BACKGROUND: Postoperative pulmonary complications (PPCs) are major adverse events in neurosurgical patients. This study aimed to develop and validate machine learning models predicting PPCs after neurosurgery. METHODS: PPCs were defined according to the European Perioperative Clinical Outcome standards as occurring within 7 postoperative days. Data of cases meeting inclusion/exclusion criteria were extracted from the anesthesia information management system to create three datasets: The development (data of Huashan Hospital, Fudan University from 2018 to 2020), temporal validation (data of Huashan Hospital, Fudan University in 2021) and external validation (data of other three hospitals in 2023) datasets. Machine learning models of six algorithms were trained using either 35 retrievable and plausible features or the 11 features selected by Lasso regression. Temporal validation was conducted for all models and the 11-feature models were also externally validated. Independent risk factors were identified and feature importance in top models was analyzed. RESULTS: PPCs occurred in 712 of 7533 (9.5%), 258 of 2824 (9.1%), and 207 of 2300 (9.0%) patients in the development, temporal validation and external validation datasets, respectively. During cross-validation training, all models except Bayes demonstrated good discrimination with an area under the receiver operating characteristic curve (AUC) of 0.840. In temporal validation of full-feature models, deep neural network (DNN) performed the best with an AUC of 0.835 (95% confidence interval [CI]: 0.805-0.858) and a Brier score of 0.069, followed by Logistic regression (LR), random forest and XGBoost. The 11-feature models performed comparable to full-feature models with very close but statistically significantly lower AUCs, with the top models of DNN and LR in temporal and external validations. An 11-feature nomogram was drawn based on the LR algorithm and it outperformed the minimally modified Assess respiratory RIsk in Surgical patients in CATalonia (ARISCAT) and Laparoscopic Surgery Video Educational Guidelines (LAS VEGAS) scores with a higher AUC (LR: 0.824, ARISCAT: 0.672, LAS: 0.663). Independent risk factors based on multivariate LR mostly overlapped with Lasso-selected features, but lacked consistency with the important features using the Shapley additive explanation (SHAP) method of the LR model. CONCLUSIONS: The developed models, especially the DNN model and the nomogram, had good discrimination and calibration, and could be used for predicting PPCs in neurosurgical patients. The establishment of machine learning models and the ascertainment of risk factors might assist clinical decision support for improving surgical outcomes. TRIAL REGISTRATION ChiCTR 2100047474; https://www.chictr.org.cn/showproj.html?proj=128279 .
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Algorithms ; Lung Diseases/etiology* ; Machine Learning ; Neurosurgical Procedures/adverse effects* ; Postoperative Complications/diagnosis* ; Risk Factors ; ROC Curve

The Kirsten rat sarcoma viral oncogene homolog ( KRAS ) mutation is one of the most prevalent activating alterations in cancer. It indicates a poor overall prognosis due to its highly invasive nature. Although several KRAS inhibitors have been developed in recent years, a significant clinical challenge has emerged as a substantial proportion of patients eventually develop resistance to these therapies. Therefore, identifying determinants of drug resistance is critical for guiding treatment strategies. This review provides a comprehensive overview of the mutation landscape and molecular mechanisms of KRAS activity in various cancers. Meanwhile, it summaries the progress and prospects of small molecule KRAS inhibitors undergoing clinical trials. Furthemore, this review explores potential strategies to overcome drug resistance, with the ultimate goal of steering toward patient-centric precision oncology in the foreseeable future.
Humans ; Drug Resistance, Neoplasm/drug effects* ; Proto-Oncogene Proteins p21(ras)/metabolism* ; Mutation/genetics* ; Neoplasms/genetics* ; Antineoplastic Agents/therapeutic use*

OBJECTIVE To investigate whether aldo-keto reductases(AKRs)can act as a nitrore-ductase(NR)and bioactivate aristolochic acid Ⅰ(AA-Ⅰ)to produce AA-Ⅰ-DNA adducts.METHODS① Human-induced hepatocytes(hiHeps)and human bladder RT4 cells were used as tool cells and treated with AA-Ⅰ0,0.5,1.0 and 2 μmol·L-1 for 24 h.Cell viability was detected using the CCK-8 method,and the half maximal inhibition concentration(IC50)was calculated using the CCK-8 method and the level of DNA adduct production was calculated.②hiHeps and RT4 cells were treated with AKR inhibitor luteotin(0,5,10 and 25 μmol·L-1)+AA-Ⅰ 0.2 and 1.0 μmol·L-1 for 24 h,respectively,and the levels of DNA adducts were detected by a liquid chromatography-tandem mass spectrometer(LC-MS/MS).③hiHeps cells were incubated with 80 nmol·L-1 small interfering RNAs(si-AKRs)for 48 h and treated with AA-Ⅰ1.0 μmol·L-1 for 24 h.Real-time qualitative PCR(RT-qPCR)method was used to detect the mRNA expression of AKRs gene and LC-MS/MS technology was used to investigate the effect of specific AKR gene knockdown on DNA adduct levels.④500 nmol·L-1 human AKR recombinant proteins AKR1A1 and AA-Ⅰwere incubated in vitro under anaerobic conditions and the formation of AA-Ⅰ-DNA adducts was detected.RESULTS ①The IC50 of AA-Ⅰto hiHeps and RT4 cells was 1.9 and 0.42 μmol·L-1,respec-tively.The level of DNA adduct production of the two cell lines was significantly different(P<0.01).② Luteolin≥5 μmol·L-1 significantly inhibited the production of AA-Ⅰ-DNA adducts in both cells(P<0.05),and there was a concentration-dependent effect in hiHeps cells(P<0.01,R=0.84).③In the AKR family,the knockdown of AKR1A1 gene up to 80%inhibited the generation of AA-Ⅰ-DNA adducts by 30%-40%.④The AA-Ⅰ-DNA adducts were detected in the incubation of recombinant protein AKR1A1 and AA-Ⅰ under anaerobic conditions in vitro,approximately 1 adduct per 107 nucleotides.CONCLU-SION AKR1A1 is involved in AA-Ⅰ bioactivation,providing a reference for elucidation of the carcino-genic mechanism of AA-Ⅰ.

The awake prone position plays an important role in the treatment of hypoxemia and the improvement of respiratory distress symptoms in non-intubated patients. It is widely used in clinical practice because of its simple operation, safety, and economy. To enable clinical medical staff to scientifically and normatively implement prone position for awake patients without intubation, the committees of consensus formulation, guided by evidence-based methodology and Delphi method, conducted literature search, literature quality evaluation and evidence synthesis around seven topics, including indications and contraindications, evaluation, implementation, monitoring and safety management, termination time, complication prevention and health education of awake prone position. After two rounds of expert letter consultation, Expert consensus on implementation strategy of awake prone positioning for non-intubated patients in China (2023) was formulated, and provide guidance for clinical medical staff.
Humans ; Consensus ; Prone Position ; Wakefulness ; China ; Dyspnea

Objective: To understand the characteristics and trends of colorectal cancer incidence and mortality in Lishui residents from 2014 to 2018,so as to provide basis for the development of prevention and treatment measures of colorectal cancer. Methods : The incidence and mortality data of colorectal cancer in Lishui from 2014 to 2018 were collected through the information management system of chronic disease surveillance in Zhejiang Province. The incidence,mortality and annual percentage change(APC)of colorectal cancer were calculated and analyzed in different genders,ages and regions were analyzed. Results: From 2014 to 2018,there were 4 403 new cases of colorectal cancer in Lishui,with the crude and standardized incidence rate of 34.89/100 000 and 20.99/100 000,respectively. There were 2 369 deaths,with a crude mortality rate of 18.77/100 000 and a standardized mortality rate of 10.17 /100 000. The crude incidence rate and crude mortality rate in males were higher than those in females(39.71/100 000 vs. 29.77/100 000,21.31/100 000 vs. 16.08/100 000,both p<0.05). There were no statistically significant differences between urban and rural residents in the crude incidence rate and crude mortality rate(37.24/100 000 vs. 34.44/100 000,19.75/100 000 vs. 18.45/100 000,both p<0.05). The crude incidence rate and crude mortality rate increased with age. The APC of the mortality rate of colorectal cancer among urban residents was 11.31%,showing an increasing trend from 2014 to 2018(p<0.05). Conclusion The incidence and mortality of colorectal cancer are high in Lishui,and the focus groups are men,people aged over 40 years and urban residents.

Objective:To investigate the clinical features, treatment methods and prognostic factors of extranodal nasal type NK/T lymphoma (ENKTL).Methods:The clinical data of 45 patients treated in Renmin Hospital of Wuhan University from January 2013 to June 2019 were retrospectively analyzed. Short-term efficacy was compared among low-risk, medium-risk and high-risk three groups according to PINK score. According to the treatment methods, the patients of stage Ⅰ-Ⅲ were divided into radiotherapy group and radiotherapy+ chemotherapy group. Chi-square test was used to compare the treatment outcomes. The effects of diagnosis time, clinical staging, symptom B, erythrocyte sedimentation rate (ESR), lactate dehydrogenase (LDH), Ki-67, prognostic index of NK lymphoma (PINK) and treatment methods on overall survival (OS) and progression-free survival (PFS) were analyzed by using Kaplan-Meier method, log-rank test was used for univariate analysis, and Cox proportional hazard model was used for multivariate prognostic analysis.Results:The median age of 45 patients was 51 years old. There were 39 cases (86.7%) of stage Ⅰ-Ⅱ, 4 cases (8.9%) of stage Ⅲ, 2 cases(4.4%) of stage Ⅳ. The median time from first onset to diagnosis was 3.0 months (1.0-36.0 months), and serum EBV-DNA positive rate was 95.6% (43/45). The complete remission (CR) rate and progression of the disease (PD) rate were statistically different of different risk groups ( χ2 = 10.952, P < 0.01; χ2 = 12.217, P = 0.002). Among 43 patients of stage Ⅰ-Ⅲ, there were 11 patients in the radiotherapy alone group, including 4 cases (36.3%) of CR, 3 cases (27.3%) of partial remission (PR), 4 cases (36.4%) of PD; and 32 patients in the chemotherapy combined with radiotherapy group, including 23 cases (71.9%) of CR, 4 cases (12.5%) of PR, 5 cases (15.6%) of PD. The difference in CR rate of both groups was statistically significant ( χ2 = 4.418, P = 0.036). Univariate analysis suggested that PINK score and B symptom were related to OS ( χ2 = 8.140, P = 0.017; χ2 = 5.545, P = 0.019). PINK score and clinical staging were associated with PFS ( χ2 = 12.517, P = 0.002; χ2 = 10.016, P = 0.002); Cox multivariate analysis indicated that clinical staging was an independent influencing factor of PFS ( HR = 4.104, 95% CI 1.571-10.725, P = 0.004). Conclusions:ENKTL with specific location has longer clinical diagnosis time, and the positive rate of EBV-DNA is high. The patients with B symptom and high PINK score have poor OS, and patients with late clinical staging and high PINK score have short PFS. Clinical staging is considered as an independent factor affecting PFS. The PINK score risk stratification has a guiding significance in the short-term efficacy evaluation, and the chemotherapy combined with radiotherapy can increase CR rate for patients less than stage Ⅳ.

Objective: To study the effects of endoscopic submucosal dissection(ESD) on long-term quality of life (QOL) and gastric function of patients with distal early gastric cancer (EGC), compared with those of surgery. Methods: Patients with EGC who received ESD or surgical resection in Peking Union Medical College Hospital over 1 year ago were selected to be followed up. QLQ-C30, SF-36, EQ-5D and dyspeptic symptom rating scale were used to evaluate QOL. Five-hour gastric emptying rate was used to evaluate distal gastric function. Electronic gastroscopy was used to observe whether the anastomotic stoma was stenotic. According to the age at resection, 1 to 1 matching was performed between the distal 1/3 gastric ESD (E_P) group and the distal subtotal gastrectomy (S_P) group, and then the QOL and gastric function between the two groups were compared. Results: Twenty-five patients were included in group E_P and group S_P respectively. According to QLQ-C30, the scores of cognitive function were 83.3 (83.3, 83.3) in group E_P and 83.3 (83.3, 100.0) in group S_P (P=0.056). The proportion of patients with symptoms (fatigue, nausea and vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea and financial difficulties) between the two groups were not statistically different. There was no statistical difference in the scores of EQ-5D and SF-36 between the two groups. According to dyspeptic symptom rating scale, 56.0% patients in group E_Phad burning sensation, but only 28.0% in group S_P had this symptom (P=0.054). 20.0% of patients in group S_Preported nausea, while only 4.0% in group E_P had this symptom (P=0.084). Gastric emptying results showed that the proportion of patients with abnormal 5-hour gastric emptying rate was 31.8% in group E_P, while there was no abnormal emptying in group S_P (P=0.003). Gastroscopy results showed that one patient in group E_P had pyloric stenosis, but 5-hour gastric emptying rate was normal. All anastomotic stomas in group S_p were unobstructed. Conclusion ESD and surgical resection for distal EGC show similar long-term effects on QOL of patients. But the long-term gastric emptying function may decrease after distal gastric ESD.

Objective: To learn the characteristics of gastric cancer incidence and mortality in Lishui from 2014 to 2018，and to provide basis for prevention and control strategies for gastric cancer. Methods: The data of gastric cancer in Lishui from 2014 to 2018 was collected from Zhejiang Chronic Disease Surveillance Information Management System. The incidence and mortality rates of gastric cancer were calculated，and the trend of them was evaluated by annual percentage change（APC）. Results: The crude incidence rate of gastric cancer in Lishui was 44.77/100 000（5 650 cases）and the standardized one was 26.93/100 000. From 2014 to 2018，the incidence rates of gastric cancer showed a decreasing trend（APC=-0.79%，P<0.05）. The crude mortality rate of gastric cancer in Lishui was 25.39/100 000（3 205 cases）and the standardized one was 14.21/100 000. From 2014 to 2018，the mortality rates of gastric cancer were stable（APC=-4.61%，P>0.05）. The standardized incidence and mortality rates of gastric cancer in males were 34.77/100 000 and 18.35/100 000，which were higher than 16.77/100 000 and 8.52/100 000 in females（P<0.05）. The standardized incidence and mortality rates of gastric cancer in rural residents were 46.07/100 000 and 26.11/100 000，which were higher than 38.49/100 000 and 22.02/100 000 in urban residents. The incidence and mortality rates increased with age after 15 years old，and reached the peak at the age group of 80-84 years old. Conclusion The incidence and mortality of gastric cancer in Lishui from 2014 to 2018 were at a high level，which were higher in males than in females and were higher in rural than in urban areas；while the incidence had a downward trend.

Objective To evaluate the diagnostic efficiency and prognostic value of 18F-fluorodeoxyglucose (FDG) PET/CT for response assessment after treatment in patients with diffuse large B-cell lymphoma (DLBCL) when using the Deauville criteria and International Harmonization Project (IHP) criteria.Methods A total of 212 patients (119 males,93 males,average age:59.6(10-88) years) with DLBCL from February 2010 to June 2018 were analyzed.All subjects underwent restaging PET/CT after treatment.Images were evaluated with the IHP criteria,Deauville score of 3-5 (DC3) and Deauville score of 4-5 (DC4).The diagnostic efficiency of the 3 criteria for treatment effect was assessed and follow-up results were used as the gold standard.Spearman rank correlation analysis was used.Progression-free survival (PFS) and overall survival (OS) were analyzed by Kaplan-Meier analysis and Cox proportional hazards model.Results The positive predictive value and accuracy of DC4 for treatment effect evaluation were 96.8％(61/63) and 94.3％(200/212),those of IHP criteria were 75.3％(67/89) and 87.7％(186/212)respectively,and those of DC3 were 82.9％ (68/82) and 92.0％ (195/212) respectively.IHP criteria results and Deauville scores were correlated(rs =0.926,P＜0.05).The 2-year PFS rates in IHP-,DC3-and CD4-positive groups were 78.7％,76.5％ and 69.8％,respectively,and those in IHP-,DC3-and CD4-negative groups were significantly higher (95.6％,94.7％,97.2％;x2=14.415,18.293 and 26.920,all P＜0.05).The similar results were found for OS rates (x2 =9.597,11.149 and 17.416,all P＜0.05).The 2-year PFS rates in Deauville score of 1,2,3,4,5 groups were 95.3％,91.7％,93.3％,88.9％ and 55.6％ respectively (x2 =48.199,P＜0.05).Cox-regression analysis showed significant correlation between Deauville criteria and 2-year PFS rate (P＜0.05).Conclusions PET/CT with DC4,DC3 and IHP criteria have high predictive values for treatment outcome,and DC4 is the best.Cox regression analysis shows significant risk of progression by Deauville criteria.

Objective To study the protective effect of breastfeeding on the occurrence of type 2 diabetes mellitus(T2DM) in women with gestational diabetes mellitus(GDM).Methods A total of 660 GDM women were enrolled in this prospective co-hort study.Blood glucose levels were detected 6 to 9 weeks after delivery(baseline)and then on a year basis for 2 years.The re-lated data of T2DM were collected.Stata 12.0 and SPSS 20.0 were used for data analysis.Results In total,615 women completed the follow-up tests.Seventy-eight(12.7%)were diagnosed as having T2DM,and the incidence rate was 5.919/(1000 person·month) .Twenty-four in formula feeding group were diagnosed as having T2DM,and the incidence rate was 8.153/(1000 person· month).Forty-two in mixed feeding group were diagnosed with T2DM,and the incidence rate was 5.657/(1000 person · month).Twelve in breastfeeding group were diagnosed as having T2DM,and the incidence rate was 4.091/(1000 person· month).Weibull regression model analysis showed that after adjustment of confounding factors,the hazard ratios in mixed feed-ing group and breastfeeding group versus formula feeding group were 0.52(95% CI:0.28~0.89)and 0.43(95% CI:0.23~0.82),respectively(P=0.023).Conclusion Breastfeeding can effectively reduce the risk for T2DM in GDM women.It is effec-tive to control the occurrence of T2DM by strengthening the follow-up of GDM women and postpartum weight control.