Objective:To compare the safety of radial artery puncture in elderly patients aged 75 years and older who are undergoing neurointerventional procedures.Methods:A single-center retrospective study was conducted, involving 350 elderly patients aged 75 years and older who received neurointerventional treatment at Beijing Tiantan Hospital, Capital Medical University, from June to December 2022.The participants were divided into two groups based on the puncture site: femoral artery puncture and radial artery puncture.The safety indicators compared between the two groups included puncture failure, changes in puncture site, general puncture complications(such as subcutaneous bleeding, puncture site hematoma, and vasospasm), severe puncture complications(including distal limb ischemia and pseudoaneurysm), and lower limb venous thrombosis.Multivariate Logistic regression analysis was conducted to evaluate the impact of different puncture methods on the occurrence of complications.Results:Among the 350 patients, 280 underwent femoral artery puncture, while 70 underwent radial artery puncture.There were no statistically significant differences in baseline characteristics between the two groups(all P>0.05).The proportions of patients using antiplatelet drugs prior to surgery, puncture failure rates, rates of change in puncture sites, and the incidence of severe complications-including distal limb ischemia and pseudoaneurysm-were not significantly different between the two groups( χ2=2.051, 0.075, 0.588, 3.175; P=0.152, 0.784, 0.443, 0.075).In the femoral artery puncture group, 20.4%(57 cases)of patients experienced general puncture complications(including subcutaneous bleeding, puncture site hematoma, and vasospasm), whereas only 8.6%(6 cases)in the radial artery puncture group experienced such complications, revealing a statistically significant difference between the two groups( χ2=5.720, P=0.022).Multivariate Logistic regression analysis indicated that, compared to femoral artery puncture, radial artery puncture was associated with a reduced risk of all complications( OR=0.272, 95% CI: 0.139-0.532, P<0.001), general puncture complications( OR=0.375, 95% CI: 0.153-0.919, P=0.032)and lower limb venous thrombosis( OR=0.219, 95% CI: 0.050-0.954, P=0.043). Conclusions:In elderly patients aged 75 years and older who are undergoing neurointerventional procedures, radial artery puncture is associated with a reduced incidence of general puncture complications and lower limb venous thrombosis when compared to femoral artery puncture, indicating a superior safety profile.

The many-banded krait, Bungarus multicinctus, has been recorded as the animal resource of JinQianBaiHuaShe in the Chinese Pharmacopoeia. Characterization of its venoms classified chief phyla of modern animal neurotoxins. However, the evolutionary origin and diversification of its neurotoxins as well as biosynthesis of its active compounds remain largely unknown due to the lack of its high-quality genome. Here, we present the 1.58 Gbp genome of B. multicinctus assembled into 18 chromosomes with contig/scaffold N50 of 7.53 Mbp/149.8 Mbp. Major bungarotoxin-coding genes were clustered within genome by family and found to be associated with ancient local duplications. The truncation of glycosylphosphatidylinositol anchor in the 3'-terminal of a LY6E paralog released modern three-finger toxins (3FTxs) from membrane tethering before the Colubroidea divergence. Subsequent expansion and mutations diversified and recruited these 3FTxs. After the cobra/krait divergence, the modern unit-B of β-bungarotoxin emerged with an extra cysteine residue. A subsequent point substitution in unit-A enabled the β-bungarotoxin covalent linkage. The B. multicinctus gene expression, chromatin topological organization, and histone modification characteristics were featured by transcriptome, proteome, chromatin conformation capture sequencing, and ChIP-seq. The results highlighted that venom production was under a sophisticated regulation. Our findings provide new insights into snake neurotoxin research, meanwhile will facilitate antivenom development, toxin-driven drug discovery and the quality control of JinQianBaiHuaShe.

Objective:To investigate the effect and regulation of umbilical cord-derived mesenchymal stem cells (UC-MSCs) on islets function and NOD-like receptor family, pyrin domain containing 3 (NLRP3) and autophagy in type 2 diabetic mellitus (T2DM) mice.Methods:Experimental study. Twenty, 8-week-old, male C57BL/6J mice were selected and divided into a normal control group ( n=5) and a high-fat feeding modeling group ( n=15). The model of T2DM was established by high-fat feeding combined with intraperitoneal injection of low-dose streptozotocin. After successful modeling, those mice were divided into a diabetes group ( n=7) and a UC-MSCs treatment group ( n=7). The UC-MSCs treatment group was given UC-MSCs (1×10 6/0.2 ml phosphate buffer solution) by tail vein infusion once a week for a total of 4 weeks; the diabetes group was injected with the same amount of normal saline, and the normal control group was not treated. One week after the treatment, mice underwent intraperitoneal glucose tolerance tests and intraperitoneal insulin tolerance tests, and then the mice were sacrificed to obtain pancreatic tissue to detect the expressions of interleukin-1β (IL-1β) and pancreatic and duodenal homeobox 1 (PDX-1) by immunofluorescence. The bone marrow-derived macrophages were stimulated with lipopolysaccharide and adenosine triphosphate (experimental group) in vitro, then co-cultured with UC-MSCs for 24 h (treatment group). After the culture, enzyme-linked immunosorbent assay was used to detect the secretion level of IL-1β in the supernatant, and immunofluorescence staining was used to detect the expression of NLRP3 inflammasome, and related autophagy proteins. Statistical analysis was performed using unpaired one-way analysis of variance, repeated measure analysis of variance. Results:In vivo experiments showed that compared with the diabetes group, the UC-MSCs treatment group partially repaired islet structure, improved glucose tolerance and insulin sensitivity (all P<0.05), and the expression of PDX-1 increased and IL-1β decreased in islets under confocal microscopy. In vitro experiments showed that compared with the experimental group, the level of IL-1β secreted by macrophages in the treatment group was decreased [(85.9±74.6) pg/ml vs. (883.4±446.2) pg/ml, P=0.001], the expression of NLRP3 inflammasome and autophagy-related protein P62 was decreased, and the expressions of microtubule-associated protein 1 light chain 3β (LC3) and autophagy effector Beclin-1 were increased under confocal microscopy. Conclusions:UC-MSCs can reduce the level of pancreatic inflammation in T2DM mice, preserving pancreatic function. This might be associated with the ability of UC-MSCs to inhibit the activity of NLRP3 inflammasomes in macrophages and enhance autophagy levels.

As an important element of medical and health sector innovation, the translation of scientific and technological achievements plays a key role in promoting their clinical application and meeting the medical needs of the people. The authors sorted out the problems in such translation at these affiliated hospitals in terms of " people", " finance", " material", and " system". Starting from 2017, the Tenth People′s Hospital Affiliated to Tongji University has explored such practices as establishing hospital-led clinical medical science and technology innovation parks and technology service limited companies. These practices aimed to address the issues of insufficient hospital scientific and technological innovation capabilities and the gap between the hospital′s operation mechanism to translate its scientific and technological achievements and the enterprises and the market. The clinical medical science and technology innovation park integrating administration, industry, education, research, medicine and application, has taken multiple measures to attract excellent research talents and projects from within and beyond the hospital, promote the implementation of innovative scientific research projects. The hospital also established a health industry mode with engagement of social capital from large enterprises. The Technology Services Co., Ltd. was based on the incubation and translation of hospital achievements, combining market and clinical needs, promoting multi-party cooperation between hospitals and external enterprises, improving the chain operation mechanism of hospital scientific and technological achievements translation work, and alleviating the problem of insufficient research pilot funds and productibility funds by means of hospital-led fundraising. The number of patent authorizations of hospitals had increased from 23 cases in 2018 to 105 in 2022, and the amount of patent conversion had increased from 2 million yuan in 2020 to 11 million yuan in 2022. It is recommended that affiliated hospitals of universities further improve the organizational structure of achievement translation, strengthen their professional talent teams, improve their operation mechanism of achievement translation, build a platform for medical school-enterprise cooperation, and improve the evaluation mechanism of translation assessment, in order to promote a virtuous cycle of hospital′s scientific and technological achievement translation work.

OBJECTIVES: To investigate the effect of borneol on cutaneous toxicity of gilteritinib and to explore possible compounds that can intervene with the cutaneous toxicity. METHODS: C57BL/6J male mice were given gilteritinib by continuous gavage for 28 d and the damage to keratinocytes in the skin tissues was observed with hematoxylin and eosin (HE) staining, TUNEL assay and immunohistochemistry. Human keratinocytes HaCaT were treated with gilteritinib, and cell death and morphological changes were examined by SRB staining and microscopy; apoptosis of HaCaT cells was examined by Western blotting, flow cytometry with propidium iodide/AnnexinⅤ double staining and immunofluorescence; the accumulation of cellular reactive oxygen species (ROS) was examined by flow cytometry with DCFH-DA. Compounds that can effectively intervene the cutaneous toxicity of gilteritinib were screened from a natural compound library using SRB method, and the intervention effect of borneol on gilteritinib cutaneous toxicity was further investigated in HaCaT cells and C57BL/6J male mice. RESULTS: In vivo studies showed pathological changes in the skin with apoptosis of keratinocytes in the stratum spinosum and stratum granulosum in the modeling group. Invitro studies showed apoptosis of HaCaT cells, significant up-regulation of cleaved poly (ADP-ribose) polymerase (c-PARP) and gamma-H2A histone family member X (γ-H2AX) levels, and increased accumulation of ROS in gilteritinib-modeled skin keratinocytes compared with controls. Screening of the natural compound library revealed that borneol showed excellent intervention effects on the death of HaCaT cells. In vitro, cell apoptosis was significantly reduced in the borneol+gilteritinib group compared to the gilteritinib control group. The levels of c-PARP, γ-H2AX and ROS in cells were significantly decreased. In vivo, borneol alleviated gilteritinib-induced skin pathological changes and skin cell apoptosis in mice. CONCLUSIONS Gilteritinib induces keratinocytes apoptosis by causing intracellular ROS accumulation, resulting in cutaneous toxicity. Borneol can ameliorate the cutaneous toxicity of gilteritinib by reducing the accumulation of ROS and apoptosis of keratinocytes in the skin tissue.
Male ; Humans ; Animals ; Mice ; Reactive Oxygen Species/metabolism* ; Poly(ADP-ribose) Polymerase Inhibitors/pharmacology* ; Mice, Inbred C57BL ; Apoptosis ; Poly(ADP-ribose) Polymerases/metabolism*

Interleukin (IL)-17A, a pro-inflammatory cytokine, is a fundamental function in the onset and advancement of multiple immune diseases. To uncover the primary compounds with IL-17A inhibitory activity, a large-scale screening of the library of traditional Chinese medicine constituents and microbial secondary metabolites was conducted using splenic cells from IL-17A-GFP reporter mice cultured under Th17-priming conditions. Our results indicated that some aureane-type sesquiterpene tetraketides isolated from a wetland mud-derived fungus, Myrothecium gramineum, showed remarkable IL-17A inhibitory activity. Nine new aureane-type sesquiterpene tetraketides, myrogramins A-I ( 1, 4- 11), and two known ones ( 2 and 3) were isolated and identified from the strain. Compounds 1, 3, 4, 10, and 11 exhibited significant IL-17A inhibitory activity. Among them, compound 3, with a high fermentation yield dose-dependently inhibited the generation of IL-17A and suppressed glycolysis in splenic cells under Th17-priming conditions. Strikingly, compound 3 suppressed immunopathology in both IL-17A-mediated animal models of experimental autoimmune encephalomyelitis and pulmonary hypertension. Our results revealed that aureane-type sesquiterpene tetraketides are a novel class of immunomodulators with IL-17A inhibitory activity, and hold great promise applications in treating IL-17A-mediated immune diseases.

Objective:To analyze the characteristics of sleep disorders in patients with Parkinson disease (PD) and to explore the relationship between respiratory events and rapid eye movement sleep with hypotonia.Methods:Thirty-nine PD patients compared with 75 controls matched with gender, age and body mass index(BMI) were collected in the Dalian Municipal Central Hospital from January 1, 2019 to September 31, 2019. Both groups underwent polysomnography monitoring. The characteristics of sleep disorders were analyzed and discussed.Results:Apnea and hypopnea index (AHI) during total sleep, AHI during non-rapid eye movement(NREM) sleep, AHI during rapid eye movement (REM) sleep, obstructive apnea index, mixed apnea index, central apnea index, total apnea index, hypopnea index, the time with pulse oximetry <90% and oxygen desaturation index in the PD group were lower than those in the control group: 3.70(0.80, 20.00) /h vs. 17.30(7.30, 28.20)/h, 2.30(0.70, 13.90)/h vs. 15.20(4.90, 27.50)/h, 2.30(0.00, 29.80)/h vs. 16.90(5.70, 39.50)/h, 0.30(0.00, 5.10)/h vs. 3.10(0.50, 7.80)/h, 0.00(0.00, 0.20)/h vs. 0.20(0.00, 0.60)/h, 0.00(0.00, 0.30)/h vs. 0.30(0.00, 0.80)/h, 0.70(0.00, 6.00)/h vs. 3.90(0.80, 10.70)/h, 1.70(0.50, 8.90)/h vs. 8.70(2.70, 14.90)/h, 0.00(0.00, 0.40)min vs. 0.20(0.00, 1.70)min, 4.10(1.10, 18.40)% vs. 16.50(9.30, 30.80)%, and the differences were statistically significant ( P<0.05). The mean pulse oximetry and minimum pulse oximetry in the PD group were higher than those in the control group: 96.00(95.00, 97.00)% vs. 95.00(94.00, 96.00)%, 89.00(82.00, 91.00)% vs. 85.00(81.00, 89.00)%, and the differences were statistically significant ( P<0.05). PD group was divided into PD with RSWA group (PD + RSWA) and PD without RSWA group (PD-RSWA) according to whether there was atonia or not. AHI during REM sleep in the PD+RSWA group was lower than that in the PD-RSWA group: 0.00(0.00, 5.40)/h vs. 5.75(0.52, 34.57)/h, and the difference was statistically significant ( P<0.05). Conclusions:PD has a protective effect on nocturnal respiratory events, which may be due to the increased muscle tone of upper airway.

Acute gastrointestinal dysfunction is a common and important complication of sepsis. As no exiting formal definition and classification of gastrointestinal dysfunction, most of the treatment strategies for gastrointestinal dysfunction are not based on clinical evidence, but on their own clinical experience. Experts of traditional Chinese medicine, integrated traditional Chinese and Western medicine and Western medicine from various disciplines in Shanghai are organized by the Shanghai Society of Integrated Traditional Chinese and Western Medicine and the Emergency Department Branch of Shanghai Physicians Association. After repeated discussion, literature search and formulation of the outline, we developed consensus on gastrointestinal dysfunction secondary to sepsis with integrating Traditional Chinese Medicine and Western medicine by consulting extensively on clinical experts in the fields of emergency medicine, gastroenterology, general surgery, infectious medicine and traditional Chinese medicine, and holding several expert forums and consultation meetings. This clinical expert consensus focused on acute gastrointestinal injury (AGI) classification and inducer of sepsis. In this consensus, the common symptoms, diagnosis, classifications, treatment strategies and suggestions of acute gastrointestinal injury or dysfunction secondary to sepsis were explored from the aspect of both Traditional Chinese Medicine and Western medicine.

Objective:To investigate the risk factors of hyperglycemia during pregnancy and its correlation with adverse pregnancy outcomes based on the retrospective analysis of glucose metabolism of pregnant women in Chongming area.Methods:A total of 604 singleton pregnant women who underwent prenatal examination and delivered normally in the Chongming branch of Xinhua Hospital from September 2019 to May 2021 were enrolled in the study. All subjects were divided into normal glucose tolerance gestation (NGTG) group and gestational diabetes mellitus (GDM) group. Pregnant women whose blood glucose exceeded normal but did not meet the diagnostic criteria of GDM were classified into the intermediate state gestational blood glucose (ISGBG) group. Questionnaire, physical examination, and relevant laboratory tests were completed. Data were analyzed using the Statistical Product and Service Solutions 13.0 (SPSS, Chicago, IL).Results:The incidence rate of GDM was 20.86% (126/604), ISGBG was 40.39% (244/604), and NGTG was 38.74% (234/604) in 604 pregnant women. Multivariate logistic regression analysis showed that gestational age ( OR=1.092, P<0.001), serum triglyceride ( OR=1.625, P=0.001) and free T 3 levels ( OR=1.995, P=0.002) were independent risk factors for GDM. The incidence of pregnancy-induced hypertension, cesarean section, macrosomia, the total incidence of adverse pregnancy outcomes and fetal birth weight in ISGBG and GDM were significantly higher than those in NGTG ( P<0.05 or P<0.01). Conclusion:The incidence of GDM in Chongming area is high, especially higher in that of ISGBG. As both GDM and ISGBG lead to increased adverse pregnancy outcomes, early monitoring should be paid more attention to pregnant women in ISGBG in addition to the early intervention of GDM.

Objective    To systematically evaluate the expression of programmed cell death receptor 1 (PD-1) and programmed cell death ligand 1 (PD-L1) in esophageal squamous cell carcinoma and its relationship with prognosis. Methods    The literature from PubMed, EMbase, The Cochrane Library, Web of Science, CNKI and Wanfang data from inception to February 22, 2020 was searched by computer. Data were extracted and the quality of literature was evaluated using RevMan 5.3 software for meta-analysis. Egger's and Begg's tests were used to evaluate publication bias, and Stata 15.1 software was used for sensitivity analysis. Results     A total of 16 articles were included, and there were 3 378 patients with esophageal squamous cell carcinoma. The methodological index for nonrandomized studies (MINORS) scores were all 12 points and above. The meta-analysis results showed that the positive expression rates of PD-1 and PD-L1 in tumor cells were 37.8% (190/504) and 41.7% (1 407/3 378), respectively. The positive expression of PD-L1 in tumor immune infiltrating cells was 41.7% (412/987). The overall survival (OS) of the tumor cell with high PD-L1 expression was lower than that with low PD-LI expression (HR=1.30, 95%CI 1.01-1.69, P=0.04). The OS of the tumor immune infiltrating cell with high PD-L1 expression was significantly higher than that with low PD-LI expression (HR=0.65, 95%CI 0.53-0.80, P<0.000 1). Conclusion    PD-L1 has a high expression rate in esophageal squamous cell carcinoma and is an important factor for the prognosis of esophageal squamous cell carcinoma.