Objective:To examine the postoperative morphological changes in outer retinal wave-like changes (ORC) in eyes with rhegmatogenous retinal detachment (RRD).Methods:A retrospective clinical study. From March 2020 to March 2024, 64 eyes of 64 RRD patients diagnosed at The Second Affiliated Hospital of Zunyi Medical University were included. The cohort included 39 males (39 eyes) and 25 females (25 eyes), with a mean age of (45.3±15.7) years and a mean retinal detachment duration of (16.6±13.5) days. Macular involvement was observed in 51 eyes. Scleral buckling surgery (SB), pars plana vitrectomy (PPV), and SB+PPV were performed in 17, 44, and 3 eyes respectively. Best corrected visual acuity (BCVA) and spectral domain optical coherence tomography examinations were performed in all affected eyes. BCVA examination was performed using the standard logarithmic visual acuity chart, and the visual acuity was converted to logarithm of the minimum angle of resolution (logMAR) during statistics. Combined with the ORC situation before the operation, the morphological repositioning of outer retinal folds (ORF) after the operation was classified into types Ⅰ, Ⅱ and Ⅲ. One week and one and three months after the operation, relevant examinations were performed using the same equipment and methods as before the operation. The structural characteristics of ORC and the morphology of ORF after surgery were observed. The comparison between groups was conducted using the independent sample t test or the Mann-Whitney U test. Results:Among the 64 eyes, preoperative ORC was present in 46 eyes (71.9%, 46/64) and absent in 18 eyes (28.1%, 18/64). The 18 eyes without ORC had retinal detachment durations of either ≤4 days or ≥42 days. Postoperatively, ORF was observed in 51 eyes (79.7%, 51/64) and absent in 13 eyes (20.3%, 13/64). Among the 51 eyes with macular holes involved, 24 eyes (47.1%, 24/51) had ORF after the operation and 27 eyes (52.9%, 27/51) had no ORF. Among the 46 and 18 eyes with and without ORC, the ORF after surgery was 28 (60.9%, 28/46) and 1 (5.6%, 1/18) eyes, respectively. There was a statistically significant difference in the reduction rate of ORF after surgery between eyes with and without ORC ( χ2=15.974, P<0.001). Among the 46 eyes with ORC, the proportions of ORF to types Ⅰ, Ⅱ and Ⅲ after surgery were 24 (52.2%, 24/46), 20 (43.5%, 20/46), and 2 (4.3%, 2/46) eyes, respectively. There was no statistically significant difference in the incidence of ORF after different surgical methods in eyes with ORC ( P>0.05). One week and one month after the surgery, the logMAR BCVA of the affected eyes with and without ORF was 0.97±0.47, 0.69±0.34 and 0.85±0.32, 0.54±0.21, respectively. The BCVA of those without ORF was better than that of those with ORF, but the differences were not statistically significant ( t=0.237, 0.408; P>0.05). Conclusions:The occurrence of ORC in RRD eyes has a certain relationship with the time of retinal detachment. For RRD eyes with ORC before the operation, the repositioning morphology after the operation is more likely to show changes in ORF. The transformation from ORC to ORF after ORC surgery has no correlation with the surgical method.

Objective:To explore the related risk factors of diaphragmatic hernia after thoraco-laparoscopic minimally invasive Mckeown esophagectomy (MIME).Methods:This is a retrospective controlled study. A retrospective analysis was conducted on the clinical data of patients who underwent MIME at the Department of Thoracic Surgery, Fourth Hospital of Hebei Medical University, from January 2016 to December 2023. A total of 619 patients were included. There were 423 males and 196 females, aged (63.7±7.6) years (range: 37 to 87 years). The diagnosis of diaphragmatic hernia after MIME was made based on clinical symptoms and CT scans. Patients were divided into two groups: the diaphragmatic hernia group ( n=16) and the non-diaphragmatic hernia group ( n=603). Clinical data, including age, gender, body mass index (BMI), smoking history, tumor location (upper, middle, and lower thoracic esophagus), preoperative neoadjuvant therapy history, and tumor staging, were collected and analyzed. A BMI of 25 kg/m2 and age of 65 years were used as cutoff values. The χ2 test and Fisher′s exact test were used to compare the data between the two groups, and Logistic regression was employed for risk factor analysis. The diaphragmatic hernia group and non-diaphragmatic hernia group were matched in a 1∶3 ratio with a caliper value of 0.02 by propensity score matching. Kaplan-Meier method was used for survival analysis and compared using the log-rank test for between-group differences. Results:The proportion of patients with diaphragmatic hernia after MIME who underwent surgical treatment was 6/16. Statistically significant differences were observed between the diaphragmatic hernia group and the non-diaphragmatic hernia group in terms of age ( χ2=16.057, P<0.01), BMI ( χ2=16.057, P<0.01), and tumor location ( χ2=12.048, P=0.002). Multivariate logistic regression analysis revealed that age ≥65 years ( OR=1.236, P=0.023) and BMI<25 kg/m2 ( OR=0.810, P<0.01) were independent risk factors for the development of diaphragmatic hernia after MIME. Survival analysis showed no significant difference in long-term survival between patients with and without diaphragmatic hernia after MIME ( P=0.187), and whether patients with diaphragmatic hernia underwent surgery was not associated with long-term prognosis ( P=0.560). Conclusion:Patients with BMI<25 kg/m 2 and age ≥65 years are independent risk factors for diaphragmatic hernia after MIME. The occurrence of diaphragmatic hernia is not associated with prognosis, and whether patients with diaphragmatic hernia undergo surgery does not affect the prognosis.

Objective:To examine the postoperative morphological changes in outer retinal wave-like changes (ORC) in eyes with rhegmatogenous retinal detachment (RRD).Methods:A retrospective clinical study. From March 2020 to March 2024, 64 eyes of 64 RRD patients diagnosed at The Second Affiliated Hospital of Zunyi Medical University were included. The cohort included 39 males (39 eyes) and 25 females (25 eyes), with a mean age of (45.3±15.7) years and a mean retinal detachment duration of (16.6±13.5) days. Macular involvement was observed in 51 eyes. Scleral buckling surgery (SB), pars plana vitrectomy (PPV), and SB+PPV were performed in 17, 44, and 3 eyes respectively. Best corrected visual acuity (BCVA) and spectral domain optical coherence tomography examinations were performed in all affected eyes. BCVA examination was performed using the standard logarithmic visual acuity chart, and the visual acuity was converted to logarithm of the minimum angle of resolution (logMAR) during statistics. Combined with the ORC situation before the operation, the morphological repositioning of outer retinal folds (ORF) after the operation was classified into types Ⅰ, Ⅱ and Ⅲ. One week and one and three months after the operation, relevant examinations were performed using the same equipment and methods as before the operation. The structural characteristics of ORC and the morphology of ORF after surgery were observed. The comparison between groups was conducted using the independent sample t test or the Mann-Whitney U test. Results:Among the 64 eyes, preoperative ORC was present in 46 eyes (71.9%, 46/64) and absent in 18 eyes (28.1%, 18/64). The 18 eyes without ORC had retinal detachment durations of either ≤4 days or ≥42 days. Postoperatively, ORF was observed in 51 eyes (79.7%, 51/64) and absent in 13 eyes (20.3%, 13/64). Among the 51 eyes with macular holes involved, 24 eyes (47.1%, 24/51) had ORF after the operation and 27 eyes (52.9%, 27/51) had no ORF. Among the 46 and 18 eyes with and without ORC, the ORF after surgery was 28 (60.9%, 28/46) and 1 (5.6%, 1/18) eyes, respectively. There was a statistically significant difference in the reduction rate of ORF after surgery between eyes with and without ORC ( χ2=15.974, P<0.001). Among the 46 eyes with ORC, the proportions of ORF to types Ⅰ, Ⅱ and Ⅲ after surgery were 24 (52.2%, 24/46), 20 (43.5%, 20/46), and 2 (4.3%, 2/46) eyes, respectively. There was no statistically significant difference in the incidence of ORF after different surgical methods in eyes with ORC ( P>0.05). One week and one month after the surgery, the logMAR BCVA of the affected eyes with and without ORF was 0.97±0.47, 0.69±0.34 and 0.85±0.32, 0.54±0.21, respectively. The BCVA of those without ORF was better than that of those with ORF, but the differences were not statistically significant ( t=0.237, 0.408; P>0.05). Conclusions:The occurrence of ORC in RRD eyes has a certain relationship with the time of retinal detachment. For RRD eyes with ORC before the operation, the repositioning morphology after the operation is more likely to show changes in ORF. The transformation from ORC to ORF after ORC surgery has no correlation with the surgical method.

Objective:To explore the related risk factors of diaphragmatic hernia after thoraco-laparoscopic minimally invasive Mckeown esophagectomy (MIME).Methods:This is a retrospective controlled study. A retrospective analysis was conducted on the clinical data of patients who underwent MIME at the Department of Thoracic Surgery, Fourth Hospital of Hebei Medical University, from January 2016 to December 2023. A total of 619 patients were included. There were 423 males and 196 females, aged (63.7±7.6) years (range: 37 to 87 years). The diagnosis of diaphragmatic hernia after MIME was made based on clinical symptoms and CT scans. Patients were divided into two groups: the diaphragmatic hernia group ( n=16) and the non-diaphragmatic hernia group ( n=603). Clinical data, including age, gender, body mass index (BMI), smoking history, tumor location (upper, middle, and lower thoracic esophagus), preoperative neoadjuvant therapy history, and tumor staging, were collected and analyzed. A BMI of 25 kg/m2 and age of 65 years were used as cutoff values. The χ2 test and Fisher′s exact test were used to compare the data between the two groups, and Logistic regression was employed for risk factor analysis. The diaphragmatic hernia group and non-diaphragmatic hernia group were matched in a 1∶3 ratio with a caliper value of 0.02 by propensity score matching. Kaplan-Meier method was used for survival analysis and compared using the log-rank test for between-group differences. Results:The proportion of patients with diaphragmatic hernia after MIME who underwent surgical treatment was 6/16. Statistically significant differences were observed between the diaphragmatic hernia group and the non-diaphragmatic hernia group in terms of age ( χ2=16.057, P<0.01), BMI ( χ2=16.057, P<0.01), and tumor location ( χ2=12.048, P=0.002). Multivariate logistic regression analysis revealed that age ≥65 years ( OR=1.236, P=0.023) and BMI<25 kg/m2 ( OR=0.810, P<0.01) were independent risk factors for the development of diaphragmatic hernia after MIME. Survival analysis showed no significant difference in long-term survival between patients with and without diaphragmatic hernia after MIME ( P=0.187), and whether patients with diaphragmatic hernia underwent surgery was not associated with long-term prognosis ( P=0.560). Conclusion:Patients with BMI<25 kg/m 2 and age ≥65 years are independent risk factors for diaphragmatic hernia after MIME. The occurrence of diaphragmatic hernia is not associated with prognosis, and whether patients with diaphragmatic hernia undergo surgery does not affect the prognosis.

BACKGROUND: Mutations in the structural domain of the epidermal growth factor receptor (EGFR) kinase represent a critical pathogenetic factor in non-small cell lung cancer (NSCLC). Small-molecule EGFR-tyrosine kinase inhibitors (TKIs) serve as first-line therapeutic agents for the treatment of EGFR-mutated NSCLC. But the resistance mutations of EGFR restrict the clinical application of EGFR-TKIs. In this study, we constructed a clinically relevant PC-9 EGFRD19/T790M/C797S cellular model featuring the mutation type within the EGFRD19/T790M/C797S. This model aims to investigate the inhibitory effects of small-molecule EGFR-TKIs and to provide a cellular platform for developing a new generation of innovative drugs that target resistance associated with EGFR mutations. METHODS: Clustered regularly interspaced short palindromic repeats/CRISPR-associated nuclease 9 (CRISPR/Cas9) technology was employed to knock in the EGFRT790M/C797S mutant fragment into NSCLC PC-9 cells, originally harboring the EGFRD19 mutation, to generate the PC-9 EGFRD19/T790M/C797S cell model. This model, with the EGFRD19/T790M/C797S mutant, was used to investigate the inhibitory effects of EGFR-TKIs on cell proliferation through MTS assay. Additionally, Western blot analysis was conducted to assess the regulation of EGFR protein expression and the phosphorylation levels of downstream signaling molecules, including protein kinase B (AKT) and mitogen-activated protein kinase (MAPK). RESULTS: PC-9 EGFRD19/T790M/C797S cells, with the EGFRD19/T790M/C797S mutation, were successfully generated using CRISPR/Cas9 technology. In terms of proliferation inhibition, the marketed first-, second-, and third-generation EGFR-TKIs that were ineffective against the EGFRD19/T790M/C797S mutation showed weak proliferation inhibitory activity against this cell line, and the proliferation inhibition (half maximal inhibitory concentration, IC50)>1000 nmol/L; in contrast, the fourth-generation EGFR-TKIs in development, which have better efficacy against the EGFRD19/T790M/C797S mutation, showed strong proliferation inhibition in this cell model. On mechanistic validation, the first-, second-, and third-generation EGFR-TKIs had weak inhibitory activity on the phosphorylation of EGFR and the downstream AKT/MAPK signaling pathway in this cell line, whereas the fourth generation of EGFR-TKIs under development significantly inhibited the phosphorylation of EGFR and the downstream AKT/MAPK signaling pathway in this cell line. CONCLUSIONS Using CRISPR/Cas9 technology, the EGFRT790M/C797S mutant fragment was successfully knocked into PC-9 cells to create cell lines harboring the EGFRD19/T790M/C797S mutation. The study demonstrated that the EGFR-TKIs showed different sensitivities to whether the EGFRD19/T790M/C797S mutation was effective or not and different inhibitory effects on the phosphorylation of EGFR and downstream pathways, which demonstrated that this cell line depended on the activation of the EGFRD19/T790M/C797S mutation and EGFR/AKT/MAPK signaling pathway for proliferation. This study provides a clinically relevant cellular evaluation and mechanism validation system for the development of a new generation of innovative drugs targeting EGFR mutation resistance.
ErbB Receptors/metabolism* ; Carcinoma, Non-Small-Cell Lung/metabolism* ; Humans ; Drug Resistance, Neoplasm/genetics* ; Lung Neoplasms/metabolism* ; Protein Kinase Inhibitors/pharmacology* ; Mutation ; Cell Line, Tumor ; Cell Proliferation/drug effects* ; Antineoplastic Agents/pharmacology*

The global COVID-19 coronavirus pandemic has infected over 109 million people, leading to over 2 million deaths up to date and still lacking of effective drugs for patient treatment. Here, we screened about 1.8 million small molecules against the main protease (M^pro) and papain like protease (PL^pro), two major proteases in severe acute respiratory syndrome-coronavirus 2 genome, and identified 1851M^pro inhibitors and 205 PL^pro inhibitors with low nmol/l activity of the best hits. Among these inhibitors, eight small molecules showed dual inhibition effects on both M^pro and PL^pro, exhibiting potential as better candidates for COVID-19 treatment. The best inhibitors of each protease were tested in antiviral assay, with over 40% of M^pro inhibitors and over 20% of PL^pro inhibitors showing high potency in viral inhibition with low cytotoxicity. The X-ray crystal structure of SARS-CoV-2 M^pro in complex with its potent inhibitor 4a was determined at 1.8 Å resolution. Together with docking assays, our results provide a comprehensive resource for future research on anti-SARS-CoV-2 drug development.
Humans ; Antiviral Agents/chemistry* ; COVID-19 ; COVID-19 Drug Treatment ; High-Throughput Screening Assays ; Molecular Docking Simulation ; Protease Inhibitors/chemistry* ; SARS-CoV-2/enzymology* ; Viral Nonstructural Proteins

Objective:To investigate the clinicopathological characteristics and prognostic factors of patients with esophageal cancer.Methods:The retrospective case-control study was conducted. The clinicopathological data of 447 patients with esophageal cancer who were admitted to the Fourth Hospital of Hebei Medical University from January 1, 2017 to December 31, 2020 were collected. There were 312 males and 135 females, aged 60(range, 37?82)years. Observation indica-tors: (1) clinicopathological characteristics; (2) treatment; (3) follow-up; (4) analysis of prognostic factors for esophageal cancer. Follow-up using telephone interview or outpatient examination was conducted to detect survival of patients up to December 2021. The total survival time was from the surgery date to death or the last follow-up. Patients with duration of follow-up more than 2 years were included for survival and prognostic analysis. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M(range). Count data were represented as absolute numbers. Kaplan-Meier method was used to draw survival curves and calculate survival rates. Log-Rank test was used for survival analysis. Univariate analysis was conducted using the Log-rank test. Multivariate analysis was conducted using the COX hazard regression model. Results:(1) Clinicopathological characteristics. Of the 447 patients, 69.80%(312/447) were males and 30.20%(135/447) were females, and there were 3, 18, 101, 229, 93, 3 cases aged 30?39 years, 40?49 years, 50?59 years, 60?69 years, 70?79 years, 80?89 years, respectively. About the pathological type, there were 424 cases with squamous carcinoma, 11 cases with small cell carcinoma, 4 cases with adenosquamous carcinoma, 3 cases with sarco-matoid carcinoma, 2 cases with adenocarcinoma, 1 case with neuroendocrine carcinoma, 1 case with undifferentiated carcinoma, and 1 case with adenoid cystic carcinoma. There were 2 cases with tumor located at cervicothoracic segment, 49 cases with tumor located at upper thoracic segment, 273 cases with tumor located at mid-thoracic segment, and 123 cases with tumor located at lower thoracic segment. There were 6, 24, 74, 59, 192, 80, 12 cases in stage pT0, pT1a, pT1b, pT2, pT3, pT4a, pT4b of pathological T staging, respectively. There were 207, 63, 142, 28, 7 cases in stage pN0, pN1, pN2, pN3, pN4 of pathological N staging by Japan Esophagus Society (JES), respectively. There were 207, 128, 76, 36 cases in stage pN0, pN1, pN2, pN3 of pathological N staging by Union for International Cancer Control (UICC), respectively. About TNM staging, there were 25, 53, 127, 174, 68 cases in stage 0, Ⅰ, Ⅱ, Ⅲ, Ⅳa of JES staging, and 16, 9, 53, 35, 108, 96, 45, 85 cases in stage 0, Ⅰa, Ⅰb,Ⅱa, Ⅱb, Ⅲa, Ⅲb, Ⅲc of UICC staging, respectively. (2) Treatment. Of the 447 patients, 63 cases underwent neoadjuvant therapy(12 cases combined with immunotherapy), 384 cases underwent no neoadjuvant therapy. There were 347, 97, 2, 1 cases with surgical approach as right thoracic approach, left thoracotomy approach, cervical abdominal approach, left thoracoabdominal approach, respectively. There were 316, 5, 126 cases with surgical platform as totally endoscopic esophagec-tomy, Hybrid surgery, open surgery, respectively. There were 350 and 97 cases with digestive recons-truction as posterior mediastinal approach and intrathoracic approach, respectively. Surgical margin as R 0, R 1, R 2 resection was detected in 323, 116, 8 cases, respectively. Six of 447 patients died during the hospital stay. (3) Follow-up. All the 447 patients were followed up for 25(range, 2?48)months, including 233 cases with the follow-up more than 2 years. The median survival time of 233 patients was unreached, and the postoperative 2-year survival rate was 76.8%. (4) Analysis of prognostic factors for esophageal cancer. Results of univariate analysis showed that gender, neoadjuvant therapy, surgical margin, pT staging, pN staging by JES, pN staging by UICC, TNM staging by JES, TNM staging by UICC were related factors influencing prognosis of 233 patients with esophageal cancer ( χ2=6.62, 17.81, 32.95, 37.93, 27.06, 35.56, 45.24, 37.84, P<0.05). Results of multivariate analysis showed that gender, surgical margin, TNM staging by JES were independent factors influencing prognosis of 233 patients with esophageal cancer ( hazard ratio=0.48, 1.94, 1.46, 95% confidence intervals as 0.25?0.91, 1.07?3.52, 1.16?1.84, P<0.05). Conclusions:The incidence of esophageal cancer is relatively high in males, with the onset age mainly distribute in 60?69 years and the mainly pathological type as squamous carcinoma. Patients with esophageal cancer have advanced tumor staging, low proportion of neoadjuvant therapy, high R 0 resection rate of surgical treatment. Gender, surgical margin, TNM staging by JES are independent factors influencing prognosis of patients with esophageal cancer.

BACKGROUND: Video assisted thoracic surgery (VATS) is the main surgical method for lung cancer. The aim of this study was to analyze the reasons for conversion to thoracotomy in 83 cases among 1,350 consecutive cases who underwent video-assisted thoracic surgery (VATS) lobectomy by a single surgical team, in order to achieve a deeper understanding of the rules and the opportunity for conversion to thoracotomy in VATS lobectomy under normal conditions. METHODS: The clinical data of 1,350 patients who underwent VATS lobectomy between September 21, 2009 and June 1, 2020, by a single surgical team in the Fifth Department of Thoracic Surgery of the Fourth Hospital of Hebei Medical University were retrospectively analyzed. There were 773 males and 577 females, aged 8-87 years, with a median age of 61.3 years, including 83 cases of benign diseases, 38 cases of lung metastases, and 1,229 cases of primary lung cancer. The cases with stage I, II and IIIa were 676, 323 and 230, respectively. The cases of left upper, left lower, right upper, right middle, right lower, right middle and upper and right middle and lower lobectomy were 301 (22.30%), 231 (17.11%), 378 (28.00%), 119 (8.81%), 262 (19.41%), 16 (1.19%) and 43 (3.19%), respectively. RESULTS: In the cohort of 1,350 consecutive patients with VATS lobectomy, 83 patients (6.15%) were converted to thoracotomy for different reasons. The conversion rate of benign lesions was significantly higher than that of malignant tumors (P<0.05). The conversion rate in stage IIIa was significantly higher than that in stage I and II (P<0.05). The conversion rate of combined lobectomy was significantly higher than that of single lobectomy (P=0.001). The conversion rate of left upper lobectomy was significantly higher than that of other single lobectomy (P<0.001). The conversion rate of right middle lobectomy was significantly lower than that of other single lobectomy (P=0.049). The main reasons for conversion were vascular injury (38.55%), lymph node interference (26.51%) and dense adhesion in thoracic cavity (16.87%). In the conversion group, the total operation time was (236.99±66.50) min and the total blood loss was (395.85±306.38) mL. The operation time in patients converted to thoracotomy due to lymph node interference was (322.50±22.68) min, which was significantly longer than that in the other groups (P<0.05). The intraoperative blood loss in patients converted to thoracotomy due to vascular injury was (560.94±361.84) mL, which was significantly higher than that in the other groups (P<0.05). With the increase in surgical experience, the number of vascular injuries gradually decreased at the early stage, mid-stage and late stage (P=0.045). CONCLUSIONS In VATS lobectomy, benign lung lesions and more advanced malignant tumors led to more surgical difficulties and higher conversion rate. The conversion rate was different in different lobectomy sites, with the highest in left upper lobectomy, and the lowest in right middle lobectomy. Vascular injury, lymph node interference and dense adhesion were the main reasons for conversion to thoracotomy, which led to prolonged operation time and increased blood loss. With the increasing number of surgical cases, the rate of conversion to thoracotomy in VATS lobectomy continues to decline, which may be mainly due to the more advanced treatment of pulmonary vessels.