Inhibition or/and induction of CYP3A4 are the major mechanisms underlying the common clinical drug-drug interactions, which has been gained attention in new drug discovery and development as well as clinical practice. Quantitative prediction of drug-drug interactions at the early stage of drug development is advantageous for reducing the cost and duration of development and providing more information for the later clinical studies. The review summarizes the update progress on quantitative prediction of in vivo drug-drug interactions derived from models based on in vitro inhibition or/and induction for CYP3A4.

H+/oligopeptide cotransporter PEPT1 mainly located at the brush border membrane of intestinal epithelium cell. transports dipeptide/tripeptide which is the degradation products of protein in digestive tract. Peptide-like drugs such as ?-lactam antibiotics,angiotensin-converting enzyme inhibitor (ACEI) and non-peptide drugs valaciclovir also can be transported and uptaked by PEPT1. PEPT1 is important for maintaining the homeostasis and the absorption of drugs in gastrointestinal tract. With the further research of PEPT1 gene, protein structure, and functional activity, we have known the factors about regulation of PEPT1 expression in membrane, their functional activities and substrate affinities. Some associated mechanism of regulation have been studied. As the wide substrate specificities of PEPT1, it becomes the target molecular on drug development and implication for drug delivery. Studies about interactions of PEPT1 with drugs are important for knowing the interactions of drugs, evaluating bioavailability of drug by intestinal absorption, researching the target treatment in anti-tumor drugs and individualization administration.

Objective To predict the B cell epitope for MUC1 antigen. Methods The secondary structure and surface properties of MUC1, such as physical and chemical characters, hydrophilicity, antigenicity, were analyzed with various methods. Results Many distinct antigenic epitopes in MUC1 were identified by computation: 1-10, 24-54, 65-77, 84-91, 108-134, 140-156, 159-174, 179-196, 199-210, 220-233, 237-265, 270-299, 316-337, 351-362, 369-396, 411-420, and 445-502. Conclusion Prediction of the B cell epitope for MUC1 can provide a base for the studies of structure and function of MUC1, construction of its mutants, and selection of new expression forms of MUC1.

Objective To analyze the risk factors of liver metastasis from gastric cancer. Methods The clinical data of 225 patients with liver metastasis from gastric cancer who had been admitted to our hospital from January 1996 to December 2001 were retrospectively analyzed. Synchronous liver metastasis was observed in 123 patients and metachronous liver metastasis in 102 patients. The risk factors of liver metastasis from gastric cancer were evaluated. Results The gender of patients, location and size of gastric cancer foci, differentiation and invasion depth of gastric cancer, Lanren classification, lymph node metastasis and lymph node metastasis in region Ⅷ, vascular invasion, extrahepatic metastasis, ascites and peritoneal metastasis were the significant factors associated with liver metastasis from gastric cancer (X2 = 43.560-263. 907, P<0.05). All the factors except the size of gastric cancer foci, extrahepatic metastasis and ascites were found to be the significant factors associated with different types of liver metastasis from gastric cancer (X2 = 6.673-26. 555, P < 0.05 ). Logistic regression analysis demonstrated that the gender of patients, lymph node metastasis and peritoneal metastasis were the factors that determined the types of liver metastasis from gastric cancer. Conclusion The gender of patients, lymph node metastasis and peritoneal metastasis are the important factors to evaluate the occurrence of different types of liver metastasis from gastric cancer.

Primary pulmonary mucinous adenocarcinoma is a subtype of lung adenocarcinoma, and its epidemiology is similar to other pulmonary adenocarcinoma. Because of its low incidence rate, the survival data of patients with pulmonary mucinous adenocarcinoma are few and often contradictory. KRAS mutations often occur in pulmonary mucinous adenocarcinoma, but EGFR mutations are rare. The expression of PD-L1 in pulmonary mucinous adenocarcinoma is very low. Patients with early pulmonary mucinous adenocarcinoma can benefit from surgery. Lobectomy is still the standard operation at present, but sub lobectomy may also be effective for early pulmonary mucinous adenocarcinoma. Other treatment options include platinum based dual drug chemotherapy, targeted therapy targeting driving genes, and the recent rise of immunotherapy. Future new targets and corresponding treatments should require more research to confirm.

Carcinoma of the esophagus is one of the common malignant tumors, and surgical treatment is still the main method for the treatment of esophageal cancer. With the development of thoracoscopic and laparoscopic instruments, minimally invasive esophagectomy is more and more widely used in the treatment of esophageal cancer. At present, minimally invasive esophagectomy mainly includes thoracoscopic and laparoscopic esophagectomy, mediastinoscopic esophagectomy, robot assisted esophagectomy, etc. At present, there are many studies on the comparison between minimally invasive esophagectomy and open esophagectomy. Although it is not clear which minimally invasive surgical method is more superior, each method may be superior to open esophagectomy in terms of blood loss, pulmonary complications and hospital stay. No matter what method is used, surgeons must be trained in a structured system to improve the level of experience required for independent operation. Ultimately, with the implementation of experienced doctors, the minimally invasive method in esophagectomy is superior to open esophagectomy in technically feasible cancer cases.

Objective To study the levels of serum cytokines in schizophrenic patients and their changes in antipsychotic medica-tion treatment .Methods The levels of serum cytokines including IL-10 ,IL-6 ,IL-13 ,IL-4 ,IFN ,TNF-α,IL-1a and IL-1RA were de-tected in 34 healthy adults and 53 schizophrenia patients by adopting the flow fluorescence method .Results The serum levels of IL-6 ,IL10 and TNF-αbefore treatment in schizophrenic patients were significantly higher than those in the control group (P<0 .05) . After treatment ,the levels of serum IL-1a ,IL-6 and TNF-α in schizophrenic patients were significantly lower than those before treatment(P<0 .05) .Conclusion Serum IL-6 and TNF-α levels are correlated with the disease condition of schizophrenia .IL-10 plays a role in early anti-inflammation of schizophrenia .

BACKGROUND:The application of robot-assisted technology for total knee arthroplasty is one of the current research hotspots.Since the 1980s,robot-assisted technology has been introduced into total knee arthroplasty outside China to achieve accurate osteotomy and good recovery of lower limb alignment.After decades of use,the robot has continuously improved its performance with new iterations,but has been criticized for increasing perioperative time and surgical trauma. OBJECTIVE:To summarize the advantages and disadvantages of current orthopedic surgical robots in total knee arthroplasty. METHODS:PubMed database and CNKI were searched to analyze the advantages and disadvantages of robot-assisted total knee arthroplasty in surgical trauma.English search terms were"arthroplasty,replacement,knee,knee replacement arthroplasty,procedure,robotic surgical,total knee arthroplasty,arthroplasty,replacement,knee,robotic-assisted".The Chinese search terms were"robot-assisted,robotic arm,knee osteoarthritis,arthritis".After the initial screening of all articles according to the inclusion and exclusion criteria,62 articles with high quality and relevance were reviewed. RESULTS AND CONCLUSION:(1)Robot-assisted total knee arthroplasty did not increase the degree of surgical trauma in patients,and showed a lower trauma effect than conventional manual total knee arthroplasty.(2)Robot-assisted total knee arthroplasty has the advantages of accurate auxiliary osteotomy,individualized prosthesis implantation,better protection of soft tissue around the knee joint,reduction of analgesic drug use,reduction of postoperative inflammatory index changes,and shortening of hospital stay.However,there are also shortcomings such as prolonged operation time,increased complications,and increased medical costs.(3)It is concluded that preliminary clinical application studies have shown that robot-assisted total knee arthroplasty can reduce surgical trauma,but it is necessary to be alert to potential risks.Simultaneously,its exact advantages compared with conventional manual total knee arthroplasty need to be verified by large-sample randomized controlled studies and long-term follow-up.

Objective:To compare the early clinical outcomes between domestic robot-assisted total knee arthroplasty (RA-TKA) and conventional manual total knee arthroplasty (CM-TKA) for patients with primary knee osteoarthritis.Methods:Embase, Pubmed, Web of Science, Zhi.com and Wanfang databases from January 2015 to April 2023 were searched for clinical controlled trials (RCTs) comparing the clinical outcomes between RA-TKA and CM-TKA. After literature screening, quality evaluation and data extraction according to the criteria required, Revman 5.3 software was applied to perform a Meta-analysis of the literature data. The operation time, intraoperative bleeding, hip-knee-ankle angle (HKA), HKA bias value, frontal femoral component (FFC), frontal tibia component (FTC), lateral femoral component (LFC), lateral tibia component (LTC), Knee Society Score (KSS), visual analogue scale (VAS), Western Ontario and McMaster University Osteoarthritis Index (WOMAC), knee mobility, Hospital for Specialty Surgery (HSS) knee score, length of hospital stay, and rate of complications were compared between the RA-TKA and CM-TKA patients.Results:Eight RCTs and 449 patients were included, with 221 patients in the RA-TKA group and 228 ones in the CM-TKA group. The Meta-analysis showed that the RA-TKA group had significantly longer operation time ( MD=18.41, 95% CI: 11.28 to 25.23, P<0.001), significantly better HKA ( MD=0.41, 95% CI: 0.06 to 0.76, P=0.020), significantly better HKA bias value ( MD=-0.92, 95% CI: -1.25 to -0.60, P<0.001), significantly better FTC ( MD=0.38, 95% CI: 0.08 to 0.67, P=0.010), significantly better LTC ( MD=1.71, 95% CI: 0.94 to 2.48, P<0.001), and significantly better knee mobility ( MD=-2.23, 95% CI: -4.18~-0.27, P=0.030) than the CM-TKA group. However, the differences were not statistically significant between the 2 groups in the intraoperative bleeding, FFC, LFC, KSS, VAS, WOMAC, HSS, length of hospital stay, or rate of complications ( P>0.05). Conclusion:Use of a domestic robot to assist conventional manual TKA can significantly improve the accuracy of prosthesis fixation and reconstruct the alignment of lower limb better, showing potential advantages in promoting functional recovery of the knee for the patients.

OBJECTIVETo evaluate the impact of primary site, NIH risk and imatinib treatment on the prognosis of patients with gastrointestinal stromal tumors(GIST).

METHODSClinicopathological data of 156 adult patients with GIST treated by imatinib in the Cancer Institute and Hospital of Tianjin Medical University from January 2006 to December 2010 were retrospectively analyzed. According to NIH risk classification, 30 patients were at moderate risk and 126 at high risk. Sixty-seven patients had advanced GIST. Prognosis of patients with different primary tumor site, different NIH risk and different treatment was compared respectively.

RESULTSImatinib therapy was well tolerated in all the patients. Eighty-nine cases received radical operation and adjuvant imatinib treatment. Among 67 advanced GIST cases, 26 received radical operation and adjuvant imatinib treatment, 27 received palliative operation and adjuvant imatinib treatment, and 14 received simple adjuvant imatinib treatment without operation. All the patients had routine follow-up, ranging from 9 to 56(median 27) months. The overall survival (OS) rate was 96% in 1-year, 86% in 2-year, and 71% in 3-year. The OS rate was 95% in 1-year, 77% in 2-year, and 65% in 3-year for patients at high risk, and all 100% in 1-, 2-, 3-year for patients at moderate risk, the differences was statistically significant (P=0.001). The OS rate was 97% in 1-year, 90% in 2-year, and 84% in 3-year for patients with gastric GIST, and 95% in 1-year, 69% in 2-year, and 52% in 3-year for patients with non-gastric GIST, the difference was significant(P=0.000). The OS rate was 98% in 1-year, 95% in 2-year, and 90% in 3-year for patients undergoing radical resection and adjuvant imatinib therapy. For 67 advanced GIST patients with imatinib therapy, none had complete remission, 41 had part remission, 15 had stable disease, indicating 56 advanced GIST cases(83.6%) obtaining clinical benefit. The OS rate was 91% in 1-year, 58% in 2-year, and 43% in 3-year.

CONCLUSIONSThe prognosis of high, and non-gastric and advanced GIST patients is poor. Radical resection combined with early imatinib treatment can improve the prognosis of GIST patients.

Antineoplastic Agents ; therapeutic use ; Benzamides ; therapeutic use ; Combined Modality Therapy ; Follow-Up Studies ; Gastrointestinal Neoplasms ; drug therapy ; pathology ; Gastrointestinal Stromal Tumors ; drug therapy ; Humans ; Imatinib Mesylate ; Piperazines ; therapeutic use ; Prognosis ; Pyrimidines ; therapeutic use ; Retrospective Studies ; Survival Rate