With the continuous development of society, a large number of new chemicals are continuously emerging, which presents a challenge to current risk assessment and safety management of chemicals. Traditional toxicology research methods have certain limitations in quickly, efficiently, and accurately assessing the toxicity of many chemicals, and cannot meet the actual needs. In response to this challenge, computational toxicology that use mathematical and computer models to achieve the prediction of chemical toxicity has emerged. In the meantime, as researchers increasingly pay attention to understanding the interaction mechanisms between exogenous chemical substances and the body from the system level, and multiomics technologies develop rapidly such as genomics, transcriptomics, proteomics, and metabolomics, huge amounts of data have been generated, providing rich information resources for studying the interactions between chemical substances and biological molecules. System toxicology and network toxicology have also developed accordingly. Of these, network toxicology can integrate these multiomics data to construct biomolecular networks, and then quickly predict the key toxicological targets and pathways of chemicals at the molecular level. This paper outlined the concept and development of network toxicology, summarized the main methods and supporting tools of network toxicology research, expounded the application status of network toxicology in studying potential toxicity of exogenous chemicals such as agricultural chemicals, environmental pollutants, industrial chemicals, and foodborne chemicals, and analyzed the development prospects and limitations of network toxicology research. This paper aimed to provide a reference for the application of network toxicology in other fields.

BACKGROUND: m6A RNA methylation modification plays an important role in the occurrence and progression of lung cancer and regulates tumor immunity. Current studies mostly focus on the differential expression of some specific m6A effectors and infiltrating immune cell. m6A methylation modification is the result of mutual adjustment and balance between effectors, and changes in the expression of one or two effectors are far from enough to reflect the panorama of m6A methylation. The role of m6A in the immune microenvironment of lung adenocarcinoma (LUAD) is still poorly understood. The aim of this study is to investigate the effect of different m6A modification patterns in immune microenvironment of LUAD. METHODS: LUAD data was obtained from The Cancer Genome Atlas (TCGA), University of California Santa Cruz Xena (UCSC Xena) and Gene Expression Omnibus (GEO) databases. Gene mutation, differential expression and survival analysis were performed for 24 m6A effectors. The m6A modification pattern was constructed by unsupervised clustering method, and the m6A clusters survival analysis, gene set variation analysis, immune score and immune cell infiltration analysis were performed. The association between LRPPRC protein expression levels and infiltration of CD8+ cytotoxic T lymphocytes and CD68+ macrophages in the tumor microenvironment was validated by immunohistochemistry in LUAD tissue microarray with 68 cases. RESULTS: The mutations of m6A effector were found in 150 of 567 LUAD cases with a frequency of 26.46%. 6 readers and 3 writers were significantly up regulated in LUAD tissues compared with normal tissues. IGF2BP1 and HNRNPC are the independent risk factors for prognosis of LUAD. Abundant cross-talks among writers, erasers and readers were demonstrated. Three m6A modification patterns with different immune cell infiltration characteristics and clinical prognosis were established. Among m6A effectors, LRPPRC was found to be inversely associated with the infiltration of CD8+ cytotoxic T lymphocytes and CD68+ macrophages, and was validated in 68 LUAD tissues. CONCLUSIONS m6A modification patterns play non-negligible roles in regulating the immune microenvironment. LRPPRC has potential to be a new biomarker for checkpoint inhibitor immunotherapy.
Adenocarcinoma/genetics* ; Adenocarcinoma of Lung/pathology* ; Adenosine/metabolism* ; Gene Expression Regulation, Neoplastic ; Humans ; Lung Neoplasms/pathology* ; Methylation ; Tumor Microenvironment/genetics*

【Objective】 To compare the clinical efficacy of minimally invasive percutaneous approach with Wiltse approach in the treatment of thoracolumbar fracture without neurological deficit in young and middle-aged patients. 【Methods】 A prospective study was conducted in 108 patients with thoracolumbar fracture without neurological symptoms treated in Department of Orthopedics， The First Affiliated Hospital of Xi’an Jiaotong University from March 2015 to March 2018. We randomly assigned 54 patients to minimally invasive percutaneous approach group （Group A） and 54 ones to Wiltse approach group （Group B）. We compared the operation time， intraoperative blood loss， incision length， the number of intraoperative fluoroscopy times， and postoperative hospital stay of Group A and Group B. We also compared the VAS scores of the two groups before and 3 days after surgery and at each review， the vertebral frontal height compression ratio and Cobb Angle before and immediately after surgery， 3 months 1 year and 3 years after surgery， and ODI index before surgery and 3 months， 1 year and 3 years after surgery. 【Results】 All the 108 patients were followed up. There were no significant differences in operation time， intraoperative blood loss or postoperative hospital stay between the two groups （P>0.05）. The number of intraoperative fluoroscopy times was significantly smaller in Group B than in Group A （P<0.05）， and the incision length was shorter than that in Group A （P<0.05）. The two groups did not significantly differ in VAS score or ODI index before operation （P>0.05）， after operation， or at follow-up， while the anterior vertebral body height ratio and Cobb angle were significantly lower in Group B than in Group A （P<0.0125）. 【Conclusion】 Minimally invasive percutaneous approach and Wiltse approach are both safe and effective in the treatment of thoracolumbar fracture without neurological deficit. However， the number of intraoperative fluoroscopy times of Wiltse approach was significantly reduced， the incision length was smaller than that of the percutaneous pedicle group， and the postoperative anterior vertebral compression rate and Cobb Angle were lower than those of the percutaneous group， indicating better clinical efficacy.

Objective:To investigate the effect of self fixing mesh with " Y-shaped" placement in laparoscopic transabdominal preperitoneal repair of female inguinal hernia.Methods:From February 2019 to September 2020, a total of 40 female patients who underwent TAPP (Keyhole method) in Shaanxi Provincial People′s Hospital were researched.Random number table method was used.According to different patch placement methods, the patients were divided into the self fixing mesh with " Y-shaped" placement group (21 cases) and with normal placement group (19 cases). The operative time, placement time, length of stay, Visual Analogue Scale (VAS), postoperative complication were compared between two groups.Results:All 40 patients completed TAPP, and all patients were followed up successfully, with a median follow-up time of 12.5 months.The operation time and patch placement time were (54.9±9.0) min and (10.8±2.5) min in the Y-shaped placement method group and (62.8±11.2) min and (20.3±3.5) min in the conventional placement method group, respectively; the differences between the two groups were statistically significant ( t=2.490, P=0.017; t=.925, P<0.001). There was no statistically significant difference between the two groups in length of stay, VAS score 1 day after surgery and postoperative complications(all P>0.05). Conclusion:In laparoscopic female inguinal hernia repair (keyhole method), the " Y" shape placement method can effectively shorten the time of self fixing patch placement, thus shorten the operation time, and does not increase the risk of complications.

【Objective】 To optimize the purification conditions of heparin affinity chromatography in the purification of human coagulation factor Ⅸ by response surface method and establish the optimal chromatography process parameters. 【Methods】 The effect of sample loading temperature on purification efficiency was analyzed through single factor test. Three-factor three-level response surface method was used to optimize the chromatographic elution conditions. The Folin phenol method and the automatic hemagglutination analyzer were used to determine the total protein content and human coagulation factor Ⅸ titer, respectively. The purification effect was evaluated by activity index and process recovery rate. 【Results】 The optimized optimal chromatographic conditions were loading at 5 ℃, washing 4 CV, eluent formulation of sodium citrate 20 mmol/L, arginine hydrochloride 18.7 mmol/L, NaCl 611.6 mmol/L and pH 7.5; under this optimal setting, the recovery rate of the chromatographic process was (46.6±2.9) %, titer of factor Ⅸ rated to (68.4±4.7) IU/mL and specific activity was (62.8±3.3) IU/mg. 【Conclusion】 The optimized parameters of heparin affinity chromatography process by response surface method can produce better purification effect on human coagulation factor Ⅸ.

Objective To investigate the characteristics of the phenylalanine hydroxylase( PAH)gene muta﹣tions in patients With phenylketonuria(PKU)in Guangxi region,in order to provide clinical data for genetic counseling and prenatal gene diagnosis. Methods Thirty－seven children diagnosed as PKU in the Maternal and Children＇s Hos﹣pital of Guangxi Zhuang Autonomous Region Were enrolled in the study betWeen January 2009 and December 2017. Ve﹣nous blood Was collected and the PAH gene sequence Was determined by Sanger sequencing after amplification With the polymerase chain reaction technique. The neW gene mutations Were defined based on the national and international literature revieW and databases. MeanWhile,100 healthy individuals Were selected as the control group for gene sequen﹣cing to confirm Whether the mutation Was a neW one. Results Thirty－seven cases of PKU Were detected for 68 muta﹣tions,With the detection rate being 91. 89%(68／74). Six mutations Were identified in exon 7,Which accounted for 31. 08% of all,exon 12(18. 92%),exon 8(10. 81%)and exon 6(10. 81%)folloWed. A total of 25 different muta﹣tions Were identified Which including 14 missense mutations(56. 00%),7 nonsense mutations(28. 00%),3 splicing junction mutations(12. 00%),and 1 deletion mutation(4. 00%). The most common mutations included c. 1223G＞A (p. R408Q),c. 728G＞A(p. R243Q)and c. 721C＞T( p. R241C),accounting for 14. 86%,13. 51%,and 10. 81%, respectively. After querying international databases,including PAH mutation database and Human Gene Mutation Data﹣base and forecasting softWare,three kinds of mutations c. 314C＞ T(p. T105I),c. 583A＞ G(p. K195E),c . 851G＞A(p. C284Y)Were verified as novel PAH gene mutations. Conclusions The mutation spectrum of the PAH gene in Guangxi has been identified. And 3 kinds of mutations have been identified. This may accumulate valuable information for gene diagnosis and prenatal diagnosis of PKU in Guangxi region.

OBJECTIVETo investigate the application value of the clearance of No.253 lymph nodes with priority to fascial space and preserving left colic artery (LCA) in patients undergoing laparoscopic radical proctectomy.

METHODSFrom August 2015 to August 2016, 97 consecutive middle-low rectal cancer patients underwent laparoscopic radical proctectomy using the clearance of No.253 lymph nodes with priority to fascial space and preserving LCA at Department of General Surgery, Tangdu Hospital. Among 97 patients, 45 were females , 52 were males, mean age was (64.3±5.5) years and mean BMI was (22.4±1.8) kg/m. Brief steps of this clearance: traditional medial approach was the commencement of the dissection at the membrane bridge line in front of iliac vascular bifurcation, then entering into the Toldt's space; superior rectal artery served as the top of the tent and the Toldt's space was extended as far as possible; blunt separation was developed caudally (reaching 2 cm below the sacral promontory), cephalad (reaching the lower part of the pancreas), left laterally (reaching Toldt's line), dextrally (reaching abdominal aorta); after giving priority to fascias space, from the root of inferior mesenteric artery, LCA was exposed and No.253 lymph nodes were dissected. This regimen was suitable for the rectal adenocarcinoma patients without distant metastasis.

RESULTSThere was no tension in the intestine and mesenteria after anastomosis in all the 97 patients. One patient received LCA ligation during the clearance, because of thinner LCA resulting in bleeding. The other 96 cases completed the clearance and operation successfully. The mean No.253 lymphadenectomy time was 11-27(17.1±5.3) minutes. The mean number of harvested No.253 lymph node was 0-6(4±2). The No.253 lymph nodes of 6 patients were positive. No.253 regional mesentery was complete in 95 patients. The total harvested number of lymph node was 11-26(17.3±5.3). Six patients with positive lymph nodes aged from 68 to 72 years old and all of them underwent TME operation 6-8 weeks after neoadjuvant chemoradiotherapy. The mean operative time was 89-189(125±35) minutes. The mean estimated blood loss was 10.5-38.6(22.4±10.5) ml. The first exhaust time was 3.0-6.0(5.6±2.1) days. The mean time to extracting the drainage tube was 3.0-5.0(4.5±2.5) days. Anastomotic fistula appeared in 1 case and hemorrhage appeared in 1 case, and these 2 cases were cured by conservative treatment. No perioperative death occurred. The mean postoperative hospital stay was 3.0-10.0(3.6±2.6) days.

CONCLUSIONThe clearance of No.253 lymph nodes with priority to fascial space and preserving LCA in laparoscopic radical proctectomy is safe and feasible.

Aged ; Digestive System Surgical Procedures ; methods ; Female ; Humans ; Laparoscopy ; Lymph Node Excision ; Lymph Nodes ; Male ; Mesenteric Artery, Inferior ; surgery ; Middle Aged ; Rectal Neoplasms ; surgery

Objective: To investigate the clinical, biochemical and genetic features of four carnitine-acylcarnitine translocase deficiency cases. Methods: Four cases diagnosed with carnitine-acylcarnitine translocase deficiency from Guangxi Maternal and Child Health Hospital were studied. DNA was extracted from dry blood filter for gene analysis. SLC25A20 gene analysis was performed in 1 case and the whole exon sequence analysis was performed in 3 cases. Results: Retrospective study on unrelated carnitine-acylcarnitine translocase deficiency patients, the age of onset was 1-28 d, the age of death were 1.5-30 d, main clinical features were hypoglycemia (4 cases), arrhythmia (2 cases), sudden death (2 cases). Biochemical test showed hypoglycemia (1.2-2.0 mmol/L) , elevated creatine kinase (955-8 361 U/L) and creatine kinase isozyme(199-360 U/L), normal or decreased free carnitine level (3.70-27.07 μmol/L) , elevated long-chain acylcarnitine (palmityl carnitine 1.85-14.84 μmol/L). The gene tests showed that all 4 cases carried SLC25A20 gene c.199-10T> G homozygous mutation, inherited from their parents. By analyzing the haplotype, we found that the mutation loci of C. 199-10T> G were all in the same haplotype. Conclusion The c.199-10T> G mutation is an important molecular cause of carnitine-acylcarnitine translocase deficiency, which has relatively high frequency in Guangxi population, and is related to the founder effect.

Objective To investigate the application value of the modified Overlap method in digestive tract reconstruction of totally laparoscopic total gastrectomy (TLTG).Methods The retrospective cohort study was conducted.The clinicopathological data of 50 patients with gastric cancer who underwent TLTG with Overlap anastomosis between January 2016 and December 2016 in the Tangdu Hospital of the Fourth Military Medical University were collected.Twenty-six patients using classic Overlap method and 24 patients using modified Overlap method were respectively allocated into the classic Overlap group and modified Overlap group.All the patients underwent D2 lymph node dissection.Patients in the classic Overlap group underwent totally laparoscopic catastalsis side-to-side esophagojejunostomy.During digestive tract reconstruction in the modified Overlap group,there was no esophageal transection before anastomosis,and gastric fundus traction fully exposed to the lower esophagus.Esophagus was spun anticlockwise,and a hole was opened at the left posterior esophageal wall.Transection of jejunum was 25 cm away from Treitz ligment,and opening a hole at mesenteric margin was 6 cm away from distal jejunum to transected end of jejunum.Esophagus-distal jejunum side-to-side anastomosis was done using 60 mm linear stapler,and then laterally closing openings and transecting esophagus.Observation indicators:(1) intra-and post-operative recovery:total operation time,time of esophagus-jejunum anastomosis,volume of intraoperative blood loss,number of lymph node dissected,time to anal exsufflation,cases with complications and duration of postoperative hospital stay;(2) follow-up and survival.Follow-up using outpatient examination and telephone interview was performed to detect the postoperative tumor-free survival and tumor recurrence or metastasis up to March 2017.Measurement data with normal distribution were represented as (x)±s and comparison between groups was analyzed using the independent-sample t test.Comparison of count data was analyzed using the chi-square test or Fisher exact probability.Results (1) Intra-and post-operative recovery:all the 50 patients underwent successful TLTG using Overlap method,without conversion to open surgery.Total operation time and time of esophagus-jejunum anastomosis were respectively (278.6± 14.9) minutes,(46.5 ± 4.4) minutes in the classic Overlap group and (253.3 ± 12.8) minutes,(20.4 ± 2.3) minutes in the modified Overlap group,with statistically significant differences between the 2 groups (t =5.459,22.482,P＜0.05).Volume of intraoperative blood loss,number of lymph node dissected,time to anal exsufflation,cases with complications and duration of postoperative hospital stay were respectively (73±25) mL,34±6,(2.7± 1.0) days,2,(9.7± 1.6) days in the classic Overlap group and (71 ± 22) mL,35± 5,(2.6± 1.3) days,2,(9.8± 1.5) days in the modified Overlap group,with no statistically significant difference between the 2 groups (t =0.175,-0.616,0.293,-0.217,P＞ 0.05).Two patients in the classic Overlap group were respectively complicated with esophagus-jejunum anastomotic fistula and pancreatic leakage,2 patients in the modified Overlap group were respectively complicated with pulmonary infection and subcutaneous emphysema,and they were improved by symptomatic treatment.(2) Follow-up and survival:41 of 50 patients were followed up for 3-15 months,with a median time of 7 months,including 20 in the classic Overlap group and 21 in the modified Overlap group.During follow-up,patients had tumor-free survival,without tumor recurrence and metastasis.Conclusion Compared with classic Overlap method,the modified Overlap method can simplify the anastomotic procedures,shorten operation time and achieve similar efficacy,and it is also a simple and effective method for digestive tract reconstruction after TLTG.

Objective To analyze molecular characteristics of 5 congenital hypothyroidism (CH) patients due to dyshormonogenesis.Method We enrolled 5 CH patients due to dyshormonogenesis who were identified in Newborn Screening Center of Guangxi Zhuang Autonomous Region,China.Blood samples were collected from the patients and their parents,and genomic DNA was extracted from peripheral blood leukocytes.All exons of DUOX2,TG,TPO and NIS gene together with their exon-intron boundaries were screened by next-generation sequencing.Specimens from 100 normal controls were tested for these novel variations.Result No TPO,NIS or TG gene mutations were identified.Direct sequencing of the DUOX2 gene revealed that patient 1 had a compound heterozygote for c.3340delC and p.R683L,patient 2 was homozygous for p.K530X and patient 3 was a heterozygote for p.E879K.Both biallelic and monoallelic heterozygous mutations in DUOX2 were associated with transient CH.Novel mutations included c.3340delC and p.R683L,analysis of 100 healthy subjects without thyroid disease did not show the same change.Conclusion Genetic analysis of TPO,NIS,DUOX2 and TG gene in 5 unrelated CH patients with thyroid dyshormonogenesis revealed two novel DUOX2 mutations,both were biallelic and monoallelic heterozygous mutations in DUOX2 associated with transient CH.