Based on the viewpoint of "sweat pore-qi and liquid-kidney collaterals"， it is believed that children's nephrotic syndrome is caused by the core mechanism of sweat pore constraint and closure， qi and liquid imbalance， and kidney collaterals impairment， and it is proposed that the treatment principle is to nourish the sweat pore， regulate qi and fluid， and supplement the kidney and unblock the collaterals. In clinic， guided by sequential therapy and according to the different disease mechanism characteristics of the four stages， including early stage of the disease， hormone induction stage， hormone reduction stage， hormone maintenance stage， the staged dynamic identification and treatment was applied. For early stage of the disease with edema due to yang deficiency， modified Zhenwu Decoction （真武汤） was applied to warm yang and drain water； for hormone induction stage with yin deficiency resulting in effulgent fire， modified Zhibai Dihuang Pill （知柏地黄丸） plus Erzhi Pill （二至丸） was used to enrich yin and reduce fire； for hormone reduction stage with qi and yin deficiency， modified Shenqi Dihuang Decoction （参芪地黄汤） was used to boost qi and nourish yin； for hormone maintenance stage， modified Shenqi Pill （肾气丸） was used to supplement yin and yang. Meanwhile， the treatment also attaches importance to the combination of vine-based or worm medicinals to dredge collaterals， so as to providing ideas for clinical treatment.

ObjectiveTo investigate the potential mechanism of Liangxue Tuizi Formula （凉血退紫方， LXTZF） in treating Henoch-Schönlein Purpura （HSP） by examining its regulatory effect on neutrophil extracellular trap （NETs） dysregulation via the rapidly accelerated fibrosarcoma kinase （RAF）/mitogen-activated protein kinase （MEK）/extracellular signal-regulated kinase （ERK） signaling pathway. MethodsSeventy Wistar rats were randomly allocated into a blank control group （n=14） and a modeling group （n=56）. Rats in the modelling group underwent an eight-week modelling period to establish HSP rat models with blood-heat syndrome via modified ovalbumin （OVA） induction method combined with oral administration of heat-property Chinese herbal medicine. Fifty successfully modeled rats were subsequently randomly divided into five groups （n=10 per group）， model group， compound glycyrrhizin group， LXTZF group， RAF inhibitor group， and LXTZF + RAF agonist group. Additionally， 10 rats were selected from the original blank control group for the final experiment. From the 11th week of modelling， rats in the blank control group and the model group received 1 ml/（100 g·d） ultrapure water via oral administration， in addition to 0.5 ml/（kg·d） 0.9% sodium chloride solution via intraperitoneal injection. The LXTZF group and the compound glycyrrhizin group received 7.5 g/（kg·d） LXTZF granule suspension via gavage， 13.5 mg/（kg·d） compound glycyrrhizin suspension via gavage， respectively. The RAF inhibitor group received 1 mg/（kg·d） GW5074 suspension via intraperitoneal injection and ultrapure water via oral administration； the LXTZF + RAF agonist group received 7.5 g/（kg·d） LXTZF granule suspension via gavage and 1 mg/（kg·d） paclitaxel suspension via intraperitoneal injection. All administrations were performed once daily for 4 weeks. After intervention， skin tissue histopathology was examined by hematoxylin and eosin （H&E） staining， immunoglobulin A （IgA） deposition was assessed via immunofluorescence， serum levels of neutrophil elastase （NE）， tumor necrosis factor-α （TNF-α）， and vascular cell adhesion molecule-1 （VCAM-1） were measured using enzyme-linked immunosorbent assay （ELISA）， serum myeloperoxidase （MPO） level was determined by a colorimetric assay； the mRNA expression levels of RAF， MEK， and ERK in skin tissue were detected by real-time quantitative polymerase chain reaction （RT-qPCR）； and the protein expression of RAF， MEK， ERK， as well as phosphorylated MEK （p-MEK） and phosphorylated ERK （p-ERK）， were analyzed by Western Blot. ResultsSkin tissue in the blank control group rats remained normal， whereas the model group exhibited neutrophil infiltration and haemorrhage with red blood cell rupture. In all drug intervention groups， neutrophil infiltration and haemorrhagic exudation reduced markedly， with LXTZF group demonstrating the most pronounced improvement. Compared with the blank control group， rats in the model group exhibited enhanced IgA fluorescence intensity in skin tissue， elevated serum levels of NE， MPO， TNF-α and VCAM-1， increased mRNA expression of RAF， MEK， ERK1 and ERK2， as well as heightened RAF protein levels and p-MEK/MEK and p-ERK/ERK ratios （P＜0.05）. Compared with the model group， the drug intervention groups exhibited reduced IgA fluorescence intensity in skin tissue， along with decreased serum levels of NE， MPO， TNF-α， and VCAM-1 （P＜0.05）. In LXTZF group and RAF inhibition groups， reduced mRNA expression of RAF， MEK， ERK1， and ERK2 was observed in rat skin tissue， alongside decreased RAF protein levels and reduced p-MEK/MEK and p-ERK/ERK ratios （P＜0.05）. Compared with LXTZF + RAF agonist group， the compound glycyrrhizin group， LXTZF group， and RAF inhibitior group exhibited reduced IgA fluorescence intensity in skin tissue， decreased serum NE， MPO， TNF-α， and VCAM-1 levels， and decreased MEK mRNA expression and p-MEK/MEK ratio （P＜0.05）. ConclusionThe potential mechanism by which LXTZF treats Henoch-Schönlein purpura with blood heat syndrome may involve blocking the RAF/MEK/ERK signaling pathway in skin tissue， and suppressing excessive formation of NETs， thereby reducing IgA deposition in dermal microvessels and attenuating systemic inflammatory responses.

Objective To investigate the effect of palmitoleic acid(POA)on pyroptosis of cardiomyocytes after hy-poxia/reoxygenation-induced injury in the human myocardium.Methods The experiment comprised a control group(Control,normal culture),a hypoxia/reoxygenation group(HR),a palmitoleic acid-treated group(HR+POA),and an anhydrous ethanol control group(HR+ET).Cardiomyocytes viability was assessed using CCK-8 assay,and the level of pyroptosis of cardiomyocytes was measured through the double staining with Hoechst33342/PI and LDH assay.ELISA was employed to detect the release of inflammatory factors IL-1 β and IL-18 in the cell culture supernatant.qRT-PCR and Western blot were utilized to determine the relative expression levels of mRNA and protein of pyroptosis-related genes,namely NLRP3,ASC,Caspase-1,GSDMD,IL-1 β and IL-18,respective-ly.Results CCK-8 assay showed that the survival of hypoxic/reoxygenated cardiomyocytes increased with the ad-dition of POA at concentrations ranging from 25 to 100 μmol/L,as compared to the HR group;a hypoxia/reoxy-genation model of cardiomyocyte was established.The expression of protein and mRNA increased in NLRP3,ASC,Cleaved caspase-1,GSDMD-N,IL-Iβ and IL-18 vs the control group(P＜0.05),the positive percentage of Ho-echst33342/PI staining in cardiomyocytes increased significantly(P＜0.05),the release of LDH,IL-Iβ,and IL-18 increased(P＜0.05).After intervention with 100 μmol/L POA,the protein and mRNA expression levels of NLRP3,ASC,Cleaved caspase-1,GSDMD-N,IL-Iβ,and IL-18 were significantly reduced in the HR+POA group vs HR+ET group(P＜0.05).The positive percentage of Hoechst33342/PI staining in cardiomyocytes de-creased significantly,and the levels of LDH,IL-Iβ and IL-18 significantly decreased(P＜0.05).Conclusion Palmitoleic acid may alleviate hypoxia/reoxygenation-induced injury of cardiomyocytes by inhibiting pyroptosis and inflammatory response after hypoxia/reoxygenation in human myocardium.

The problems caused by proximal contact loss(PCL)of dental implants have been a mainstream research topic in recent years,and scholars are unanimously committed to analyzing their causes and related factors,aiming to identify solutions to the problems related to PCL.The effects of the anterior component of force(ACF),the lifelong re-molding of the adult craniofacial jaw and alveolar socket,and the osseointegration characteristics of dental implants are the main causes of PCL.On the one hand,the closing movement of the mandible causes the ACF of the tooth to move through the posterior molar cusp.Moreover,drifting between the upper and lower posterior teeth and mandibular anteri-or teeth can cause the anterior teeth of the upper and lower jaws to be displaced labially.On the other hand,reconstruc-tion of the jaw,alveolar socket and tooth root,the forward horizontal force of the masticatory muscles,the dynamic com-ponent of the jaw and the forward force generated by the oblique plane of the tooth cusp can cause the natural tooth to experience near-middle drift.Additionally,natural teeth can shift horizontally and vertically and rotate to accommodate remodeling of the stomatognathic system and maintain oral function.Nevertheless,the lack of a natural periodontal mem-brane during implant osseointegration,the lack of a physiological basis for near-medium drift,the small average degree of vertical motion and the integrated silence of dental implants without the overall drift characteristics of natural teeth increases the probability of PCL.The high incidence of PCL is clearly associated with the duration of prosthesis delivery and the mesial position;but it is also affected by the magnitude of the bite force,occlusion,the adjacent teeth,restora-tion design,implant location,jaw,and patient age and sex.PCL has shown a significant correlation with food impaction,but not a one-to-one correspondence,and did not meet the necessary and sufficient conditions.PCL is also associated with peri-implant lesions as well as dental caries.PCL prevention included informed consent,regular examinations,se-lection of retention options,point of contact enhancement,occlusal splints,and the application of multipurpose digital crowns.Management of the PCL includes adjacent contact point additions,orthodontic traction,and occlusal adjust-ment.Existing methods can solve the problem of food impaction in the short term with comprehensive intervention to seek stable,long-term effects.Symmetric and balanced considerations will expand the treatment of issues caused by PCL.

Objective:To investigate the safety of early antiplatelet therapy for non-cardioembolic mild stroke patients with thrombocytopenia.Methods:Data of acute ischemic stroke patients with baseline National Institutes of Health Stroke Scale(NIHSS)score≤3 and a platelet count<100×109/L were obtained from a multicenter register.Those who required anticoagulation or had other contraindications to antiplatelet therapy were excluded.Short-term safety outcomes were in-hospital bleeding events,while the long-term safety outcome was a 1-year all-cause death.The short-term neurological outcomes were evaluated by modified Rankin scale(mRS)score at discharge.Results:A total of 1868 non-cardioembolic mild stroke patients with thrombocytopenia were enrolled.Multivariate regression analyses showed that mono-antiplatelet therapy significantly increased the proportion of mRS score of 0-1 at discharge(OR=1.657,95%CI:1.253-2.192,P<0.01)and did not increase the risk of intracranial hemorrhage(OR=2.359,95%CI:0.301-18.503,P>0.05),compared with those without antiplatelet therapy.However,dual-antiplatelet therapy did not bring more neurological benefits(OR=0.923,95%CI:0.690-1.234,P>0.05),but increased the risk of gastrointestinal bleeding(OR= 2.837,95%CI:1.311-6.136,P<0.01)compared with those with mono-antiplatelet therapy.For patients with platelet counts≤75×109/L and>90×109/L,antiplatelet therapy significantly improved neurological functional outcomes(both P<0.05).For those with platelet counts(>75-90)×109/L,antiplatelet therapy resulted in a significant improvement of 1-year survival(P<0.05).For patients even with concurrent coagulation abnormalities,mono-antiplatelet therapy did not increase the risk of various types of bleeding(all P>0.05)but improved neurological functional outcomes(all P<0.01).There was no significant difference in the occurrence of bleeding events,1-year all-cause mortality risk,and neurological functional outcomes between aspirin and clopidogrel(all P>0.05).Conclusions:For non-cardioembolic mild stroke patients with thrombocytopenia,antiplatelet therapy remains a reasonable choice.Mono-antiplatelet therapy has the same efficiency as dual-antiplatelet therapy in neurological outcome improvement with lower risk of gastrointestinal bleeding.

Objective To investigate the efficacy of low-dose inhaled nitric oxide (iNO) in the treatment of severe hypoxemia after Sun’s operation. Methods The clinical data of patients undergoing Sun’s operation for acute Type A aortic dissection in our hospital from January 2020 to June 2022 were retrospectively analyzed. Patients who received conventional treatment before November 2021 were enrolled as a control group. After November 2021, iNO was used in our hospital, and the patients who received iNO as an iNO group. The preoperative clinical baseline data, perioperative clinical data and oxygenation index were compared between the two groups. Results A total of 54 patients were included in the control group, including 45 males and 9 females, with an average age of 53.0±10.9 years. A total of 27 patients were included in the iNO group, including 21 males and 6 females, with an average age of 52.0±10.6 years. The preoperative body mass index of the two groups was greater than 25 kg/m2, white blood cell count, C-reactive protein were significantly higher than normal level, but there was no statistical difference between the groups (P＞0.05). There were no statistical differences in intraoperative data between the two groups (P＞0.05). The iNO group had significantly shorter duration of mechanical ventilation, postoperative ICU stay, and postoperative hospital stay than the control group (P<0.001). After 12 h of iNO treatment, hypoxic condition improved obviously, oxygenation indices in 12 h, 24 h, 36 h,48 h, 60 h and 72 h in the iNO group were significantly higher than those in the control group (P<0.05). Conclusion The treatment of severe hypoxemia after Sun’s surgery with low-dose of iNO is safe and effective, can significantly improve oxygenation function, and has significant advantages in shortening ventilator use time, postoperative ICU stay and postoperative hospital stay, but it is not significant in changing postoperative mortality.

Hepato-pancreato-biliary diseases (HPBD) are often complicated. The diagnosis and treatment of HPBD involve many disciplines. The malignant degree of hepatobiliary pancreatic system is high, and the prognosis of patients is poor. The multidisciplinary team (MDT) brings specialists from different disciplines together to make a comprehensive and individualized treatment for patients. MDT is emerging in HPBD in recent years. MDT helps improve the accuracy of diagnosis and prognosis. However, there are still some controversies and obstacles in the application of MDT for patients with HPBD. We reviewed the development, current status and experience of MDT in the field of HPBD, analyze the current controversy and obstacles, and providing reference for its future application.

Based on WANG Xugao's “thirty methods of treating the liver”， it is believed that the occurrence and development of childhood tic disorders follow the dynamic progression from liver qi disease to liver fire disease and then liver wind disease. The basic pathogenesis of three stages are characterized by binding constraint of liver qi， liver fire hyperactivity， and internal stirring of liver wind. Moreover， liver-blood deficiency and stagnation， and malnutrition of liver yin as the main point in terms of the imbalance of liver qi， blood， yin， and yang should be considered， as well as the imbalance relationship of the five zang organs such as the involvement of other organs and the gradually reach of the other organs. Guided by the principles of “thirty methods of treating the liver”， the treatment of tic disorders in liver qi stage should focus on soothing the liver and rectifying qi， soothing the liver and unblocking the collaterals， using Xiaochaihu Decoction （小柴胡汤） and Sini Powder （四逆散）. The treatment of tic disorders in liver fire stage involves clearing， draining and resolving liver heat， using Longdan Xiegan Decoction （龙胆泻肝汤）， Xieqing Pill （泻青丸）， Danggui Longhui Pill （当归龙荟丸）， and Huagan Decoction （化肝煎）. The treatment of tic disorders in liver wind stage involves extinguishing wind and subduing yang， using Lingjiao Gouteng Decoction （羚角钩藤汤） and Liuwei Dihuang Pill （六味地黄丸）. Throughout the treatment process， attention should be paid to harmonizing the liver's qi， blood， yin， and yang， as well as addressing the pathology of other organs.

Objective To investigate the effect of Mysm1 on the differentiation of neural stem cells(NSCs)into astrocytes and the possible mechanism.Methods NSCs were prepared from E12.5 cortices of wild-type C57BL/6 mice,cultured in vitro and induced to differentiate into astrocytes.Immunofluorescence staining,real-time quantitative PCR and Western blot assay were used to detect the expressions of Mysm1 during the differentiation of NSCs into astrocytes in vitro.Lentivirus was used to knock down Mysm1 expressions in NSCs before real-time quantitative PCR and Western blot assay were used to detect the knockdown efficiency.Immunofluorescence staining and Western blot assay were used to compare the differentiation of NSCs into astrocytes before and after Mysm1 knockdown in vitro.Transcriptomics was adopted to detect the differential gene after knockdown of Mysm1 in NSCs in vitro.Western blot assay was used to verify the changes of proteins associated with the differential gene.Cut-Tag was used to detect the enrichment of Mysm1 in the promoter region of glial fibrillary acidic protein(GFAP)genes during the differentiation of NSCs into astrocytes in vitro.After overexpression of GFAP following knockdown of Mysm1,immunofluorescence staining and Western blot assay were used to compare the differentiation of NSCs into astrocytes before and after overexpression in vitro.Results The expression of Mysm1 was gradually increased when NSCs were induced to differentiate into astrocytes in vitro.Mysm1 knockdown inhibited the differentiation of NSCs into astrocytes in vitro.Mysm1 affected the differentiation of NSCs into astrocytes by regulating the expression of GFAP.Overexpression of GFAP after Mysm1 knockdown partially rescued the ability of NSCs to differentiate into astrocytes.Conclusion Mysm1 regulates the differentiation of NSCs into astrocytes by epigenetically controlling GFAP transcription.

Objective:To discuss the effect of the small ubiquitin-like modifier-specific protease 1(SENP-1)/hypoxia-inducible factor 1α(HIF-1α)pathway on chronic intermittent hypoxia(CIH)-induced vascular endothelial injury in the rats,and to clarify the related mechanism.Methods:The SD rats were randomly divided into control group and CIH group,and then the rats in each group were further divided into 2,4,and 6-week subgroups,and there were 8 rats in each subgroup.The rats in CIH group were exposed to CIH in a CIH chamber to induce CIH and create the obstructive sleep apnea hypopnea syndrome(OSAHS)models,while the rats in control group were exposed to normoxic conditions.The serum and thoracic aorta tissue of the rats in various groups were collected at each time point.HE staining was used to observe the thoracic aorta vascular injury of the rats in various groups;ELISA method was used to detect the levels of nitric oxide(NO),endothelin-1(ET-1),von Willebrand factor(vWF),and thrombomodulin(TM)in serum of the rats in various groups;Western blotting method was used to detect the expression levels of SENP-1,HIF-1α,and vascular endothelial growth factor A(VEGFA)proteins in thoracic aorta tissue of the rats in various groups.In vitro,the aortic endothelial cells(rAECs)of the rats were cultured and infected with SENP-1 shRNA adenovirus(sh-SENP-1)to construct the cell line with low expression of SENP-1.The CIH was used to induce the vascular endothelial cell injury,and the cells were divided into CIH group,CIH+sh-NC group,and CIH+sh-SENP-1 group;control group was set up separately.CCK-8 method was used to detect the proliferation activities of the cells in various groups;ELISA method was used to detect the activities of lactate dehydrogenase(LDH)in the supernatant and the levels of NO,ET-1,malondialdehyde(MDA),and activities of superoxide dismutase(SOD)in the cells in various groups;flow cytometry was used to detect the apoptotic rates of the cells in various groups;Western blotting method was used to detect the expression levels of SENP-1,HIF-1α,and VEGFA proteins in the cells in various groups.Results:With the extension of CIH induction time,compared with control group,the thoracic aorta endothelium in CIH group gradually became rough and significantly thickened,the level of serum NO of the rats in CIH group was decreased(P＜0.05),and the levels of serum ET-1,vWF,and TM,and the expression levels of SENP-1,HIF-1α,and VEGFA proteins in thoracic aorta tissue were increased(P＜0.05).Compared with control group,the proliferation activity of the cells in CIH group was decreased(P＜0.05),the LDH activity in the supernatant,the levels of ET-1,MDA,and the apoptotic rate in the cells were increased(P＜0.05),while the levels of NO and activity of SOD in the cells were decreased(P＜0.05),and the expression levels of SENP-1,HIF-1α,and VEGFA proteins in the cells were increased(P＜0.05).Compared with CIH group,the proliferation activity of cells in CIH+sh-SENP-1 group was increased(P＜0.05),the activity of LDH in the supernatant,the levels of ET-1,MDA,and the apoptotic rate of the cells were decreased(P＜0.05),while the level of NO and activity of SOD in the cells were increased(P＜0.05),and the expression levels of SENP-1,HIF-1α,and VEGFA proteins were decreased(P＜0.05).Conclusion:The SENP-1/HIF-1α pathway is highly activated in the thoracic aorta injury tissue of the rats induced by CIH.Silencing SENP-1 expression can reduce CIH-induced vascular endothelial cell injury,and its mechanism may be related to downregulating the activation level of SENP-1/HIF-1α pathway.