Approximately 8%to 15%of patients with metastatic colorectal cancer(mCRC)harbor BRAF mutation,and the V600E mutation is the most common form of BRAF mutation.The prognosis of patients with metastatic colorectal cancer harboring BRAF V600E mutation is poor.Initial standard chemotherapy is often ineffective,necessitating an intensive follow-up treatment,which usually provides limited effic-acy.Consequently,the disease becomes notably difficult to treat and progresses rapidly,resulting in a decreased overall patient survival rate.This review details the research advancements in treatment of BRAF V600E-mutant metastatic colorectal cancer.

Objective:To investigate the incidence and treatment of gastric cancer in 16 medical centers in Tianjin from 2020 to 2021.Methods:The retrospective and descriptive study was conducted. The clinical data of 3 122 gastric cancer patients who underwent surgery in 16 medical centers, including Tianjin Medical University Cancer Institute & Hospital, et al, in Tianjin from 2020 to 2021 were collected. There were 2 112 males and 1 010 females, aged (64±11)years. Observation indicators: (1) general data of patients; (2) treatment situations; (3) postoperative complications. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M(range). Count data were descri-bed as absolute numbers or percentages, and comparison between groups was conducted by the chi-square test. Results:(1) General data of patients. From 2020 to 2021, a total of 3 122 gastric cancer patients received surgeries in 16 medical centers in Tianjin, including 2 112 males and 1 010 females. There were 1 443 cases in 2020, including 976 males and 467 females, aged (63±11) years. There were 1 679 cases in 2021, including 1 136 males and 543 females, aged (65±11) years. Of the 3 122 pati-ents, cases in stage Ⅰ, Ⅱ, Ⅲ, Ⅳ were 696, 667, 1 466, 293, accounting for 22.293%(696/3 122), 21.365%(667/3 122), 46.957%(1 466/3 122), 9.385%(293/3 122), respectively. Cases with early gastric cancer, locally advanced gastric cancer, advanced gastric cancer account for 17.265%(539/3 122), 73.350%(2 290/3 122), 9.385%(293/3 122). There were 2 829 patients without distant metastasis and 293 patients with distant metastasis. For the 2 829 patients without distant metas-tasis, cases in stage T1, T2, T3, T4a, T4b accounted for 19.053%(539/2 829), 12.089%(342/2 829), 20.148%(570/2 829), 41.499%(1 174/2 829), 7.211%(204/2 829)respectively, cases in stage N0, N1, N2, N3 account for 37.328%(1 056/2 829), 16.331%(462/2 829), 15.836%(448/2 829), 30.505%(863/2 829). For the 293 advanced gastric cancer patients with distant metastasis, 190 cases had peri-toneal metastasis, 47 cases had lymph node metastasis, 27 cases had ovarian metastasis, 37 cases had liver metastasis, 14 cases had other metastasis (some patients had ≥2 distant metastases). (2) Treatment situations. ① For the 539 with early gastric cancer, cases undergoing endoscopic submu-cosal dissection, laparoscopic surgery, open surgery were 22, 150, 86 in 2020, versus 19, 212, 50 in 2021, showing a significant difference between them ( χ2=19.42, P<0.05). For the 498 patients with early gastric cancer who underwent laparoscopic or open surgery, cases undergoing open surgery including total gastrectomy, distal gastrectomy, proximal gastrectomy were 25, 81, 30, and cases undergoing laparoscopic surgery including total gastrectomy, distal gastrectomy, proximal gastrec-tomy were 18, 309, 35, respectively, showing a significant difference between them ( χ2=40.62, P<0.05). For the 2 290 patients with locally advanced gastric cancer, cases undergoing open surgery and laparoscopic surgery were 446 and 617 in 2020, versus 410 and 817 in 2021, showing a significant difference between them ( χ2=17.75, P<0.05). For the 2 290 patients with locally advanced gastric cancer, cases undergoing open surgery including total gastrectomy, distal gastrectomy, proxi-mal gastrectomy were 336, 377, 143, and cases undergoing laparoscopic surgery including total gastrectomy, distal gastrectomy, proximal gastrectomy were 377, 920, 137, respectively, showing a significant difference between them ( χ2=89.64, P<0.05). Of the 293 patients with advanced gastric cancer, 175 cases underwent surgeries due to hemorrhage, stenosis, perforation, 76 cases under-went surgery after chemotherapy, 42 cases underwent surgery directly. ② For 756 cases of 3 122 pati-ents undergoing total gastrectomy, 357 and 4 cases received open digestive tract reconstruction including Roux-en-Y and other anastomosis, versus 380 and 15 cases with laparoscopic digestive tract reconstruction including Roux-en-Y and other anastomosis, showing a significant difference between them ( χ2=5.57, P<0.05). For 1 687 cases undergoing distal gastrectomy, 84, 160, 158, 55 cases received open digestive tract reconstruction including Billroth Ⅰ anastomosis, Billroth Ⅱ + Braun anastomosis, Roux-en-Y anastomosis, uncut Roux-en-Y anastomosis, versus 154, 489, 417, 170 cases with laparoscopic digestive tract reconstruction including Billroth Ⅰ anastomosis, Billroth Ⅱ + Braun anastomosis, Roux-en-Y anastomosis, uncut Roux-en-Y anastomosis, showing a significant difference between them ( χ2=10.90, P<0.05) . Of the 539 patients with early gastric cancer, 65 cases had lymph node metastasis, in which 18 of 306 stage T1a cases had lymph node metastasis and 47 of 233 stage T1b cases had lymph node metastasis. The number of detected lymph nodes for the 2 290 patients with advanced gastric cancer was 31±15, including ≥16 for 2 059 cases and ≥30 for 1 276 cases. Of the 3 122 patients, cases with neoadjuvant therapy, complete response and incomplete response was 128, 13 and 115 in 2020, versus 250, 49 and 201 in 2021, showing a significant difference between them ( χ2=5.51, P<0.05). (3) Postoperative complications. Of the 3 122 patients, 746 cases had postoperative complications, with an incidence of 23.895%(746/3 122). There were 62 patients with grade 3 or more complications. Reoperation was conducted in 34 patients. There were 14 cases of postoperative death. The duration of postoperative hospital stay and hospital expense were (11±5)days and (98 114±46 598)yuan for the 3 122 patients, (26±14)days and (122 066±68 317)yuan for cases with complications, (40±21)days and (196 926±12 747)yuan for cases with grade 3 or more complications. Conclusion:Compared with 2020, cases undergoing laparoscopic surgery and distal gastrectomy for gastric cancer in Tianjin increases in 2021, and the digestive tract reconstruction also differs. The number of patients with neoadjuvant chemotherapy and complete response rate for advanced gastric cancer increases.

Objective:To observe any therapeutic effect of combining botulinum toxin type A (BTX-A) with rehabilitation training in treating Parkinson′s disease (PD) patients with striatal foot deformity (SFD).Methods:A total of 68 PD patients with SFD were randomly divided into a control group and a treatment group. Both groups were given routine medication with pramipexole and dopamine receptor agonists and received lower limb rehabilitation training, including passive activity training, strength training and walking training. The treatment group was additionally injected with BTX-A. Sciatic pain was quantified using a visual analogue scale. The Unified Parkinson′s Disease Rating Scale-lower limb motor lower limb motor function (UPDRS-LLM) scale, the Berg balance scale and the modified Barthel index were applied to test all of the participants before the experiment and on the 7th, 14th and 30th day of the treatment.Results:The average scores of the control group on all of measures at were significantly better than those of the control group at the same time points, and by the 14th and 30th day had improved significantly compared with those before treatment.Conclusion:Supplementing rehabilitation training with BTX-A can significantly improve foot deformity and relieve the muscle tension and spastic pain of PD patients with SFD, promoting the motor functioning of their lower limbs, their balance and their performance in the activities of daily living.

Bioactive peptides play important roles in promoting human health, such as lowering blood pressure, blood sugar and blood lipid, anti-obesity, and anti-cancer. Thus, exploring functional bioactive peptides and developing efficient production technologies are of crucial importance. Herein, we review the development of function discovery and production technology for natural bioactive peptides. Presently, the top-down and bottom-up approaches are mainly used for the function discovery and production of natural active peptides. The top-down approach includes the direct extraction and identification for functional discovery, and the direct extraction, enzymatic hydrolysis and microbial fermentation for production. The bottom-up approach includes the polypeptide modification and database mining for functional discovery, and the chemical synthesis, enzyme synthesis, recombinant expression and cell-free synthesis for production. The top-down approach is usually associated with complicated process, lower efficiency, higher cost, harder quality control, and uncertain functionality, while the bottom-up approach is more suitable for the development of peptide drugs but difficult to be used for functional foods. With the technology development of sequencing and mass spectrometry, it is easier to obtain the proteomic information of various organisms at the molecular level. Based on the proteomic information, the top-down and bottom-up approaches can be combined to overcome the disadvantages of using these two approaches alone, thus providing a new strategy for the rapid development and production of natural active peptides.
Fermentation ; Humans ; Mass Spectrometry ; Peptides/metabolism* ; Proteomics ; Technology

Objective:To investigate the clinical effect of deep brain stimulation (DBS) in the treatment of Parkinson′s disease (PD).Methods:32 PD patients treated in Hunan Brain Hospital from January 2016 to December 2018 were selected for the study. Guided by MRI and supplemented by electrophysiological stimulation to correct the target, PD patients were treated with DBS for the nucleus accumbens. Based on Webster and Unified Parkinsons Disease Rating Scale (UPDRS) scores before and after DBS treatment, the clinical treatment effects were evaluated. And the content of Aβ1-42, interleukin (IL)-1β, IL-6, uric acid (UA), malondialdehyde (MDA), homocysteine (Hcy), S-nitrosylated dynamin-relatedprotein 1 (SNO-Drp1) and Drp1 was measured before and after DBS treatment. The ratio of SNO-Drp1/Drp1 was also measured.Results:The Webster score and UPDRS score of PD patients after DBS treatment were lower than those before DBS treatment ( P<0.05). The Aβ1-42 and Drp1content of PD patients after DBS treatment was higher than that before DBS treatment ( P<0.05), while the content of IL-1β, UA, MDA, Hcy and the ratio of SNO-Drp1/Drp1 were lower than before treatment ( P<0.05). Conclusions:DBS has confirmed a good clinical effect in the treatment of PD patients and significantly improved the quality of life of patients.

Autophagy is one of the most common protective mechanisms during plant stress response. We studied the effect of exogenous Cd on autophagy in celery, by using transcriptome sequencing technique to analyze the differentially expressed genes under different Cd concentrations (0, 2, 4 and 8 mg/L). Eight differentially expressed autophagy-related genes were screened and identified by qRT-PCR. Cd had obvious toxic effect on celery, in a dose-dependent manner. Eight differentially expressed autophagy-related genes were screened, among which ATG8a, ATG8f, ATG13, AMPK-1 and AMPK-2 were up-regulated, whereas ATG12, VPS30 and VPS34 were first up-regulated and then decreased. The up-regulated expression of differential genes may resist Cd toxicity by increasing autophagosome structures; however, 8 mg/L Cd exceeded the autophagosome tolerance limit of celery, resulting in decreased expression of multiple autophagy-related genes. The above results can provide help for subsequent functional study of autophagy-related genes, and provide a reference for further exploring the tolerance mechanism of celery to Cd toxicity.

Objective To evaluate the therapeutic value of endoscopic jejunal tube placement, endoscopic clipping, and over the scope clip ( OTSC) for digestive fistula. Methods Data of 38 patients with digestive fistulas at the First Affiliated Hospital of Soochow University admitted from July 2015 to July 2017 were retrospectively analyzed. Treatments were chosen according to the size and the site of the fistulas. Thirteen patients underwent jejunal tube placement ( the jejunal tube group ) , 20 underwent endoscopic clipping( the endoscopic clipping group) , and 5 underwent OTSC( the OTSC group) . The technical success rate, clinical cure rate and postoperative hospital stay were analyzed. Results All patients received the endoscopic operation successfully with no significant complications. In the jejunal tube group, 4 patients′fistulas fully healed, lesion was smaller after treatment in 3 patients, lesion didn′t change in 5 patients, and 1 patient died. The complete cure rate was 30. 8％ (4/13), and the postoperative hospital stay was 47. 4± 14. 1 days. For the endoscopic clipping group, 16 patients′ fistulas fully healed, lesion was no smaller compared with that before treatment in 3 cases, and 1 patient died. The complete cure rate was 80. 0％ ( 16/20) , and the postoperative hospital stay was 17. 9 ± 8. 9 days. Total patients in the OTSC group were completely cured, with 100. 0％( 5/5) of complete cure rate. One patient with refractory esophageal fistula underwent OTSC repeatedly with endoscopic clipping, and the healing time of fistula was 102 days. The postoperative hospital stay of 4 others was 5. 3±1. 7 days. The cure rate of fistula was higher (P=0. 03, P<0. 001) and the postoperative hospital stay was shorter ( P=0. 04, P<0. 001) in the OTSC group compared with the clipping group and the jejunal tube group. Conclusion Endoscopic management is safe and effective for digestive fistulas with less trauma, easy performance and short time of healing.

Tibial dyschondroplasia (TD) cases has not been reported in Tibetan chickens (TBCs), but it is commonly seen in commercial broilers characterized by lameness. The underlying mechanism remains unclear. Hypoxia-inducible factors (HIFs) are important regulators of cellular adaptation to hypoxic conditions. In this study, we investigated the role of HIF-1α,
Anoxia ; Blotting, Western ; Chickens ; Growth Plate ; Osteochondrodysplasias ; Poultry ; Reverse Transcriptase Polymerase Chain Reaction ; RNA ; Thiram

Classical swine fever (CSF), one of OIE-listed diseases, is a highly contagious and economically important disease of pigs. Classical swine fever virus (CSFV) is the causative agent of CSF. The capsid (C) protein and the glycoproteins Erns, E1 and E2, are structural components of the virus. E2 is the most immunogenic protein of the CSFV glycoproteins, inducing neutralizing antibodies that provide protection against lethal CSFV challenge. In a previous study, we developed a murine MAb HQ06 against the E2 protein of CSFV. In this study, the variable region genes from HQ06 and constant regions gene of swine antibody are fused and cloned into the eukaryotic expression vectors to establish a cell line which can stably express a chimeric porcinized MAb (cHQ06) against E2 in CHO cell. The purified cHQ06 antibody protein was determined to be successfully generated, which exhibited high reactivity between cHQ06 and the E2 protein of CSFV by enzyme-linked immunosorbent assay (ELISA) and Western blotting. More importantly, we investigated the neutralizing activity of cHQ06 against CSFV. In conclusion, this study generated cHQ06 for efficient and stable production which can be used against to develop novel diagnostic assays, investigate the structure and function of the E2 protein and generate novel preparations of diagnosis and treatment.