Metabolic reprogramming is a common phenomenon in cancer, with aerobic glycolysis being one of its important characteristics. Hypoxia-inducible factor-1α (HIF1Α) is thought to play an important role in aerobic glycolysis. Meanwhile, naringin is a natural flavanone glycoside derived from grapefruits and many other citrus fruits. In this work, we identified glycolytic genes related to HIF1Α by analyzing the colon cancer database. The analysis of extracellular acidification rate and cell function verified the regulatory effects of HIF1Α overexpression on glycolysis, and the proliferation and migration of colon cancer cells. Moreover, naringin was used as an inhibitor of colon cancer cells to illustrate its effect on HIF1Α function. The results showed that the HIF1Α and enolase 2 (ENO2) levels in colon cancer tissues were highly correlated, and their high expression indicated a poor prognosis for colon cancer patients. Mechanistically, HIF1Α directly binds to the DNA promoter region and upregulates the transcription of ENO2; ectopic expression of ENO2 increased aerobic glycolysis in colon cancer cells. Most importantly, we found that the appropriate concentration of naringin inhibited the transcriptional activity of HIF1Α, which in turn decreased aerobic glycolysis in colon cancer cells. Generally, naringin reduces glycolysis in colon cancer cells by reducing the transcriptional activity of HIF1Α and the proliferation and invasion of colon cancer cells. This study helps to elucidate the relationship between colon cancer progression and glucose metabolism, and demonstrates the efficacy of naringin in the treatment of colon cancer.
Glycolysis ; Colonic Neoplasms/metabolism* ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism* ; Phosphopyruvate Hydratase/metabolism* ; Flavanones/pharmacology* ; Cell Line, Tumor ; Databases, Genetic ; Cell Proliferation/drug effects* ; Transfection ; Warburg Effect, Oncologic

Objective:To study the treatment outcomes of combining percutaneous transhepatic one-step biliary fistulation (PTOBF) followed by two stages cholangioscopic treatment for type Ⅰ and Ⅱa hepatolithiasis which developed after Roux-en-Y cholangiojejunostomy, and in treatment of cholangiojejunostomy stenosis.Methods:The clinical data of 95 patients with type Ⅰ and Ⅱa hepatolithiasis which developed after Roux-en-Y cholangiojejunostomy and were treated at Shandong Second Provincial General Hospital from September 2016 to December 2020 were analyzed retrospectively. There were 36 males and 59 females, with the age of (51.2±15.3) years (range 14 to 75 years). These patients initially underwent PTOBF rigid choledochoscopy, followed by electronic choledochoscopy via the fistula tract after 6-8 weeks. The hepatolithiasis removal, complications and hepatolithiasis recurrence rates, and the cholangio-intestinal anastomotic stenosis rate and treatments were recorded. The follow-up was performed to analyse prognosis.Results:All 95 patients successfully underwent PTOBF rigid choledochoscopy and electronic choledochoscopy via the fistula tract. In 92 patients (96.8%), stones were completely removed. In 3 patients, small amounts of peripheral bile duct stones were left behind. Of 49 patients had cholangio-intestinal anastomotic strictures. On cholangioscopic examination, the strictures were caused by anastomotic knots in the suture line in 25 patients and cicatricial stenosis in 24 patients. After biliary balloon dilation and removal of anastomotic suture line knots, the strictures were relieved in 49 patients. There were 2 patients who developed biliary bleeding and 2 patients pleural effusion after PTOBF rigid choledochoscopy. Hepatolithiasis recurred in 4 patients in 6 to 36 months later.Conclusion:PTOBF followed by two stages cholangioscopic treatment were safe and effective in treatment of type Ⅰ and Ⅱa hepatolithiasis after Roux-en-Y cholangiojejunostomy. A high hepatolithiasis removal rate was obtained. Balloon dilation and removal of biliary intestinal anastomotic suture knots effectively relieved biliary intestinal anastomotic stenosis. The long-term results needs to be further determined.

Objective:To explore the carrier status of carbapenems-resistant Klebsiella pneumoniae (CRKP) plasmids in burn patients and analyze the correlation of these plasmids with the transmission of CRKP. Methods:A retrospective observational study was conducted. A total of 26 CRKP strains, which were isolated from the clinic-related samples of 22 burn patients (with 20 males and 2 females, aged (42±16) years) admitted to the First Affiliated Hospital of Army Medical University (the Third Military Medical University) from January to December 2017, were collected and individually numbered. The plasmids of the strains were extracted by alkali lysis. After determination of the plasmid concentration by a nucleic acid concentration detector, the agarose gel electrophoresis was used to visualize the bands, and rough plasmids typing was performed. The plasmid of the smallest numbered CRKP in each plasmid type was transformed into competent Escherichia coli ( E. coli) strain Top10 (hereinafter referred to as TOP10 strain). The growth of each transformed strains and a Top10 strain cultivated in ampicillin containing Luria-Bertani (LB) agar medium overnight was observed, and the proportion of successful transformation was calculated. The plasmids from the smallest numbered plasmid carrying CRKP strain of successfully transformed Top10 strains (hereinafter referred to as the smallest successfully transformed strain) and correspondingly numbered CRKP were extracted, and then, the agarose gel electrophoresis was used to visualize the bands. Aforementioned successfully transformed strains and a TOP10 strain were used for the antimicrobial susceptibility testing with 17 antibiotics commonly used in clinic. The plasmid from the smallest successfully transformed strain was sequenced using the next-generation sequencing technology. Bioinformatics analyses such as protein-coding gene prediction and protein sequence alignment were performed successively. The sequence was subsequently named pKP03-NDM1 according to the carrying of drug resistance gene. According to the whole genome sequence of the plasmid carried by the smallest successfully transformed strain, the polymerase chain reaction, agarose gel electrophoresis, and gene sequencing were used to detect the New Delhi metallo-beta lactamase-1 ( blaNDM-1) of plasmids in the remaining 25 strains of CRKP. The ST typing in multilocus sequence typing of 26 strains of CRKP was analyzed based on the literature. Results:Plasmids were successfully extracted from 26 CRKP, with mass concentrations ranging from 19.3 to 189.8 ng/μL. Each of the 26 CRKP carrying plasmids showed at least one band longer than 2 500 bp in the agarose gel electrophoresis, which were roughly divided into 6 patterns of A, B, C, D, E, and F. After overnight cultivation, no growth of strains was observed in LB agar medium containing ampicillin inoculated with the TOP10 strain or TOP10 strains transformed by the plasmid of CRKP patterning A, B, D, or E. In contrast, TOP10 strains transformed by the pattern C plasmid from NO.3 CRKP and the pattern F plasmid from NO.15 CRKP resulted in numerous colony growths, and those transformed strains were named as TOP10-pKP03 and TOP10-pKP15, respectively. The proportion of successful transformation was 1/3. The plasmid carried by TOP10-pKP03 showed a single band in the agarose gel electrophoresis, which was the same size as the largest band of the plasmid from NO.3 CRKP. The TOP10 strain was sensitive to the 17 antibiotics commonly used in clinic. TOP10-pKP03 and TOP10-pKP15 were resistant to penicillins, cephalosporins, and carbapenems but remained sensitive to monocyclic β-lactam, aminoglycosides, quinolones and tigecycline. The full length of the plasmid carried by TOP10-pKP03 was 41 190 bp. In addition to blaNDM-1, this plasmid carried bleMBL, T4SS, bleomycin resistance gene, conjugation transfer elements, and relaxase, etc. The plasmid showed 99% nucleotide identity similarity and the same length to the plasmid pJN24NDM1 extracted from an E. coli isolate JN24. Totally 16 (61.5%) CRKP were confirmed to carrying blaNDM-1 gene, among the ST typing of the 16 strains, 11 strains were ST11, while ST215, ST260, ST395, ST2230, and new ST had 1 strain each. Among the ST typing of 10 blaNDM-1-negative CRKP, 8 strains were ST11, while ST395 and ST2230 had 1 strain each. Conclusions:A blaNDM-1 gene carrying plasmid pKP03-NDM1 was extracted and sequenced from CRKP isolated from burn patients, with a high plasmid carrying rate. Meanwhile, this plasmid may mediate inter-CRKP and CRKP- E. coli horizontal transfer of blaNDM-1, leading to transmission of antimicrobial resistance.

Objective:To understand the basic situation of noise hazards in wood furniture manufacturing, stone processing and special equipment manufacturing industries in Shenzhen City, and to provide basis for preventing and controlling noise hazards.Methods:In August 2019, stratified random sampling ws used to select 21 wood funiture manafacturing, 15 stone processing and 24 special equipment manufactruing as survey object. Through the methods of occupational health field investigation, noise intensity measurement and occupational health examination data collection, the noise hazards of 60 enterprises in three industries were statistically analyzed.Results:There were 154, 44 and 113 noise detection points in wood furniture manufacturing, stone processing and special equipment manufacturing enterprises, and 101, 27 and 78 out of standard points respectively, and the exceeding standard rates were 65.6% (101/154) , 61.4% (27/44) and 69.0% (78/113) , respectively. There were 1670, 172 and 856 workers exposed to noise in the three industries. Among them, 1198, 134 and 703 people had taken occupational health examination. The physical examination rates were 71.7% (1198/1670) , 77.9% (134/172) and 82.1% (703/856) , respectively. The abnormal rates were 19.1% (229/1198) , 51.5% (69/134) and 37.8% (266/703) , respectively.Conclusion:High intensity noise working environment, too long noise exposure time, incorrect wearing of personal protective equipment and neglect of occupational health examination are important reasons for hearing loss of noise exposed personnel.

Objective:To understand the basic situation of noise hazards in wood furniture manufacturing, stone processing and special equipment manufacturing industries in Shenzhen City, and to provide basis for preventing and controlling noise hazards.Methods:In August 2019, stratified random sampling ws used to select 21 wood funiture manafacturing, 15 stone processing and 24 special equipment manufactruing as survey object. Through the methods of occupational health field investigation, noise intensity measurement and occupational health examination data collection, the noise hazards of 60 enterprises in three industries were statistically analyzed.Results:There were 154, 44 and 113 noise detection points in wood furniture manufacturing, stone processing and special equipment manufacturing enterprises, and 101, 27 and 78 out of standard points respectively, and the exceeding standard rates were 65.6% (101/154) , 61.4% (27/44) and 69.0% (78/113) , respectively. There were 1670, 172 and 856 workers exposed to noise in the three industries. Among them, 1198, 134 and 703 people had taken occupational health examination. The physical examination rates were 71.7% (1198/1670) , 77.9% (134/172) and 82.1% (703/856) , respectively. The abnormal rates were 19.1% (229/1198) , 51.5% (69/134) and 37.8% (266/703) , respectively.Conclusion:High intensity noise working environment, too long noise exposure time, incorrect wearing of personal protective equipment and neglect of occupational health examination are important reasons for hearing loss of noise exposed personnel.

Objective:To evaluate the safety and efficacy of the treatment for oppressive spinal by microwave ablation combined with percutaneous fixation and open decompression.Methods:From January 2015 to September 2018, 20 patients with 26 spinal metastatic were treated with microwave ablation combined with percutaneous fixation and open decompression, including 13 males and 7 females with an average age of 43.85±18.67 years (range, 16-79 years). The locations of the lesions included: 9 in the thoracic, 11 in the lumbar. The tumors' type: myeloma 2 cases, leukemia 1 case, liver cancer 4 cases, osteosarcoma 2 cases, lung cancer 5 cases, kidney cancer 1 case, esophagus cancer 1case, cervical cancer 1 case, intestinal cancer 1 case, prostate cancer 1 case, adenoid cystic cancer 1case. Preoperatively all the patients suffered with the local pain and the spinal cord or nerve root compression symptoms. All 20 cases were examined with CT or MRI to determine the lesions and the sizes of metastasis, as well as to evaluate the ablation zone. The entry of the pedicle screws were performed by Wiltse method through paravertebral muscles. After that the lesions were treated with partial resection for decompression of spinal cord or nerve root, and followed with microwave ablation at the metastasis site. Thermometer was used to monitor the temperature at the central and posterior edges of the vertebral body. The surrounding important tissue were cooled by ice saline. 13 patients were performed with vertebroplasty for enhancement the intensity of the vertebral body. The visual analogue scale (VAS) score was used to evaluate the effect of pain relief after surgery. The postoperative neurological function and performance status were evaluated using Frankel grading and Eastern Cooperative Oncology Group (ECOG).Results:Each lesion was heated for 5.43±2.07 min (range, 3-10 min). The power of microwave ablation was 40-60 W. The mean blood loss during operation was 852.50±514.40 ml (range, 100-1 700 ml). The mean operating time was 4.11±0.99 h (range, 2.5-6.0 h). The temperature inside the lesion was 70-85 ℃. The temperature of the surrounding tissue was maintained at<43 ℃ by repeated frozen saline flush. All cases were followed up for 8.45±2.01 months (range, 6-14 months) without any recurrence. The VAS score of the 20 patients at 48 h, 1 month, 3 months and 6 months after operation were 1.55±1.23, 2.70±0.87, 2.40±1.14 and 3.05±1.00 points, which were all statistically lowerthan the preoperative score 5.95±1.18 ( P<0.05). The Frankel grading of 14 patients had at least one grade improvement 6 months after operation. There were 8 patients shown markedly improved ECOG score 6 months after surgery. Only one case suffered from reduced myodynamiaof lower limb and covered in one month after system treatment. Conclusion:The microwave ablation combined with percutaneous fixation and open decompression could resolve the spinal and nerve compression, relieve the pain in metastatic spinal oppression, reconstruct the stability, and improve the quality of lives, which is a safe and effective palliative surgical method.

Objective:To investigate the clinical effects of modified fascia flap from cutaneous branch of dorsal metacarpal artery in repairing the wound at the proximal and middle finger segments.Methods:From January 2017 to September 2018, 12 patients with wounds at the proximal and middle finger segments were admitted to the Affiliated Hospital of Zunyi Medical University, including 8 males and 4 females, aged 35-70 years. The areas of wounds ranged from 3.4 cm×2.4 cm to 6.5 cm×4.0 cm. The modified fascia flaps from cutaneous branch of dorsal metacarpal artery were resected to repair the wounds, with the size ranging from 3.5 cm×2.5 cm to 6.7 cm×4.1 cm. The flap donor sites of 5 patients were repaired with direct intermittent suture, the flap donor sites of 4 patients were repaired with full-thickness skin grafts from ipsilateral medial forearm, and the flap donor sites of 3 patients were repaired with wrist pedicled flaps. The survival of the flaps was recorded. Healing of donor site and recipient site was followed. The hand functions were evaluated with trial standard for the evaluation of the functions of the upper limbs of the Hand Surgery Society of the Chinese Medical Association.Results:All the flaps survived in 12 cases. During 3 to 12 months of follow-up, the flaps recovered satisfactorily in texture and shape. The donor sites of 11 patients were healed, and the skin graft edge area was partially necrotic in the other patient but healed later after dressing change. The distances of two-point discrimination of the patients ranged from 5.6 to 9.0 mm. Hand functions were evaluated as excellent in 5 cases, good in 4 cases, and fair in 3 cases.Conclusions:Modified fascia flap from cutaneous branch of dorsal metacarpal artery for repairing the wounds at the proximal and middle finger segments has reliable blood supply. The operation is simple and safe with short course of treatment, which is worthy of clinical promotion.

Objective: To study the changes of monocyte cytokines in peripheral blood of n-hexane neuropathy patients induced by P₀ protein, and to explore the role of autoimmunity in n-hexane neuropathy patients. Methods: In May 2018, 5 patients with peripheral neuropathy diagnosed as n-hexane poisoning were selected as case group in Shenzhen Prevention and Treatment Center for Occupational Disease in 2017. 6 workers exposure to n-hexane and 6 workers without n-hexane exposure were selected as contact group and control group. Peripheral blood mononuclear cells(PBMC) were isolated from venous blood. Results: The number of spots produced by INF-γ and IL-10 increased after stimulation with P₀ protein in case group, and the positive rate was significantly higher than control group and the contact group. Conclusion Autoimmunity induced by P₀ protein may be involved in the occurrence of myelin sheath damage in n-hexane neuropathy patients.

OBJECTIVE Dynamics of serum and urine metabolites in hepatic injury rats induced by ethanolic extract from Rhizoma Dioscoreae Bulbiferae(RDB)was investigated by 1H-NMR-based metabo?nomic methods in order to discover early biomarkers of liver toxicity induced by RDB. METHODS Rats were ig adminisetred with RDB at a dose of 5 g·kg-1 for 28 d. Rats were sacrificed 3,7,14 and 28 d af?ter RDB administration,as well as after a recovery period,respectively. Blood was taken for routine bio?chemical analysis by an automatic biochemical analyzer. Liver/body mass indexes were calculated ,and liver pathological changes were observed with hematoxylin-eosin staining. Urine samples were collected before and 3,7,14 and 28 d after RDB administration,respectively,as well as after withdrawal. Metabo?nomic analysis was carried out for serum and urine samples. Principal component analysis and orthogonal partial least squares-discriminant analysis were used for screening and identifiying early biomarkers. RESULTS Compared with the control group,total bilirubin (TB) and total cholesterol (TC) values were increased in 3-28 d in RDB group(P<0.05,P<0.01). Total bile acid(TBA)was elevated in 7-28 d (P<0.05,P<0.01). TB,TC and TBA became normal after discontinuation with RDB. There was no significant difference between RBD-treated group and control group in the activity of glutamic-pyruvic transaminase and glutamic-oxaloacetic transaminase,and the content of glucose also was not different between the two groups. The ratio of liver/body mass was elevated at 3-28 d(P<0.01)but returned to normal after withdraval of RDB. The enlargement and necrosis of hepatocytes were observed 7 d after RDB administration,and lesion degree was aggravated with the extension of RDB delivery time. Meta?bonomic analysis showed that the serum lipids (low density lipoprotein/very low density lipoprotein (LDL/VLDL),glutamic acid,choline phosphate and glycerolphosphatecholine were increased in the early stage. Pyruvate and N-acetylglutamate were decreased in urine. These metabolites became normal 7 d after discontinuation with RDB. CONCLUSION The serum lipids (LDL/VLDL),glutamic acid,glycerol phosphate choline,as well as urine pyruvic acid salt and N-acetyl glutamate may be used as the early biomarkers for liver toxicity induced by RDB.

Objective To evaluate the prevalence of subclinical atherosclerosis in rheumatoid arthritis (RA) and the related risk factors.Methods Fifty RA patients without overt atherosclerotic disease and 121 control subjects matched for age and sex were recruited.Duplex carotid sonography was used to measure intima-media thickness (IMT) and plaque formation assessment.Differences between RA and the control group were compared, and the risk factors were explored.RA patients then were divided into two subgroups according to IMT and the comparison between the two subgroups were completed.T test, Mann-Whitney U test, chi-square test, Pearson's correlation and Logistic regression analysis were used for statistical analysis.Results Although RA patients had lower level of serum lipids and body mass index than the control group, the mean IMT value was significantly higher in the RA group than that in the control group [(0.78±0.18) mm vs (0.62±0.14) mm, t=5.853, P=0.000], and plaque formation was more prevalent [56.0％(28/50) vs 36.4％ (44/121),x2=5.596, P=0.018].The difference was especially significant in the younger groups (＜50 years old group and 50-60 years old group).Logistic regression showed that the presence of RA [OR=7.34, 95％CI (2.53, 21.25)], male [OR=2.0, 95％CI (91.25, 3.17)] and old age [OR=1.1, 95％CI (1.04, 21.15)] were the independent risk factors for abnormal IMT (thickened or the presence of carotid plaques).The RA patients were divided into two subgroups according to IMT.Compared with patients with normal IMT, patients with abnormal IMT were older and more common in postmenopausal, and had longer RA duration and higher cholesterol level.In treatment, less patients with abnormal IMT had been taking methotrexate (MTX) for more than 3 months compared with patients with normal IMT.Among these parameters, old age [OR=1.13, 95％CI (1.03, 1.23)] was shown to be the independent risk factor for abnormal IMT in RA patients, and more than 3 months of MTX treatment [OR=0.12, 95％CI (0.02, 0.71)] was the protective factor.Conclusion Atherosclerosis occurs frequently and prematurely in patients with RA and the presence of RA is an independent risk factor for atherosclerosis.Early primary prevention for atherosclerosis should be recommended.MTX probably has a positive effect on preventing atherosclerosis for RA patients, which needs to be confirmed by further study.