OBJECTIVE: To identify the CDYL-interacting proteins in murine testis and investigate the mechanism of CDYL involved in spermatogenesis. METHODS: CDYL-interacting partners in testis were identified using co-immunoprecipitation coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS). Expression pattern of CDYL-interacting protein MYH9 was analyzed through immunohistochemistry (IHC), confocal immunofluorescence (IF) and Western blot (WB) in mouse testicular cells. The effect of the Cdyl conditional knockout (CdylcKO) in spermatogenic cell on Myh9 expression was quantified via RT-qPCR, WB and IF imaging in both spermatids and spermatozoa from cauda epididymides. RESULTS: Direct interaction between MYH9 and CDYL was confirmed in murine testis. During spermiogenesis, MYH9 exhibited co-localization with CDYL at the manchette structure, and binding to F-ACTIN, the component of manchette. In cauda epididymal spermatozoa, MYH9 signal concentrated on acrosomal region and continuously distributed along the tail length. Conditional deletion of Cdyl in spermatogenic cell resulted in the transcriptional downregulation of Myh9. In spermatids, CdylcKO led to reduced but retained MYH9 localization to the disorganized manchette structure. In spermatozoa from CdylcKO mice, abnormalities of MYH9 localization were observed, including attenuation of acrosomal signal and/or partial vanishment/enhancement of tail signal. CONCLUSION In murine spermatids, MYH9 protein is localized to the manchette structure, with its expression and subcellular distribution is affected by CDYL protein. CDYL-MYH9 interaction is essential for the spermiogenesis.
Animals ; Male ; Mice ; Testis/metabolism* ; Myosin Heavy Chains/metabolism* ; Spermatogenesis ; Mice, Knockout

A major challenge facing photodynamic therapy (PDT) is that the activity of the immune-induced infiltrating CD8⁺ T cells is subject to the regulatory T lymphocytes (Tregs), leaving the tumor at risk of recurrence and metastasis after the initial ablation. To augment the antitumor response and reprogram the immunosuppressive tumor microenvironment (TME), a supramolecular photodynamic nanoparticle (DACss) is constructed by the host-guest interaction between demethylcantharidin-conjugated β-cyclodextrin (DMC-CD) and amantadine-terminated disulfide-conjugated FFVLGGGC peptide with chlorin e6 decoration (Ad-ss-pep-Ce6) to achieve intelligent delivery of photosensitizer and immunomodulator for breast cancer treatment. The acid-labile β-carboxamide bond of DMC-CD is hydrolyzed in response to the acidic TME, resulting in the localized release of DMC and subsequent inhibition of Tregs. The guest molecule Ad-ss-pep-Ce6 can be cleaved by a high level of intracellular GSH, reducing photosensitizer toxicity and increasing photosensitizer retention in the tumor. With a significant increase in the CTL/Treg ratio, the combination of Ce6-based PDT and DMC-mediated immunomodulation adequately achieved spatiotemporal regulation and remodeling of the TME, as well as improved primary tumor and in situ lung metastasis suppression with the aid of PD-1 antibody.

Objective: To investigate the incidence and treatment of perioperative anemia in patients with gastrointestinal neoplasms in Hubei Province. Methods: The clinicopathological data of 7 474 patients with gastrointestinal neoplasms in 62 hospitals in 15 cities (state) of Hubei Province in 2019 were collected in the form of network database. There were 4 749 males and 2 725 females. The median age of the patients was 62 years (range: 17 to 96 years). The hemoglobin value of the first time in hospital and the first day after operation was used as the criterion of preoperative anemia and postoperative anemia. Anemia was defined as male hemoglobin <120 g/L and female hemoglobin <110.0 g/L, mild anemia as 90 to normal, moderate anemia as 60 to <90 g/L, severe anemia as <60 g/L. The t test and χ² test were used for inter-group comparison. Results: The overall incidence of preoperative anemia was 38.60%(2 885/7 474), and the incidences of mild anemia, moderate anemia and severe anemia were 25.09%(1 875/7 474), 11.37%(850/7 474) and 2.14%(160/7 474), respectively. The overall incidence of postoperative anemia was 61.40%(4 589/7 474). The incidence of mild anemia, moderate anemia and severe anemia were 48.73%(3 642/7 474), 12.20%(912/7 474) and 0.47%(35/7 474), respectively. The proportion of preoperative anemia patients receiving treatment was 26.86% (775/2 885), and the proportion of postoperative anemia patients receiving treatment was 14.93% (685/4 589). The proportions of preoperative anemia patients in grade ⅢA, grade ⅢB, and grade ⅡA hospitals receiving treatment were 26.12% (649/2 485), 32.32% (85/263), and 29.93% (41/137), and the proportions of postoperative anemia patients receiving treatment were 14.61% (592/4 052), 22.05% (73/331), and 9.71% (20/206). The proportion of intraoperative blood transfusion (16.74% (483/2 885) vs. 3.05% (140/4 589), χ²=434.555, P<0.01) and the incidence of postoperative complications (17.78% (513/2 885) vs. 14.08% (646/4 589), χ²=18.553, P<0.01) in the preoperative anemia group were higher than those in the non-anemia group, and the postoperative hospital stay in the preoperative anemia group was longer than that in the non-anemia group ((14.1±7.3) days vs. (13.3±6.2) days, t=5.202, P<0.01). Conclusions: The incidence of perioperative anemia in patients with gastrointestinal neoplasms is high. Preoperative anemia can increase the demand for intraoperative blood transfusion and affect the short-term prognosis of patients. At present, the concept of standardized treatment of perioperative anemia among gastrointestinal surgeons in Hubei Province needs to be improved.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Anemia/epidemiology* ; Blood Transfusion ; Female ; Gastrointestinal Neoplasms/surgery* ; Humans ; Length of Stay ; Male ; Middle Aged ; Retrospective Studies ; Treatment Outcome ; Young Adult

OBJECTIVE: To examine whether the combination of Naoxintong Capsule with standard care could further reduce the recurrence of ischemic stroke without increasing the risk of severe bleeding. METHODS: A total of 23 Chinese medical centers participated in this trial. Adult patients with a history of ischemic stroke were randomly assigned in a 1:1 ratio using a block design to receive either Naoxintong Capsule (1.2 g orally, twice a day) or placebo in addition to standard care. The primary endpoint was recurrence of ischemic stroke within 2 years. Secondary outcomes included myocardial infarction, death due to recurrent ischemic stroke, and all-cause mortality. The safety of drugs was monitored. Results were analyzed using the intention-to-treat principle. RESULTS: A total of 2,200 patients were enrolled from March 2015 to March 2016, of whom 143 and 158 in the Naoxintong and placebo groups were lost to follow-up, respectively. Compared with the placebo group, the recurrence rate of ischemic stroke within 2 years was significantly lower in the Naoxintong group [6.5% vs. 9.5%, hazard ratio (HR): 0.665, 95% confidence interval (CI): 0.492-0.899, P=0.008]. The two groups showed no significant differences in the secondary outcomes and safety, including rates of severe hemorrhage, cerebral hemorrhage and subarachnoid hemorrhage (P>0.05). CONCLUSION The combination of Naoxintong Capsule with standard care reduced the 2-year stroke recurrence rate in patients with ischemic stroke without increasing the risk of severe hemorrhage in high-risk patients. (Trial registration No. NCT02334969).
Adult ; Humans ; Secondary Prevention/methods* ; Ischemic Stroke ; Stroke/prevention & control* ; Cerebral Hemorrhage/complications* ; Double-Blind Method ; Platelet Aggregation Inhibitors

Objective: To analyze the effect of acupuncture versus hormone replacement therapy (HRT) for premature ovarian insufficiency (POI). Methods: China National Knowledge Infrastructure (CNKI), Wanfang Academic Journal Full-text Database (Wanfang), Chongqing VIP Database (CQVIP), China Biology Medicine Disc (CBM), Web of Science, Cochrane Library, PubMed, and Excerpta Medica Database (EMBASE) were searched up to January 31st, 2019 to identify randomized controlled trials (RCTs) evaluating the effect of acupuncture for POI. The primary outcome was the level of basal serum follicle- stimulating hormone (FSH). Secondary outcomes included serum levels of luteinizing hormone (LH), estradiol (E2) and anti-Müllerian hormone (AMH). Two authors extracted data independently and assessed the risk of bias and the methodological quality using the Cochrane's tool. Meta-analysis was conducted by RevMan version 5.3. Results: Eight eligible RCTs with a total of 496 POI patients were included in the meta-analysis. The pooled results showed that there was a significant reduction in the basal serum FSH level (MD=-5.82, 95％CI:-9.76 to -1.87, I2=82％, P=0.004) and a remarkable elevation in the basal E2 level (SMD=0.93, 95％CI: 0.34 to 1.52, I2=88％, P=0.002) in the acupuncture group when compared with the control. Subgroup analysis showed that compared with HRT, a significant decrease in the FSH level was observed in both acupuncture alone (MD=-4.53, 95％CI:-8.96 to -0.10, I2=73％, P=0.04) and acupuncture plus HRT (MD=-9.60, 95％CI:-17.60 to -1.61, I2=50％, P=0.02), while a remarkable elevation of E2 was only found in acupuncture plus HRT (SMD=1.43, 95％CI: 1.03 to 1.82, I2=0％, P<0.00001). There was no significant difference in the LH level between acupuncture and HRT (MD=-3.16, 95％CI:-9.41 to 3.10, I2=0％, P=0.32), only one trial reported AMH, and no significant difference was found between acupuncture and HRT. Conclusion: The present study indicated that acupuncture had an advantage over HRT in reducing serum FSH level and increasing serum E2 level in women with POI. However, evidence supporting the finding is limited due to the small sample size, potential methodological flaws and significant heterogeneity. Hence, this conclusion still needs to be verified by high-quality RCTs.

Objective:To develop an diagnostic equipment with artificial intelligence (AI) real-time assistance under endoscopy (endoscopic AI equipment) for the detection of gastrointestinal protruding lesions, and to evaluate its performance and safety.Methods:From January to December 2017, at Endoscopy Center of West China Hospital, Sichuan University, the endoscopic images of individuals who underwent routine gastroscopy and colonoscopy were collected. The model was established based on convolutional neural network and the endoscopic AI equipment was developed. From June to December 2019, a prospective, single center, blinded and parallel controlled study was conducted to compare the differences in evaluation of protruding lesions of the same patient under gastroscopy or colonoscopy between endoscopist and the endoscopic AI equipment and to evaluated the impact of lesion size (lesions <5 mm and ≥5 mm) on the detection of endoscopic AI equipment. The main outcome measure was the detection time difference in reporting the protruding lesion between endoscopic AI equipment and endoscopist; and the secondary indicator was the accuracy of endoscopic AI equipment in detecting the protruding lesion. Wilcoxon rank sum test and chi-square test were used for statistical analysis.Results:A total of 71 582 white light endoscopy images were used for endoscopic AI equipment training, which included 41 376 images of protruding lesions. The endoscopic AI equipment was successfully developed and obtained the registration certificate of medical devices of the People′s Republic of China (Sichuan Instrument Standard, 20202060049). The accuracy, sensitivity, and specificity of endoscopic AI equipment in detecting protruding lesions were 96.4%, 95.1% and 92.8%, respectively. The detection time of each protruding lesions under gastroscopy of endoscopic AI equipment was 1.524 seconds faster than that of endoscopist; but the detection time of each protruding lesions under colonoscopy was 0.070 seconds slower than that of endoscopist, and the differences were statistically significant ( Z=-5.505 and -4.394, both P<0.01). The detection time of each protruding lesions under gastroscopy or colonoscopy of endoscopic AI equipment was not inferior to that of endoscopist. The detection rate of protruding lesions under colonoscopy by endoscopic AI equipment was 89.9% (249/277) and the sensitivity was 89.9%; the detection rate of protruding lesions under colonoscopy was 87.0% (450/517) and the sensitivity was 86.9%. There were no statistically significant differences in the detection time difference, sensitivity and missed diagnostic rate between the lesions <5 mm and ≥5 mm detected by endoscopic AI equipment under gastroscopy (all P>0.05). The sensitivity of endoscopic AI equipment in detecting the lesions ≥5 mm under colonoscopy was higher than that of lesions <5 mm (96.8% vs. 84.9%), and the missed diagnostic rate was lower than that of lesions <5 mm (3.2%, 3/94 vs. 15.1%, 61/405), and the differences were statistically significant ( χ2=9.615 and 9.612, both P=0.002). No adverse events on patients and medical staffs occurred, and there were no cases of equipment electricity leakage, and abnormal work reported during the use of endoscopic AI equipment. Conclusions:The endoscopic AI equipment can report the protruding lesions simultaneously with endoscopists, and the accuracy is close to 90%, which is expected to be a practical assistant for endoscopists to avoid missed detection of protruding lesions.

To establish a quality constant evaluation system of Alismatis Rhizoma decoction pieces,in order to provide reference for regulating the market circulation of this decoction pieces. A total of 18 batches of Alismatis Rhizoma decoction pieces were collected from different pharmaceutical factories,and the morphological parameters of each sample were tested. The content of alisol B 23-acetate in Alismatis Rhizoma decoction pieces was determined by HPLC in the 2015 edition of Chinese Pharmacopoeia,and the parameters such as quality constant and relative quality constant were calculated. The quality constant range of 18 batches of Alismatis Rhizoma decoction pieces was 0. 390-2. 076. If 18 batches of Alismatis Rhizoma decoction pieces were divided into 3 grades,taking 80% of the maximum quality constant as first grade,50% to 80% as second grade,and the rest as third grade,then the quality constant of firstgrade samples was ≥1. 66,the quality constant of second-grade samples was ≥1. 04 and <1. 66,and the quality constant of third-grade samples was <1. 04. The established quality constant evaluation method is objective and feasible,which can be used to classify the grade of Alismatis Rhizoma decoction pieces and provide a reference method to control the quality of this decoction pieces.
Alisma ; chemistry ; Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal ; standards ; Quality Control ; Rhizome ; chemistry