In epidemiological statistics, the incidence rate and mortality rate of malignant lung tumors rank among the top. Non-small cell lung cancer (NSCLC) constitutes an important part of lung cancer and has become a key focus of clinical research and treatment. Among the genomic characteristics of NSCLC, the Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation is one of the main tumor drivers, accounting for approximately 25% of all NSCLC cases. The existence of this mutation is closely related to the treatment response and prognosis of patients. Therefore, the treatment strategy for KRAS-mutated NSCLC is an important topic in the field of tumor research. In the current era, immunomodulatory therapy has rapidly gained popularity and developed rapidly in oncology due to its unique mechanism of action and remarkable clinical efficacy. The treatment strategies targeting the KRAS-mutated of NSCLC have gradually become a research hotspot. The advent of immune checkpoint inhibitors (ICIs) has opened up a new therapeutic avenue for patients with such cancers, and clinical studies have shown significant effects in improving survival rates. Nevertheless, there are still many challenges in the application of immunotherapy, such as the complexity of the tumor microenvironment, individual differences among patients, and drug resistance mechanisms. This article reviews the progress of immunotherapy for KRAS-mutated NSCLC, focusing on the specific application of immunotherapy, the exploration of combination therapies, and the results of related clinical trials. At the same time, it discusses the possible future development directions of KRAS-mutated NSCLC treatment, providing a reference for clinical treatment practice.
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Humans ; Carcinoma, Non-Small-Cell Lung/immunology* ; Lung Neoplasms/immunology* ; Proto-Oncogene Proteins p21(ras)/immunology* ; Immunotherapy/methods* ; Mutation ; Animals

Background The residues of pharmaceutical and personal care products (PPCPs) in aquatic environments have become an increasingly prominent urban pollution issue, attracting widespread attention. The analysis of PPCPs pollution in water environments holds profound implications in Zhengzhou, a strategically important city in central China. Objective To analyze the pollution characteristics of PPCPs, such as antidepressants and antibiotics, in rivers of Zhengzhou and assess associated ecological risk. Methods Water samples were collected from three rivers of Zhengzhou, and 13 PPCPs (5 antibiotics and 8 antidepressants) were analyzed quantitatively by high performance liquid chromatography-triple quadrupole mass spectrometry (HPLC-MS/MS) after automatic solid phase extraction. Risk quotient (RQ) was applied to assess ecological risk of PPCPs with high concentration. Results The primary antibiotics pollutants were norfloxacin and ofloxacin, both with a detection rate of 100%. Among antidepressants, venlafaxine and citalopram showed the highest detection rates at 92.3% and 88.5%, respectively. The detected antibiotics with the highest average concentrations included ofloxacin and sulfamethoxazole with concentrations of 99.8 ng·L⁻¹and 96.2 ng·L⁻¹, respectively, while antidepressants venlafaxine and citalopram were detected with the highest average concentrations of 15.2 ng·L⁻¹and 1.35 ng·L⁻¹, respectively. The inter-river comparisons revealed statistically significant differences in contaminant loads (P<0.05). The sums of average PPCP concentrations at sampling points in the Jialu River and Suoxu River were 83.4 ng·L⁻¹ and 100.4 ng·L⁻¹, respectively. The Xiaoqing River exhibited higher pollution levels than both the Jialu and Suoxu Rivers, with a total average concentration of 478.4 ng·L⁻¹, where ofloxacin and sulfamethoxazole were identified as the predominant pollutants. The results of ecological risk assessment indicated the RQ contributed by sulfamethoxazole ranged between 0.50−0.95 in the Xiaoqing River, suggesting a controllable risk but requiring prioritized mitigation strategies. The RQ values of norfloxacin were distributed within the range of 0.10-0.30, indicating a moderate ecological risk. The RQ values for ofloxacin and venlafaxine remained below 0.10, indicating a lower risk level. Conclusion PPCPs contamination is positive in the rivers of Zhengzhou, and sulfamethoxazole and ofloxacin are the primary cantaminants. The Xiaoqing River exhibits the highest pollution levels. The initial risk assessment show that sulfamethoxazole and norfloxacin pose potential ecological risks, requiring prioritized contamination management.

Objective: To evaluate the therapeutic potential and underlying mechanisms of action of propolis in db/db mice. Methods: The chemical composition of propolis was analyzed using UHPLC-MS/MS. Thirty mice, including six wt/wt and 24 db/db mice, were randomly assigned to four groups (n = 6 per group): control, model, metformin (250 mg/kg), low dose propolis (100 mg/kg), and high dose propolis (HDP; 400 mg/kg). Treatments were administered orally for four weeks. Body weight and FBG levels were recorded weekly, and an oral glucose tolerance test was conducted on the 25th day. Serum levels of FIN, GSP, connecting peptide, AST, ALT, HDL, LDL, TG, and TC were quantified using ELISA. Liver histopathology was assessed using H&E and PAS staining. Western blotting was performed to examine the expression levels of NF-κB, phosphorylated NF-κB, IκBα, pIκBα, and AKT in liver tissues. Results: The top 10 metabolites of propolis were identified in positive and negative ion modes. The HDP group exhibited a significant reduction in FBG levels, body weight, connecting peptide levels, homeostatic model assessment of β-cell function scores, and homeostasis model assessment of insulin resistance scores (all P < .05). GSP levels were significantly reduced in both treatment groups (all P < .001). The HDP group also exhibited a reduction in TC and LDL levels (both P < .05), whereas HDL levels increased in both treatment groups (all P < .05). Liver weight, AST levels, and ALT levels were reduced in both treatment groups (all P < .05). Histological analysis revealed improved liver morphology. Protein analysis demonstrated downregulation of phosphorylated NF-κB and phosphorylated IκB, alongside upregulation of AKT. Conclusion Propolis exhibited significant antihyperglycemic effects in db/db mice, potentially by modulating the AKT and NF-κB signaling pathways, highlighting its potential as a therapeutic agent for diabetes management.

Objective:To summarize the clinical treatment of complete left bundle branch block (CLBBB) after the transcatheter closure of ventricular septal defect (VSD).Methods:A case series study was conducted on the treatments and outcomes of 25 children with CLBBB after transcatheter VSD closure in Guangdong Provincial People′s Hospital from January 2010 to December 2023.Paired sample t test was used to evaluate the effect of occlude removal. Results:Among the 25 patients, 12 were males (48%), and 13 were females (52%).The age at surgery was 3.18 (2.51-3.86) years, the height before surgery was 95.0 (90.0-97.5) cm, and the weight before surgery was 13 (12-15) kg.Fourteen children were early-onset cases (≤ 1 month), while the other 11 were late-onset cases (> 1 month).The mean follow-up time was (6.63±3.93) years.Of the 14 early-onset cases, 6 children underwent occluder removal within 1 month and restored normal heart rhythm or incomplete right bundle branch block; 4 children underwent occluder removal after 1 month, of whom 2 recovered, 1 remained CLBBB, and 1 had complete atrioventricular block (CAVB); the other 4 children received drug treatment, of whom 2 had normal heart rhythm, 1 had left anterior fascicular block, and 1 died of cardiac shock and heart failure.All the 11 late-onset cases were first treated by drugs, of whom 3 recovered, and the other 8 remained CLBBB.One of the 8 cases received occluder removal at 8 months after surgery and recovered, 1 had CAVB, and the other 6 remained CLBBB.Conclusions:For patients with CLBBB after transcatheter closure of VSD, drug therapy is not always effective, and CLBBB is easy to recur.Therefore, occluder removal is recommended to be done immediately after CLBBB is discovered.Patients with persistent CLBBB should be followed up regularly, and pacemaker implantation may be performed if necessary.

Osteoporotic proximal humeral fracture (OPHF) is one of the common osteoporotic fractures in the aged, with an incidence only lower than vertebral compression fracture, hip fracture, and distal radius fracture. OPHF, secondary to osteoporosis and characterized by poor bone quality, comminuted fracture pattern, slow healing, and severely impaired shoulder joint function, poses a big challenge to the current clinical diagnosis and treatment. In the field of diagnosis, treatment, and rehabilitation of OPHF, traditional Chinese and Western medicine have accumulated rich experience and evidence from evidence-based medicine and achieved favorable outcomes. However, there is still a lack of guidance from a relevant consensus as to how to integrate the advantages of the two medical systems and achieve the integrated diagnosis and treatment. To promote the diagnosis and treatment of OPHF with integrated traditional Chinese and Western medicine, relevant experts from Orthopedic Expert Committee of Geriatric Branch of Chinese Association of Gerontology and Geriatrics, Youth Osteoporosis Group of Orthopedic Branch of Chinese Medical Association, Osteoporosis Group of Orthopedic Surgeon Branch of Chinese Medical Doctor Association, and Osteoporosis Committee of Shanghai Association of Integrated Traditional Chinese and Western Medicine have been organized to formulate Expert consensus on the diagnosis and treatment of osteoporotic proximal humeral fracture with integrated traditional Chinese and Western medicine ( version 2024) by searching related literatures and based on the evidences from evidence-based medicine. This consensus consists of 13 recommendations about the diagnosis, treatment and rehabilitation of OPHF with integrated traditional Chinese medicine and Western medicine, aimed at standardizing, systematizing, and personalizing the diagnosis and treatment of OPHF with integrated traditional Chinse and Western medicine to improve the patients ′ function.

Objective To explore the application value of prognostic nutritional index (PNI) in the postoperative complications of McKeown surgery for da Vinci robotic esophageal cancer. Methods The clinical data of the patients who underwent da Vinci robotic McKeown surgery for esophageal cancer in the Department of Thoracic Surgery of the First Hospital of Lanzhou University from January 2019 to June 2022 were retrospectively collected. According to the receiver operating characteristic (ROC) curve, the optimal cut-off value of PNI for predicting postoperative complications was explored. The patients were divided into a high PNI group and a low PNI group according to the cut-off value, and the differences in basic characteristics, surgery-related indexes and postoperative complications between the two groups were analyzed. According to the occurrence of postoperative complications, the patients were divided into a non-complication group and a complication group. Univariate and multivariate analyses were used to explore the influence of relevant indicators on the occurrence of postoperative complications in da Vinci robotic McKeown surgery for esophageal cancer. Results Finally 120 patients were collected, including 95 males and 25 females, with an average age of 62.82 years. The preoperative hemoglobin content, preoperative blood lymphocyte count, preoperative serum albumin and preoperative blood total cholesterol in the high PNI group were higher than those in the low PNI group (P<0.05). There were statistical differences between the two groups in the incidences of postoperative overall complications, pulmonary infection, pleural effusion and poor incision healing (P<0.05). The relevant indicators that may cause postoperative complications were included in univariate analysis, and the results showed that age, operation time, intraoperative blood loss, preoperative blood lymphocyte count, preoperative hemoglobin content, preoperative blood mononuclear cell count, preoperative blood monocyte count, serum albumin level and PNI were possible influencing factors of postoperative complications after da Vinci robotic McKeown surgery for esophageal cancer. Incorporating these influencing factors into multivariate analysis, the results showed that age, PNI, operation time and intraoperative blood loss were independent influencing factors of postoperative complications. Conclusion PNI has certain predictive value in the postoperative complications of da Vinci robotic McKeown surgery for esophageal cancer. PNI is an independent factor affecting postoperative complications. Improving the level of PNI in esophageal cancer patient before surgery may help reduce the occurrence of postoperative complications.

Objective To investigate the effect of multi-sided foramen ultrafine drainage tube with metal support on the formation of thoracic residual cavity after uniportal video-assisted thoracoscopic (VATS) upper lobectomy. Methods The clinical data of the patients who underwent uniportal VATS upper lobectomy for lung cancer in the Department of Thoracic Surgery of the First Hospital of Lanzhou University from January 2021 to April 2022 were retrospectively analyzed. According to the type of ultrafine drainage tube used in the surgery, the patients were divided into a test group (using metal-supported multi-sided foramen ultrafine drainage tube) and a control group (using ordinary 12F ultrafine drainage tube). The incidence of postoperative thoracic residual cavity and operation-related data were compared between the two groups. Results A total of 200 patients were enrolled, including 126 males and 74 females, with a mean age of 57.52 years. There were 90 patients in the test group, and 110 patients in the control group. The incidence of postoperative thoracic residual cavity in the test group was lower than that in the control group (P=0.045). The differences in the postoperative bedtime, postoperative visual analogue scale, postoperative analgesic pump using time, postoperative hospitalization time, times of postoperative thoracentration and drainage, postoperative drainage time and hospitalization cost between the two groups were statistically significant (P<0.05). The incidences of postoperative lung infection, pleural effusion and atelectasis complications were lower in the test group than those in the control group (P<0.05). The differences in the preoperative anesthesia time, operation time, intraoperative bleeding and postoperative lung leakage were not statistically significant (P>0.05). Conclusion The use of multi-sided foramen ultrafine drainage tube with metal support can reduce the incidence of thoracic residual cavity after uniportal VATS upper lobectomy, and can reduce pain and economical burdens and the incidence of operation-related complications, accelerating the recovery of patients after surgery. The application of multi-sided foramen ultrafine drainage tube with metal support in uniportal VATS upper lobectomy can be widely used in the clinic.

Objective To investigate the clinical effect of metal supported multi-sided versus ordinary ultra-fine drainage tube in the uniportal video-assisted thoracic surgery (VATS) lower pulmonary lobectomy. Methods From January 2021 to June 2022, the clinical data of patients who underwent uniportal VATS lower lobectomy in our hospital were retrospectively analyzed. According to the different types of ultra-fine drainage tubes used in the surgery, the patients were divided into an experimental group (using multi-sided hole 10F ultra-fine drainage tubes with metal support) and a control group (using ordinary 12F ultra-fine drainage tubes). The clinical data of the two groups were compared. Results A total of 190 patients were enrolled, including 108 males and 82 females. There were 90 patients in the experimental group aged 56.60±10.14 years; and 100 patients in the control group aged 57.07±11.04 years. The incidences of postoperative lung infection and pleural effusion in the experimental group were lower than those in the control group, with statistically significant differences (P<0.05). The postoperative visual analogue scale score, the need to adjust the chest drainage tube after the surgery, the need for chest puncture after the surgery, the time of postoperative chest tube removal, and the hospitalization cost were statistically different (P<0.05). There was no statistical difference in the length of postoperative hospital stay or the incidences of postoperative lung leakage, arrhythmia, and atelectasis complications (P>0.05). Conclusion Compared with the ordinary ultra-fine drainage tubes, multi-sided hole ultra-fine drainage tubes with metal support can reduce the incidences of lung infection and pleural effusion complications after the uniportal VATS lower lobectomy, reduce the pain and economic burden, which can be applied in the uniportal VATS lower lobectomy.

AIM:To improve the success rate of experimental modeling of non-alcoholic fatty liver(NAFLD)in rats by high-fat diet through comparing three different formulations of high-fat diets in con-structing non-alcoholic fatty liver rats model,so as to provide a reliable animal model for the study of non-alcoholic fatty liver disease.METHODS:SPF-grade male SD rats were divided into four groups randomly:control group,high-fat diet group1(HFD1),high-fat diet group2(HFD2),high-fat diet group3(HFD3).Each group was given the corre-sponding feed for 8 weeks while modeling.The da-ta on general observation,body weight changes,and ingestion of the rats were recorded during the modeling period.After 8 weeks'feeding,liver ultra-sound,CT and MRI examination were performed for the rats of each group to check the status.Blood and liver samples were collected.Changes in liver function(ALT,AST),blood lipids(TC,TG,HDL-C,LDL-C),and inflammatory indexes(IL-1β,IL-6,TNF-α)were detected.The morphology of the liv-ers was observed with the naked eyes,and the liv-er index and Lee's index were calculated at the end of 8 weeks.The effects of different high-fat diets on the establishment of NAFLD model in SD rats were comprehensively evaluated by comparing the difference of above indexes among the groups.RE-SULTS:Compared with the control group,rats in the HFD1,HFD2 and HFD3 groups showed poor mental deterioration,decreased activity,severe hair loss,decreased food intake,increased body weights,and significantly increased liver index and Lee's in-dex,along with increased liver volume,blunt edge,steatosis and lipid deposition,and the trend was even more pronounced in the HFD3 group.Com-pared with the control group,the serum levels of ALT,AST,TC,TG,LDL-C,IL-1β,IL-6 and TNF-α were significantly increased,while the contents of HDL-C was significantly decreased in the HFD1,HFD2 and HFD3 group,especially in the HFD3 group.Com-pared with the control group,the B ultrasonogra-phy showed an enlarged liver with enhanced paren-chymal echo and pipe unsharpness,CT showed that the liver and spleen CT ratio decreased obvi-ously,and the MRI images showed obvious differ-ence of liver signal intensity between in/out of phase image in the HFD1,HFD2 and HFD3 group,and the most significant imaging changes was ob-served in the HFD3 group.CONCLUSION:The above three kinds of high-fat diets can establish NAFLD model in SD rats after 8 weeks'feeding,the models induced by HFD3 was better than those in-duced by the other two groups.NAFLD lesion is rel-atively serious and expected to last longer in HFD3 group,which are more suitable for investigating the underlying mechanisms of non-alcoholic fatty liver disease and development of lipid-lowering drugs.

Objective:To explore the evaluation effect of ultrasonography and Pirani score on tarsal deformity, treatment effect and pseudo-correction of congenital clubfoot in infants and young children, and the correlation between the two methods.Methods:This is a retrospective case series study. The clinical data of 26 children (40 feet) with congenital clubfoot who were evaluated by ultrasonography in the Third Affiliated Hospital of Zhengzhou University from January 2020 to January 2023 were retrospectively collected. There were 16 males and 10 females. The age at the first ultrasound examination was ( M(IQR)) 9.0 (18.0) days (range: 1 to 46 days). All patients were treated with Ponseti method by the same physician. The Pirani scores before and after treatment and at the last examination, and the talonavicular angle, calcaneocuboid angle and tibiocalcaneal angle measured by ultrasound were collected, and the treatment and follow-up were recorded. Paired sample t test, repeated measures analysis of variance or Kruskal-Wallis test were used for data comparison, and Spearman correlation analysis was used for correlation analysis. The receiver operating characteristic curve was used to calculate the efficacy of ultrasound in evaluating different Pirani scores. Results:The number of plaster fixation in 26 children was 4.0 (1.0) times (range: 2 to 8 times). The medial talonavicular angle and posterior tibiocalcaneal angle were significantly improved after treatment and at the last follow-up compared with those before treatment, and the differences were statistically significant (all P<0.01). There was no difference in lateral calcaneocuboid angle before and after treatment and at the last follow-up ( F=1.971, P>0.05). Pseudo-correction occurred in 2 cases (2 feet) during the treatment, with an incidence of 5%. Correlation analysis showed that there was a moderate positive correlation between talonavicular angle and Pirani midfoot score ( r=0.480, P<0.01). There was no correlation between calcaneocuboid angle and Pirani midfoot score ( r=0.114, P=0.105). There was a moderate negative correlation between tibial heel angle and Pirani hindfoot score ( r=-0.566, P<0.01). The cut-off point of Pirani midfoot score of 1.5 was 38.78°, the sensitivity was 0.90, the specificity was 0.56, and the area under the curve was 0.75. The cut-off value of angle was 27.51 °, the sensitivity was 0.16, the specificity was 0.92, and the area under the curve was 0.44.The cut-off points of Pirani midfoot score of 3.0 were 45.08°and 9.96°, the sensitivity was 0.94 and 0.91, the specificity was 0.37 and 0.42, and the area under the curve was 0.59 and 0.62, respectively. The cut-off values of Pirani hindfoot score of 2.0 and 3.0 were 167.46° and 160.15°, respectively. The sensitivity was 0.75 and 0.67, the specificity was 0.81 and 0.83, and the area under the curve was 0.78 and 0.71, respectively. Conclusion:Ultrasound can complement with Pirani score, visually and dynamically observe the morphology and position changes of talonavicular joint, calcaneocuboid joint and tibiotalocalcaneal joint, monitor the recovery and pseudo-correction of tarsal bones, and better evaluate the therapeutic effect.