BACKGROUND: Ghildren refractory clubfoot includes idiopathic multiple contracture, untreated idiopathic clubfoot in older children and failure cases of repeated operations. It is very difficult to treat this type of children patients. It has important significance in the exploration of new therapeutic methods.OBJECTIVE: To improve the therapeutic effectiveness of refractory clubfoot in children with Ilizarov method.DESIGN: a self-controlled study.SETTING: Department of Orthopedics, Nanjing Children' s Hospital, Nanjing Medical University.PARTICIPANTS: Totally 3 cases of children idiopathic multiple contracture, 2 cases of idiopathic clubfoot in children aged more than 10 years old without treatment and 6 cases of postoperative recurrent idiopathic clubfoot were admitted by the Department of Orthopedics of Nanjing Children' s Hospital Affiliated to Nanjing Medical University during 1999 to 2000. All cases manifested abnormal ankylosis and shortening deformity in foot.METHODS: Twelve refractory clubfeet in eleven patients were treated with the Ilizarov method. After achilles tendon lengthening and posterior release,kieschner' wires or olive wires with tension were penetrated through multiple planes of the middle lower 1/3 of tibia, calcaneus and the 1st to the 5th metatarsals, which were fixed respectively to external bone fixer of a ring,half-ring or horseshoe shape and connected with each other by multiple screw bars into a three-dimensional external bone fixing set. Plantarflexion, inversion, adduction and shortening deformities were corrected by the adjustment of the distance between each part of the external bone fixing set through extension, compression, and rotation, etc., and navicular and cuboid osteotomy.MAIN OUTCOME MEASURES: All 11 cases were followed up for 2 to 10 years with an average period of 4. 5 years. Indices like foot morphology,talocrural articualr activity range and deformity correction were observed during the follow up.RESULTS: The results were excellent in 5 cases (6 feet), good in 4 cases (4 feet), fair 2 cases(2 feet) according to the Garceau standard scale. The rate of excellent and good clinical results was 83.3%. Mild forefoot adduction was left in 2 feet of 2 cases and quite obvious tarsal articular ankylosis was found in 4 feet of 4 cases; however, there were no significant differences of gait and load bearing between these patients and normal children.CONCLUSION: The Ilizarov technique is a safe and effective method for the treatment of refractory children clubfoot while its indications should be controlled strictly.

Objective To investigate the clinical features of drug-induced autoimmune hepatitis (DIAIH) and its therapeutic strategies,and to provide a reference for early diagnosis and treatment of this disease and prevention of chronicity.Methods The clinical data of 116 patients with drug-induced liver injury (DILI) or DIAIH confirmed by medical history,liver biochemistry,and liver biopsy were analyzed retrospectively.Among these patients,13 had DIAIH and 103 had simple DILI (30 patients in the hepatocytetype group and 73 in the cholestasis/mixed-type group).The population characteristics,major drugs inducing the diseases,clinical manifestations,liver biochemical parameters,liver pathological features,and clinical outcome were compared between groups.The Kruskal-wallis H test was used for comparison and the Mann-Whitney U test was used for comparison between any two groups.The chi-square test was used for comparison of categorical data,and the R×C chi-square test was used for comparison of rates between the three groups;in the case of significant differences,the R×C contingency table was used for comparison between any two groups.Results The patients with DIAIH had a mean age of 53.54±8.28 years,and the mean age was 35.13±13.46 and 46.99±14.82 years for the hepatocyte-type group and cholestasis/mixedtype group,respectively.The disease was mainly induced by a combination of various drugs.The patients with DIAIH had significantly higher serum levels of alanine aminotransferase,aspartate aminotransferase,γ-glutamyltransferase,and alkaline phosphatase and a significantly higher positive rate of anti-nuclear antibody than those with DILI (all P ＜ 0.05).In patients with DIAIH,the liver pathological features and the features of response to treatment were as follows:obvious interface hepatitis,proliferation of small bile ducts,and mixed inflammatory cell infiltration in the portal area,including eosinophils and plasma cells,and the short-term corticosteroid therapy had a good therapeutic effect.Conclusion DIAIH has a low incidence and is more common in the female population,with the features of tissue injury in both DILI and autoimmune hepatitis.The short-term corticosteroid therapy can prevent disease progression and reduce chronicity.

Objective:To explore the practical value of general anesthesia with non-intubated spontaneous breathing in uniportal thoracoscopic surgery in elderly patients.Methods:Clinical data of 86 elderly patients undergone uniportal thoracoscopy surgery during hospitalization at our hospital between March 2020 and December 2021 were retrospectively reviewed and analyzed.Based on the anesthesia intubation method, they were divided into a non-intubated spontaneous breathing video-assisted thoracic surgery group(NI-VATS group)and a one-lung ventilation video-assisted thoracic surgery group(OLV-VATS group), with 43 cases in each group.Data were compared on the inflammatory indexes, preparation time for anesthesia, time to awakening after anesthesia, intraoperative lung collapse score, mediastinal flutter score, time to postoperative feeding, digestive tract complications, sore throat, postoperative pulmonary atelectasis, and hospitalization time.Results:Compared with the OLV-VATS group, the NI-VATS group had a shorter anesthesia preparation time [(19.8±2.6)min vs.(32.3±4.5)min, t=-15.77, P<0.001]and a shorter time to awakening [(6.8±2.1)min vs.(11.9±2.9)min, t=-9.485, P<0.001], slightly poorer operating field during surgery, an unfavorable lung collapse score [(2.5±0.7) vs.(1.8±0.7) t=4.704, P<0.001], worse mediastinal flutter [(2.1±0.6) vs.(1.3±0.5), t=6.514, P<0.001]. Lower procalcitonin(PCT)[(0.189±0.130)μg/L vs.(0.264±0.123)μg/L, t=-2.744, P=0.007), a shorter time to postoperative feeding [(3.4±1.0)h vs.(5.5±1.0)h, t=-9.55, P<0.001], and lower rates of digestive tract reactions(4.7% vs.20.9%, χ2=5.108, P=0.024)and throat pain(4.7% vs.23.3%, χ2=6.198, P=0.013), and a shorter length of hospital stay [(3.8±0.3)d vs.(4.9±0.8)d, t=-7.266, P<0.001]. Conclusions:For the elderly patients undergoing uniportal thoracoscopic surgery, non-intubated spontaneous breathing may somewhat obstruct the operating field, but it can shorten the time of anesthesia and the time to awakening, does not increase complications from anesthesia and surgery, favors rapid postoperative recovery for patients and therefore should be promoted.

Objective: To investigate the role and mechanism of action of Yiqi Huoxue Recipe (YQHXR) in regulating autophagy and reversing liver fibrosis in rats with carbon tetrachloride (CCl4)-induced liver fibrosis. Methods: Healthy male Wistar rats were intraperitoneally injected with a mixture of CCl4 (30%) and olive oil (70%) twice a week for 8 weeks to establish a rat model of liver fibrosis. The rats administered normal diet were used as control group. Furthermore, YQHXR or Fuzheng Huayu Recipe (FZHYR) was intragastrically administered to the rats. The serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured using an automatic biochemical analyzer. Hematoxylin-eosin (HE) staining and Masson staining were performed to observe the degree of fibrosis in rat liver. The protein expression of α-smooth muscle actin (α-SMA) and type I collagen α1 chain (Col1A1) in liver tissue was measured by immunohistochemistry. Furthermore, the mRNA and protein expression of α-SMA, Col1A1, autophagy-related protein 7 (Atg7), microtubule-associated protein 1 light chain 3 (LC3), and ubiquitin-binding protein (SQSTM1/p62) were determined using qRT-PCR and Western blotting, respectively. Comparison between multiple groups was made by one-way analysis of variance, and comparison between any two groups was made using the LSD test. P < 0.05 was considered as statistically significant. Results: The YQHXR group and FZHYR group had significantly lower serum levels of ALT and AST than the model group (ALT: 66.8±10.42 U/L and 73.2±10.33 U/L vs 106.80±18.24 U/L, F = 31.672, P < 0.001; AST: 122.6±16.65 U/L and 125.4±16.92 U/L vs 278.4±66.14 U/L, F = 25.539, P < 0.001). The pathological grades of hepatic fibrosis were S5.64±0.22, S3.70±0.35, and S3.90±0.34 in the model group, YQHXR group, and FZHYR group, respectively (F = 362.188, P < 0.001). Compared with the control group, the YQHXR group and FZHYR group had significantly reduced mRNA and protein expression of α-SMA, Col1A1, Atg7, and LC3B and significantly increased expression of p62 (all P < 0.05), and the differences were greatest in the YQHXR group. Conclusion YQHXR and FZHYR can prevent or reverse liver fibrosis by regulating hepatocyte autophagy and inhibiting hepatic stellate cell activation and collagen deposition.

Objective:The incidence of early-onset colorectal cancer (EOCRC) is increasing globally; however, the molecular characteristics and prognosis of sporadic EOCRC are unclear. In this systematic review and meta-analysis, we aimed to investigate the incidence of gene mutations and their association with cancer survival in sporadic EOCRC, focusing on six common gene mutations ( TP53, BRAF, KRAS, NRAS, PTEN, and APC). Methods:Ovid Embase and Ovid Medline electronic databases were searched for studies involving patients with sporadic EOCRC (i.e., diagnosed with colorectal cancer before the age of 50 years and with no evidence of hereditary syndromes predisposing to colorectal cancer). The included articles were evaluated using quality assessment tools. Meta-analysis was performed using random-effects and fixed-effects models. Cochran's Q statistic and the I2 index were used to assess heterogeneity. The incidence of the six common gene mutations listed above in sporadic EOCRC and their association with cancer survival were evaluated.Results:(1) Incidence of specific gene mutations in sporadic EOCRC. A total of 34 articles were included in this meta-analysis. The incidence of APC gene mutation was 36% (from 13 articles, 95%CI: 19%-55%, P=0.043); of KRAS gene mutation 30% (from 26 articles, 95%CI: 24%-35%, P=0.190); of BRAF gene mutation 7% (from 18 articles, 95%CI: 5%-11%, P=0.422); of NRAS gene mutation 4% (from five articles, 95%CI: 3%-5%, P=0.586); of PTEN gene mutation 6% (from six articles, 95%CI: 4%-10%, P=0.968); and of TP53 gene mutation 59% (from 13 articles, 95%CI: 49%-68%, P=0.164). (2) Association between gene mutations and survival in sporadic EOCRC . A total of six articles were included in this meta-analysis. Compared with wild-type BRAF, mutant BRAF was significantly associated with increased overall mortality risk in patients with EOCRC (pooled HR=2.85, 95%CI: 1.45-5.60, P=0.002). Subgroup analysis showed that the incidence of BRAF gene mutation was higher in Eastern than in Western countries, whereas the incidence of TP53, KRAS, NRAS, and APC gene mutations was lower. There was no significant difference in the incidence of PTEN gene mutation between different regions. Conclusion:Compared with colorectal cancer occurring in the general population, the incidence of APC and KRAS mutations is lower in EOCRC, whereas the incidence of TP53 mutation remains consistent. BRAF mutation is associated with increased overall mortality risk in patients with EOCRC.

Objective:The incidence of early-onset colorectal cancer (EOCRC) is increasing globally; however, the molecular characteristics and prognosis of sporadic EOCRC are unclear. In this systematic review and meta-analysis, we aimed to investigate the incidence of gene mutations and their association with cancer survival in sporadic EOCRC, focusing on six common gene mutations ( TP53, BRAF, KRAS, NRAS, PTEN, and APC). Methods:Ovid Embase and Ovid Medline electronic databases were searched for studies involving patients with sporadic EOCRC (i.e., diagnosed with colorectal cancer before the age of 50 years and with no evidence of hereditary syndromes predisposing to colorectal cancer). The included articles were evaluated using quality assessment tools. Meta-analysis was performed using random-effects and fixed-effects models. Cochran's Q statistic and the I2 index were used to assess heterogeneity. The incidence of the six common gene mutations listed above in sporadic EOCRC and their association with cancer survival were evaluated.Results:(1) Incidence of specific gene mutations in sporadic EOCRC. A total of 34 articles were included in this meta-analysis. The incidence of APC gene mutation was 36% (from 13 articles, 95%CI: 19%-55%, P=0.043); of KRAS gene mutation 30% (from 26 articles, 95%CI: 24%-35%, P=0.190); of BRAF gene mutation 7% (from 18 articles, 95%CI: 5%-11%, P=0.422); of NRAS gene mutation 4% (from five articles, 95%CI: 3%-5%, P=0.586); of PTEN gene mutation 6% (from six articles, 95%CI: 4%-10%, P=0.968); and of TP53 gene mutation 59% (from 13 articles, 95%CI: 49%-68%, P=0.164). (2) Association between gene mutations and survival in sporadic EOCRC . A total of six articles were included in this meta-analysis. Compared with wild-type BRAF, mutant BRAF was significantly associated with increased overall mortality risk in patients with EOCRC (pooled HR=2.85, 95%CI: 1.45-5.60, P=0.002). Subgroup analysis showed that the incidence of BRAF gene mutation was higher in Eastern than in Western countries, whereas the incidence of TP53, KRAS, NRAS, and APC gene mutations was lower. There was no significant difference in the incidence of PTEN gene mutation between different regions. Conclusion:Compared with colorectal cancer occurring in the general population, the incidence of APC and KRAS mutations is lower in EOCRC, whereas the incidence of TP53 mutation remains consistent. BRAF mutation is associated with increased overall mortality risk in patients with EOCRC.

Objective:To investigated the expression and localization of the long non-coding RNA(lncRNA)STAG3L5P in oral squamous cell carcinoma(OSCC)cells and its effects on OSCC cell proliferation and migration.Methods:STAG3L5P expression in HNSC and OSCC was ana-lyzed online using gene expression profiling interactive analysis 2(GEPIA2)and the University of California Santa Cruz Xena(UCSC Xena)database,respectively.STAG3L5P expression in OSCC cell lines was detected using real-time fluorescence quantitative PCR(qPCR).Nuclear-cytoplasmic RNA fractionation assays were carried out to pinpoint the location of STAG3L5P.Cell counting kit-8(CCK-8)and Transwell migra-tion assays were used to assess OSCC cell proliferation and migration changes.The effect of STAG3L5P overexpression on epithelial-mesen-chymal transition(EMT)related gene expression was detected by qPCR and Western blot.The effect of STAG3L5P overexpression on PI3K/AKT pathway activity was also assessed by Western blot.Results:STAG3L5P was highly expressed in OSCC,and its expression correl-ated significantly with histological grade.STAG3L5P expression was significantly higher in OSCC cell lines than in normal cells.The level of cytoplasmic STAG3L5P in OSCC cells was significantly higher than that in the nucleus.The proliferation and migration capacity of OSCC cells overexpressing STAG3L5P were significantly enhanced compared to negative control OSCC cells.N-cadherin and vimentin mRNA and protein levels were significantly increased by STAG3L5P overexpression,while E-cadherin protein expression was decreased.Overexpression of STAG3L5P also increased activity of p-PI3K and p-AKT.Conclusions:STAG3L5P is up-regulated in OSCC,and STAG3L5P overexpression can promote OSCC cell proliferation and migration.This effect may be related to activation of the PI3K/AKT pathway,thus promoting EMT.

Objective:To evaluate the clinical value of ultrasound attenuation parameters (UAP) in diagnosing the liver steatosis degree in patients with chronic liver disease, and to explore the relevant factors that affect UAP detection values.Methods:130 cases with chronic liver disease diagnosed as liver steatosis by liver biopsy during January 2014 to May 2019 were selected from the Hepatology Department of Integrated Traditional Chinese and Western Medicine of the Third Hospital of Hebei Medical University. UAP and liver stiffness (LSM) were detected by iLivTouch, and the body mass index (BMI) was calculated. Simultaneously, serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ-glutamyltransferase (GGT), total bilirubin (TBil), triglycerides (TG), total cholesterol (TC), low-density lipoprotein (LDL) levels and peripheral platelet (PLT) counts were measured. The correlation between UAP and liver steatosis was analyzed based on the liver histopathological results. SPSS 21.0 statistical software was used for statistical analysis. Receiver operating characteristic curve (ROC) was used to analyze the accuracy and specificity of UAP in the diagnosis of liver steatosis in patients with chronic liver disease. Spearman’s rank correlation analysis was used to study the relevant factors affecting UAP value.Results:The histopathological changes of liver biopsy showed that there were 43 cases of grade F1, 47 cases of F2, 32 cases of F3 and 8 cases of F4. UAP and BMI ( r = 0.363, P < 0.001), and UAP and liver steatosis degree ( r = 0.380, P < 0.001) were positively correlated. BMI and the liver steatosis degree were independent predictors of UAP value. The cut-off points for UAP to diagnose liver steatosis degree were 276 dB/m for F≥2, 288 dB/m for F≥2, 293 dB/m for F≥3, and F = 4, respectively. The sensitivity and specificity was 0.379, 0.500, 0.750, and 0.930, 0.922, 0.836, respectively. Conclusion:Ultrasonic attenuation parameters cannot only determine the presence or absence of liver steatosis in patients with chronic liver disease, but also can better assess the liver steatosis degree.

Background and purpose:Long noncoding RNA(lncRNA)can regulate gene transcription,mRNA shear,stabilization and translation,and it is an important regulatory factor in a variety of biological processes.This study aimed to investigate the expression and clinical features of lncRNA FLJ30679 in oral squamous cell carcinoma(OSCC)and its effect on the malignant biological behavior of OSCC.Methods:The expression of FLJ30679 in head and neck squamous cell carcinoma(HNSCC)tissues and normal tissues was analyzed by the UCSC Xena database for expression and prognosis.The expression of FLJ30679 in OSCC cell lines was detected by real-time fluorescence quantitative polymerase chain reaction(RTFQ-PCR).The subcellular localization of FLJ30679 in OSCC cells was detected by RNA nuclear-cytoplasmic fractionation assays.FLJ30679 Smart Silencer was used to establish the FLJ30679 knockdown group(SS-FLJ30679),and overexpression plasmid of FLJ30679 was used to establish FLJ30679 overexpression group(FLJ30679).The effects of altered FLJ30679 expression on the proliferative and migration capacity of OSCC cells were examined by cell counting kit-8(CCK-8)and transwell migration assays.RTFQ-PCR and Western blot were used to determine the effect of altered FLJ30679 expression on the expression of epithelial-mesenchymal transition(EMT)-related genes in OSCC cells.The effects of altered FLJ30679 expression on the phosphoinositide 3-kinase(PI3K)/protein kinase(AKT)pathway were detected by Western blot.Results:Online query of database showed that FLJ30679 expression was higher in HNSCC tissues compared to normal tissues(P＜0.01).HNSCC patients with higher FLJ30679 expression had lower overall survival(P＜0.01).The RTFQ-PCR results showed that FLJ30679 was expressed at a higher level in six OSCC cell lines compared with normal cells,and was predominantly localized in the nucleus.The ability of OSCC cells in the SS-FLJ30679 group to proliferate and migrate was significantly lower compared with the SS-NC group(P＜0.01).OSCC cells in the FLJ30679 overexpression group had significantly higher proliferative and migratory capacities than those in the vector group(P＜0.001).RTFQ-PCR and Western blot results showed that FLJ30679 knockdown resulted in upregulation of mRNA and protein expression levels of E-cadherin(P＜0.01)and downregulation of mRNA and protein expression levels of N-cadherin and vimentin(P＜0.01).FLJ30679 overexpression resulted in downregulation of protein expression levels of E-cadherin(P＜0.01)and upregulation of mRNA and protein expression levels of N-cadherin and vimentin(P＜0.05).Western blot results showed that knockdown of FLJ30679 resulted in decreased protein expression levels of phosphorylated-PI3K(p-PI3K)and phosphorylated-AKT(p-AKT)(P＜0.001),and overexpression of FLJ30679 resulted in increased protein expression levels of p-PI3K and p-AKT(P＜0.01).Conclusion:The expression of FLJ30679 was increased in OSCC tissues and cells.It promoted the proliferation and migration ability of OSCC cells,which may be caused by FLJ30679 promoting EMT via PI3K/AKT pathway.

Objective:To clarify the clinical efficacy of Yiqi Huoxue recipe in the treatment of liver fibrosis of chronic viral hepatitis.Methods:An open, positive-drug, parallel-controlled study method was applied. A total of 207 cases of liver fibrosis with chronic hepatitis B and C diagnosed with liver biopsy and transient elastography were selected. According to the principle of syndrome differentiation in traditional Chinese medicine, self-made Yiqi Huoxue recipe ( n = 127) and Fuzheng Huayu capsule ( n = 80) were used for the treatment course of 24-48 weeks. Change score of TCM symptom, liver biochemistry, liver stiffness measurement (LSM), and noninvasive liver fibrosis index [aspartate transaminase to platelet ratio index (APRI), and fibrosis-4 score (FIB-4)] were compared between the two groups to evaluate the therapeutic effect of Yiqi Huoxue recipe on liver fibrosis. Results:Yiqi Huoxue recipe group and Fuzheng Huayu capsule group baseline LSM, APRI and FIB-4 was compared, and there was no statistically significant difference between them ( P > 0.05). Yiqi Huoxue recipe and Fuzheng Huayu capsule received patients had improved symptom scores to a certain extent. Hepatic facies, discomfort over liver area, and soreness and weakness of waist and knees ( P < 0.05) was significantly improved in Yiqi Huoxue recipe than Fuzheng Huayu capsule. Liver biochemical indicators (ALT, AST, GGT, ALP) had gradually relapsed with the extension of treatment duration and the normalization rate between the two groups after 24 to 48 weeks had reached 100% vs. 100%, 100% vs. 93.8%, 96.8% vs. 92.3% and 87.5% vs. 81.8%. After 12 weeks of treatment, APRI values ??of both groups had significantly reduced, and after 48 weeks of treatment, LSM values of both groups had significantly improved. Moreover, Yiqi Huoxue recipe FIB-4 score was significantly improved after 48 weeks of treatment, and the difference was statistically significant compared to Fuzheng Huayu capsule group ( P < 0.05). After treatment, LSM, APRI, and FIB-4 total effectiveness in the two groups were 80.0% vs. 63.6%, P = 0.046; 68.4% vs. 52.0%, P = 0.052; 68.4% vs. 62.0%, P = 0.437, respectively. LSM total effectiveness was significantly higher in Yiqi Huoxue recipe treated group than Fuzheng Huayu capsule group. Conclusion:Traditional Chinese medicine Yiqi Huoxue decoction can be used as an optimal treatment for liver fibrosis of chronic viral hepatitis.