OBJECTIVEIn order to study the relation between polymorphisms of methylenetetrahydrofolate reductase C677T (MTHFR) and susceptibility of stomach cancer (SC).

METHODSWe conducted a case-control study with 107 cases of SC and 200 population-based controls in Huaian city of Jiangsu province, China. The epidemiological data were collected, and DNA of peripheral blood leukocytes was obtained from all of the subjects. MTHFR genotypes were detected by PCR-RFLP method.

RESULTS(1) The frequency of MTHFR variant genotypes (C/T + T/T) among the cases (79.4%) was significantly higher than the controls (68.5%) (P = 0.041 6); the crude OR for SC was 1.78 (95% CI: 0.99 - 3.22). After adjustment for sex and age, the OR for SC was 1.89 (95% CI: 1.08 - 3.32). (2) Subjects who had MTHFR variant genotypes and having smoking habit were at a significantly higher risk of developing SC (OR = 7.72, 95% CI: 2.23 - 26.79) compared with those who had wild-type homozygotes (C/C) genotype and no smoking habit. Individuals who had variant genotypes and who had habit of frequent alcohol drinking were at an increased risk of developing SC (OR = 3.08, 95% CI: 1.30 - 7.23) compared with those with C/C genotype and low consumption of alcohol. As compared with subjects with C/C genotype and low consumption of alcohol and no smoking habit, individuals who had variant genotypes and who had habits of frequent alcohol drinking and smoking had 12.96 (95% CI: 2.76 - 70.46) folds risk developing SC.

CONCLUSIONSThese results in the present study suggested that the polymorphisms of MTHFR C677T was associated with risk of developing SC, and there was a coordinated effect between MTHFR genotypes and habits of smoking and alcohol drinking in the development of SC.

Alcohol Drinking ; Female ; Genetic Predisposition to Disease ; Humans ; Male ; Methylenetetrahydrofolate Reductase (NADPH2) ; Middle Aged ; Oxidoreductases Acting on CH-NH Group Donors ; genetics ; Point Mutation ; Polymorphism, Genetic ; Risk Factors ; Smoking ; Stomach Neoplasms ; epidemiology ; genetics

OBJECTIVE: To explore the genetic basis for a child with metachromatic leukodystrophy (MLD). METHODS: Clinical data of the patient was collected. Genomic DNA was extracted from peripheral blood samples of the child and his family members. Potential variant was screened by whole exome sequencing (WES), and candidate variant was verified by Sanger sequencing. The pathogenicity the variant was analyzed by multiple sequence alignment of the amino acid sequence and three-dimensional model prediction of its protein product. RESULTS: The child was found to harbor compound heterozygous variants c.257G>A (p.R86Q) and c.467del (p.G156Afs*6) of the ARSA gene, among which the c.467del (p.G156Afs*6) frameshift variation was unreported previously. Multiple sequence alignment showed that the site of the c.257G>A (p.R86Q) missense variant is highly conserved. Three-dimensional structure modeling analysis showed that the partial deletion due to the p.G156Afs*6 variant may cause significant alteration of the structure of ARSA protein. CONCLUSION The discovery of novel variant in ARSA has enriched the mutational spectrum of MLD and may facilitate the understanding of the genotype-phenotype correlation of MLD.
Cerebroside-Sulfatase/genetics* ; DNA ; Genetic Association Studies ; Humans ; Leukodystrophy, Metachromatic/genetics* ; Mutation

Objective:To analyze the global research hotspots in the field of pediatrics based on the Essential Science Indicators (ESI) database and explore the inspiration to domestic editors and pediatrics researchers.Methods:The journal distribution, country (region) distribution, cooperation, organization distribution, funding, publication language, hot topic words and other data of highly cited papers in the field of pediatrics in ESI database were collected and analyzed.Results:A total of 682 highly cited pediatrics papers were collected from 77 pediatrics journals included in Science Citation Index(SCI). Most of the highly cited pediatrics papers (182) were found to be published in Pediatrics.All 682 paper were published in English and frequently, characterized by multiple authors, institutions and fund support.Of 682 highly cited pediatrics papers, 435 papers were published in the United States(the first), 123 papers in England(the second) and 86 paper in Canada(the third). Novel coronavirus pneumonia, coronavirus, SARS coronavirus, autism and multiple system inflammatory syndrome are the main frontiers of global pediatric research at present.Specifically, focal pediatric system diseases mainly include respiratory system diseases, digestive system diseases, cardiovascular diseases, etc. Conclusions:ESI-based analysis of global research hotspots in the field of pediatrics provides reference materials for domestic and foreign pediatrics researchers to understand the global academic frontiers and development trends in the field of pediatrics and select topics for future scientific research.More importantly, this analysis can help domestic editors of pediatrics journals to plan topics and organize hot papers, so as to improve the academic quality and international influence of the journals.

Objective: To investigate the distribution of the septocutaneous perforators in the medial arm and its clinical applications. Methods: Between March 2014 and August 2018, 39 patients (45 arms) were included in the study. A coordinate system originating at the medial epicondyle was established, with the y-axis running to the axillary apex and expressed in relative value. The y-axis was trisected and each third from proximal to distal were designated as A, B, and C, respectively. Based on this, the medial arm flap was used to reconstruct defects in the head and neck, hand, axilla, elbow and chest wall. Results: An average of 4.6 perforators were identified along the medial intermuscular septum of the arm, located at 0.87±0.08, 0.50±0.09 and 0.20±0.06 on the y-axis, with a prevalence of 95.6%, 100% and 86.7%, respectively. Among the 45 flaps, 30 were used as pedicled distant flaps and 15 as perforator-based propeller flaps, with an average size of 18.7 cm×8.1 cm. The average length of the perforator pedicle was 3.1 cm. One pedicled distant flap developed hematoma after pedicle division but recovered with hematoma removal. One perforator-based propeller flap had partial loss of the distal third, requiring surgical debridement followed by a local flap transfer. Two perforator-based propeller flaps had venous congestion but survived completely with conservative therapy. The remaining flaps healed uneventfully. Donor-site morbidity was minimal. The patients were followed up for 6 months to 3 years (average 12.6 months) with satisfactory aesthetic appearance, greatly improved function and no tumor recurrence. Conclusions The constant perforators could be found in each third of the medial arm. The perforator-based medial arm flap could be used for various soft-tissue defect reconstructions.

Objective To explore the feasibility and technique of reconstruction of extensive softtissue defects at upper extremities using the pre-expanded paraumbilical perforator (PUP) flaps.Methods Pre-expanded PUP flap was used to reconstruct large soft-tissue defect at the upper extremity according to the size,shape,and location of the defect in a multiple-staged procedure.Results From Sept.2009 to Sept.2015,81 patients underwent defect reconstruction using the pre-expanded PUP flaps.93 preexpanded PUP flaps were used.Unilateral flap was used in 70 patients.Bilateral flaps were used to reconstruct the circumferential forearm defects in eight patients (16 flaps).Bilateral flaps were used to reconstruct bilateral forearm defects in three patients (6 flaps).The size of the flaps ranged from 8 cm ×6 cm to 40 cm × 15 cm.Small-sized distal flap necrosis occurred in five patients after division of the proximal pedicle of the flap.The patients were followed up for 1 to 5 years (average 3.5 years) with satisfactory functional and aesthetic outcomes.Dysfunction of the shoulder and elbow joints was not noticed postoperatively.Conclusions The pre-expanded paraumbilical perforator flap provides a valuable option for different defects reconstruction at the upper extremity.

Objective:To discuss the effect of Wnt/β-catenin signaling pathway inhibitor methyl 3-｛[(4-methyl-phenyl)sulfonyl]amino ｝ benzoate(MS AB)on the fibrogenic response of the human endometrial stromal cells(HESCs),and to provide the foundation for the application of MSAB in the target therapy of intrauteriue adhesion(JUA).Methods:The normal HESCs were cultured in vitro and divided into two groups:control group and transforming growth factor β1(TGF-β1)group;the HESCs from the adhesion part of the IUA patients were cultured in vitro,regarded as IUA group.Western blotting method was used to detect the expression levels of fibrotic marker protein type Ⅰ collagen α1(COL1A1)in the cells in various groups at different time points(0,12,24,48,and 60 h)after treated with TGF-β1.MTT assay was used to detect the proliferation activities of the cells in various groups.Western blotting method was used to detect the expression levels of the fibrotic marker protein COL1A1,stromal marker proteins such as N-cadherin and α-smooth muscle actin(α-SMA),and Wnt/β-catenin signaling pathway-related protein β-catenin in the cells in control and IUA groups.Based on the MSAB concentrations,the normal HESCs were divided into 0(control),0.25,0.50,0.75,and 1.00 μmol·L-1 MSAB groups,and MTT assay was used to detect the survival rates of the cells in various groups.After treated with MSAB,the normal HESCs were divided into control group(normal HESCs),TGF-β1 group(10 μg·L-1 TGF-β1 induced normal HESCs for 24 h then the drug was withdrawn,replaced with complete culture medium,and the cells continued to be cultured for 24 h),and MSAB group(10 μg·L-1 TGF-β1 induced normal HESCs for 24 h then the drug was withdrawn,replaced with a complete medium containing 0.75 μmol·L-1 MSAB and the cells continued to be cultured for 24 h).Real-time fluorescence quantitative PCR(RT-qPCR)method was used to detect the expression levels of epithelial-mesenchymal transition(EMT)-related transcription factors Snail,Slug,Smuc,ZEB1,and ZEB2,and COL1A1 mRNA in the cells in various groups.Western blotting method was used to detect the expression levels of COL1A1,N-cadherin,α-SMA,β-catenin,and c-myc proteins in the cells in various groups.Results:Compared with control group(after treated with TGF-β1 for 0 h),the expression levels of COL1A1 proteins in the HESCs after treated with TGF-β1 for 12,24,48,and 60 h in TGF-β1 group were increased(P＜0.05 or P＜0.01).Compared with control group,there was no significant difference in the proliferation activity of the HESCs in IUA and TGF-β1 groups(P＞0.05).Compared with control group,the expression levels of COL1A1,β-catenin,N-cadherin,and α-SMA proteins in the cells in IUA group were increased(P＜0.05 or P＜0.01).Compared with control group,the survival rates of the cells in 0.75 and 1.00 μmol·L-1 MSAB groups were decreased(P＜0.05 or P＜0.01).Compared with control group,the expression levels of Snail,Slug,and COL1A1 mRNA in the cells in TGF-β1 group were increased(P＜0.05 or P＜0.01);compared with TGF-β1 group,the expression levels of Snail,Slug,and COL1A1 mRNA in the cells in MSAB group were decreased(P＜0.05 or P＜0.01).Compared with control group,after treated with TGF-β1 for 24 h,the expression levels of COL1A1,N-cadherin,α-SMA,β-catenin,and c-myc proteins in the cells in TGF-β1 group were increased(P＜0.01);compared with TGF-β1 group,the expression levels of COL1A1,N-cadherin,α-SMA,β-catenin,and c-myc proteins in the cells in MSAB group were decreased(P＜0.05 or P＜0.01).Conclusion:MSAB can inhibit the fibrogenic responses of the HESCs in vitro,and the results provide the theoretical basis for the application of MSAB in the target therapy of IUA.

Objective:To investigate the effects of self-made Gujin Xiaoji Mixture combined with warming needle therapy on the clinical efficacy and immune function of patients with advanced non-small cell lung cancer (NSCLC) with qi and yin deficiency syndrome.Methods:This experiment was a randomized controlled trial study. 180 patients with advanced NSCLC qi and yin deficiency syndrome in the oncology centre of Qingdao Hospital of Traditional Chinese Medicine were selected as the observation subjects from March 2021 to August 2022, and were divided into 2 groups using the random number table method, with 90 cases in each group. The control group received conventional chemotherapy combined with Sintilimab injection, 21 days as a cycle, with a total of 4 cycles of treatment; and the observation group received Gujin Xiaoji Mixture combined with warming needle therapy based on the control group, 7 days as one course of treatment, with a total of 12 courses. Both groups were followed up for 12 months. The TCM syndrome scores were performed before and after treatment. The functional assessment of cancer therapy-lung (FACT-L) was used to evaluate the quality of life of patients; flow cytometry was used to detect the levels of CD3 +, CD4 +, CD8 + and NK cell, and the CD4 +/CD8 + ratio was calculated; adverse drug reactions and progression free survival of patients during treatment were observed and recorded, the efficacy of TCM syndrome and objective efficacy of solid tumors were evaluated. Results:After treatment, the observation group's post-treatment TCM syndrome score (5.67±1.99 vs. 7.12±2.31, t=-4.53) was lower than that of the control group ( P<0.001); mobility (23.03±2.80 vs. 20.69±2.46, t=5.96), daily living (23.06±2.56 vs. 20.71± 2.33, t=6.42), emotional status (18.44±2.32 vs. 16.12±2.71, t=6.18), and other factors (33.14±4.11 vs. 27.39±4.64, t=8.81) and total score (97.68±7.23 vs. 84.91±7.49, t=11.64) were higher than those in the control group ( P<0.01). In the observation group, after treatment, the levels of CD3 + [(65.14±6.06)% vs. (59.84±5.74)%, t=6.02], CD4 + [(40.09±4.09)% vs. (35.69±3.86)%, t=7.43], NK cell [(29.11±4.81)% vs. (22.38±4.51)%, t=9.68] and CD4 +/CD8 + [(1.52±0.27) vs. (1.14±0.12), t=12.63] were higher than those in the control group ( P<0.01), and CD8 + [(26.82±3.79)% vs. (31.76±4.65)%, t=-7.81] level was lower than that of the control group ( P<0.01). After treatment, the objective remission rate in the observation group was 7.8% (7/90), and the disease control rate was 87.8% (79/90), while the objective remission rate after treatment in the control group was 5.5% (5/90), and the disease control rate was 82.2% (74/90), and there were no statistical significance in the comparison of objective remission rate and disease control rate of the 2 groups ( χ2=0.09, 0.70, P=0.765, 0.407). The total effective rate after treatment was 62.2% (56/90) in the observation group and 34.4% (31/90) in the control group, and the difference between the 2 groups was statistically significant ( Z=-3.89, P<0.001). WBC [(4.27±1.12)×10 9/L vs. (3.84±1.11)×10 9/L, t=2.58] and haemoglobin [(119.93±17.25)g/L vs. (109.76±15.61)g/L, t=4.15] levels of the observation group were higher than those in the control group after treatment ( P<0.01). During follow-up, the median progression-free survival was 6.2 months in the observation group and 5.5 months in the control group patients, and the difference between the 2 groups was not statistically different ( t=0.11, P>0.05). Conclusion:The combination of Gujin Xiaoji Mixture with warming needle therapy can effectively improve the clinical symptoms of patients with advanced NSCLC with deficiency of qi and yin syndrome, improve the immunity and clinical efficacy of patients, alleviate the adverse effects of drugs, and prolong the progression-free survival period.

Objective To explore the feasibility and technique of reconstruction of extensive softtissue defects at upper extremities using the pre-expanded paraumbilical perforator (PUP) flaps.Methods Pre-expanded PUP flap was used to reconstruct large soft-tissue defect at the upper extremity according to the size,shape,and location of the defect in a multiple-staged procedure.Results From Sept.2009 to Sept.2015,81 patients underwent defect reconstruction using the pre-expanded PUP flaps.93 preexpanded PUP flaps were used.Unilateral flap was used in 70 patients.Bilateral flaps were used to reconstruct the circumferential forearm defects in eight patients (16 flaps).Bilateral flaps were used to reconstruct bilateral forearm defects in three patients (6 flaps).The size of the flaps ranged from 8 cm ×6 cm to 40 cm × 15 cm.Small-sized distal flap necrosis occurred in five patients after division of the proximal pedicle of the flap.The patients were followed up for 1 to 5 years (average 3.5 years) with satisfactory functional and aesthetic outcomes.Dysfunction of the shoulder and elbow joints was not noticed postoperatively.Conclusions The pre-expanded paraumbilical perforator flap provides a valuable option for different defects reconstruction at the upper extremity.

OBJECTIVE To investigate the mechanism of Cichorium glandulosum in the treatment of liver fibrosis by using network pharmacology and experimental validation. METHODS A "component-target-pathway" network was constructed with the help of TCMSP, Pubchem, SwissTargetPrediction and Genecards databases, and the STRING database was used to predict the targets of Cichorium glandulosum against liver fibrosis. KEGG and GO enrichment analysis was performed in the DAVID database, and molecular docking of active ingredients and key targets was docked in AUTODOCK. PDGF-BB was used to induce activation of cells and verify the effects of six compounds, including quercetin, quercetin, chicoric acid, caffeic acid, chlorogenic acid, and isochlorogenic acid, on the proliferation, apoptosis, and liver fibrosis indicators of HSC-T6 cells. Western blotting was used to detect the expression of Ras, ERK1, ERK2, C-fos, and JNK proteins in HSC-T6 cells. RESULTS Network pharmacology screened 239 common targets between the components and liver fibrosis, PPI analysis showed that SRC, STAT3, HSP90AA1 and other targets were key targets, KEGG analysis showed that the pathways affected by Cichorium glandulosum included cancer pathways, metabolic pathways, etc. GO analysis predicted that Cichorium glandulosum mainly affected processes such as signal transduction. The molecular docking results showed that the target that could bind well with the components MAPK1, and the components that could bind well with the target aesculetin, caffeic acid and chlorogenic acid. Compared with the model group, the inhibition effect of the six compounds on PDGF-BB-induced HSC-T6 cell activation was stronger, and all 6 compounds had the effects to reverse the index of liver fibrosis, in which aesculetin had the strongest activity(P<0.01). The expression of Ras, ERK1, ERK2, C-fos, and JNK in HSC-T6 cells decreased after the interventions of 6 compounds. CONCLUSION Each component of Cichorium glandulosum has different anti liver fibrosis effects, which are related to the inhibition of ERK/RAS pathway activation.

Objective To explore the feasibility and technical tips of the reconstruction of defects around the knee using the reverse-flow thigh flaps based on different branches of the lateral circumflex femoral artery ( LCFA) .A classification method of these flaps was proposed .Methods According to the characteristics of the defects and the LCFA arborizing condition , an optimal reverse-flow thigh flap was chosen for defect reconstruction .Results From 2010 to 2016, 23 patients underwent defect reconstruction using the reverse-flow thigh flaps .The flaps were classified into four different types according to the origin of the perforating vessels on which the flap was based , including the descending ( typeⅠ) , oblique ( typeⅡ) , rectus femoris ( type Ⅲ) , and transverse branches ( type Ⅳ) .In our series of patients , 7 type Ⅰflaps, 10 typeⅡ, 5 typeⅢ, and 1 typeⅣwere included.The reverse flow from the rectus femoris branch was combined and a dual pedicle was formed in 5 patients.The flap size ranged from 8 cm ×7cm to 24 cm × 12 cm.The perforating vessels included septocutaneous in 7 cases and musculocutaneous in the remaining 16.The pedicle length and distance from the pivot point to the superolateral border of the patella were 8.5 cm to 25 cm (mean, 17 cm) and 5 cm to 16 cm (mean, 11.48 cm) respectively.Pre-transfer donor site expansion was conducted in 5 patients.The donor sites were managed by direct closure in 18 cases, free skin grafting in 4, and transferring a pedicled deep inferior epigastric artery perforator flap in the remaining 1.All flaps survived after the surgery except one in which the venous congestion of the flap occurred postoperatively , resolved after using conservative treatment .The patients were followed for 1 to 48 months, tumor recurrence was not noticed and all patients were satisfied with the reconstructive outcomes .Conclusions LCFA-based classification system of the reverse-flow thigh flaps would provide surgeons more options when a defect around knee needs to be reconstructed .