Recent advances in the application of Mendelian randomization to chronic kidney disease.

OBJECTIVE: Chronic kidney disease (CKD) is a condition influenced by both genetic and environmental factors and has been a focus of extensive research. Utilizing Mendelian randomization, researchers have begun to untangle the complex causal relationships underlying CKD. This review delves into the advances and challenges in the application of MR in the field of nephrology, shifting from a mere summary of its principles and limitations to a more nuanced exploration of its contributions to our understanding of CKD. METHODS: Key findings from recent studies have been pivotal in reshaping our comprehension of CKD. Notably, evidence indicates that elevated testosterone levels may impair renal function, while higher sex hormone-binding globulin (SHBG) levels appear to be protective, predominantly in men. Surprisingly, variations in plasma glucose and glycated hemoglobin levels seem unaffected by genetically induced changes in the estimated glomerular filtration rate (eGFR), suggesting an independent pathway for renal function impairment. RESULTS: Furthermore, lifestyle factors such as physical activity and socioeconomic status emerge as significant influencers of CKD risk and kidney health. The relationship between sleep duration and CKD is nuanced; short sleep duration is linked to increased risk, while long sleep duration does not exhibit a clear causal effect. Additionally, lifestyle factors, including diet, exercise, and mental wellness activities, play a crucial role in kidney health. New insights also reveal a substantial causal connection between both central and general obesity and CKD onset, while no significant links were found between genetically modified LDL cholesterol or triglyceride levels and kidney function. CONCLUSION: This review not only presents the recent achievements of MR in CKD research but also illuminates the path forwards, underscoring critical unanswered questions and proposing future research directions in this dynamic field.

A New Risk Factor for Cervical Anastomotic Leakage-Role of The Relative Gastric Length in the Surgical Treatment of Esophageal Cancer.

BACKGROUND: Blood supply is especially weak near the gastric fundus. Making the anastomosis in this area would increase the risk of anastomotic leakage (AL). In cervical anastomosis, the gastric conduit needs to travel through the thorax. Therefore, the relative length between the stomach and the thorax is an essential factor in deciding if the poorly supplied area could be removed. This study was to explore if a small relative gastric length was a risk of cervical AL. If all other conditions are equal, could intrathoracic anastomosis be a better choice? METHODS: Patients who underwent esophagectomy with a preoperative barium swallow in West China Hospital between 2014 and 2017 were included. The length of the greater curvature and the thorax were obtained from the barium esophagogram. The ratio between the length of the greater curvature and the thorax was the relative gastric length calculated from the greater curvature (RGL-G). RESULTS: A total of 782 patients were enrolled in the final analysis. The cervical AL group had a significantly higher ratio of patients with an RGL-G less than 1.3 (26.7% vs. 8.9%, p = 0.003). The multivariate logistic regression proved that RGL-G less than 1.3 was a risk factor for cervical anastomotic leakage (p = 0.012). Correspondingly, RGL-G less than 1.3 was not a risk factor (6.3% vs. 14.3%, p = 0.289) in the intrathoracic anastomosis group. CONCLUSIONS: RGL-G less than 1.3 was a new risk factor for cervical AL, but it would not be a problem for intrathoracic anastomosis.

Safety profile of preoperative administration of low-molecular-weight heparin on minimally invasive lung cancer surgery: a randomized controlled trial.

BACKGROUND: Venous thromboembolism remains a common but preventable complication for cancerous lung surgical patients. Current guidelines recommend thromboprophylaxis for lung patients at high risk of thrombosis, while a consensus about specific administration time is not reached. This study was designed to investigate the safety profile of preoperative administration of low-molecular-weight-heparin (LMWH) for lung cancer patients. METHODS: From July 2017 to June 2018, patients prepared to undergo lung cancer surgery were randomly divided into the preoperative LMWH-administration group (PRL) for 4000 IU per day and the postoperative LMWH-administration group (POL) with same dosage, all the patients received thromboprophylaxis until discharge. Baseline characteristics including demographics and preoperative coagulation parameters were analyzed, while the endpoints included postoperative coagulation parameters, postoperative drainage data, hematologic data, intraoperative bleeding volume and reoperation rate. RESULTS: A total of 246 patients were collected in this RCT, 34 patients were excluded according to exclusion criterion, 101 patients were assigned to PRL group and 111 patients belonged to POL group for analysis finally. The baseline characteristic and preoperative coagulation parameters were all comparable except the PRL group cost more operation time (p = 0.008) and preoperative administration duration was significantly longer (p < 0.001). The endpoints including postoperative day 1 coagulation parameters, mean and total drainage volume, drainage duration, intraoperative bleeding volume and reoperation rate were all similar between the two groups. Moreover, coagulation parameters for postoperative day 3 between the two groups demonstrated no difference. CONCLUSION: Preoperative administration of low-molecular-weight-heparin demonstrated safety and feasibility for lung cancer patients intended to receive minimally invasive surgery. TRIAL REGISTRATION: ChiCTR2000040547 ( www.chictr.org.cn ), 2020/12/1, retrospectively registered.

[Three Dimensional Measurement of the Space Distance Between the Hilum and Clinical Stage T 1 Non-small Cell Lung Cancer and Its Relationship with Lymph Node Metastasis].

OBJECTIVE: The aim of this study was to develop a novel method to quantitatively define the tumor location of clinical stage T 1 (cT 1) non-small cell lung cancer (NSCLC) and to evaluate its impact on lymph node metastasis in a large cohort group. METHODS: We developed a novel method to transform the datum of 2D CT scans to 3D datum and to quantitatively measure the distance between the tumor and hilum through the Pythagorean theorem. Multiple logistic regression analysis was applied to identify the risk factors associated with lymph node metastasis. RESULTS: A total of 399 patients (166 male and 233 female) with cT 1 NSCLC were enrolled in this study. The mean age was (57.48±10.88) yr., the mean distance between tumor and hilum was (5.44±1.96) cm, and the mean tumor diameter was (1.77±0.65) cm. Patients were divided into lymph node positive group (N + group) and lymph node negative group (N － group). By multiple logistic regression analysis, we identified 4 risk variables associated with lymph node metastasis. Gender (odds ratio ( OR)=2.118， P=0.022), distance between tumor and hilum ( OR=0.843， P=0.040), differentiation (moderate vs. high， OR=15.547， P=0.008；poor vs. high， OR=70.749， P=0.000), and cancer embolus ( OR=24.769， P=0.004) were independent risk variables associated with lymph node metastasis. CONCLUSION: Distance between tumor and hilum was identified as an independent risk factor associated with lymph node metastasis in cT 1 NSCLC.

Lung Adenocarcinoma has a Higher Risk of Lymph Node Metastasis than Squamous Cell Carcinoma: A Propensity Score-Matched Analysis.

BACKGROUND: Controversy still exists in which subtype of non-small-cell lung cancer [squamous cell carcinoma (SCC) or adenocarcinoma] is more likely to have lymph node (LN) metastasis. The aim of this study is to compare the pattern of LN metastasis in two cohorts of matched patients surgically treated for SCC or adenocarcinoma. METHODS: A retrospective analysis of patients undergoing lobectomy or segmentectomy with systematic lymphadenectomy without preoperative treatment for lung SCC or adenocarcinoma was conducted in this study. Data for analysis consisted of age, gender, tumor size, lobe-specific tumor location, tumor location (peripheral or central), and pathologic findings. We conducted the propensity score-matched (PSM) analysis to eliminate potential bias effects of possible confounding factors. RESULTS: From January 2015 to December 2016 in our department, we finally included a total of 387 patients (including 63 patients with SCC and 324 patients with adenocarcinoma) for analysis. For the unmatched cohort, there was no sufficient evidence of significantly different number of positive LNs (P = 0.90) and rate of LN metastasis (P = 0.23) between SCC patients and adenocarcinoma patients. However, potential confounding factors, for example gender, tumor size, tumor location, tumor differentiation, and total number of dissected LNs, were significantly different between patients with SCC and those with adenocarcinoma. In the analysis of matched cohort after PSM analysis, those above confounding factors were comparable between the two groups. However, patients with adenocarcinoma had significantly more mean positive LNs (2.2 and 0.7; P = 0.008) and a higher rate of LN metastasis (53% and 29%; P = 0.016) than those with SCC. CONCLUSIONS: Lung adenocarcinoma had a higher risk of LN metastasis than SCC, suggesting that different therapeutic modalities may be indicated for the two different subtypes of lung cancer.

The Role of Surgery in Treating Resectable Limited Disease of Esophageal Neuroendocrine Carcinoma.

BACKGROUND: Esophageal neuroendocrine carcinoma (NEC) is a rare malignant tumor. The role of surgery in resectable limited disease of esophageal NEC remains unclear. How to select a specific group of limited disease of esophageal NEC who might benefit from surgery remains to be answered. METHODS: Patients undergoing esophagectomy for resectable limited disease of esophageal NEC in our department from January 2007 to June 2015 were analyzed. TNM staging system was applied to describe those patients, and according to their different long-term prognosis after surgery, those patients were subgrouped into surgery response limited disease (SRLD) group and surgery non-response limited disease (SNRLD) group. Both univariate and multivariate analyses were applied to identify potential prognostic factors. RESULTS: A total of 72 patients with resectable limited disease of esophageal NEC were identified for analysis. The median survival time of those patients was 21.5 months. There was no significant survival differences among stage I, stage IIA, and stage IIB patients, but all these patients had significantly longer survival than stage III patients. Therefore, stage I, stage IIA, and stage IIB patients were aggregated together as SRLD group, and stage III patients were aggregated as SNRLD group. SRLD patients obtained significantly longer survival than SNRLD patients in both univariate analysis and multivariate analysis. Moreover, adjuvant therapy could significantly benefit SRLD patients (P = 0.004) but could not benefit SNRLD patients (P = 0.136). CONCLUSIONS: Different responses to surgery existed in resectable limited disease of esophageal NEC indicating the need of further subgrouping for those patients. The resectable limited disease of esophageal NEC could be further subgrouped into SRLD group and SNRLD group according to the TNM staging system.

[Diagnosis and Surgical Treatment of Lung Ground-glass Opacities:a Review of 663 Cases].

OBJECTIVES: To retrospectively investigate the clinical characteristics, surgical treatments of the patients with lung ground-glass opacities (GGO). METHODS: All the patients, who underwent surgical resection of GGO in our department from Jan. 2013 to Dec. 2016 were retrospectively reviewed. The clinicpathological features were analyzed. RESULTS: A total of 663 patients were included in this study. The rate of malignancy was 92.6% (614/663). The diameter of GGO in benign group [(0.8±0.2) cm] was significant smaller than that in malignant group [ (1.5±0.8) cm](P<0.001). The rate of irregular margin in malignant group was far higher than that in benign group (93.8% vs. 20.4%, P<0.001), but other CT signs such as vacuole sign, plural retraction, speculation and lobulation did not show significant difference between the two groups. A total of 652 (98.3%) cases were resected by video-assisted thoracoscopic surgery (VATS), and only 11 (1.7%) cases were resected by thoracotomy. A total of 336 (50.7%) patients underwent lobectomy, 226 (34.1%) underwent segmentectomy and 101 (15.2%) undewent wedge resection. The rate of surgery-related complications was 9.0% (60/663), and one (0.2%) patient died. CONCLUSIONS: With careful selection of GGO by experienced surgeons, the rate of malignancy is very high. Surgical resection may be recommended for highly suspected malignant cases. Sublobar resection or lobcotomy by VATS can achieve good treatment effect.

A novel derivative of tetrandrine (H1) induces endoplasmic reticulum stress-mediated apoptosis and prosurvival autophagy in human non-small cell lung cancer cells.

H1, a bromized derivative of tetrandrine, has been reported to induce apoptosis in human cancer cells. But, the underlying mechanism of apoptosis triggered by H1 is unclear. In the present study, we found that H1 triggered death receptor 5 (DR5)-dependent apoptosis in non-small cell lung cancer (NSCLC) cells. Further study showed that H1 activated ER stress through enforcing the expression of Bip/GRP78, IRE1α, p-eIF2α, and CHOP. Moreover, abrogating CHOP expression blocked DR5 upregulation and subsequent apoptosis, indicating that CHOP was essential for DR5-dependent apoptosis induced by H1. In addition, H1 greatly downregulated cellular FLICE-inhibitory protein (c-FLIP), and enhanced expression of c-FLIP protected cancer cells from apoptosis in spite of H1 therapy. Furthermore, we discovered that H1 induced autophagy in human NSCLC cells. Interestingly, the autophagy induced by H1 played a protective function in NSCLC cells and effectively weakened caspase-mediated apoptosis. In summary, these findings suggest that H1 induces DR5-dependent apoptosis in human NSCLC cells via stimulating ER stress signaling pathway, and pharmacologically inhibiting autophagy will be an efficient approach to synergize H1-caused apoptosis in lung cancer cells.

[Long term outcomes of patients with stage I lung cancer treated by single-direction video-assisted thoracoscopic surgery lobectomy or segmentectomy].

OBJECTIVE: To observe the outcome of stage I lung cancer treated by single-direction video-assisted thoracoscopic surgery (SD-VATS) major lung resection. METHODS: Between May 2006 and December 2013, a total of 3 743 patients with lung cancer underwent surgical treatment in Department of Thoracic Surgery, West China Hospital. The clinical date of 783 patients with stage I lung cancer treated by SD-VATS lobectomy/segmentectomy was analyzed retrospectively. There were 388 males and 395 females with a mean age of (59 ± 10) years (range 25 to 86 years). There were 740 cases of lobectomy and 43 cases of segmentectomy. Twenty patients underwent conversion to open thoracotomy. The methods of Kaplan-Meier survival analysis and Cox proportional hazard regression model were used to investigate the long term outcome and prognostic factors. RESULTS: The mean operating time was (145 ± 54) minutes (range 70 to 460 minutes). The median intraoperative blood loss was 50 (70) ml (range 5 to 1 200 ml). The postoperative morbidity and 90-day mortality were 13.3% and 1.0%, respectively. 5.9% patients were lost to follow-up. Finally 730 patients were enrolled into prognostic analysis with a mean follow-up time of (37 ± 18) months (range 5 to 92 months). The 5-year overall survival (OS), disease free survival (DFS), and cancer specific survival (CSS) were 83.8%, 74.4%, and 86.6%, respectively. The 5-year OS of IA and IB were 90.7% and 79.8% respectively. Univariate and multivariate analysis indicated that age ≥ 60 years (OR = 1.786, 95% CI: 1.081 to 2.948, P = 0.023), non-adenocarcinoma (OR = 1.647, 95% CI: 1.204 to 2.253, P = 0.002), and higher T status (OR = 2.709, 95% CI: 1.031 to 7.121, P = 0.043) were independently associated with poor OS; higher T status (OR = 5.118, 95% CI: 2.330 to 11.240, P = 0.000) and higher pathological stage status (OR = 0.369, 95% CI: 0.137 to 0.991, P = 0.048) were independently associated with poor DFS; non-adenocarcinoma (OR = 1.717, 95% CI: 1.224 to 2.409, P = 0.002) and higher T status (OR = 5.029, 95% CI: 1.432 to 17.659, P = 0.012) were independently associated with poor CSS. CONCLUSION: SD-VATS lung cancer resection is a safe and feasible method for the treatment of stage I lung cancer resulting good outcomes.

Management of thoracic esophageal perforation.

BACKGROUND: The aim of this study was to characterize an optimal strategy in managing thoracic esophageal perforation, focusing on the differential diagnosis and treatment of patients with contained versus noncontained perforations and on the importance of the time interval between injury and repair and how that affects the outcome of a primary repair. METHODS: A retrospective study was conducted. A strict definition of contained or noncontained perforation was based on a combination of esophagography, chest CT scan, and endoscopy as well as monitoring systemic symptoms. Management options for our cohort included conservative therapy, primary repair and debridement, esophagectomy, and mesh-covered stents. Patients were stratified into two groups according to the time interval after injury: ≤ 48-h group and >48-h group. RESULTS: Between January 1997 and January 2013, a total of 66 consecutive patients (47 males and 19 females, mean age = 49.1 ± 16.2 years) were treated for thoracic esophageal perforation. Perforation was confirmed by esophagography in 51 patients and by endoscopy in 15 patients. Eighteen patients were assigned to the contained perforation group. All these patients were successfully cured without surgery. The noncontained group included 48 patients; its mortality rate was 7.7 % (3/39) with surgery and 55.6 % (5/9) with stent placement. Compared with the contained group, the noncontained group had a significantly longer length of stay (LOS) (16 ± 3.2 vs. 26.3 ± 18.7 days; p < 0.05) and a higher mortality rate (0 vs. 22.9 %, p < 0.05). In the two time-interval groups, patient characteristics, including age, gender, and comorbidities, etiologic cause, length and location of the perforation, and the incidence of using tissue buttress were similar (p > 0.05). The incidence of postoperative leak was significantly higher in >48-h group (0 in ≤ 48-h group vs. 37.5 % in >48-h group; p < 0.01). In addition, the >48-h group had a significantly longer LOS (18.0 ± 9.1 days in ≤ 48-h group vs. 31.5 ± 18.6 days in >48-h group; p < 0.01). The two deaths occurred in the >48-h group (0 in ≤ 48-h group vs. 12.5 % in >48-h group; p > 0.05) due to postoperative leaks. CONCLUSIONS: Contained or noncontained perforation should be rigorously differentiated. Then, for a contained perforation, conservative therapy coupled with repeated imaging is reasonable treatment. For a noncontained perforation, a primary repair can be safely performed within 48 h after injury. After that, a primary repair is still reasonable but is associated with an increased risk of postoperative leaks.

Comparison of B cells' immune response induced by PEDV virulent and attenuated strains.

Porcine epidemic diarrhea virus (PEDV) is an acute, highly contagious enterovirus that infects pigs of all ages. The B cells are important for antigen presentation, antibody production, and cytokine secretion to resist infection. However, the role of B cells in PEDV infection remains unclear. In this study, the effects of PEDV virulent (QY2016) and attenuated strains (CV777) on B cells sorted from neonatal piglets, nursery piglets, and gilts were investigated. The results showed that PEDV-QY2016 and PEDV-CV777 could significantly increase the expression of CD54 and CD27 in B cells from neonatal piglets. The percentages of CD80, MHC II, and IgM expressed on neonatal piglet B cells infected with PEDV-QY2016 were significantly lower than those expressed on the B cells infected with PEDV-CV777. Both PEDV-QY2016 and PEDV-CV777 could stimulate IFN-α and GM-CSF secretions in neonatal piglet B cells; IL-1, IFN-α, and IL-4 secretion in nursery piglet B cells; and IL-1, TGF-ß secretion, and GM-CSF in gilt B cells. Furthermore, both PEDV-QY2016 and PEDV-CV777 could induce the secretion of IgA, IgM, and IgG in nursery piglet B cells but could not induce the secretion of IgA, IgM, and IgG in neonatal piglet B cells. The secretion of IgA, IgM, and IgG was significantly higher by the PEDV-CV777 strains infected B cells than those by the PEDV-QY2016 strains infected gilt B cells. In conclusion, the surface molecule expression, cytokine secretion, and antibody production of B cells induced by PEDV are closely related to the ages of pigs and the virulence of the PEDV strain.

Effects of porcine epidemic diarrhea virus infection on CD21+ B cells activation.

Porcine epidemic diarrhea virus (PEDV) is a devastating pathogen of acute- gastrointestinal infectious diseases, which can cause vomiting, diarrhea, dehydration and high morbidity and mortality among neonatal piglets. Humoral immunity plays a vital role in the host anti-PEDV infection process, but the mechanism of PEDV-induced B-cell immune response remains unknown. In this study, the effects of PEDV infection on CD21+ B cell activation were systematically analyzed through animal experiments. Enzyme-linked immunosorbent assays (ELISA) revealed that low levels of serum-specific IgA, IgM, or IgG were detected in piglets after PEDV infection, respectively. Serum interleukin (IL)-6 levels increased significantly at 4 d after infection, and the levels of IL-4, B-cell activating factor (BAFF), interferon (IFN)-γ, transforming growth factor (TGF)-ß and IL-10 decreased at 7 d after infection. Fluorescence-activated cell sorting (FACS) showed that expression levels of CD21, MHC Ⅱ, CD40, and CD38 on B cell surfaces were significantly higher. In contrast, the proportions of CD21+IgM+ B cells were decreased in peripheral blood mononuclear cells (PBMCs) from the infected piglets. No differences were found in the percentage of CD21+CD80+ and CD21+CD27+ B cells in PBMCs from the infected piglets. In addition, the number of CD21+B cells in PBMCs stimulated with PEDV in vitro was significantly lower. No significant change in the mRNA expression of BCR molecules was found while the expression levels of paired immunoglobulin-like receptor B (PIR-B), B cell adaptor molecule of 32 kDa (Bam32) and BAFF were decreased. In conclusion, our research demonstrates that virulent strains of PEDV profoundly impact B cell activation, leading to alterations in phenotypic expression and BCR signaling molecules. Furthermore, this dysregulation results in compromised specific antibody secretion and perturbed cytokine production, highlighting the intricate immunological dysfunctions induced by PEDV infection.

[Length of operation with video-assisted thoracoscopic lobectomy].

OBJECTIVE: To determine the duration of the resection of pulmonary lobe (RPL) and the effect of video-assisted thoracoscopic surgery (VATS) procedure on the duration of RPL. METHODS: The records of 126 patients who had VATS lobectomy from October 2009 to October 2010 with a single-direction thoracoscopic procedure in one hospital were reviewed. RESULTS: The patients included 65 (52%) men and 61 (48%) women with a mean age of 56 years (range, 15 years to 82 years). Four cases were excluded because of intraoperative complication. The average length of operation of RPL in the 122 patients without intraoperative complications was 38.98 min +/- 13.243 min (range, 17 min to 100 min), and the average length of the entire operation was 153.36 min +/- 39.64 min (range, 70 min to 245 min). Regardless which lobes, the average length of a single RPL remained the same (P > 0.05). The RPL of bilobectomies took longer than a single lobectomy (P < 0.05). However, no significant differences in the length of the entire operations were found between bilobectomy and single lobectomy (P > 0.05). CONCLUSION: The length of RPL reflects the difficulties of the core step of thoracoscopic lobectomy. Single-direction thoracoscopic lobectomy is an easy procedure to manipulate.

[Safety and technical feasibility of single-direction VATS lobectomy: a review of 1040 cases].

OBJECTIVE: To evaluate the safety and technical feasibility of single-direction video-assisted thoracoscopic lobectomy for patients with pulmonary diseases. METHODS: From May 2006 to Sep 2012, 1040 patients with pulmonary diseases were treated by single-direction video-assisted thoracoscopic lobectomy. These included 565 men (54.3%) and 475 women (45.7%), with a mean age of (56.3 +/- 13.2) years. The patients suffered from lung cancer (800), benign disease (205), pulmonary metastases (34), and lymphoma (1). Their perioperative data were collected and reviewed. RESULTS: Of the 1040 patients, 7 died (0.67%); 18 (1.73%) were converted to open surgery; 134 had postoperative complications (12.88%). The patients underwent an average of (169 +/- 64) min operations, lost an average of (93 +/- 113) mL (range, 5-935 mL) blood, had an average of (3.3 +/- 1.9) cm (range, 1.2-12 cm) diameters of mass removed and an average (15.8 +/- 7.7) (range, 5-52) lymph nodes dissected. The patients had an average of (3.8 +/- 2.6) days (range, 1-16 days) drainage during an average of (7.0 +/- 2.8) days (range, 4-19 days) postoperative hospital stay. CONCLUSION: Single-direction thoracoscopic lobectomy is a safe and feasible surgical procedure in the treatment of pulmonary diseases.

[Immune functions of patients following lobectomy for lung cancers: a comparative study between video-assisted thoracoscopic surgery and posterolateral thoracotomy].

OBJECTIVE: To compare acute inflammatory responses and immunosuppression to lobectomy in lung cancer patients with video-assisted thoracoscopic surgery (VATS) and posterolateral thoracotomy (PLT). METHODS: A total of 103 patients who underwent either a VATS (n = 51) or a PLT (n = 52) lobectomy for early non-small cell lung cancers (NSCLC, stage I ) were recruited for this study. Blood samples of the participants were taken preoperatively and at 24 h and 72 h post-operatively for analyses of C-reactive protein (CRP), interleukin (IL)-6, IL-2 receptors (IL-2R), and serum amyloid A (SAA). Blood samples taken pre-operatively and at 2 d and 7 d post operations were also analyzed for total lymphocytes, NK cells, CD4+ T, and CD8+ T. RESULTS: Patients in the VATS group lost significantly less blood than those in the PLT group (P = 0.001). Patients in the PLT group had significantly higher serum SAA than those in the VATS group (P = 0. 006). Significant reduction of CD8+ T was found in the patients with PLT after operations (P < 0.01). Patients in the PLT group had significantly lower at CD8+ T 7 d post operations than those in the VATS group (P = 0.015). CONCLUSION: VATS pulmonary lobectomy is associated with reduced acute inflammatory responses and immunosuppression compared with the PLT approach.

Screening and identification of CNIH4 gene associated with cell proliferation in gastric cancer based on a large-scale CRISPR-Cas9 screening database DepMap.

BACKGROUND: Gastric cancer is a common malignant tumor of digestive tract. The study aimed to identify candidate genes associated with the proliferation and survival of gastric cancer cell through CRISPR-cas9 screening data, which may provide new therapeutic targets for gastric cancer patients. METHODS: Candidate genes related to gastric cancer cell viability by CRISPR-cas9 screening from Depmap and genes differentially expressed between gastric cancer tissues and normal gastric tissues from TCGA were overlapped. WGCNA and KEGG analysis was conducted to performed to identify key pathways and genes. Using CMap, we identified small molecules that might reverse candidate gene expression of gastric cancer. LASSO regression was used to construct a signature to predict overall survival of gastric cancer patients. CCK8 assay was performed to assess the effects of candidate gene on gastric cancer cell proliferation. RESULTS: A total of 710 candidate genes related to gastric cancer cell viability in the DepMap were identified and overlapped with differentially expressed genes in TCGA database, which were enriched in the cell cycle pathway. CMap analysis suggested that molecule drug LY294002 might be a novel choice for gastric cancer treatment. Using Cox univariate analysis and Lasso analysis, we developed a prognostic model including 12 candidate genes, and conducted subgroup analysis and external validation. Moreover, knockdown of the key candidate gene CNIH4 inhibited the proliferation of gastric cancer cells. CONCLUSION: Cell cycle pathway and CNIH4, identified by CRISPR-cas9 screening, were a key pathway and gene that regulate cell viability in gastric cancer. CNIH4 has significant prognostic values and can serve as a new target for gastric cancer patient treatment.

Robot-assisted thymectomy in large anterior mediastinal tumors: A comparative study with video-assisted thymectomy and open surgery.

BACKGROUND: The aim of this study was to evaluate the safety and effectiveness of robot-assisted thymectomy (RAT) in large anterior mediastinal tumors (AMTs) (size ≥6 cm) compared with video-assisted thymectomy (VAT) and open surgery. METHODS: A total of 132 patients with large AMTs who underwent surgical resection from January 2016 to June 2022 were included in this study. A total of 61 patients underwent RAT, 36 patients underwent VAT and 35 patients underwent open surgery. Perioperative outcomes were compared. RESULTS: There were no significant differences in tumor size (p = 0.141), or pathological types (p = 0.903). Compared with the open group, the RAT and VAT groups were associated with a shorter operation time (115.00 vs. 160.00, p = 0.012; 122.50 vs. 160.00, p = 0.071), and less blood loss (50.00 vs. 200.00, p < 0.001; 50.00 vs. 200.00, p < 0.001), respectively. The rate of conversion in the RAT group was similar to that in the VAT group (6.56% vs. 13.89%, p = 0.229). Concomitant resection was less frequently performed in the VAT group than in the RAT and open groups (5.56% vs. 31.15%, p = 0.040; 5.56% vs. 31.43%, p = 0.006). VAT patients had a lower drainage volume (365.00 vs. 700.00 and 910.00 mL, p < 0.001), shorter duration of chest tube (2.00 vs. 3.00 and 4.00, p < 0.001), and shorter hospital stay (5.00 vs. 6.00 and 7.00, p < 0.001) than the RAT and open groups. There was no 30-day mortality in any group. No difference was seen in R0 resection rates (p = 0.846). The postoperative complication rates were similar among the three groups (p = 0.309). Total in-hospital costs (66493.90 vs. 33581.05 and 42876.40, p < 0.001) were significantly higher in the RAT group. CONCLUSIONS: RAT is safe and effective for the resection of large AMTs compared to VAT and open surgery. Vascular resection in RAT is technically feasible. A long-term follow-up is required.

Short-term outcomes of enhanced recovery after surgery protocol in robotic-assisted McKeown esophagectomy for esophageal cancer: a single-center retrospective cohort study.

Background: This study aimed to evaluate the short-term outcomes of enhanced recovery after surgery (ERAS) protocol in perioperative robotic-assisted McKeown esophagectomy (RAME) among esophageal cancer patients. Methods: For this retrospective study, all patients who had undergone RAME with esophageal cancer using ERAS protocol and conventional management strategy at the surgery center of our hospital from February 2019 to March 2022 were performed for analysis. Results: A total of 211 patients were included. Compared to the conventional group, the ERAS group has shorter median operative time [207 (147.5-267.5) vs. 244 (183-305), P<0.001], time to first flatus (P<0.001), time to out-of-bed activity (P=0.045), and time to liquid diet (P<0.001). In addition, the ERAS group has lower postoperative pain scores (3.62 ± 0.87 vs. 4.54 ± 0.91), shorter duration of analgesia pump [2 (1-3) vs. 3 (2.5-5.5)], shorter postoperative hospital stay [(9 (6-47) vs. 11 (6-79)], shorter postoperative hospital stay within neoadjuvant treated patients [8 (7-43) vs. 13 (8-67], shorter postoperative ICU stay [1 (0-7) vs. 2 (0-15)], and less reoperation rate (7.6% vs. 16.8%). Furthermore, the overall complication rate was significantly lower in the ERAS group (26.1%) than in the conventional group (50.4%). Notably, the ERAS group had lower thoracic fluid drainage volume than the conventional group on postoperative 2-7 days (P<0.05). Conclusions: The application of ERAS protocol in esophageal cancer patients treated with RAME showed advantages of quick postoperative recovery in contrast to the conventional management strategy.

Role of Lower Esophageal Squamous Cell Carcinoma Margin Location on Abdominal Lymph Node Metastasis Risk.

BACKGROUND: Different sites of esophageal cancer are accompanied by different regional lymph node metastasis (LNM) risks. We aimed to investigate the impact of a lower tumor margin on abdominal LNM risk. METHODS: We enrolled patients who underwent esophagectomy for esophageal squamous carcinoma (ESCC) from 2014 to 2017 in West China Hospital. Overall survival (OS) analysis was performed. We measured the distance between the lower tumor margin and esophagogastric junction (LED) with upper gastrointestinal contrast-enhanced X-ray (UGCXR). Multivariate logistic regression analysis and propensity score matching (PSM) were performed to explore the relationship between LED and the risk of abdominal LNM. Abdominal LNM risk in ESCC was stratified based on the location of the lower tumor margin. A model predicting abdominal LNM risk was constructed and presented with a nomogram. RESULTS: The included patients had an abdominal LNM rate of 48.29%. In multivariate logistic regression analysis, LED was identified as a risk factor for abdominal LNM. Subgroup analysis of middle ESCC showed that patients with an LED less than 10 cm had a significantly higher rate of abdominal LNM than those with an LED greater than 10 cm. The abdominal LNM rate in middle ESCC patients with an LED less than 10 cm was 32.2%, while it was 35.1% in lower ESCC patients whose lower tumor margin did not invade the esophagogastric junction (EGJ), which was comparable after PSM. CONCLUSIONS: LED could help surgeons evaluate the risk of abdominal LNM preoperatively and better guide dissection of abdominal lymph nodes according to risk level.

Survival analysis and nomogram for pulmonary sarcomatoid carcinoma: an SEER analysis and external validation.

OBJECTIVE: Uncommon and particularly deadly, pulmonary sarcomatoid carcinoma (PSC) is an aggressive type of lung cancer. This research aimed to create a risk categorisation and nomogram to forecast the overall survival (OS) of patients with PSC. METHODS: To develop the model, 899 patients with PSC were taken from the Surveillance, Epidemiology, and End Results database from the USA. We also used an exterior verification sample of 34 individuals with PSC from Fujian Provincial Hospital in China. The Cox regression hazards model and stepwise regression analysis were done to screen factors in developing a nomogram. The nomogram's ability to discriminate was measured employing the area under a time-dependent receiver operating characteristic curve (AUC), the concordance index (C-index) and the calibration curve. Decision curve analysis (DCA) and integrated discrimination improvement (IDI) were used to evaluate the nomogram to the tumour-node-metastasis categorisation developed by the American Joint Committee on Cancer (AJCC-TNM), eighth edition, and an additional sample confirmed the nomogram's accuracy. We further developed a risk assessment system based on nomogram scores. RESULTS: Six independent variables, age, sex, primary tumour site, pathological group, tumour-node-metastasis (TNM) clinical stage and therapeutic technique, were chosen to form the nomogram's basis. The nomogram indicated good discriminative ability with the C-index (0.763 in the training cohort and 0.746 in the external validation cohort) and time-dependent AUC. Calibration plots demonstrated high congruence between the prediction model and real-world evidence in both the validation and training cohorts. Nomogram outperformed the AJCC-TNM eighth edition classification in both DCA and IDI. Patients were classified into subgroups according to their risk ratings, and significant differences in OS were observed between them (p<0.001). CONCLUSION: We conducted a survival analysis and nomogram for PSC. This developed nomogram holds potential to serve as an efficient tool for clinicians in prognostic modelling.