Personalized drug response prediction from molecular data is an important challenge in precision medicine for treating cancer.Computational methods have been widely explored and have become increasingly accurate in recent years.However,the clinical application of prediction methods is still in its infancy due to large discrepancies between preclinial models and patients.We present a novel disentangled synthesis transfer network(DiSyn)for drug response prediction specifically designed for transfer learning from preclinical models to clinical patients.DiSyn uses a domain separation network(DSN)to disentangle drug response related features,employs data synthesis technology to increase the sample size and iteratively trains for better feature disentanglement.DiSyn is pretrained on large-scale unlabeled cancer samples and validated by three datasets,The Cancer Genome Atlas(TCGA),Investigation of Serial Studies to Predict Your Therapeutic Response With Imaging And moLecular Analysis 2(I-SPY2)and Novartis Institutes for Biomedical Research Patient-Derived Xenograft Encyclopedia(NIBR PDXE),achieving competitive performance with the state-of-the-art methods on cancer patients and mice.Furthermore,the application of DiSyn to thousands of breast cancer patients show the heterogeneity in drug responses and demonstrate its potential value in biomarker discovery and drug combination prediction.

Personalized drug response prediction from molecular data is an important challenge in precision medicine for treating cancer. Computational methods have been widely explored and have become increasingly accurate in recent years. However, the clinical application of prediction methods is still in its infancy due to large discrepancies between preclinial models and patients. We present a novel disentangled synthesis transfer network (DiSyn) for drug response prediction specifically designed for transfer learning from preclinical models to clinical patients. DiSyn uses a domain separation network (DSN) to disentangle drug response related features, employs data synthesis technology to increase the sample size and iteratively trains for better feature disentanglement. DiSyn is pretrained on large-scale unlabeled cancer samples and validated by three datasets, The Cancer Genome Atlas (TCGA), Investigation of Serial Studies to Predict Your Therapeutic Response With Imaging And moLecular Analysis 2 (I-SPY2) and Novartis Institutes for Biomedical Research Patient-Derived Xenograft Encyclopedia (NIBR PDXE), achieving competitive performance with the state-of-the-art methods on cancer patients and mice. Furthermore, the application of DiSyn to thousands of breast cancer patients show the heterogeneity in drug responses and demonstrate its potential value in biomarker discovery and drug combination prediction.

Objective To evaluate the recognition capability of AI-enabled Cellsee CS-BM1 automatic cell morphology analyzer for pe-ripheral blood smears and its roles in assisting manual classification,and explore the application value of AI system in the diagnosis network of tiered primary medical units.Methods The blood samples which triggered the re-examination rules were collected from six primary medical units,including the Laboratory Department of Shanghai Jiahui International Hospital,and so on,from March to No-vember 2023.The smears of peripheral blood were prepared and AI analyzer was used for pre-classification to evaluate its recognition performance in identifying the samples with abnormal WBC and RBC.The sensitivity,specificity,and accuracy of WBC classification by six junior and intermediate technicians,both with and without AI assistance,were analyzed.Additionally,the roles of the AI system in tiered diagnosis of primary medical units were also evaluated.Results The sensitivity,specificity,and accuracy of AI system in recognizing malignant primitive cells were 92.86％,95.16％,and 95.10％,respectively.The sensitivities of AI system in recognizing immature granulocytes,reactive lymphocytes,and nucleated RBCs were all greater than 90％.The sensitivity of AI system in identif-ying abnormal morphology of RBCs reached 99.59％,along with rapid quantitative analysis for various anomalous types of RBCs.In AI-assisted mode,the sensitivity of recognition for all cell types was improved to varying degrees by junior and intermediate technicians,and the sensitivity for recognizing malignant primitive cells,reactive lymphocytes,and immature granulocytes increased to 58.24％,53.39％,and 62.37％for junior technicians,and to 92.06％,83.24％,and 83.12％for intermediate technicians,respectively.The improvements for junior technicians were particularly significant,with increases of 12.46％,10.61％,and 3.71％for each cell type,respectively.Both groups achieved higher specificity and accuracy.Through AI pre-classification and manual review,a variety of pe-ripheral blood cell-related diseases were accurately diagnosed in the tiered healthcare practice of primary medical units,including 339 cases(11.13％)of red blood cell diseases,5 cases(0.16％)of platelet diseases,2 343 cases(76.90％)of infection-related disea-ses,and 28 cases(0.92％)of malignant hematological diseases.In addition,332 cases(10.90％)which lacked an obvious related cause or required further examinations were identified as well.Conclusion AI pre-classification has demonstrated strong cell recogni-tion capabilities and may assist technicians in improving the sensitivity,specificity,and accuracy of blood cell classification.AI could en-hance the disease-screening capabilities in the tiered diagnosis network of primary medical units,presenting a broad application prospect.

Objective To evaluate the recognition capability of AI-enabled Cellsee CS-BM1 automatic cell morphology analyzer for pe-ripheral blood smears and its roles in assisting manual classification,and explore the application value of AI system in the diagnosis network of tiered primary medical units.Methods The blood samples which triggered the re-examination rules were collected from six primary medical units,including the Laboratory Department of Shanghai Jiahui International Hospital,and so on,from March to No-vember 2023.The smears of peripheral blood were prepared and AI analyzer was used for pre-classification to evaluate its recognition performance in identifying the samples with abnormal WBC and RBC.The sensitivity,specificity,and accuracy of WBC classification by six junior and intermediate technicians,both with and without AI assistance,were analyzed.Additionally,the roles of the AI system in tiered diagnosis of primary medical units were also evaluated.Results The sensitivity,specificity,and accuracy of AI system in recognizing malignant primitive cells were 92.86％,95.16％,and 95.10％,respectively.The sensitivities of AI system in recognizing immature granulocytes,reactive lymphocytes,and nucleated RBCs were all greater than 90％.The sensitivity of AI system in identif-ying abnormal morphology of RBCs reached 99.59％,along with rapid quantitative analysis for various anomalous types of RBCs.In AI-assisted mode,the sensitivity of recognition for all cell types was improved to varying degrees by junior and intermediate technicians,and the sensitivity for recognizing malignant primitive cells,reactive lymphocytes,and immature granulocytes increased to 58.24％,53.39％,and 62.37％for junior technicians,and to 92.06％,83.24％,and 83.12％for intermediate technicians,respectively.The improvements for junior technicians were particularly significant,with increases of 12.46％,10.61％,and 3.71％for each cell type,respectively.Both groups achieved higher specificity and accuracy.Through AI pre-classification and manual review,a variety of pe-ripheral blood cell-related diseases were accurately diagnosed in the tiered healthcare practice of primary medical units,including 339 cases(11.13％)of red blood cell diseases,5 cases(0.16％)of platelet diseases,2 343 cases(76.90％)of infection-related disea-ses,and 28 cases(0.92％)of malignant hematological diseases.In addition,332 cases(10.90％)which lacked an obvious related cause or required further examinations were identified as well.Conclusion AI pre-classification has demonstrated strong cell recogni-tion capabilities and may assist technicians in improving the sensitivity,specificity,and accuracy of blood cell classification.AI could en-hance the disease-screening capabilities in the tiered diagnosis network of primary medical units,presenting a broad application prospect.

Objective To investigate the impact of not using drainage on clinical outcomes after arthroscopic autologous semitendinosus tendon reconstruction with anterior cruciate ligament reconstruction.Methods From March 2022 to June 2023,59 patients undergoing arthroscopic autologous semitendinosus tendon reconstruction with anterior cruciate ligament reconstruction in Lincang People's Hospital were collected and randomly divided into the non-drainage group consisting of 29 cases(observation group)and the 24-hour drainage group consisting of 30 cases(control group).The pain levels of the two groups of patients were recorded on the 1st,3rd,7th,14th,and 30th day after the surgery by using a visual analog scale.Additionally,the knee joint range of motion,length of hospital stay,and occurrence of postoperative complications were monitored.The circumference of the thigh was measured before and after the surgery,and the difference was calculated.Results Repeated measures analysis of variance revealed that there were statistically significant within-subject differences in pain ratings,thigh circumference,and knee joint range of motion(P<0.05),but no statistically significant between-subject differences(P>0.05).Independent samples t-tests showed that on the first day after the surgery,the observation group had lower pain ratings(P<0.001),and higher thigh circumference and knee joint range of motion compared to the control group(P<0.05).There were no statistically significant differences in pain ratings,knee joint range of motion,and thigh circumference between the two groups at the remaining follow-up times(P>0.05);The observation group had a shorter hospital stay than the control group(P<0.001);Both groups of patients had no complications such as lower limb nerve damage,deep vein thrombosis,knee joint infection,or hematomas requiring puncture and aspiration.Conclusion In the early postoperative period following arthroscopic autologous hamstring tendon reconstruction of the anterior cruciate ligament,the omission of drainage does not affect the clinical outcomes in terms of pain,knee joint mobility,and thigh circumference.Moreover,omitting drainage reduces the level of pain experienced by patients on the first day after the surgery,improves the knee joint mobility,and decreases the length of hospital stay.Therefore,in arthroscopic autologous hamstring tendon reconstruction of the anterior cruciate ligament,it is not recommended to routinely use drainage for preventive purposes.

Objective:To investigate the preoperative nutritional status of cardiac surgery patients in southwest China, analyze the incidence and characteristics of nutritional risk, and provide basis for establishing a standardized individualized nutritional intervention program for cardiac surgery patients.Methods:A cross-sectional survey was conducted on the nutritional status and intervention status of preoperative patients in cardiac surgery department of 23 general hospitals in Yunnan, Guizhou, Sichuan and Chongqing districts. At 00: 00 on July 7, 2022, the patients aged > 18 years old in cardiac surgery departments of the above hospitals who planned to undergo surgical treatment were enrolled as the survey objects to investigate the nutritional status on July 6, 2022 (the survey date), including basic information (general information, nutrition indicators, etc.), nutrition screening and evaluation (nutrition risk screening and organ support, etc.), nutrition treatment (nutrition supplement methods and prescriptions, etc.) and nutrition awareness of medical staff.Results:The 126 questionnaires were collected, of which 125 were valid (99.2%). ① Basic information: of the 125 patients, 67 patients were male (53.6%) and 58 patients were female (46.4%). The age ranged from 19 years old to 86 years old, with an average of (53.13±14.74) years old. Body mass index (BMI) was (22.21±3.78) kg/m 2. The age and BMI of men were significantly higher than those of women [age (years old): 56.63±13.34 vs. 49.09±15.35, BMI (kg/m 2): 22.74±3.86 vs. 21.59±3.61, both P < 0.05]. Of the 125 patients, 75 had valvular disease and 50 were with non-valvular diseases, which mainly included congenital heart disease [19 cases (15.2%)], aortic dissection [13 cases (10.4%)], coronary heart disease [12 cases (9.6%)], etc. The course of disease was 0.5 hour to 36 years, of which 93 patients (74.4%) were more than 6 months and 32 patients (25.6%) were equal to or less than 6 months. The proportion of female patients with disease duration > 6 months was significantly higher than that of male patients [87.9% (51/58) vs. 62.7% (42/67), P < 0.01]. The basic diseases mainly included hypertension [38 cases (30.4%)], coronary heart disease [12 cases (9.6%)], diabetes [7 cases (5.6%)], chronic obstructive pulmonary disease [COPD, 6 cases (4.8%)], etc. Among 125 patients, total protein (TP) < 60 g/L in 24 cases (19.2%), albumin (Alb) < 40 g/L in 64 cases (51.2%), anemia [male hemoglobin (Hb) < 120 g/L, female Hb < 110 g/L] in 33 cases (26.4%). A total of 60 cases of prealbumin data were collected, of which 23 cases (38.3%) were less than 200 mg/L.② Nutrition screening and assessment: 33.6% of the 125 patients did not undergo routine nutrition screening after admission, including the provincial and municipal tertiary hospitals. Among the 83 patients undergoing nutritional screening, 41 (32.8%) were at nutritional risk. Further analysis of patients with nutritional risk showed that of the 41 patients, 20 were male (48.8%) and 21 were female (51.2%); 27 cases (65.9%) was with valvular diseases and 14 cases (34.1%) was with non-valvular diseases; the course of disease was more than 6 months in 30 cases (73.2%), and ≤ 6 months in 11 cases (26.7%). Statistical comparison of the above 83 patients showed that women, basic disease, long term-valvular disease, anemia, low TP, and low Alb before operation were more prone to innutrition. ③ Nutritional therapy: of the 125 patients, 5 were receiving mechanical ventilation (4.0%) and 2 were using vasoactive drugs (1.6%); there were 5 cases with gastrointestinal dysfunction (4.0%), mainly manifested as abdominal distension, abdominal pain, constipation and diarrhea. One patient was treated with enteral nutrition through gastric tube combined with parenteral nutrition support, 124 patients were fed orally, and an irregular phenomenon of injecting amino acid fat emulsion through peripheral vein in 2 patients. ④ Nutrition awareness of medical staff: 124 (99.2%) of the 125 patients had a nutrition department in their hospital; 71 cases (56.8%) received nutrition education, of which 37 cases (52.1%) were consulted by the nutrition department. Of all the cases, only 38 (30.4%) were consulted by the nutrition department, of which 1 (2.6%) did not receive nutrition education after consultation. Conclusions:At present, the incidence of preoperative malnutrition in patients undergoing cardiac surgery is high in southwest China. The incidence of malnutrition in patients with basic diseases, long term-valvular disease, low TP, low Alb and anemia before operation is higher, and the incidence of malnutrition is hidden in women. The course of disease of women is longer than that of men at the time of treatment, and malnutrition is more likely to occur. The attending physicians should pay attention to the above groups. It is necessary to establish a standardized individualized nutritional intervention program and apply it to actual clinical diagnosis and treatment, so as to ultimately improve the prognosis of patients undergoing cardiac surgery and increase the benefits of patients in treatment.

Objective To evaluate the clinical effect of dacryocystorhinostomy under nasal endoscope combined with lacrimal duct catheterization.Methods The retrospective comparative study was used to analyze 120 patients with chronic dacryocystitis in our hospital from June,2012 to May,2016,of whom 60 patients were treated with traditional dacryocystorhinostomy,and 60 patients were treated with dacryocystorhinostomy under nasal endoscope combined with lacrimal duct catheterization.Half year after the operation the patients were re-examined for the patency of their lacrimal passages and postoperative complication.The disappearance of tearing and the unobstructed patency of the lacrimal passages were set as the standard of a successful operation.The statistically analyzing was performed.Results Six months after operation,the success rate of dacryocystorhinostomy under nasal endoscope combined with lacrimal duct catheterization was 93.3％,the success rate of traditional dacryocystorhinostomy was 90.0％,without statistical difference between two types of operation (P ＞ 0.05).The skin scar formation rate in dacryocystorhinostomy under nasal endoscope combined with lacrimal duct catheterization was 0,while 100％ in traditional dacryocystorhinostomy,with statistical significant difference (P =0.00).The success rate of two-stage operation was 100％ after dacryocystorhinostomy under nasal endoscope combined with lacrimal duct catheterization for recurrence,while 16.7％ after traditional dacryocystorhinostomy,the difference is of statistical significance (P =0.048).Conclusions Dacryocystorhinostomy under nasal endoscope combined with lacrimal duct catheterization is not only reliable,effective method for treating chronic dacryocystitis,but also with less iatrogenic trauma,and no scar.

Objective To investigate the effects of thymosin α1 (Tα1) on plasma TNF-α and IL-10 of rats with acute liver failure.Methods The model of acute liver failure in rats was established.The rats in intervention group were injected with Tα1;their plasma ALT, AST and TBIL contents as well as plasma TNF-α and IL-10 levels were assayed at different time points for HE staining of liver sections.Results ① ALT, AST and TBIL in model group and intervention group increased over time.Plasma ALT, AST and TBIL were significantly lower in intervention group than in model group at the same time point (P<0.05).② Manifestations of acute liver failure such as structural disorder of liver tissue, obvious necrosis of liver cells and infiltration of inflammatory cells were observed in model group and intervention group, and worsened over time.At the same time point, liver cell necrosis and infiltration of inflammatory cells were less severe than those in model group.③ TNF-α and IL-10 were significantly higher in model and intervention groups than in control group (P<0.05).Plasma TNF-α and IL-10 showed a rising trend over time in the former groups (P<0.05).At the same time point, TNF-α was significantly lower but IL-10 was significantly higher in intervention group than in model group.Conclusion Thymosin α1 has a protective effect on acute hepatic failure in rats, and it can significantly alleviate liver inflammation and necrosis.The mechanism is related to inhibition of pro-inflammatory cytokine TNF-α and upregulation of anti-inflammatory cytokine IL-10.

Objective To observe the influence of the clinical pathway management intervention on medical service behaviors.Methods The clinical cases data in a grade A class 3 hospital of Zhangjiakou City,Hebei Province during 2011-2013 were retrospectively analyzed.The influence of implementing the clinical pathway management on the diagnosis results,medical records writing quality,clinical medication,operation,hospitalization time,medical costs,assisted examination items selection were observed and analyzed.Results The admission and discharge diagnosis coincidence rate and preoperative and postoperative diagnostic coincidence rate of 3 diseases entities in the two groups were 100%,the difference had no statistical significance (P>0.05);the medical record grade-A rate in the implementing clinical pathway group was significantly higher than that in the non-implementing clinical pathway group,the medical record grade-B rate was significantly lower than that in the non-implementing clinical pathway group,the difference was statistically significant (P<0.05);the antibacterial drugs cost and drugs proportion in the implementing clinical pathway group were significantly lower than those in the non-implementing clinical pathway group,the medication proportion within the directory in the implementing clinical pathway group was significantly higher than that in the non-implementing clinical pathway group,the difference was statistically significant (P<0.05);the preoperative preparation time in the implementating clinical pathway group was less than that in the non-implementing clinical pathway group,the difference was statistically significant(P<0.05),the grade-A healing rate had no significant difference between the two groups (P>0.05);the average hospitalization time,total costs,drug costs,laboratory fee and examination fee in the implementing clinical pathway group were lower than those in the non-implementing clinical pathway group,the difference was statistically significant (P<0.05);the operation fee,healthy material fee and nursing fee had no statistically significant difference was statistically significant(P<0.05).Conclusion Implementing the clinical pathway can standardize the doctor′s diagnosis and treatment behaviors and makes the medical work to develop to be more favorable for patients.

Objective:To establish an LC-MS/MS method for the simultaneous determination of acetaminophen and its five metabolites in mice plasma,and investigate the metabolism of acetaminophen by using the method.Methods:Para aminobenzoic acid was used as the internal standard.The plasma samples were precipitated by methanol,and then separated on a C18 column with the mobile phase of methanol and 5 mmol·L-1 ammonium acetate buffer solution containing 0.1% formic acid (55∶45).The flow rate was 0.5 ml·min-1,and the column temperature was 25℃.An electrospray ionization source was applied and operated in a positive ion mode using MRM:APAP,-,m/z 152.0→110.0;APAP-cys,-,m/z 271.2→140.1;APAP-glut,-,m/z 457.0→328.0;APAP-NAC,-,m/z 313.4 →208.0;APAP-sulf,-,m/z 232.4→152.1;APAP-gluc,-,m/z 328.2→152.1;IS,-,m/z 138.2→120.0.Results:The method exhibited good linearity over the concentration range of 0.2-10 μg·ml-1for APAP,1.0-20 μg·ml-1 for APAP-gluc,1.0-20 μg·ml-1 for APAP-sulf,1.0-20 μg·ml-1 for APAP-glut,0.4-15 μg·ml-1 for APAP-NAC and 0.2-10 μg·ml-1 for APAP-cys (r≥0.990 0).The inter-day accuracy and precision of acetaminophen and its five metabolites were all below 15%.The average recovery was between 85% and 115%,and RSDs were all below 15%.Conclusion:The LC-MS/MS method is proved to be quick,sensitive and accurate,and suitable for the determination of acetaminophen and its five metabolites in mice plasma.