Objective:We aimed to develop a novel visualized model based on nomogram to predict postoperative overall survival.Methods:This was a multicenter, retrospective, observational cohort study, including participants with histologically confirmed gastric and colorectal cancer who underwent radical surgery from 11 medical centers in China from August 1, 2015 to June 30, 2018. Baseline characteristics, histopathological data and nutritional status, as assessed using Nutrition Risk Screening 2002 (NRS 2002) score and the scored Patient-Generated Subjective Global Assessment, were collected. The least absolute shrinkage and selection operator regression and Cox regression were used to identify variables to be included in the predictive model. Internal and external validations were performed.Results:There were 681 and 127 patients in the training and validation cohorts, respectively. A total of 188 deaths were observed over a median follow-up period of 59 (range: 58 to 60) months. Two independent predictors of NRS 2002 and Tumor-Node-Metastasis (TNM) stage were identified and incorporated into the prediction nomogram model together with the factor of age. The model's concordance index for 1-, 3- and 5-year overall survival was 0.696, 0.724, and 0.738 in the training cohort and 0.801, 0.812, and 0.793 in the validation cohort, respectively.Conclusions:In this study, a new nomogram prediction model based on NRS 2002 score was developed and validated for predicting the overall postoperative survival of patients with gastric colorectal cancer. This model has good differentiation, calibration and clinical practicability in predicting the long-term survival rate of patients with gastrointestinal cancer after radical surgery.

ObjectiveThrough improving the potential of vascular endothelial growth factor receptor (VEGFR)-humanized mouse model (hKDR^+/+) with C57BL/6N background to allow the growth of different mouse tumor cell lines, to establish novel tumor-bearing mouse models which can support in vivo tumorigenesis of different mouse tumor cell lines and be used to evaluate drugs targeting VEGFR.MethodsFirstly, a method to evaluate the in vivo activity of antibody targeting VEGFR based on the hKDR^+/+ humanized mouse model was established. Recombinant activating gene 1 (Rag1) knockout mice (Rag1^-/-) were established using CRISPR/Cas9 technology. Then these Rag1^-/- mice were crossed with hKDR^+/+ mice to get a double gene modified homozygous hKDR^+/+/Rag1^-/- mouse model by screening. Finally, tumor cell lines derived from different mouse strains were tested on the double gene-modified mouse model to compare the differences in tumor growth. ResultsAntibodies designed for VEGFR showed significant anti-tumor activity in hKDR^+/+ mice, which significantly reduced tumor volume and weight compared with the PBS group (P<0.01, P<0.05). The number of B cells and T cells in the peripheral blood of Rag1^-/- mice and hKDR^+/+/Rag1^-/- mice decreased (P<0.05, P<0.001). Tumors were observed in hKDR^+/+/Rag1^-/-, Rag1^-/-, wild-type, and hKDR^+/+ mice after 7 d of inoculation of MC38 cells derived from C57BL/6 mice. Tumors were only observed in groups of hKDR^+/+/Rag1^-/- and Rag1^-/- mice, but not in the wild-type and hKDR^+/+ mice after 10 d of inoculation with CT26 cells derived from BALB/c mice. After 3 weeks of inoculation, the tumor volume of hKDR^+/+/Rag1^-/- mice was significantly larger than that of Rag1^-/- mice (P<0.01). ConclusionRag1 knockout mice were obtained and a novel hKDR^+/+/Rag1^-/- double genes modified mouse model was further screened. The tumor cell lines from different mouse strain origins were more prone to growth in mice with Rag1 gene deficiency. The results suggest that the reduced immune response of hKDR^+/+ humanized mice will improve the capacity of supporting the growth of mouse tumor lines in the model. As a result, more tumor-bearing mouse models may be constructed for the evaluation of drugs targeting VEGFR in this way.

Objective:To observe the clinical efficacy of secukinumab in the treatment of active psoriatic arthritis (PsA).Methods:Thirty active PsA patients in the out-patient clinic of the First Affiliated Hospital of the PLA Air Force Military Medical University between July 2020 to December 2021 were included in this study. Patients were categorized into one group with axial involvement ( n=17, 57%) and the other group with peripheral joint involvement ( n=13, 43%) according to arthritis subtypes. Patients in both groups received a subcutaneous injection of 300 mg of secukinumab at 0, 1, 2, 3, and 4 weeks, and then every 4 weeks. The CRP, ESR, VAS pain score (VAS-pain, 0~10 cm), physician comprehensive assessment of disease activity by VAS score (VAS-gh, 0~10 cm), psoriasis involvement area and severity index (PASI), skin quality of life index (DLQI), psoriatic arthritis disease activity index (DAPSA), psoriatic arthritis activity score (PASDAS), Bath ankylosing spondylitis activity index (BASDAI) were recorded at week 0, week 12, and week 24. DAP-SA response (score ≤4) and minimum disease activity (MDA) were also used to assess the proportion of overall patients who responded to secukinumab treatment. The measurement data with normal distribution were analyzed by repeated measure analysis of variance. Non-normally distributed data were expressed as median (IQR). Count data were expressed as frequency and percentage (%) and analyzed by Fisher exact probability method. Results:The mean duration of skin disease in both axial involvement and peripheral joint involvement groups was (14±8)years and (12±7)years ( t=0.70, P=0.256), respectively. The mean duration of arthritis symptoms in both groups was (3.2±3.7)years and (1.8±2.1)years ( t=1.17, P=0.125), respectively. All patients completed 24 weeks of secukinumab treatment. At 24 weeks, VAS-pain, VAS-gh, PASI, DLQI, DAPSA, PASDAS and BASDAI were all decreased significantly ( P<0.05). Patients with axial involvement seemed more likely to benefit in CRP [2.4 (1.7, 3.5) mg/L vs 8.0 (5.3, 14.0) mg/L, Z=-2.69, P=0.007] and VAS-pain[1.0 (0, 2.0) vs (5.0, 6.0), Z=-3.47, P<0.001]improvement ( P<0.005). Both groups achieved PASI 100, which meant achieving clearance of skin dis-ease. The DAPSA remission rate and MDA of the patients with axial involvement were 88% and 82%, re-spectively, and the DAPSA remission rate and MDA were 92% and 92%, respectively. Secukinumab was found to be safe and well tolerated with no adverse event reported or observed during 24-week treatment. Conclusion:In real-world observations, secukinumab is proven to be safe and effective for the treatment of PsA, with rapid relieving of skin and joint symptoms and reduction of disease activity. Patients with axial involvement may benefit more notably than patients with peripheral arthritis subtype.

Objective:To investigate the effects of compound fermented milk on intestinal microbiota, short chain fatty acid (SCFA), intestinal motility and mucosal barrier in mice with constipation.Methods:Twenty-seven C57BL/6JNifdc mice were randomly divided into three groups: control group, model group and intervention group. The model group and the intervention group were given loperamide intragastrically for two weeks. Starting from the second week, the intervention group was treated with compound fermented milk for 7 d. The control group was given normal saline. Food intake, water intake, weight change, fecal moisture content, time of first-time black stool and small intestine propulsion rate were detected. Expression of serotonin C receptor (5-HTR2C), zona occludins-1 (ZO-1) and mucin-2 (MUC-2) at mRNA level in colon was analyzed. Western blot was used to measure the expression of Raf/ERK/MAPK-related proteins. SCFA level in intestinal tract was detected by gas chromatography. Intestinal microbiota diversity was analyzed by high-throughput sequencing.Results:Compared with the control group, the first black stool excretion time was significantly prolonged in the model group ( P<0.01). Moreover, fecal moisture content, small intestine propulsion rate and the expression of 5-HTR2C and ZO-1 at mRNA level in colon were significantly decreased ( P<0.01). Compared with the model group, the first black stool excretion time was significantly shortened ( P<0.05); fecal moisture content, small intestine propelling rate ( P<0.05), the expression of colon 5-HTR2C and ZO-1 at mRNA level ( P<0.05), phosphorylation of Raf/ERK/MAPK pathway in the colon, intestinal SCFA-producing bacteria and intestinal SCFA content were increased in the intervention group. Conclusions:Compound fermented milk had a therapeutic effect on constipation in a mouse model by increasing the abundance of SCFA-producing bacteria and SCFA content, enhancing the phosphorylation of the Raf/ERK/MAPK pathway to up-regulate the expression of 5-HTR2C at mRNA level in the colon, and increasing the expression of ZO-1 at mRNA level in the colon. Intestinal peristalsis and intestinal mucosal barrier function were enhanced, thus improving the symptom of constipation.

Objective:To investigate the neuroprotective effect of cerebroprotein hydrolysate (CH) -Ⅰ on cerebral ischemia-reperfusion injury in rats and its mechanism.Methods:Eighty adult healthy male SD rats were randomly divided into sham operation group, model group, CH-Ⅰ intervention group and cerebrolysin (CBL) positive control group. The model of ischemia-reperfusion injury was induced by temporarily occluding the left middle cerebral artery with suture-occluded method. The CH-Ⅰ and CBL groups intraperitoneally injected with CH-Ⅰ and CBL at 0, 3, 6 and 12 h after reperfusion at the dose of 20 mg/kg. The sham operation group and the model group were injected with the same volume of normal saline. At 24 h after reperfusion, the behavior changes of the rats were detected by the modified neurological severity score (mNSS). The volume of cerebral infarction was detected by TTC staining. The morphology and structure of neurons in ischemic cortex were observed by Nissl staining. The apoptosis of neurons in ischemic cortex was detected by TUNEL staining. The expression changes of phosphorylated extracellular signal-regulated kinase (pERK) 1/2, phosphorylated mitogen-activated protein kinase/extracellular signal-regulated kinase (pMEK) 1/2, phosphorylated cAMP response element binding protein (pCREB) and brain-derived neurotrophic factor (BDNF) in the ischemic cortex were detected by Western blot.Results:At 24 h after reperfusion, the mNSS score and cerebral infarct volume in the model group were significantly higher and larger than those in the sham group (all P<0.001). The mNSS scores and cerebral infarct volumes in the CH-Ⅰ and CBL groups were significantly reduced compared with those in the model group (all P<0.05), but there was no significant difference between the CH-Ⅰ group and the CBL group. Nissl and TUNEL staining showed that the degenerative cell index and apoptotic cell index in the CH-Ⅰ group were significantly lower than those in the model group (all P<0.01), but there were no significant difference between the CH-Ⅰ group and the CBL group. Western blot analysis showed that compared with the sham operation group, the pMEK1/2, pERK1/2 and pCREB expressions in ischemic cortex were significantly enhanced and the BDNF expression was significantly attenuated in the model group ( P<0.05). Compared with the model group, pMEK1/2, pERK1/2, and pCREB expressions in the CH-Ⅰ group were significantly decreased (all P<0.05), and the BDNF expression was significantly increased ( P<0.05). Conclution:CH-Ⅰ can reduce cerebral infarct volume and improve neurological function, and its mechanism may be associated with the inhibition of the MEK-ERK-CREB pathway as well as the enhancement of BDNF expression.

Objective:To investigate the clinical efficacy of endoscopic magnetic compression bilio-enteric anastomosis for the treatment of biliary obstruction after complex abdominal surgery.Methods:The retrospective and descriptive study was conducted. The clinical data of 3 patients with biliary obstruction after complex abdominal surgery who were admitted to the First Affiliated Hospital of Xi′an Jiaotong University between January 2012 and December 2019 were collected. There were 2 males and 1 female, aged from 27 to 57 years, with a median age of 56 years. The 3 patients underwent endoscopic magnetic compression bilio-enteric anastomosis to complete internal drainage of bile ducts after several unsuccessful endoscopic or interventional therapy. Observation indicators: (1) surgical situations; (2) postoperative situations; (3) follow-up. Follow up using outpatient examination was performed to detect the biliary stent, liver function and patency of anastomotic stoma up to December 2019.Results:(1) Surgical situations: all the 3 patients underwent successful endoscopic magnetic compression bilio-enteric anastomosis, including 2 cases with magnetic compression choledochoduodenal anastomosis and 1 case with magnetic compression choledochojejunostomy. The length of biliary stricture, length and width of magnetic device subsidiary magnet/patent magnet, time of magnetic compression for the 3 patients were 7.1 mm, 3.0 mm, 2.0 mm, 7 mm/8 mm, 6 mm/6 mm, 5 mm/5 mm, 130 minutes, 90 minutes, 75 minutes, respectively. (2) Postoperative situations: the time to biliary tract recanalization after operation for the 3 patients were 15 days, 8 days, 9 days, respectively. None of the patients encountered gastrointestinal perforation, hemorrhage or infection. (3) Follow-up: the biliary stents were inserted into the anastomotic stoma for the 3 patients after biliary tract recanalization, including a catheter of percutaneous transhepatic cholangiodrainage (PTCD) with 12 Fr size, a biliary plastic stent with 7 Fr size, a catheter of PTCD with 14 Fr size, respectively. The biliary stents were removed after 17 months, 2 months, and 6 months from the 3 patients, respectively. The 3 patients were followed up for 40 months, 20 months, and 5 months respectively after removing biliary stents, and the concentration of total bilirubin, concentration of aspartate aminotransferase, concentration of alanine aminotransferase for the 3 patients were 5-19 μmol/L, 25-40 U/L, and 20-35 U/L, respectively. The results of ultrasonic examination or magnetic resonance cholangiopancreatography examination showed that no intra-hepatic bile duct dilation or stricture of choledochojejunostomy was found within the 3 patients. One of the 3 patients was hospitalized for biliary tract infection after 37 months from removing biliary stents, and the results of ultrasonic examination or magnetic resonance cholangiopancreatography examination showed intrahepatic cholelithiasis. The cholelithiasis was removed under endoscopy and stricture of choledochojejunostomy was not found within patient by the endoscopic examination or cholangiography examination.Conclusion:The endoscopic magnetic compression bilio-enteric anastomosis is a safe and feasible technique for the treatment of biliary obstruction after complex abdominal surgery with good long-term effects.

Objective:To analyze the clinical outcome and feasibility for patients who underwent total parathyroidectomy without autotransplantation (TPTX) for secondary hyperparathyroidism (SHPT).Methods:From April 2012 to December 2015,220 SHPT patients underwent TPTX in the department of Breast and Thyroid Surgery of China-Japan Friendship Hospital.The clinical data and effect were assessed retrospectively.Results:All the 220 patients were on permanent dialysis with mean duration of dialysis (7.93 ± 3.75) years.A durable reduction in mean PTH,Ca and P were observed after TPTX (P＜0.01).The mean hospital stay was (7.8 ± 2.8) days.TPTX produced a rapid improvement in clinical symptoms.Incidence of hypocalcemia was 73.46％.Severe complications such as recurrent laryngeal nerve palsy or inactive dynamic osteopathia,haven't been observed postoperatively.The rate of persistent status (PTH≥300 pg/mL) was 9.1％.One (0.45％) died of infectious shock perioperatively.Conclusions:TPTX was a safe and feasible surgical procedure for patients with SHPT.It was worth of being applied.Not missing the parathyroid during operation was the key point for successful TPTX.Intensive monitoring and maintaining stable normocalcemia were the key point to reduce complication.

The purpose of this study was to compare the pharmacokinetic profiles of tetramethylpyrazine phosphate (TMPP) in plasma and extracellular fluid of the cerebral cortex of rats via three delivery routes: intranasal (i.n.), intragastric (i.g.) and intravenous (i.v.) administration. After i.n., i.g. and i.v. administration of a single-dose at 10 mg/kg, cerebral cortex dialysates and plasma samples drawn from the carotid artery were collected at timed intervals. The concentration of TMPP in the samples was analyzed by HPLC. The area under the concentration-time curve (AUC) and the ratio of the AUCbrain to the AUCplasma (drug targeting efficiency, DTE) was calculated to evaluate the brain targeting efficiency of the drug via these different routes of administration. After i.n. administration, TMPP was rapidly absorbed to reach its peak plasma concentration within 5 min and showed a delayed uptake into cerebral cortex (t max=15 min). The ratio of the AUCbrain dialysates value between i.n. route and i.v. injection was 0.68, which was greater than that obtained after i.g. administration (0.43). The systemic bioavailability obtained with i.n. administration was greater than that obtained by the i.g. route (86.33% vs. 50.39%), whereas the DTE of the nasal route was 78.89%, close to that of oral administration (85.69%). These results indicate that TMPP is rapidly absorbed from the nasal mucosa into the systemic circulation, and then crosses the blood-brain barrier (BBB) to reach the cerebral cortex. Intranasal administration of TMPP could be a promising alternative to intravenous and oral approaches.

Objective To investigate the feasibility and safety of endoscopic treatment of ureteral calculi acute obstruction with urinary extravasation. Methods 56 patients with ureteral calculi acute obstruction and urinary extravasation were randomly divided into two groups:the treatment group and the control group,28 cases in each group. Patients in the treatment group were given URSL or percutaneous nephrostomy drainage, and the secondary fistula was given URSL stone clearance treatment. Patients in control group were given traditional ureterolithotomy treatment. The stone clearance rate, the average recovery time after surgery, postoperative wound infection rate and the abnormal rate of postoperative albumin were observed in two groups. Results In the treatment group,28 patients had no residual stones with mean postoperative recovery time of (5.2 1.3) days,postoperative fever was found in 3 cases,obvious abnormal postoperative albumin in 3 cases. In the control group,residual stones were found in 3 cases,the average recovery time after surgery was (7.9 2.6) days,postoperative fever was found in 10 cases, and obvious abnormal postoperative albumin in 11 cases. There were statistically significant differences in stone clearance rate, the average recovery time after surgery, postoperative wound infection rate and the abnormal rate of postoperative albumin between two groups (P<0.05) . Conclusion Endoscopic treatment of ureteral calculi acute obstruction and urinary extravasation has advantages including better efficacy, less trauma, less complications and quicker recovery.

Objective To investigate the clinical efficacy of the urethra URSL combined with micro-puncture and drainage treatment for pediatric calculus of lower urinary tract. Methods From January 2003 to January 2013, 66 cases with pediatric urinary tract calculi in our hospital were randomly equally divided into experimental group and control group. The experimental group was treated with transurethral bladder micro URSL combined puncture and drainage treatment, and the control group was given a simple transurethral URSL method of treatment. The operative time, postoperative urine turned clear time,pulling stone clearance after catheter time,postoperative hospital stay and the incidence of postoperative urethral stricture were observed and recorded. In addition, these data were compared between the two groups. Results The operations of two groups have successfully completed. The mean operative time, postoperative urine turned clear time, pull out the catheter stone clearance after time and postoperative hospital stay of control group was 30.2±2.45 minutes,2.5±0.5 days,2.1±0.8 days and 4.0±0. 5 days, respectively. Patients were followed up 1 year after operation, and 1 case of urethral stricture occurred. However, the mean operative time, postoperative urine turned clear time, pull out the catheter stone clearance after time and postoperative hospital stay of the test group was 20.36±2.35 minutes,1.5±0.7 days,1.1±0.25 days and 3.1±0.3 days,respectively,with no urethral stricture case occurred. There were significant differences between the two groups ( <0.05) . Conclusion Transurethral bladder URSL micro puncture and drainage combined with transurethral ureteroscopy lithotripsy treatment for children with lower urinary tract calculi has better efficacy and safety. It could shorter operative time, postoperative urine turned clear time, the gravel discharge time and average hospitalization time, reduce the incidence of postoperative secondary urethral stricture.