ObjectiveTo retrospectively analyze the effect of modified Shugan Dingji Decoction （疏肝定悸汤） on the occurrence of endpoint events in patients with paroxysmal atrial fibrillation of liver constraint and qi stagnation. MethodsA retrospective cohort study was conducted using the electronic medical record database of Longhua Hospital affiliated to Shanghai University of Traditional Chinese Medicine to screen and include patients with paroxysmal atrial fibrillation of liver constraint and qi stagnation from January 1st， 2018， to December 31th， 2021. The included patients were divided into an exposure group and a non-exposure group， each consisting of 100 cases， based on whether they received modified Shugan Dingji Decoction. General information of the patients including age， gender， body mass index， duration of illness and comorbidities， medication history， cardiac structure and function indicators such as left atrial diameter， left ventricular end-diastolic diameter， stroke volume and ejection fraction， and the occurrence of endpoint events assessed through 24-hour dynamic electrocardiography or electrocardiogram to determine the recurrence of paroxysmal atrial fibrillation were collected. Kaplan-Meier （K-M） curves and Log-Rank tests were used to conduct survival analysis on the occurrence of endpoint events in the two groups of patients. Univariate and multivariate Cox regression analyses were used to analyze the impact of various factors on entry into endpoint events. Additionally， a safety assessment was performed by comparing liver and kidney function indicators before and after treatment. ResultsIn the non-exposure group， a total of 49 cases （49.0%） experienced endpoint events， while in the exposure group， there were 26 cases （26.0%）. The Log-rank test indicated significant difference between the two groups （χ²=11.211， P=0.001）. Univariate Cox regression analysis showed that age， duration of illness， hypertension， diabetes， chronic heart failure， left atrial diameter， stroke volume， and the use of modified Shugan Dingji Decoction may be the influencing factors for the occurrence of endpoint events in patients with paroxysmal atrial fibrillation of liver constraint and qi stagnation （P＜0.05 or P＜0.01）. Multivariate Cox regression analysis showed that the risk of endpoint events in the exposure group was significantly lower than that in the non-exposure group （P＜0.01）. Patients with a duration of illness ＞12 months had a significantly higher risk of endpoint events compared to those with a duration of illness ≤12 months （P＜0.01）. Patients without concomitant hypertension had a lower risk of endpoint events compared to those with hypertension （P＜0.05）. Patients with left atrial diameter ＞40 mm had significantly higher risk of endpoint events than those with left atrial diameter ≤40 mm （P＜0.01）. There was no statistically significant difference in liver and kidney function indicators between the two groups before and after treatment （P＞0.05）. ConclusionThe use of modified Shugan Dingji Decoction is a protective factor for patients with paroxysmal atrial fibrillation of liver constraint and qi stagnation， which can help to reduce the recurrence and progression of atrial fibrillation. Long duration of illness， concomitant hypertension， and enlarged left atrial diameter are risk factors for patients to experience endpoint events.

Hepatocellular carcinoma(HCC)has become the second leading cause of cancer-related death worldwide,ranking 6th among all tumors.Due to the lack of obvious early symptoms,most patients are diagnosed in the advanced stage,and the clinical benefits of surgical resection and hepatic artery chemoembolization and radiofrequency ablation are very limited.In recent years,the advent of immune-targeted therapies has revolutionized the systemic and systemic treatment of patients with advanced HCC,however,there is a lack of strong clinical evidence on the safety and efficacy of immune and targeted therapies for special populations,including patients with human immunodeficiency virus(HIV)infection,active autoimmune disease,decompensated cirrhosis(Child B or C),patients with diabetes-associated metabolic syndrome,patients with portal hypertension,vascular invasion,or portal vein thrombosis(PVT),and patients with liver transplantation(LT).This article reviews the current research progress of immune and targeted drugs in special populations.

Objective:To investigate the correlation between the expression of GLI1 and im-mune invasion and clinical prognosis in gastric cancer.To study the effect of GLI1 expression on drug resistance in gastric cancer.Methods:The expression difference of GLI1 in gastric cancer and normal tissues was analyzed by using TCGA database,and the effect of clinical features and GLI1 gene ex-pression level on prognosis of patients with gastric cancer was analyzed.The correlation between GLI1 gene expression and tumor immune cell infiltration in gastric cancer tissues was analyzed to explore its influence on drug resistance of chemotherapy drugs and targeted drugs.Clinical samples were collect-ed to analyze the difference of GLI1 expression in gastric cancer and paracancer tissues.Results:The expression of GLI1 in gastric cancer tissues was 1.7 times that in normal tissues,and the overall sur-vival and disease-free survival of patients with high expression are shorter than those with low ex-pression(P＜0.05).The interstitial score,immune score and abundance of immunoinfiltrating cells were higher in the high expression of GLI1 in gastric cancer tissues.High expression of GLI1 reduces drug sensitivity and is positively correlated with the expression of immune checkpoint markers PDCD1(P＜0.05).GLI1 expression was significantly increased in patients with subdifferentiated gastric cancer.Conclusions:GLI1 expression is associated with the prognosis and immune infiltration of patients with gastric cancer,and it may lead to poor prognosis of patients by regulating chemotherapy resis-tance,which may be a potential therapeutic target and molecular marker for gastric cancer.

Objective To investigate the effect of early activity combined with electrical stimulation of neuromuscular system in improving intensive care unit(ICU)-acquired weakness(ICU-AW)patients with severe pneumonia.Methods A total of 150 patients with ICU-AW caused by severe pneumonia admitted to emergency intensive care unit(EICU)in a tertiary hospital in Shanghai were enrolled as the study subjects,and randomly divided into control group(75 cases)and combined group(75 cases).The control group took early exercise,and the combination group was given early exercise plus electrical stimulation of neuromuscular system.The recovery from mechanical ventilation(ICU length of stay,duration of mechanical ventilation,weaning extubation rate,ICU rollout rate),lung function[forced vital capacity(FVC),forced expiratory volume in the 1 s(FEV1)/FVC,massive inspiratory pressure(MIP)],muscle strength[Medical Research Council(MRC)score],disease severity[acute physiology and chronic health evaluation Ⅱ(APACHEⅡ)],and complications were compared between the two groups.Results The ICU length of stay and mechanical ventilation time in the combined group were significantly lower than those in the control group(P<0.05).After intervention,FVC,FEV1/FVC,MIP and MRC scores in the two groups were significantly increased(P<0.05),and compared with the control group,the combined group was significantly increased(P<0.05).After intervention,APACHEⅡ score was significantly reduced in the two groups(P<0.05),and compared with the control group,APACHEⅡ score in combined group were significantly reduced(P<0.05).The complication rate in the combined group(9.33％)was significantly lower than that of control group(24.00％)(P<0.05).Conclusions Early exercise combined with neuromuscular electrical stimulation in patients with severe pneumonia ICU-AW can effec-tively promote recovery of patients because of improved lung function.This therapy is proved to be be safe and effective.

【Objective】 To investigate the clinical features, treatment methods and prognosis of advanced renal cell carcinoma (RCC) patients in Xinjiang, especially the Han population. 【Methods】 Clinical data of 233 patients with advanced RCC treated in The First Affiliated Hospital and The Affiliated Cancer Hospital of Xinjiang Medical University were retrospectively analyzed, including 133 Han patients.The median age of patients was 52 years (range: 23 to 87), and the maximum tumor diameter was (7.73±4.04) cm.Survival curves were plotted using the Kaplan-Meier method.Multivariate and univariate Cox regression analysis were conducted for all patients, and further analysis was performed for the Han patients. 【Results】 Among the 233 patients, 131 died during the average follow-up of 27.6 months (range: 1 to 120), and the median survival time was 12 months.In this cohort, 110 patients had lymph node metastasis, and 200 had distant metastasis, among them, 21 (10.5%) patients had brain metastasis and 45 (22.5%) patients had adrenal metastasis.The 1-, 3-, and 5-year survival rate were 48.9%, 18.3% and 6.1%, respectively.Univariate analysis revealed that International mRCC Database Consortium (IMDC) score, pathological type, lymph node metastasis, distant metastasis, number of metastatic foci and treatment methods impacted the prognosis in Xinjian (P<0.05).Multivariate analysis indicated that IMDC score, pathological type and distant metastasis were significant factors influencing the prognosis, which were also the prognostic factors of the Han patients (P<0.05). 【Conclusion】 In Xinjiang, patients with advanced renal cell carcinoma have a 6.1% 5-year survival rate and a median survival time of 12 months.Brain and adrenal metastases are common.Prognostic factors include IMDC score, pathological type, and distant metastasis for all patients, including the Han patients.

OBJECTIVE To investigate the effects of Taohong siwu decoction modified granules on podocyte epithelial- mesenchymal-transition （EMT） and renal fibrosis in diabetic kidney disease （DKD） model rats. METHODS Eight rats were selected as normal group （ordinary feed）； the remaining rats were given a high-glucose and high-fat diet combined with intraperitoneal injection of streptozotocin （35 mg/kg） to induce the DKD model. Model rats were randomly divided into model group， irbesartan group [positive control， 13.5 mg/（kg·d）] and modified Taohong siwu decoction group [6.48 g/（kg·d）]， with 8 rats in each group. All groups were given relevant medicine intragastrically， once a day， for 16 consecutive weeks. Twenty-four- hour urinary total protein （24 h UTP） was detected at the end of the 4th， 8th， 12th and 16th week of administration. After the last medication， the body mass， water intake， food intake， urine output， the levels of fasting blood glucose， serum creatinine （Scr） and blood urea nitrogen （BUN） as well as mRNA and protein expressions of P-cadherin， nephrin， α -smooth muscle actin （α-SMA）， Wilms’ tumor gene 1 （WT1）， transforming growth factor-β1（ TGF-β1） and type Ⅳ collagen （Col-Ⅳ） in renal tissue were determined. The pathological and morphological changes in renal tissue were observed and the thickness of the glomerular basement membrane was determined. RESULTS Compared with the model group， 24 h UTP of rats was significantly decreased in modified Taohong siwu decoction group since the 8th weekend （P＜0.05）； the body weight of rats increased significantly， but the amount of water intake and urine decreased significantly； Scr and BUN level， mRNA expression of α-SMA， mRNA and protein expressions of TGF-β1 and Col-Ⅳ were significantly reduced， while the mRNA expressions of P-cadherin， nephrin and WT1 were increased significantly （P＜0.05）； the protein deposition of α-SMA was reduced， protein depositions of P-cadherin， nephrin and WT1 were increased； the pathological damage and fibrosis of renal tissue were relieved； the thickness of glomerular basement membrane was decreased significantly （P＜0.05）. CONCLUSIONS Taohong siwu decoction modified granules can inhibit the EMT of podocyte in DKD model rats， and alleviate renal pathological damage and podocyte damage， thus protecting renal function， and delaying the process of renal fibrosis.

OBJECTIVE To investigate the effects of Taohong siwu decoction modified granules on podocyte epithelial- mesenchymal-transition （EMT） and renal fibrosis in diabetic kidney disease （DKD） model rats. METHODS Eight rats were selected as normal group （ordinary feed）； the remaining rats were given a high-glucose and high-fat diet combined with intraperitoneal injection of streptozotocin （35 mg/kg） to induce the DKD model. Model rats were randomly divided into model group， irbesartan group [positive control， 13.5 mg/（kg·d）] and modified Taohong siwu decoction group [6.48 g/（kg·d）]， with 8 rats in each group. All groups were given relevant medicine intragastrically， once a day， for 16 consecutive weeks. Twenty-four- hour urinary total protein （24 h UTP） was detected at the end of the 4th， 8th， 12th and 16th week of administration. After the last medication， the body mass， water intake， food intake， urine output， the levels of fasting blood glucose， serum creatinine （Scr） and blood urea nitrogen （BUN） as well as mRNA and protein expressions of P-cadherin， nephrin， α -smooth muscle actin （α-SMA）， Wilms’ tumor gene 1 （WT1）， transforming growth factor-β1（ TGF-β1） and type Ⅳ collagen （Col-Ⅳ） in renal tissue were determined. The pathological and morphological changes in renal tissue were observed and the thickness of the glomerular basement membrane was determined. RESULTS Compared with the model group， 24 h UTP of rats was significantly decreased in modified Taohong siwu decoction group since the 8th weekend （P＜0.05）； the body weight of rats increased significantly， but the amount of water intake and urine decreased significantly； Scr and BUN level， mRNA expression of α-SMA， mRNA and protein expressions of TGF-β1 and Col-Ⅳ were significantly reduced， while the mRNA expressions of P-cadherin， nephrin and WT1 were increased significantly （P＜0.05）； the protein deposition of α-SMA was reduced， protein depositions of P-cadherin， nephrin and WT1 were increased； the pathological damage and fibrosis of renal tissue were relieved； the thickness of glomerular basement membrane was decreased significantly （P＜0.05）. CONCLUSIONS Taohong siwu decoction modified granules can inhibit the EMT of podocyte in DKD model rats， and alleviate renal pathological damage and podocyte damage， thus protecting renal function， and delaying the process of renal fibrosis.

OBJECTIVE To investigate the protective effect and mechanism of quercetin on the cardiac and renal functions of rats with cardiorenal syndrome （CRS） based on the phosphoinositide 3-kinase （PI3K）/protein kinase B （Akt）/nuclear factor kappa- B （NF-κB） signaling pathway. METHODS CRS model of SD rats was induced by left anterior descending coronary artery ligation combined with acute renal ischemia-reperfusion. Model rats were randomly separated into model group， quercetin low-dose group （35 mg/kg）， quercetin high-dose group （70 mg/kg）， high-dose of quercetin+740Y-P group （70 mg/kg quercetin+3.5 mg/kg PI3K/Akt/ NF-κB signaling pathway activator 740Y-P）， with 12 rats in each group. Another 12 normal rats were selected as sham operation group. They were given relevant drugs， once a day， for 14 consecutive days. After administration， the cardiac function indexes [left ventricular ejection fraction （LVEF）， end-diastolic volume （EDV）， isovolumic relaxation time （IVRT）] and renal function indicators [blood urea nitrogen （BUN）， 24-hour urine protein， and serum creatinine （Scr）] were detected， and fibrosis in the cardiac and renal tissues was observed； the levels of inflammatory indexes [interleukin-1β （IL-1β） and tumor necrosis factor-α （TNF-α）] in the serum and cardiac and renal tissues as well as the expression of PI3K/Akt/NF-κB pathway-related proteins in the cardiac and renal tissues were detected. RESULTS Compared with sham operation group， the levels of BUN， 24-hour urine protein and Scr， collagen volume fraction of cardiac and renal tissues， the levels of IL-1β and TNF-α in serum and cardiac and renal tissues， and the phosphorylation of PI3K， Akt and NF-κB p65 protein in cardiac and renal tissues were increased significantly in model group （P＜0.05）； the levels of LVEF， IVRT and EDV were reduced significantly （P＜0.05）. Compared with the model group， the above indexes were reversed significantly in quercetin low-dose and high-dose groups （P＜0.05）， and the reversal effect was better in the high-dose group （P＜0.05）. 740Y-P restored the reverse effect of high-dose quercetin on the indexes （P＜0.05）. CONCLUSIONS Quercetin can alleviate cardiac and renal fibrosis and function injury， the mechanism of which may be 20232016） associated with inhibiting the activation of the PI3K/Akt/NF-κB signaling pathway.

BACKGROUND:Most of the studies on combined orthodontic-orthognathic treatment of skeletal class Ⅲ malocclusions have focused on the improvement of the patient's lateral appearance and recovery in the later stages of the treatment,while there are fewer studies observing the microcosmic nature of the alveolar bone remodeling of the lower anterior teeth. OBJECTIVE:To evaluate the therapeutic effect of lower anterior tooth decompensation and alveolar bone remodeling in patients with skeletal class Ⅲ malocclusion before and after orthodontic-orthognathic treatment based on oral X-ray lateral films and oral cone-beam CT. METHODS:From January 2015 to May 2023,15 patients with skeletal class Ⅲ malocclusion who underwent orthodontic-orthognathic surgery at Qingdao Hospital of Rehabilitation University were enrolled.All patients underwent lateral cephalography and cone beam computed tomography before and after treatment.Cephalometric measurement items related to the angle and line distance,lip/lingual bone cracking length(d-La/d-Li)and bone cracking/bone fenestration of the lower anterior teeth before and after treatment were measured. RESULTS AND CONCLUSION:Lateral X-ray films showed that the amount of alveolar bone remodeling after decompensation of the lower anterior teeth showed significant changes compared to before treatment.The root of the tooth moved significantly towards the center of the alveolar bone,and the specific data was closer to normal data,but there were still some differences compared with normal individuals.Based on the cone-beam CT measurement,the bone cracking/bone fenestration length and width of the alveolar bone were improved in almost all the teeth after orthodontic-orthognathic combined treatment,alveolar bone remodeling in some teeth even reached the level of healthy individuals.Before treatment,most patients often experienced bone fenestration/cracking on the lip/lingual side of the lower incisor due to compensatory tooth growth.However,during the preoperative orthodontic stage,decompensation triggered alveolar bone remodeling and significant changes in tooth angle.Preoperative orthodontic treatment caused the upper anterior teeth to retract and the lower anterior teeth to tilt and control the root,but the amount of decompensation before surgery was often insufficient.In the orthognathic surgery stage,the jaw was removed through the positioning guide plate,the maxilla moved forward,and the mandible retreated.During the postoperative orthodontic process,the effect of fine adjustment was better.Although there is a certain degree of recurrence trend in the position of teeth and jawbones,the postoperative orthodontic treatment is closer to the normal value.

BACKGROUND:Acupotomy is effective in the treatment of knee osteoarthritis,but its mechanism is not very clear. OBJECTIVE:To observe the effect of acupotomy on the apoptosis of knee chondrocytes in knee osteoarthritis rats based on osteoclast associated receptor(OSCAR)-tumor necrosis factor-associated apoptosis-inducing ligand(TRAIL)-osteoprotetin(OPG)pathway. METHODS:Twenty-seven Sprague-Dawley rats were randomly divided into normal group(n=9),model group(n=9)and acupotomy group(n=9).Rats in the normal group were routinely housed without any treatment.Animal models of knee osteoarthritis were established by knee injection of papain.Acupotomy intervention was performed 1 week after modeling,once a week for a total of three times.Relevant tests were performed at the end of the intervention. RESULTS AND CONCLUSION:The Lequesne MG behavioral scores of rats in the model group were elevated compared with the normal group(P<0.01),while the Lequesne MG behavioral scores of rats in the acupotomy group were decreased comparedwith the model group(P<0.01).Hematoxylin-eosin staining results showed that compared with the normal group,the cartilage surface of the rat's knee joints in the model group was worn and uneven and the chondrocytes were swollen,ruptured,reduced in number,and arranged disorderly;while the cartilage surface of the rat's knee joints in the acupotomy group was relatively smooth,and the chondrocytes were high in number and arranged in an orderly manner,with the structure basically clear.Immunohistochemical staining results showed that compared with the normal group,the positive expressions of OSCAR and TRAIL were increased in the model group(P<0.01),while the positive expression of OPG was decreased(P<0.01).Compared with the model group,the positive expressions of OSCAR and TRAIL in the acupotomy group were decreased(P<0.01),while the positive expression of OPG was increased(P<0.01).TUNEL staining results showed that compared with the normal group,the number of apoptotic cells in the model group were increased(P<0.01);compared with the model group,the number of apoptotic cells in the acupotomy group decreased(P<0.01).RT-qRCR and western blot results showed that compared with the normal group,the protein expressions of OSCAR,TRAIL and Bax in the model group were increased(P<0.01),and the protein expressions of OPG and Bcl-2 were decreased(P<0.01);compared with the model group,the protein expressions of OSCAR,TRAIL,and Bax in the acupotomy group were decreased(P<0.01),and the protein expressions of OPG and Bcl-2 were increased(P<0.01).To conclude,acupotomy can reduce cartilage injury of the knee joint in rats with knee osteoarthritis,which may be related to the blockage of mitochondrial pathway apoptotic signaling release by the OSCAR-TRAIL-OPG pathway.