat meniscal/ligamentous injury (MLI) model. RESULTS: The quantity of M1 exceeded M2 polarized macrophages in human OA synovial tissue (mean difference 26.1% [13.6-38.6%], P < 0.001) and fluid (mean difference 10.5% [5.0-16.1%], P = 0.003). M1 to M2 polarization in vitro was most effectively promoted with 10 ng/mL α-defensin-1. Compared with untreated macrophages, the α-defensin-1 polarized macrophages modified co-cultured OA chondrocytes from a pro-catabolic state to a pro-anabolic (regenerative-like) state based on expression of COL2A1, ACN, MMP3, MMP13 and ADAMTS5. Intra-articular α-defensin-1 decreased severity of cartilage damage and synovitis in the MLI rat model. RNAseq analyses suggested insulin and Toll-like receptor signaling pathways in the chondroprotective α-defensin-1 mechanism of action. CONCLUSION: α-defensin-1 promotes M1 to M2 macrophage polarization in vitro, has beneficial effects on chondrocytes indirectly via M2 macrophage polarization, and attenuates the severity of OA in vivo, suggesting it might be a candidate treatment for OA.