[Application value of artificial intelligence in surgical precision diagnosis and treatment of rectal cancer].

Colorectal cancer is the most common malignant tumor of digestive tract, and the incidence of colorectal cancer in China is especially characterized by middle and low rectal cancer. In recent years, with the progress of computer science, artificial intelligence technology has developed rapidly, and has achieved a lot of application results in the medical field. At present, artificial intelligence technology has covered various stages of colorectal cancer, including screening, individualized assessment, auxiliary diagnosis and treatment decision-making, refined surgery and prognosis judgment, providing help for the accurate and individualized treatment of rectal cancer. However, the lack of standardized, systematic, and scalable AI models remains a major pain point for the field. Therefore, it is necessary to carry out large-scale prospective clinical studies on artificial intelligence model to further confirm its application value in the clinical diagnosis and treatment of rectal cancer.

[Three decades of progress in China's laparoscopic colorectal surgery techniques].

Laparoscopic colorectal surgery has been carried out in China for more than 30 years and has experienced a three-stage high-speed development of "exploring and designing,optimising and standardising, perfecting and re-innovating" at the technical level. Based on the support and assistance of laparoscopic technology, colorectal surgery has made rapid progress in sub-microscopic anatomy, surgical procedures, surgical concepts, instruments and equipment. Nowadays, the technology and efficacy of laparoscopic colorectal surgery have gradually reached the ceiling, and in view of the existing pain points and the future direction of development, where will we go? This article summarised the past three decades of experience and consolidate the results to guide the future practice and the way forward.

[Efficacy of omalizumab in the treatment of eosinophilic granulomatous polyangiitis with asthma as the first symptom].

Objective: To investigate the efficacy, and safety of omalizumab in the treatment of eosinophilic granulomatous with polyangiitis (EGPA) with asthma as the first symptom. Method: The clinical characteristics of 22 EGPA patients with asthma as the first symptom treated with omalizumab in the First Affiliated Hospital of Guangzhou Medical University from March 2018 to December 2020 were retrospectively analyzed. The asthma control test (ACT) score, the frequency of asthma exacerbation (AE), the Birmingham Vasculitis Activity Score (BVAS), the variation rate of peak expiratory flow (PEF), the percentage of PEF to predicted value of PEF (PEFpred%), the percentage of forced expiratory volume in first second (FEV1) to predicted value of FEV1 (FEV1pred%), the dosage of oral corticosteroid (OCS) and other clinical data [M(Q1, Q3)] were collected before and after treatment, to observe the efficacy and adverse reactions of omalizumab. Results: There were 22 subjects recruited in this study. The median age was 42 (22-70) years. Eleven of the patients were males. After treated with omalizumab for 4 months, there were 68.2%(15/21) of patients who responded to the treatment. In the response group (n=15), the patients' ACT score increased from 19.0 (16.5, 21.0) to 23.0 (21.5, 24.0) (P=0.001). The frequency of AE decreased from 0.7 (0.3, 1.0) to 0 (0, 0.7) per four mouths (P<0.001). The BVAS decreased from 4.0 (2.0, 6.0) to 2.0 (2.0, 4.0) (P=0.007). The variation rate of PEF decreased from 18.8% (14.0%, 27.7%) to 9.2% (6.8%, 11.9%) (P=0.007). The PEFpred% increased from 80.8% (73.5%, 90.7%) to 100.5% (79.4%, 114.0%) (P=0.005). The maintenance dosage of OCS reduced from 15.0 (10.0, 20.0) mg/d to 8.8 (5.0, 10.0) mg/d (P=0.005). The level of baseline eosinophil in peripheral blood of patients in non-response group was higher than that in response group [11.4% (9.2%, 22.6%) vs 3.4% (1.1%, 6.5%), P<0.05]. A total of 190 injections were performed in 22 patients, and only 4 patients (2.1%) had adverse reactions after a single injection of omalizumab, such as dizziness, swelling of injection site and pruritus. The adverse reactions were tolerable. Conclusions: Omalizumab has certain curative effect on EGPA, can reduce asthmatic symptoms and OCS maintenance dosage, and has a good safety profile. The rate of response to the treatment is higher in patients with mild eosinophilic inflammation.

[Multidimensional thinking in the era of gastrointestinal minimally invasive surgery].

Minimally invasive surgery represented by laparoscopic technique has been carried out in China for more than 30 years. Gastrointestinal minimally invasive surgery has been widely recognized and popularized. Today, when the development of minimally invasive technology has reached the ceiling, the authors, who have experienced the innovation of minimally invasive gastrointestinal surgery for more than 30 years, review the gradual, unpredictable but inevitable characteristics of the innovation and development of minimally invasive surgery; figure out that standardized promotion and systematic training are the main reasons for the success of minimally invasive surgery in gastrointestinal surgery; realize that the application and promotion of new medical technology are inseparable from the support of solid clinical and basic evidence; recognize that the re-innovation after the popularization and standardization of gastrointestinal minimally invasive surgery and how to avoid involution are the driving force to seize the development momentum of minimally invasive technology. We make a multidimensional thinking on the development of gastrointestinal minimally invasive surgery, and objectively analyze its development track, in order to calmly rise to the challenges of future technological development.

[Small steps to thousands of miles: a tribute to Chinese laparoscopic gastric cancer surgery].

Laparoscopic surgery for gastric cancer has been developed in China for more than 20 years. It has gone through the initial stage of exploration in the 1990s, the stage of learning and accumulation in the early 21st century, the stage of development and expansion in the 2010s, and the current stage of standardization, and innovation. Laparoscopic gastric cancer surgery in China has developed from less to more, from more to popular. Surgical techniques have gradually become mature, innovated, and standardized, medical evidence has accumulated, and academic exchanges have become increasingly active and valued by the world. In the future, it is expected to make new progress and breakthrough in tumor specific laparoscopic navigation surgery system, intelligent robotic gastric cancer surgery platform, functional preservation surgery for early gastric cancer under the integration of gastroenterologists and surgeons, and laparoscopic comprehensive treatment for peritoneal metastasis. By reviewing the development of laparoscopic gastric cancer surgery in China, the authors draw inspiration from the depths of history, inherit and innovate, look forward to the future, and pay tribute to the predecessors.

[Medial border of D3 lymphadenectomy for right colon cancer].

The extent of D3 lymphadenectomy for right colon cancer, especially the medial border of central lymph node dissection remains controversial. D3 lymphadenectomy and complete mesocolon excision (CME) are two standard procedures for locally advanced right colon carcinoma. D3 lymphadenectomy determines the medial border according to the distribution of the lymph nodes. The mainstream medial border should be the left side of superior mesenteric vein (SMV) according to the definition of D3, but there are also some reports that regards the left side of superior mesenteric artery (SMA) as the medial border. In contrast, the CME procedure emphasizes the beginning of the colonic mesentery and the left side of SMA should be considered as the medial border. Combined with the anatomical basis, oncological efficacy and technical feasibility of D3 lymph node dissection, we think that it is safe and feasible to take the left side of SMA as the medial boundary of D3 lymph node dissection. This procedure not only takes into account the integrity of mesangial and regional lymph node dissection, but also dissects more distant lymph nodes at risk of metastasis. It has its anatomical basis and potential oncological advantages. However, at present, this technical concept is still in the exploratory stage in practice, and the related clinical evidence is not sufficient.

[Digestive tract reconstruction after laparoscopic proximal gastrectomy for adenocarcinoma of esophagogastric junction].

The incidence of adenocarcinoma of esophagogastric junction (AEG) is increasing in recent years. Its diagnosis, lymph node metastasis and digestive tract reconstruction are all different from those of upper gastric cancer. With the development of the concept of function preserving surgery for gastric cancer, the clinical application of laparoscopic proximal gastrectomy in AEG is increasing. In this kind of operation, in addition to ensuring sufficient radical cure of tumor, the short-term smooth recovery and long-term quality of life of patients are also important. The reconstruction of digestive tract after proximal stomach operation is of great significance. According to the author's own practical experience, in clinical work, the author selects different surgical resection scope and digestive tract reconstruction methods according to Siewert classification of AEG. For Siewert Ⅱ AEG, laparoscopic PG is mostly used, and laparoscopic esophageal tubular gastric side-to-side anastomosis or double channel anastomosis is mostly used for digestive tract reconstruction. It is believed that with the emergence of long-term follow-up results and the development of multicenter randomized controlled research, some controversial questions will be better answered. We should pay attention to the individual differences of patients. For different individuals, combined with the operator's experience, on the basis of ensuring the radical cure of tumor, we should adopt appropriate surgical resection scope and digestive tract reconstruction, so as to bring better long-term quality of life for patients.

[Effectiveness and safety of robotic assisted-bronchoscopy system in locating and removing spring coils placed in the peripheral lung of beagle dogs: a pilot study].

Objective: To evaluate the effectiveness and safety of the robotic assisted bronchoscope system for localizing and removing the spring coils that placed in the peripheral lung of beagle dogs. Methods: The study was conducted from June 18th to June 20th, 2021. Metallic lung coils were placed as the simulated lesions to the periphery of the lungs of two adult male beagle dogs using a bronchoscope under general anesthesia. The navigation path was planned by the navigation function that built in the robotic bronchoscope system. After training, the doctors operated the robotic bronchoscope system to locate and remove the coils from the lung. The navigation success rate, sampling success rate, position of the coil, navigation time, sampling time, and operation time were evaluated. The damage to the airway mucosa during the operation and the vital signs of the beagles during and post-operation were accessed. Chest computerized tomography (CT) was performed post-operation to detect if there were complications such as pneumothorax and bleeding. Results: A total of 12 spring coils were successfully inserted into the two beagles. All the navigation paths of the simulated lesions were successfully planned. The navigation success rate was 12/12. The navigation time was (43.9±19.8) seconds. The distance between the tip of the flexible endoscope arm and the target point measured by the navigation system was (6.93±2.15) mm. The locations of the simulated lesions were distributed in the 6th-8th generation of bronchi. The sampling success rate was 12/12. The sampling time was (42.4±11.3) seconds. There was no pneumothorax or mediastinal emphysema after the placement of the coil. The vital signs of the beagle dogs were stable throughout the operation, and no operation-related or postoperative complications occurred. Conclusions: The robotic bronchoscope system can be used to locate and remove the spring coils from the peripheral lung of beagle dogs, and the procedure is simple and safe. It suggests that the robotic bronchoscopy system has great clinical significance in the sampling and diagnosis of peripheral lung lesions.

Mechanism of curcumin against myocardial ischaemia-reperfusion injury based on the P13K/Akt/mTOR signalling pathway.

OBJECTIVE: To investigate the pharmacodynamic mechanism of curcumin against myocardial ischaemia-reperfusion injury by regulating the phosphatidylinositol-3 kinase (PI3K)/protein kinase B (AKT)/rapamycin target protein (mTOR) signalling pathway. MATERIALS AND METHODS: The left anterior descending coronary artery was ligated for 30 min and reperfused for 3 h to establish an ischaemia-reperfusion injury model. The electrocardiogram (ECG) detection of rats was performed, and the degree of myocardial infarction was determined by 2,3,5-triphenyltetrazolium chloride staining. The expression levels of serum creatine kinase isoenzyme (CK), lactate dehydrogenase (LDH), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), malondialdehyde (MDA), nitric oxide (NO) and other related indicators were detected. The protein expressions of mTOR, phosphorylated (p)-mTOR, AKT and p-AKT were detected by Western blotting, whereas the expressions of Bcl-2 and Bax were detected by real-time polymerase chain reaction. RESULTS: The results showed that compared with the model group, curcumin could improve the ECG findings, reduce the scope of myocardial infarction, reduce the expression levels of CK-MB, LDH, AST, MDA, NO and increase those of SOD and GSH. Curcumin can also down-regulate the expression of Bax and up-regulate the protein levels of Bcl2, p-mTOR and p-AKT (p < 0.05 or p < 0.01). CONCLUSIONS: This study shows that curcumin has a significant protective effect on myocardial ischaemia-reperfusion, and its mechanism may be related to the activation of PI3K/AKT/mTOR signalling pathway and inhibition of inflammation, apoptosis and oxidative stress.

[Safety and effectiveness of oxaliplatin combined with capecitabine or oxaliplatin combined with S-1 neoadjuvant chemotherapy in the treatment of advanced gastric cancer].

Objective: To explore the safety and efficacy of oxaliplatin plus capecitabine (CapeOX) or oxaliplatin plus S-1 (SOX) regimen neoadjuvant chemotherapy in the treatment of advanced gastric cancer. Methods: A retrospective cohort study was performed. Clinical data of patients diagnosed as advanced gastric cancer undergoing CapeOX/SOX neoadjuvant chemotherapy and standard laparoscopic radical operation for gastric cancer in Ruijin Hospital of Shanghai Jiaotong University School of Medicine from April 2016 to April 2019 were retrospectively collected. Inclusion criteria were as follows: (1) age≥18 years; (2) gastric adenocarcinoma was confirmed by histopathology and the clinical stage was T3-4aN+M0; (3) tumor could be resectable; (4) preoperative neoadjuvant chemotherapy was CapeOX or SOX regimen without radiotherapy or other regimen chemotherapy; (5) no other concurrent malignant tumor; (6) the Eastern Cooperative Oncology Group (ECOG) score ≤ 1; (7) no bone marrow suppression; (8) normal liver and kidney function. Exclusion criteria were as follows: (1) patients with recurrent gastric cancer; (2) patients receiving emergency surgery due to tumor perforation, bleeding, obstruction, etc.; (3) allergy to oxaliplatin, S-1, capecitabine or any drug excipients; (4) diagnosed with coronary heart disease, cardiomyopathy, or the New York Heart Association class III or IV; (5) pregnant or lactating women. A total of 118 patients were enrolled as the neoadjuvant chemotherapy group, and 379 patients with locally advanced gastric cancer who received surgery combined with postoperative adjuvant chemotherapy over the same period simultaneously were included as the adjuvant chemotherapy group. After propensity score matching was performed including gender, age, ECOG score, tumor site, clinical stage, chemotherapy regimen and other factors by 1:1 ratio, there were 40 cases in each group. The differences between the two groups in general conditions, efficacy of neoadjuvant chemotherapy, intraoperative conditions, postoperative conditions, histopathological results, chemotherapy-related adverse events, and survival status were compared and analyzed. Results: Comparison of baseline demographics between the two groups showed no statistically significant difference (all P>0.05). In the neoadjuvant chemotherapy group, 5.0% (2/40) of patients achieved clinical complete response, 57.5% (23/40) achieved partial response, 32.5% (13/40) remained stable disease, and 5.0% (2/40) had disease progression before surgery. Objective response rate was 62.5% (25/40), and disease control rate was 95.0% (38/40). There were no statistically significant differences between neoadjuvant chemotherapy group and adjuvant chemotherapy group in terms of operation time, intraoperative blood loss, number of lymph node harvested, length of postoperative hospital stay, and postoperative mortality and morbidity (all P>0.05). Postoperative complications were well managed with conservative treatment. No Clavien-Dindo IV or V complications were observed in both groups. Pathological results showed that the proportion of patients with pathological stage T1 in the neoadjuvant chemotherapy group was significantly higher than that in the adjuvant chemotherapy group [27.5% (11/40) vs. 5.0% (2/40)], while the proportion of patients with pathological stage T3 was significantly lower than that in the adjuvant chemotherapy group [20.0% (8/40) vs. 45.0% (18/40)], with statistically significant difference (χ(2)=15.432, P=0.001). In the neoadjuvant chemotherapy group, there were 4 cases of tumor regression grade 0, 8 cases of grade 1, 16 cases of grade 2, and 12 cases of grade 3. The pathological complete response rate was 10% (4/40), the overall pathological response rate was 70.0% (28/40). There was no statistically significant difference in the incidence of chemotherapy-related adverse events between neoadjuvant chemotherapy group and adjuvant chemotherapy group [40% (16/40) vs. 37.5% (15/40), P>0.05). There were no statistically significant differences in OS (43 months vs. 40 months) and 3-year OS rate (66.1% vs. 59.8%) between neoadjuvant chemotherapy group and adjuvant chemotherapy group (P=0.428). The disease-free survival (DFS) and 3-year DFS rates of the neoadjuvant chemotherapy group were significantly superior to those of the adjuvant chemotherapy group (36 months vs. 28 months, 51.4% vs. 35.8%, P=0.048). Conclusion: CapeOX or SOX regimen neoadjuvant chemotherapy is a safe, effective and feasible treatment mode for advanced gastric cancer without increasing surgical risk and can improve the DFS of patients.

[The association between mesenteric fat hypertrophy and behavior and activity of Crohn's disease].

Objective: Mesenteric fat hypertrophy is present in about a quarter of Crohn's disease (CD) patients and it can be easily detected by bowel ultrasound (US). The purpose of this research was to assess the correlation between mesenteric fat hypertrophy and behavior and activity of CD. Methods: A total of 89 CD patients who admitted to the First Affiliated Hospital of Nanjing Medical University from August 2018 to November 2019 were recruited in this study. The total CD patients were divided into two groups depending on with or without mesenteric fat hypertrophy by US tests. Crohn's disease activity index (CDAI), simplified endoscopic score for Crohn's disease (SES-CD), serum inflammatory indicators and fecal calprotectin were assessed. Results: Mesenteric fat hypertrophy was significantly associated with stricturing behavior (B2, P<0.01). CDAI (P=0.002) , blood platelet (P=0.001) , C-reactive protein (P=0.024) , fecal calprotectin (P=0.004) and bowel wall thickness (P<0.01) in patients with mesenteric fat hypertrophy were significantly higher than those without, but not the erythrocyte sedimentation rate (P=0.110) and SES-CD (P=0.115) . Serum albumin (P=0.001) in patients with mesenteric fat hypertrophy was lower than that in patients without mesenteric fat hypertrophy. Conclusion: Mesenteric fat hypertrophy is correlated with intestinal stenosis and disease activity in patients with Crohn's disease.

[Scientific and technological innovation and achievement transformation promote the medical development].

With the worldwide adoption of minimally invasive surgery, innovation again becomes the theme. In the past hundred years, molecular biology technology, minimally invasive surgery technology, pharmaceutical research and therapies have been constantly innovated to promote the development of medicine. As the subject of medical innovation, the innovative idea from medical staff is also very important. For surgeons, the invention and improvement of a new operation or surgical instrument directly depends on curiosity and exploration. Whether a novel idea or technology can be transformed and used in clinical practice depends on its commercial prospects and the adjustment of macro health policies. The protection of intellectual property and appropriate distribution of interests are the key to ensure sustainable innovation. We should put scientific and technological innovation and achievement transformation in the important position of the "healthy China" strategy, take scientific and technological innovation as the basis and achievements transformation as the means, promote the development of China's health protection, implement the healthy China strategy, and make our own contribution to provide people with all-round health services.

[Prime of life for minimally invasive gastrointestinal and colorectal surgery].

With the development in the past 20 years, minimally invasive gastrointestinal and colorectal surgery is now in its prime of life, with a high level in terms of surgical technique, surgical standardization, innovative technology and technical training. However, in the prime of life, in order to avoid the decline, we must meet new challenges. With the advent of the era of 5G and artificial intelligence, plus a series of changes in the internal and external environment, minimally invasive surgery, and even the entire surgery will have a major impact, including changes in treatment patterns, emphasis of multidisciplinary comprehensive treatment, changes in disease spectrum, and except neoplasms, more benign and functional diseases may require minimally invasive surgery. The gastrointestinal surgery specialist relying on "craft" will likely be replaced by an artificial intelligence surgical system. In the face of challenges, we should not forget our initial intentions, and should diligently reflect on ourselves, keeping the patient-centered minimally invasive treatment concept. Meanwhile, we should go to the basic hospitals to further establish a standardized training system, continue to maintain innovative thinking and keep pace with the times, so that we can grasp the prime of life for minimally invasive gastrointestinal and colorectal surgery.

[Laparoscopic peritoneal dialysis catheter implantation in peritoneal chemotherapy for gastric cancer with peritoneal metastasis].

Objective: To investigate the clinical value of laparoscopic peritoneal dialysis catheter implantation in peritoneal chemotherapy for gastric cancer with peritoneal metastasis. Methods: From January 2019 to June 2019, the clinical data of 6 patients diagnosed as gastric cancer with peritoneal metastasis were retrospectively analyzed in the Gastrointestinal Surgery Department of Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine. Five were male and 1 was female. The median age was 69.5 (28-77) years. The median body mass index (BMI) was 22.8 (19.6-23.5). All procedures were performed under general anesthesia with endotracheal intubation. The patient's body position and facility layout in the operating room were consistent with those of laparoscopic gastrectomy. The operator's position: the main surgeon was located on the right side of the patient, the first assistant stood on the left side of the patient, and the scopist stood between the patient's legs. Surgical procedure: (1) trocar location: three abdominal trocars was adopted, with one 12 mm umbilical port for the 30° laparoscope (point A). Location of the other two trocars was dependent on the procedure of exploration or biopsy as well as the two polyester cuff position of the peritoneal dialysis catheter: Usually one 5 mm port in the anterior midline 5 cm inferior to the umbilicus point was selected as point B to ensure that the distal end of the catheter could reach the Douglas pouch. The other 5 mm port was located in the right lower quadrant lateral to the umbilicus to establish the subcutaneous tunnel tract, and the proximal cuff was situated 2 cm away from the desired exit site (point C).(2) exploration of the abdominal cavity: a 30° laparoscope was inserted from 12 mm trocar below the umbilicus to explore the entire peritoneal cavity. The uterus and adnexa should be explored additionally for women. Once peritoneal metastasis was investigated and identified, primary laparoscopic peritoneal dialysis catheter implantation was performed so as to facilitate subsequent peritoneal chemotherapy. Ascites were collected for cytology in patients with ascites. (3) peritoneal dialysis catheter placement: the peritoneal dialysis catheter was introduced into the abdominal cavity from point A. Under the direct vision of laparoscopy, 2-0 absorbable ligature was reserved at the expected fixation point of the proximal cuff (point B) for the final knot closure. Non-traumatic graspers were used to pull the distal cuff of peritoneal dialysis catheter out of the abdominal cavity through point B. The 5-mm trocar was removed simultaneously, and the distal cuff was fixed between bilateral rectus sheaths at the anterior midline port site preperitoneally. To prevent subsequent ascites and chemotherapy fluid extravasation, the reserved crocheted wire was knotted. From point C the subcutaneous tunnel tract was created before the peritoneal steath towards the port site lateral to the umbilicus. Satisfactory catheter irrigation and outflow were then confirmed. Chemotherapy regimen after peritoneal dialysis catheterization: all patients began intraperitoneal chemotherapy on the second day after surgery. On the 1st and 8th day of each 3-weeks cycle, paclitaxel (20 mg/m(2)) was administered through peritoneal dialysis catheter, and paclitaxel (50 mg/m(2)) was injected intravenously. Meanwhile, S-1 was orally administered twice daily at a dose of 80 mg·m(-2)·d(-1) for 14 consecutive days followed by 7-days rest. To observe the patients' intraoperative and postoperative conditions. Results: All the procedures were performed successfully without intraoperative complications or conversion to laparotomy. No 30 day postoperative complications were observed. The median operative time was 33.5 (23-38) min. The median time to first flatus was 1(1-2) days, and the median postoperative hospital stay was 3 (3-4) days, without short-term complications within 30 days postoperatively. The last follow-up was up to July 10, 2019, and the patients were followed for 4(1-6) months. No ascites extravasation was observed and no death occurred in the 6 patients. There was no catheter obstruction or peritoneal fluid extravasation during and after chemotherapy. Conclusion: Laparoscopic peritoneal dialysis catheter implantation was safe and feasible for patients with peritoneal metastasis of gastric cancer. The abdominal exploration, tumor staging and the abdominal chemotherapy device implantation can be completed simultaneously, which could simplify the surgical approach, improve the quality of life for patients and further propose a new direction for the development of abdominal chemotherapy.

[Clinical efficacy and safety of combined induction therapy with rituximab and ATG in highly sensitized kidney transplant recipients].

Objective: To summarize the efficacy and safety of the combination of rituximab and ATG as induction therapy in highly sensitized kidney transplant recipients. Methods: Clinical data of patients who received kidney transplantation from donation after cardiac death(DCD) in Organ Transplant Center of Second Affiliated Hospital of Guangzhou Medical University from January 1st 2015 to December 31th 2016 was retrospectively analyzed. Highly sensitized patients with over 30% active panel reactive antibody (PRA>30%) received rituximab, while non-sensitized recipients as controlled group. All selected patients were observed in the renal function, urine protein, hemogram and the variation of PRA at each time point. Acute rejection, infection required hospitalization, delayed graft function(DGF), primary nonfunction (PNF), graft dysfunction, the mortality rate of patients with good allograft function and the graft survival rate were also observed. Results: 46 groups of patients were selected into highly-sensitized group and non-sensitized group. In both groups, there was no statistical difference in the renal function, urine protein and WBC (all P>0.05). Highly sensitized recipients at day 7 and day 14 following the surgery, had a significantly lower percentage of lymphocyte counts and lymphocyte proportion compared to other groups, with statistical differences(all P<0.05). Both groups had a similar incidence of DGF(2.2%) and no occurrence of PNF. 19.5% of highly sensitized recipients experienced acute rejection and 13% in control group. More specifically, no statistical difference was noted in the rate of infection required hospitalization(30.4% vs 22.2%), graft loss(2.2% vs 0) and the mortality rate of patients with good allograft function(4.3% vs 2.2%)(all P>0.05). The graft survival rate was 97.8% in the highly-sensitized group, while 100% in the control group. And the rate of patient survival in these two groups was 95.7% and 97.8%, with no statistical differences(all P>0.05). Conclusions: Immune-induction therapy that combines Rituximab with ATG can significantly inhibit lymphocyte proliferation. It is effective and safe in treating hypersensitive patients. The survival rate of human/kidney of hypersensitive patients in the short and medium term is comparable to those with low immune risk.

Subtype-specific inherited predisposition to pemphigus in the Chinese population.

BACKGROUND: Pemphigus is a group of rare life-threatening mucocutaneous autoimmune diseases, presenting mainly as two subtypes: pemphigus vulgaris (PV) and pemphigus foliaceus (PF). Inherited predispositions to pemphigus have long been speculated but they remain poorly understood. OBJECTIVES: To identify common and specific nongenetic and genetic factors associated with pemphigus and its subtypes in the Chinese population. METHODS: A genome-wide association study (GWAS) was performed in 496 unrelated patients with pemphigus (including 365 with PV and 104 with PF) and 1105 controls without pemphigus. RESULTS: A sex preference was observed only in PV (57·5% female) and not in PF (47·1% female). For male patients only, the mean age at diagnosis was significantly lower for PV than for PF (P < 0·001). The strongest associated single-nucleotide polymorphisms are in the human leucocyte antigen (HLA) region: rs70993900 (PV; P = 1·5 × 10-45 ) and rs9469220 (PF; P = 1·1 × 10-8 ). HLA-DQB1*05:03 ranks at the top (P = 4·7 × 10-40 ; odds ratio 12·4) in both subtypes, with significantly different risk allele frequency (RAFPV = 34·2% vs. RAFPF = 18·8% vs. RAFcontrol = 4·4%), whereas HLA-DRB1*14:01 and HLA-DRB1*04:06 are PV specific. HLA-DQB1*03:03 and HLA-DQB1*03:02 show significant subtype specificity in opposite directions. All of these associations were validated in the replication series with 147 cases of pemphigus and 604 controls. Multiple novel non-HLA susceptibility loci were also identified in the GWAS. CONCLUSIONS: This study represents the largest GWAS on pemphigus in the Chinese population published to date, and has allowed us to identify HLA haplotypes significantly shared between or specific to the two main subtypes of pemphigus.

CXCL13 inhibition induce the apoptosis of MDA-MB-231 breast cancer cells through blocking CXCR5/ERK signaling pathway.

OBJECTIVE: Treatment of the high-risk triple negative breast cancer (TNBC) is a critical clinical challenge. Here we aimed to explore a novel strategy for TNBC treatment by blocking the tumor-associated chemokine CXCL13 in the MDA-MB-231 TNBC cells. MATERIALS AND METHODS: MDA-MB-231 cells were treated with anti-CXCL13 antibodies (inhibition group), or phosphate-buffered saline (PBS) (control group), followed by determining the levels of interleukin-1 (IL-1), tumor necrosis factor-alpha (TNF-α) and transforming growth factor beta-1 (TGF-ß1) with enzyme-linked immunosorbent assay (ELISA). The effects of CXCL13 inhibition on cell proliferation and apoptosis were assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay and flow cytometry, respectively. Quantitative Real Time-PCR (qRT-PCR) and Western blot were used to compare the levels of CXCL13, CXCR5, extracellular signal-regulated kinase (ERK). The levels of cyclin D1 and cleaved caspase-9 were detected by Western blot. RESULTS: The levels of IL-1, TNF-α and TGF-ß1 in MDA-MB-231 cells treated with anti-CXCL13 antibodies were significantly downregulated (p<0.05). Meanwhile, CXCL13 blockade decreased the cell proliferation and increased the apoptosis rate of MDA-MB-231 cells. The inhibition of CXCL13 led to marked reduction in CXCL13 and CXCR5 mRNA and an increase in ERK mRNA. The inhibition of CXCL13 resulted in the downregulation of CXCL13, CXCR5, p-ERK/ERK, cyclin D1 and upregulation of cleaved caspase-9 proteins. CONCLUSIONS: CXCL13 blockade effectively suppressed the proliferation of MDA-MB-231 cells by promoting cell apoptosis. This effect is presumably associated with the downregulation of CXCL13 and suppression of the CXCR5/ERK signaling pathway.

MicroRNA-338 inhibits proliferation, migration, and invasion of gastric cancer cells by the Wnt/ß-catenin signaling pathway.

OBJECTIVE: Emerging evidence suggests aberrant microRNAs (miRNAs) expression is involved in cancer development through multiple. Although miR338 has shown to have tumor suppression ability and anti-migration effects in some cancers, its regulatory role and molecular mechanism in the development of gastric cancer cells yet remains little known. This work aims to investigate miR-338 in regulating Wnt/ß-catenin pathway in epithelial-mesenchymal transition (EMT) in gastric cancers. MATERIALS AND METHODS: Human gastric cancer cells were transfected with either miR-338 mimic or erythropoietin-producing hepatocellular (Eph)A2-targeting siRNA. The biological function of miR-338 in gastric cancer cells was investigated using a MTT assay and invasion assay. Western blot assay was used to measure the levels of EphA2, GSK-3ß, phospho-GSK-3ßSer9, c-Myc, E-cadherin, Vimentin, and ß-catenin of at protein level. RESULTS: Our data showed that miR-338 inhibited proliferation, migration and invasion of human gastric cancer cells. miR-338 affected the Wnt/ß-catenin pathway by increasing p-GSK-3ßSer9 and decreasing GSK-3ßSer9 and c-Myc at protein levels. EphA2 protein level was downregulated and positively correlated with EMT markers. Both silencing of EphA2 and transfection with miR-338 mimic resulted in the up-regulation of the EMT molecular marker E-cadherin and down-regulation of Vimentin and ß-catenin at protein levels. CONCLUSIONS: This study indicated that miR-338 is a potential tumor suppressor in gastric cancer and miR-338 inhibited EMT of gastric cancer cells through deactivation of Wnt/ß-catenin signaling targeting at EphA2.