Validity of stem cell-loaded scaffolds to facilitate endometrial regeneration and restore fertility: a systematic review and meta-analysis.

Objective: Various stem cell-loaded scaffolds have demonstrated promising endometrial regeneration and fertility restoration. This study aimed to evaluate the efficacy of stem cell-loaded scaffolds in treating uterine injury in animal models. Methods: The PubMed, Embase, Scopus, and Web of Science databases were systematically searched. Data were extracted and analyzed using Review Manager version 5.4. Improvements in endometrial thickness, endometrial glands, fibrotic area, and number of gestational sacs/implanted embryos were compared after transplantation in the stem cell-loaded scaffolds and scaffold-only group. The standardized mean difference (SMD) and confidence interval (CI) were calculated using forest plots. Results: Thirteen studies qualified for meta-analysis. Overall, compared to the scaffold groups, stem cell-loaded scaffolds significantly increased endometrial thickness (SMD = 1.99, 95% CI: 1.54 to 2.44, P < 0.00001; I² = 16%) and the number of endometrial glands (SMD = 1.93, 95% CI: 1.45 to 2.41, P < 0.00001; I² = 0). Moreover, stem cell-loaded scaffolds present a prominent effect on improving fibrosis area (SMD = -2.50, 95% CI: -3.07 to -1.93, P < 0.00001; I² = 36%) and fertility (SMD = 3.34, 95% CI: 1.58 to 5.09, P = 0.0002; I² = 83%). Significant heterogeneity among studies was observed, and further subgroup and sensitivity analyses identified the source of heterogeneity. Moreover, stem cell-loaded scaffolds exhibited lower inflammation levels and higher angiogenesis, and cell proliferation after transplantation. Conclusion: The evidence indicates that stem cell-loaded scaffolds were more effective in promoting endometrial repair and restoring fertility than the scaffold-only groups. The limitations of the small sample sizes should be considered when interpreting the results. Thus, larger animal studies and clinical trials are needed for further investigation. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO, identifier CRD42024493132.

T2-weighted imaging-based radiomic-clinical machine learning model for predicting the differentiation of colorectal adenocarcinoma.

BACKGROUND: The study on predicting the differentiation grade of colorectal cancer (CRC) based on magnetic resonance imaging (MRI) has not been reported yet. Developing a non-invasive model to predict the differentiation grade of CRC is of great value. AIM: To develop and validate machine learning-based models for predicting the differentiation grade of CRC based on T2-weighted images (T2WI). METHODS: We retrospectively collected the preoperative imaging and clinical data of 315 patients with CRC who underwent surgery from March 2018 to July 2023. Patients were randomly assigned to a training cohort (n = 220) or a validation cohort (n = 95) at a 7:3 ratio. Lesions were delineated layer by layer on high-resolution T2WI. Least absolute shrinkage and selection operator regression was applied to screen for radiomic features. Radiomics and clinical models were constructed using the multilayer perceptron (MLP) algorithm. These radiomic features and clinically relevant variables (selected based on a significance level of P < 0.05 in the training set) were used to construct radiomics-clinical models. The performance of the three models (clinical, radiomic, and radiomic-clinical model) were evaluated using the area under the curve (AUC), calibration curve and decision curve analysis (DCA). RESULTS: After feature selection, eight radiomic features were retained from the initial 1781 features to construct the radiomic model. Eight different classifiers, including logistic regression, support vector machine, k-nearest neighbours, random forest, extreme trees, extreme gradient boosting, light gradient boosting machine, and MLP, were used to construct the model, with MLP demonstrating the best diagnostic performance. The AUC of the radiomic-clinical model was 0.862 (95%CI: 0.796-0.927) in the training cohort and 0.761 (95%CI: 0.635-0.887) in the validation cohort. The AUC for the radiomic model was 0.796 (95%CI: 0.723-0.869) in the training cohort and 0.735 (95%CI: 0.604-0.866) in the validation cohort. The clinical model achieved an AUC of 0.751 (95%CI: 0.661-0.842) in the training cohort and 0.676 (95%CI: 0.525-0.827) in the validation cohort. All three models demonstrated good accuracy. In the training cohort, the AUC of the radiomic-clinical model was significantly greater than that of the clinical model (P = 0.005) and the radiomic model (P = 0.016). DCA confirmed the clinical practicality of incorporating radiomic features into the diagnostic process. CONCLUSION: In this study, we successfully developed and validated a T2WI-based machine learning model as an auxiliary tool for the preoperative differentiation between well/moderately and poorly differentiated CRC. This novel approach may assist clinicians in personalizing treatment strategies for patients and improving treatment efficacy.

Diagnostic Significance of DCE-MRI-Related Quantitative Parameters for Nasal Cavity and Sinus Tumors.

Objective: Our aim was to explore the diagnostic value of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI)-related quantitative parameters for benign and malignant nasal cavity and sinus tumors. Methods: A total of 78 patients with nasal sinus tumors admitted to People's Hospital of Qingdao Chengyang District in China were enrolled in our study, Of the patients, 41 were diagnosed as having benign tumors and 37 as having malignant tumors by pathological diagnosis. All patients received DCE-MRI scans before surgery to derive time-intensity curves (TICs) and related quantitative parameters (flux rate constant [Kep], transfer constant [Ktrans], extravascular volume fraction [Ve]). The diagnostic surgical pathology results were used as the gold standard to analyze the diagnostic effect of TIC and related quantitative parameters of DCE-MRI, and the receiver operating characteristic (ROC) curves were plotted to determine the values of each parameter in predicting nasal sinus tumors. Results: The percentage of class I in the benign group was significantly higher than in the malignant group (P < .05); the percentage of class III in the benign group was significantly lower than in the malignant group (P < .05); the percentage of class II in the 2 groups was comparable (P > .05). Kep, Ktrans and Ve in the benign group were 0.338±0.124, 0.061±0.035 and 0.532±0.138, respectively; Kep, Ktrans and Ve in the malignant group were 0.785±0.211, 0.441±0.125 and 0.327±0.048, respectively. The levels of Kep and Ktrans were significantly lower in the benign group than in the malignant group (all P < .05); the levels of Ve were significantly higher in the benign group than in the malignant group (P < .05). The optimal Kep cut-off value for predicting malignant nasal sinus tumors was 0.510 min-1, with a sensitivity of 81.4% and specificity of 89.5%; the optimal Ktrans cut-off value for predicting malignant nasal sinus tumors was 0.206 min-1, with a sensitivity of 84.3% and specificity of 89.7%; the optimal Ve cut-off value for predicting malignant nasal sinus tumors was 0.384 min-1, with a sensitivity of 71.8% and specificity of 82.4%. Conclusion: DCE-MRI-related quantitative parameters are ideal for the diagnosis of benign and malignant nasal sinus tumors. This modality provides more data for the identification of the nature of the tumor, and thus merits clinical promotion and application.

Development and validation of a nomogram for preoperative prediction of tumor deposits in colorectal cancer.

BACKGROUND: Based on the clinical data of colorectal cancer (CRC) patients who underwent surgery at our institution, a model for predicting the formation of tumor deposits (TDs) in this patient population was established. AIM: To establish an effective model for predicting TD formation, thus enabling clinicians to identify CRC patients at high risk for TDs and implement personalized treatment strategies. METHODS: CRC patients (n = 645) who met the inclusion criteria were randomly divided into training (n = 452) and validation (n = 193) cohorts using a 7:3 ratio in this retrospective analysis. Least absolute shrinkage and selection operator regression was employed to screen potential risk factors, and multivariable logistic regression analysis was used to identify independent risk factors. Subsequently, a predictive model for TD formation in CRC patients was constructed based on the independent risk factors. The discrimination ability of the model, its consistency with actual results, and its clinical applicability were evaluated using receiver-operating characteristic curves, area under the curve (AUC), calibration curves, and decision curve analysis (DCA). RESULTS: Thirty-four (7.5%) patients with TDs were identified in the training cohort based on postoperative pathological specimens. Multivariate logistic regression analysis identified female sex, preoperative intestinal obstruction, left-sided CRC, and lymph node metastasis as independent risk factors for TD formation. The AUCs of the nomogram models constructed using these variables were 0.839 and 0.853 in the training and validation cohorts, respectively. The calibration curve demonstrated good consistency, and the training cohort DCA yielded a threshold probability of 7%-78%. CONCLUSION: This study developed and validated a nomogram with good predictive performance for identifying TDs in CRC patients. Our predictive model can assist surgeons in making optimal treatment decisions.

Comparison of short-term and long-term clinical effects of modified overlap anastomosis and conventional incision-assisted anastomosis in laparoscopic total gastrectomy.

BACKGROUND: To compare short-term and long-term clinical effects of modified overlap anastomosis and conventional incision-assisted anastomosis for laparoscopic total gastrectomy. METHODS: This retrospective cohort study included patients with gastric cancer admitted to the Second Affiliated Hospital of Fujian Medical University from January 2016 to March 2020. Quality of life, intraoperative and postoperative conditions were analyzed. RESULTS: Compared with the conventional assisted group, the modified overlap group showed a shorter auxiliary incision, milder postoperative pain, shorter time to the first postoperative anal exhaust, shorter time to the first postoperative liquid food intake, and shorter postoperative stay. There were no differences between the two groups regarding operation time, esophagus-jejunum anastomosis time, intraoperative blood loss, number of lymph nodes dissected, and length of the upper incision margin. There were no differences between the two groups regarding postoperative early and late complications. There were no differences between the two groups regarding the QLQ-C30 scale three years after the operation. The scores of the QLQ-STO22 scale 3 years after the operation showed significantly lower scores for dysphagia and feeding limit in the modified overlap group than those in the conventional assisted anastomosis group. There was no recurrence in the modified overlap group but one patient in the conventional assisted group. CONCLUSIONS: Patients undergoing totally laparoscopic total gastrectomy with modified overlap anastomosis have better minimal invasiveness and faster post-operative recovery than conventional incision-assisted anastomosis.

Cytotoxic lanostane-type triterpenes from the fruiting bodies of Ganoderma lucidum.

A new lanostane-type triterpene, namely 3-oxo-5α-lanosta-7,9(11)-dien-24-oic acid methyl ester (2), and three known compounds including ganoderal A (1), ganoderiol B (3) and ganodermenonol (4) were isolated from the fruiting bodies of Ganoderma lucidum by silica gel column chromatography and Sephadex LH-20 column chromatography. Their structures were determined by extensive NMR data and mass spectral analysis. The in vitro cytotoxic activity of the isolated compounds against SK-Hep-1, HepG2, Hela and Hela/VCR cancer cell lines was assessed by using MTT assay. The IC50 values of compound 1 were 43.09 ± 2.86, 42.31 ± 1.78 and 46.51 ± 1.95 µM in SK-Hep-1, HepG2 and Hela cells, respectively, after 48 h. The IC50 values of compound 4 were 44.70 ± 2.32 and 41.33 ± 2.15 µM in Hela and Hela/VCR cells, respectively, after 48 h.

Laparoscopic resection and endoscopic submucosal dissection for treating gastric ectopic pancreas.

BACKGROUND: Gastric ectopic pancreas (GEP) is a rare developmental abnormality that refers to the existence of pancreatic tissue in the stomach with no anatomical relationship with the main pancreas. It is usually difficult to diagnose through histological examination, and the choice of treatment method is crucial. AIM: To describe the endoscopic ultrasound characteristics of GEP and evaluate the value of laparoscopic resection (LR) and endoscopic submucosal dissection (ESD). METHODS: Forty-nine patients with GEP who underwent ESD and LR in the Second Affiliated Hospital of Fujian Medical University from May 2018 to July 2023 were retrospectively included. Data on clinical characteristics, endoscopic ultrasonography (EUS), ESD, and LR were collected and analyzed. The characteristics of EUS and the efficacy of the two treatments were analyzed. RESULTS: The average age of the patients was 43.31 ± 13.50 years, and the average maximum diameter of the lesions was 1.55 ± 0.70 cm. The lesion originated from the mucosa in one patient (2.04%), from the submucosa in 42 patients (85.71%), and from the muscularis propria in 6 patients (12.25%). Twenty-nine patients (59.20%) with GEP showed umbilical depression on endoscopy. The most common initial symptom of GEP was abdominal pain (40.82%). Tumor markers, including carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA-19-9), were generally within the normal range. One patient (2.04%) with GEP had increased CEA and CA-19-9 levels. However, no cancer tissue was found on postoperative pathological examination, and tumor markers returned to normal levels after resecting the lesion. There was no significant difference in surgery duration (72.42 ± 23.84 vs 74.17 ± 12.81 min) or hospital stay (3.70 ± 0.91 vs 3.83 ± 0.75 d) between the two methods. LR was more often used for patients with larger tumors and deeper origins. The amount of bleeding was significantly higher in LR than in ESD (11.28 ± 16.87 vs 16.67 ± 8.76 mL, P < 0.05). Surgery was associated with complete resection of the lesion without any serious complications; there were no cases of recurrence during the follow-up period. CONCLUSION: GEP has unique characteristics in EUS. LR and ESD seem to be good choices for treating GEP. LR is better for large GEP with a deep origin. However, due to the rarity of GEP, multicenter large-scale studies are needed to describe its characteristics and evaluate the safety of LR and ESD.

Clip-assisted endoloop ligation of the mucosal defect after resection of colorectal polyps decreased postprocedural delayed bleeding.

Background: Postprocedural delayed bleeding (PDB) remains the most common major complication of colorectal polypectomy. Incomplete clip closure of mucosal defect and unclosed injured blood vessels in gaps between clips may be the risk factors for PDB. Objectives: To observe whether completely no-gap closure of mucosal defect after polypectomy can reduce PDB occurrence. Design: Single-center, retrospective case-control study. Methods: In this study based on historical comparisons of patients in 2 time periods, only the patients with polyps sized between 6 and 15 mm were included. A new clip-assisted endoloop ligation (CAEL, treatment group) method was used between January 2019 and December 2020, and a traditional simple clip closure (SCC, control) was used Between January 2017 and December 2018 to prevent PDB after polypectomy. The rate of PDB of two groups and risk factors for PDB were evaluated. Results: Totally 4560 patients were included in the study; 2418 patients belong to CAEL group, and 2142 patients belong to SCC group. The overall rate of PDB was significantly lower in CAEL group compared to SCC group (0.6% versus 1.5%, p < 0.00). On multivariate logistic analysis, CAEL was a significant independent preventive factor for PDB (odds ratio (OR), 0.092; 95% confidence interval (CI), 0.029-0.3335; p = 0.000). Polyps located at rectum (colon versus rectum) represented a significant independent risk factor for PDB (OR, 11.888; 95% CI, 3.343-42.269; p = 0.001). Conclusion: Completely no-gap closure of mucosal defect after polypectomy further reduced the rate of PDB for polyps sized between 6 and 15 mm. CAEL may be a significant independent preventive factor for PDB. Polyps located at the rectum may be a significant independent risk factor for PDB.

A PARP1 PROTAC as a novel strategy against PARP inhibitor resistance via promotion of ferroptosis in p53-positive breast cancer.

Therapeutic targeting of the nuclear enzyme poly (ADP-ribose) polymerase 1 (PARP1) with PARP inhibitors (PARPis) in patients with a homologous recombination (HR)- deficient phenotype based on the mechanism of synthetic lethality has been shown tremendous success in cancer therapy. With the clinical use of various PARPis, emerging evidence has shown that some PARPis offer hope for breakthroughs in triple-negative breast cancer (TNBC) therapy, regardless of HR status. However, similar to other conventional cytotoxic drugs, PARPis are also subject to the intractable problem of drug resistance. Notably, acquired resistance to PARPis caused by point mutations in the PARP1 protein is hard to overcome with current strategies. To explore modalities to overcome resistance and identify patients who are most likely to benefit from PARP1-targeted therapy, we developed a proteolysis-targeted chimaera (PROTAC) to degrade mutant PARP1 in TNBC. Here, we investigated a PARP1 PROTAC termed "NN3″, which triggered ubiquitination and proteasome-mediated degradation of PARP1. Moreover, NN3 degraded PARP1 with resistance-related mutations. Interestingly, compared with other reported PARP1 degraders, NN3 exhibited a unique antitumor mechanism in p53-positive breast cancer cells that effectively promoted ferroptosis by downregulating the SLC7A11 pathway. Furthermore, NN3 showed potent activity and low toxicity in vivo. In conclusion, we propose PROTAC-mediated degradation of PARP1 as a novel strategy against mutation-related PARPi resistance and a paradigm for targeting breast cancer with functional p53 via ferroptosis induction.

Analysis of 20 patients with laparoscopic extended right colectomy.

BACKGROUND: Currently, the standard surgical procedure for right colon cancer is complete mesocolic excision. Whether preventive extended lymph node dissection for colon cancer located in the hepatic flexure or right transverse colon should be performed remains controversial because the safety and effectiveness of the operation have not been proven, and infrapyloric lymph nodes (No. 206) and lymph nodes in the greater curvature of the stomach (No. 204) have not been strictly defined and distinguished as surgical indicators in previous studies. AIM: To analyze the metastatic status of infrapyloric lymph nodes and lymph nodes of the greater curvature of the stomach and perioperative complications and systematically evaluate the feasibility and safety of laparoscopic extended right colectomy using prospective data collected retrospectively. METHODS: The study was a clinical study. Twenty patients with colon cancer who underwent laparoscopic extended right colon resection in our hospital from June 2020 to May 2021 were included. RESULTS: Among the patients who underwent extended right colon resection, there were no intraoperative complications or conversion to laparotomy; 2 patients had gastrocolic ligament lymph node metastasis, and 5 patients had postoperative complications. The patients with postoperative complications received conservative treatment. CONCLUSION: Laparoscopic extended right colon resection is safe. However, malignant tumors located in the liver flexure or the right-side transverse colon are more likely to metastasize to the gastrocolic ligament lymph nodes, and notably, the incidence of gastroparesis was high. The number of patients was small, and the follow-up time was short. It is necessary to further increase the sample size to evaluate the No. 204 and No. 206 lymph node metastasis rates and the long-term survival impact.

Sterols and triterpenoids from Ganoderma lucidum and their reversal activities of tumor multidrug resistance.

Two sterols and seven triterpenoids were isolated and identified from Ganoderma lucidum by silica gel column chromatography, preparative high-performance liquid chromatography and spectra analysis. Then, the multidrug resistance reversal activities of these compounds were assessed using MTT assay. Among these compounds, ganoderol B (3), ganoderone A (4), ganodermanondiol (6) and ganoderiol F (8) were shown to reverse the resistance of human oral epidermoid carcinoma cell line KBv200 to doxorubicin, and the reversal folds were 6.59, 4.70, 4.01 and 7.09, respectively. Ganoderiol F could increase the intracellular accumulation of doxorubicin in KBv200 cells through inhibiting P-glycoprotein transport function. Further mechanistic investigation found that ganoderiol F did not alter P-glycoprotein expression. In conclusion, ganoderiol F has potent effect in reversing P-glycoprotein mediated tumor multidrug resistance. Potential reversal agents against multidrug resistance in tumor may be found in triterpenoids from Ganoderma lucidum.[Formula: see text].

C0818, a novel curcumin derivative, induces ROS-dependent cytotoxicity in human hepatocellular carcinoma cells in vitro via disruption of Hsp90 function.

Heat shock protein 90 (Hsp90) is the most common molecular chaperone that controls the maturation of many oncoproteins critical in tumor development. Hsp90 has been considered as a promising target for cancer treatment, but the clinical significance of Hsp90 and the mechanisms of Hsp90 regulating the tumor-promoting effects in hepatocellular carcinoma (HCC) remain obscure. Previous studies have shown that curcumin, a polyphenol derived from the plant turmeric (Curcuma longa), inhibits tumor growth, which may provide an effective alternative therapy for HCC. Compared to curcumin, a novel derivative of curcumin, 3,5-(E)-Bis(3-methoxy-4-hydroxybenzal)-4-piperidinone hydrochloride (C0818) that is more potent in Hsp90 inhibition and antitumor activity. In this study, we investigated the effect of C0818 on HCC cells in vitro and its relation to Hsp90 inhibition. We showed that C0818 concentration-dependently inhibited the proliferation, the colony formation and induced apoptosis in HepG2 and Sk-Hep-1 cells. C0818 concentration-dependently inhibited DNA synthesis and induced G2/M phase arrest in HepG2 and Sk-Hep-1 cells. We further demonstrated that C0818 induced ROS- and caspase-dependent apoptosis in HCC cells through the mitochondrial-mediated pathway. C0818 induced the degradation of Hsp90 client proteins as RAS, C-Raf, P-C-Raf, Erk, P-ERK, MEK, P-MEK, Akt and P-Akt, which led to subsequent inhibition of the RAS/RAF/MEK/ERK and PI3K/AKT pathways. We revealed that C0818 could inhibit the binding of Hsp90 with its clients without affecting their transcription, which subsequently induced the degradation of Hsp90 clients by the proteasome rather than the lysosome. These results are of potential importance for elucidating a novel Hsp90 inhibitor targeting HCC.

Nomogram for predicting chylous ascites after right colectomy.

BACKGROUND: Chylous ascites following right colectomy has a high incidence which is a critical challenge. At present, there are few studies on the factors affecting chylous ascites after right colectomy and especially after D3 Lymphadenectomy. A predictive model for chylous ascites has not yet been established. Therefore, we created the first nomogram to predict the incidence of chylous ascites after right hemicolectomy. AIM: To analyze the risk factors for chylous ascites after right colectomy and establish a nomogram to predict the incidence of chylous ascites. METHODS: We retrospectively collected patients who underwent right hemicolectomy between January 2012 and May 2021 and were pathologically diagnosed with cancer. Multivariate logistic regression was used to analyze the influencing factors of chylous ascites and a nomogram was established. The predictive ability was assessed by the area under the receiver operating characteristic (ROC) curve. RESULTS: Operative time, the type of operation (standard or extended), the number of lymph nodes retrieved, and somatostatin administration were considered important risk factors. Multivariate logistic regression and nomograms can be used to accurately predict whether chylous ascites occurs. The area under the ROC curve of the model is 0.770. The C-statistic of this model is 0.770 which indicates that it has a relatively moderate ability to predict the risk of chylous ascites. CONCLUSION: We found a novel set of risk factors, created a nomogram, and validated it. The nomogram had a relatively accurate forecasting ability for chylous ascites after right hemicolectomy and can be used as a reference for risk assessment of chylous ascites and whether to prevent it after surgery.

Alleviative Effect of Ruellia tuberosa L. on Insulin Resistance and Abnormal Lipid Accumulation in TNF-α-Treated FL83B Mouse Hepatocytes.

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease, and most patients with T2DM develop nonalcoholic fatty liver disease (NAFLD). Both diseases are closely linked to insulin resistance (IR). Our previous studies demonstrated that Ruellia tuberosa L. (RTL) extract significantly enhanced glucose uptake in the skeletal muscles and ameliorated hyperglycemia and IR in T2DM rats. We proposed that RTL might be via enhancing hepatic antioxidant capacity. However, the potent RTL bioactivity remains unidentified. In this study, we investigated the effects of RTL on glucose uptake, IR, and lipid accumulation in vitro to mimic the T2DM accompanied by the NAFLD paradigm. FL83B mouse hepatocytes were treated with tumor necrosis factor-α (TNF-α) to induce IR, coincubated with oleic acid (OA) to induce lipid accumulation, and then, treated with RTL fractions, fractionated with n-hexane or ethyl acetate (EA), from column chromatography, and analyzed by thin-layer chromatography. Our results showed that the ethyl acetate fraction (EAf2) from RTL significantly increased glucose uptake and suppressed lipid accumulation in TNF-α plus OA-treated FL83B cells. Western blot analysis showed that EAf2 from RTL ameliorated IR by upregulating the expression of insulin-signaling-related proteins, including protein kinase B, glucose transporter-2, and peroxisome proliferator-activated receptor alpha in TNF-α plus OA-treated FL83B cells. The results of this study suggest that EAf2 from RTL may improve hepatic glucose uptake and alleviate lipid accumulation by ameliorating and suppressing the hepatic insulin signaling and lipogenesis pathways, respectively, in hepatocytes.

Effectiveness and Safety of Apatinib Plus Chemotherapy as Neoadjuvant Treatment for Locally Advanced Gastric Cancer: A Nonrandomized Controlled Trial.

Importance: Apatinib is a novel treatment option for chemotherapy-refractory advanced gastric cancer (GC), but it has not been evaluated in patients with locally advanced GC. Objective: To investigate the effectiveness and safety of apatinib combined with S-1 plus oxaliplatin (SOX) as a neoadjuvant treatment for locally advanced GC. Design, Setting, and Participants: This multicenter, prospective, single-group, open-label, phase 2 nonrandomized controlled trial was conducted in 10 centers in southern China. Patients with M0 and either clinical T2 to T4 or N+ disease were enrolled between July 1, 2017, and June 30, 2019. Statistical analysis was performed from December 1, 2019, to January 31, 2020. Interventions: Eligible patients received apatinib (500 mg orally once daily on days 1 to 21 and discontinued in the last cycle) plus SOX (S-1: 40-60 mg orally twice daily on days 1 to 14; oxaliplatin: 130 mg/m2 intravenously on day 1) every 3 weeks for 2 to 5 cycles. A D2 gastrectomy was performed 2 to 4 weeks after the last cycle. Main Outcomes and Measures: The primary end point was R0 resection rate. Secondary end points were the response rate, toxic effects, and surgical outcome. Results: A total of 48 patients (mean [SD] age, 63.2 [8.2] years; 37 men [77.1%]) were enrolled in this study. Forty patients underwent surgery (38 had gastrectomy, and 2 had exploratory laparotomy), with an R0 resection rate of 75.0% (95% CI, 60.4%-86.4%). The radiologic response rate was 75.0%, and T downstaging was observed in 16 of 44 patients (36.4%). The pathological response rate was 54.2% (95% CI, 39.2%-68.6%); moreover, this rate was significantly higher in patients who achieved a radiologic response compared with those who did not (12 [80.0%] vs 1 [20.0%]; P = .03) and in those who had an Eastern Cooperative Oncology Group Performance Status score of 0 (20 [76.9%] vs 10 [45.5%]; P = .03) or had tumors located in the upper one-third of the stomach (16 [61.5%] vs 7 [31.8%]; P = .04). Patients who achieved a pathological response (vs those who did not) had significantly less blood loss (median [range]: 60 [10-200] mL vs 80 [20-300] mL; P = .04) and significantly more lymph nodes harvested (median [range]: 40 [24-67] vs 32 [19-51]; P = .04) during surgery. Postoperative complications were observed in 7 of 38 patients (18.4%). Grade 3 toxic effects occurred in 16 of 48 patients (33.3%), and no grade 4 toxic effects or preoperative deaths were observed. Conclusions and Relevance: This nonrandomized controlled trial found that apatinib combined with SOX was effective and had an acceptable safety profile as a neoadjuvant treatment for locally advanced GC. A large-scale randomized clinical trial may be needed to confirm the findings. Trial Registration: ClinicalTrials.gov Identifier: NCT03192735.

Splenosis masquerading as gastric stromal tumor: A case report.

BACKGROUND: Splenosis is a rare benign disease that often disguises itself as a malignant tumor. There are few articles providing a comprehensive description of splenosis, especially cases located in the stomach being treated by laparoscopic surgery. CASE SUMMARY: A 44-year-old man presented with recurrent upper abdominal pain for more than half a year. The patient had splenic rupture caused by trauma more than 10 years ago and underwent splenectomy. An abdominal contrast-enhanced computed tomography scan revealed an irregular soft tissue density. Gastroscopy revealed an approximately 3.0 cm × 3.0 cm mucosal eminence at the posterior wall of the upper segment of the gastric body. Biopsy was not performed since the lesion was found under the mucosa and the gastric mucosa appeared normal. According to these findings, a diagnosis of gastric stromal tumor was made, although a definitive differential diagnosis was not known before surgery. When laparoscopic resection of the gastric stromal tumor was performed, an astonishing finding was made when postoperative pathology showed that the lesion comprised typical spleen tissue. CONCLUSION: This case highlights the strong similarities between splenosis and malignant tumors. A detailed medical history combined with various effective auxiliary examinations can help improve differential diagnosis.

BAFF, involved in B cell activation through the NF-κB pathway, is related to disease activity and bone destruction in rheumatoid arthritis.

B cell activating factor of TNF family (BAFF) is a member of TNF ligand superfamily and plays a key role in B cell homeostasis, proliferation, maturation, and survival. In this study, we detected BAFF level, the expressions of BAFF receptors and important molecules in NF-κB pathway in rheumatoid arthritis (RA) patients and analyzed the correlation between BAFF level and clinical variables, laboratory parameters or X-ray scores in order to elucidate the roles of BAFF in RA. A total of 50 RA patients and 50 healthy controls (HCs) were enrolled. We showed that the serum BAFF level in RA patients was significantly higher than that of HCs, and the percentages of B cell subsets (CD19+ B cells, CD19+CD27+ B cells, CD19+CD20+CD27+ B cells, and CD19+CD20-CD27+ B cells) in the serum of RA patients were significantly increased compared with those of HCs. The percentages of CD19+BAFFR+ B cells, CD19+ BCMA+ B cells, and CD19+ TACI+ B cells in RA patients were significantly increased compared with those in HCs. The expression of important molecules in the NF-κB pathway (MKK3, MKK6, p-P38, p-P65, TRAF2, and p52) was significantly higher in RA patients than in HCs, but p100 level in RA patients was lower than that in HCs. The serum BAFF level was positively correlated with C-reactive protein, rheumatoid factor, disease activity score (in 28 joints), swollen joint counts, tender joint counts, and X-ray scores. When normal B cells were treated with BAFF in vitro, the percentages of the B cell subset and the expression of BAFF receptors were significantly upregulated. BAFF also promoted the expression of MKK3, MKK6, p-P38, p-P65, TRAF2, and p52. In conclusion, this study demonstrates that BAFF level is correlated with the disease activity and bone destruction of RA. BAFF is involved in the differentiation, proliferation, and activation of B cells in RA through NF-κB signaling pathway, suggesting that BAFF might be an ideal therapeutic target for RA.

Predictors of urinary tract infection in acute stroke patients: A cohort study.

Patients with stroke have a high risk of infection which may be predicted by age, procalcitonin, interleukin-6, C-reactive protein, National Institute of Health stroke scale (NHSS) score, diabetes, etc. These prediction methods can reduce unfavourable outcome by preventing the occurrence of infection.We aim to identify early predictors for urinary tract infection in patients after stroke.In 186 collected acute stroke patients, we divided them into urinary tract infection group, other infection type groups, and non-infected group. Data were recorded at admission. Independent risk factors and infection prediction model were determined using Logistic regression analyses. Likelihood ratio test was used to detect the prediction effect of the model. Receiver operating characteristic curve and the corresponding area under the curve were used to measure the predictive accuracy of indicators for urinary tract infection.Of the 186 subjects, there were 35 cases of urinary tract infection. Elevated interleukin-6, higher NIHSS, and decreased hemoglobin may be used to predict urinary tract infection. And the predictive model for urinary tract infection (including sex, NIHSS, interleukin-6, and hemoglobin) have the best predictive effect.This study is the first to discover that decreased hemoglobin at admission may predict urinary tract infection. The prediction model shows the best accuracy.

A new demethyl abietane diterpenoid from the roots of Tripterygium wilfordii.

A new demethyl abietane diterpenoid, Triptotin K (3) together with three known compounds, friedelin (1), canophyllal (2), and triptonoterpene (4) were isolated from the roots of Tripterygium wilfordii Hook. f. by silica gel column and preparative high performance liquid chromatography. Their structures were determined by extensive NMR data and mass spectroscopic analysis. Triptotin K showed cytotoxic activities against KB, KBv200, HepG2, and MCF-7/ADM cells lines with IC50 values of 29.88, 36.50, 39.55, and 41.38 µM, respectively.

Innate immune molecule surfactant protein D attenuates sepsis-induced acute kidney injury through modulating apoptosis and NFκB-mediated inflammation.

The objective of this study is to investigate the mechanism whereby innate immune molecule surfactant protein D (SP-D) attenuates sepsis-induced acute kidney injury (AKI) through modulating apoptosis and nuclear factor kappa-B (NFκB)-mediated inflammation. In the present study, a mouse sepsis model was established by cecal ligation and puncture in SP-D knockout (KO) mice and wild-type (WT) mice. A sham-operated group was included as the control. The experimental materials were extracted 6 and 24 hours postoperatively. The plasma levels of tumour necrosis factor alpha (TNF-α) and MCP-1 were determined by enzyme-linked immunosorbent assay (ELISA). Apoptosis was measured by double staining with Annexin V/propidium iodide and flow cytometry. The levels of NFκB in renal tissues were measured by ELISA and Western blotting assay. Apoptosis was detected by TUNEL assays. There were no significant differences in plasma TNF-α levels between the WT sham group and the KO sham group at 6 and 24 hours postoperatively (P < .05), but the levels of TNF-α in the WT sepsis and KO sepsis groups were significantly higher than those in controls (P < .05). The levels of TNF-α in the KO sepsis group were significantly higher than those of the WT sepsis group (P < .05). TNF-α levels in the WT sepsis group and the KO sepsis group at 24 hours postoperatively were significantly higher than those at 6 hours postoperatively (P < .05). The levels of MCP-1 in the WT sepsis group and the KO sepsis group at 6 and 24 hours postoperatively were significantly higher than those in the control group (P < .05), and MCP-1 levels in the KO sepsis group were significantly higher than those in the WT sepsis group (P < .05). MCP-1 levels in the WT sepsis group and the KO sepsis group at 24 hours postoperatively were significantly higher than those at 6 hours postoperatively (P < .05). The expression of SP-D in WT kidneys was significantly lower at 6 and 24 hours postoperatively (P < .05). The number of TUNEL-positive cells in the kidneys from septic SP-D KO mice was significantly higher (P < .05). The levels of NFκB in septic mice were significantly increased at 6 and 24 hours after induction of sepsis compared with the sham-operated group compared with those of septic SP-D KO mice and WT mice (P < .05). Innate immune molecule SP-D significantly decreased plasma levels of inflammatory cytokines in mice and attenuated sepsis-induced AKI by inhibiting NFκB activity and apoptosis.