Downregulation of Serum PTEN Expression in Mercury-Exposed Population and PI3K/AKT Pathway-Induced Inflammation.

Objective: This study investigated the impact of occupational mercury (Hg) exposure on human gene transcription and expression, and its potential biological mechanisms. Methods: Differentially expressed genes related to Hg exposure were identified and validated using gene expression microarray analysis and extended validation. Hg-exposed cell models and PTEN low-expression models were established in vitro using 293T cells. PTEN gene expression was assessed using qRT-PCR, and Western blotting was used to measure PTEN, AKT, and PI3K protein levels. IL-6 expression was determined by ELISA. Results: Combined findings from gene expression microarray analysis, bioinformatics, and population expansion validation indicated significant downregulation of the PTEN gene in the high-concentration Hg exposure group. In the Hg-exposed cell model (25 and 10 µmol/L), a significant decrease in PTEN expression was observed, accompanied by a significant increase in PI3K, AKT, and IL-6 expression. Similarly, a low-expression cell model demonstrated that PTEN gene knockdown led to a significant decrease in PTEN protein expression and a substantial increase in PI3K, AKT, and IL-6 levels. Conclusion: This is the first study to report that Hg exposure downregulates the PTEN gene, activates the PI3K/AKT regulatory pathway, and increases the expression of inflammatory factors, ultimately resulting in kidney inflammation.

Endoscopic resection of extra-luminal gastric gastrointestinal stromal tumors using a snare assisted external traction technique (with video).

OBJECTIVE: The primary purpose of the study was to explore the clinical efficacy of the novel snare assisted endoscopic resection of extraluminal growing gastric gastrointestinal stromal tumors (gastric GISTs) using external traction, and the secondary purpose was to compare the novel snare assisted endoscopic resection of extraluminal GISTs with the standard laparoscopic procedure. METHODS: We retrospectively analyzed the patients who underwent novel external traction assisted endoscopic resection or laparoscopic resection for their extraluminal gastric GIST ≤5 cm in diameter. RESULTS: A total of 111 patients (27 in the endoscopic group and 84 in the laparoscopic group) were included in this study. There was no significant difference in tumor diameter and complication rate between the two groups. The overall procedure time was slightly higher in the endoscopic group compared to the laparoscopic group (P = 0.034). However, postoperative hospitalization time (P < 0.001) and postoperative fasting time (P = 0.005) were shorter in the endoscopic group compared to the laparoscopic group. CONCLUSION: Snare external traction-assisted endoscopic resection of extraluminal growing gastric GISTs is safe and effective, and it provides a new adjunctive method for endoscopic resection of GIST.

＜Editors' Choice＞ Advantages of gasless single-port transumbilical extracorporeal laparoscopic-assisted appendectomy in the treatment of uncomplicated acute appendicitis in children in China: a multi-institutional retrospective study.

Gasless transumbilical extracorporeal laparoscopic-assisted appendectomy is an approach used increasingly to treat uncomplicated acute appendicitis (UAA). However, there is limited information on its clinical effects and value in the Chinese pediatric population. This study retrospectively reviewed patients with UAA treated in two pediatric institutions from January 2018 through October 2021. Enrolled patients were divided into two groups by operative technique: gasless transumbilical laparoscopic-assisted appendectomy (gasless-TULAA, n=142) and conventional laparoscopic appendectomy (CLA, three-port, n=126). The perioperative clinical data, including age, sex, body mass index (BMI), operation time, time to postoperative ambulation, time to first postoperative exhaust, hospitalization expenses, and postoperative complications (incision infection, intestinal obstruction, and residual abdominal abscess), were compared between the two groups. Operations in both groups were successfully conducted without converting to open surgery. There were no significant differences (p > 0.05) in age and BMI in the two groups. Compared with CLA, gasless-TULAA showed significantly shorter operation time, earlier postoperative ambulation, shorter postoperative exhaust time, and lower hospital cost (p < 0.001). All patients were followed for 3 months, and postoperative complications were observed in three patients: two patients in the gasless-TULAA group (one with surgical wound effusion, one with intra-abdominal abscess), and one patient in the CLA group (surgical wound infection); there was no significant difference between the groups. Notably, 38 patients initially treated by gasless-TULAA were converted because of intraoperative factors. The gasless-TULAA technique had potential benefits: shortened operation time, better outcome, and greater cost-efficiency. These superiorities are worthy of future large-scale prospective study.

A serum metabolomics study based on LC-MS: Chemosensitization effects of Rauvolfia vomitoria Afzel. combined with 5- fluorouracil on colorectal cancer mice.

Colorectal cancer (CRC) is one of the malignant tumors with high incidence, and is mainly treated by chemotherapy at present. However, during CRC treatment, long-term use of traditional chemotherapeutic drugs will reduce the sensitivity of chemotherapy. Our previous studies have shown that Rauvolfia vomitoria total alkaloids (RVA) played an important role in 5-fluorouracil (5-FU) chemosensitization in CRC therapy, but its intervention mechanism has not been clarified completely in the metabolic level. Therefore, in this study, LC-MS based metabolomics was employed to explore the mechanism of 5-FU chemosensitization in CRC induced by the combination of RVA and conventional chemotherapeutic with 5-FU. The results showed that the final tumor weight of the high-dose combined group was significantly different from that of the 5-FU alone group. To evaluate the chemosensitization effects of RVA, serum samples collected from six groups (six mice in each group) with different administration methods were analyzed by HPLC-Q-Exactive Orbitrap/MS. After multivariate statistical analysis and metabolites identification, 25 different metabolites were identified between the 5-FU treatment group and combined high-dose treatment group, among which lipid and fatty acid metabolism pathways were mostly affected. These results suggest that RVA may sensitize traditional chemotherapeutic drug 5-FU and exert anti-tumor activity through influencing lipid metabolism and cell energy metabolism. Metabolomics provided a new insight into estimate of the therapeutic effect and dissection of the potential mechanisms of traditional Chinese medicine in treating colorectal cancer.

Efficient ofloxacin degradation via photo-Fenton process over eco-friendly MIL-88A(Fe): Performance, degradation pathways, intermediate library establishment and toxicity evaluation.

The high-throughput production of the eco-friendly MIL-88A(Fe) was achieved under mild reaction conditions with normal pressure and temperature. The as-prepared MIL-88A(Fe) exhibited efficient photo-Fenton catalytic ofloxacin (OFL) degradation upon visible light irradiation with good stability and reusability. The OFL (20.0 mg/L) was completely degraded within 50 min under visible light with the aid of MIL-88A(Fe) (0.25 g/L) and H2O2 (1.0 mL/L) in aqueous solution (pH = 7.0). The hydroxyl radicals (·OH) are the main active species during the photo-Fenton oxidation process. Meanwhile, the degradation intermediates and the corresponding degradation pathways were identified and proposed with the aid of both ultra-high performance liquid chromatography tandem quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS) and density functional theory (DFT) calculations. Finally, the degradation product library was firstly established to identify intermediate transformation products (TPs) with their variation of concentration, and their corresponding toxicologic activities were assessed via Toxtree and T.E.S.T software as well. Finally, the MIL-88A is efficient and stable with four cycles' catalysis operations, demonstrating good potential for water treatment.

Risk analysis in peripheral clinical T1 non-small cell lung cancer correlations between tumor-to-blood standardized uptake ratio on 18F-FDG PET-CT and primary tumor pathological invasiveness: a real-world observational study.

BACKGROUND: Sublobar resection is not suitable for patients with pathological invasiveness [including lymph node metastasis (LNM), visceral pleural invasion (VPI), and lymphovascular invasion (LVI)] of peripheral clinical T1 (cT1) non-small cell lung cancer (NSCLC), while primary tumor maximum standardized uptake value (SUVmax) on 18F-FDG PET-CT is related to pathological invasiveness, the significance differed among different institutions is still challenging. This study explored the relationship between the tumor-to-blood standardized uptake ratio (SUR) of 18F-FDG PET-CT and primary tumor pathological invasiveness in peripheral cT1 NSCLC patients. METHODS: This retrospective study included 174 patients with suspected lung neoplasms who underwent preoperative 18F-FDG PET-CT. We compared the differences of the clinicopathological variables, metabolic and morphological parameters in the pathological invasiveness and less-invasiveness group. We performed a trend test for these parameters based on the tertiles of SUR. The relationship between SUR and pathological invasiveness was evaluated by univariate and multivariate logistics regression models (included unadjusted, simple adjusted, and fully adjusted models), odds ratios (ORs), and 95% confidence intervals (95% CIs) were calculated. A smooth fitting curve between SUR and pathological invasiveness was produced by the generalized additive model (GAM). RESULTS: Thirty-eight point five percent of patients had pathological invasiveness and tended to have a higher SUR value than the less-invasiveness group [6.50 (4.82-11.16) vs. 4.12 (2.04-6.61), P<0.001]. The trend of SUVmax, mean standardized uptake value (SUVmean), metabolic tumor volume (MTV), total lesion glycolysis (TLG), mean CT value (CTmean), size of the primary tumor, neuron-specific enolase (NSE), the incidence of LNM, adenocarcinoma (AC), and poor differentiation in the tertiles of SUR value were statistically significant (P were <0.001, <0.001, 0.010, <0.001, <0.001, 0.002, 0.033, <0.001, 0.002, and <0.001, respectively). Univariate analysis showed that the risk of pathological invasiveness increased significantly with increasing SUR [OR: 1.13 (95% CI: 1.06-1.21), P<0.001], and multivariate analysis demonstrated SUR, as a continuous variable, was still significantly related to pathological invasiveness [OR: 1.09 (95% CI: 1.01-1.18), P=0.032] after adjusting for confounding covariates. GAM revealed that SUR tended to be linearly and positively associated with pathological invasiveness and E-value analysis suggested robustness to unmeasured confounding. CONCLUSIONS: SUR is linearly and positively associated with primary tumor pathological invasiveness independent of confounding covariates in peripheral cT1 NSCLC patients and could be used as a supplementary risk maker to assess the risk of pathological invasiveness.

Clinical Features and Outcomes of Pulmonary Artery Sarcoma.

OBJECTIVES: A retrospective cohort study was designed to describe the clinical features and outcomes of pulmonary artery sarcoma (PAS). METHODS: Twenty-two (22) consecutive patients diagnosed with PAS by pathological examination were enrolled and followed up until they died or until January 2020. The medical records were retrospectively reviewed to evaluate the clinical characteristics, image findings, and outcomes. RESULTS: 1) Twenty-one (21, 95.5%) patients were firstly misdiagnosed. Dyspnoea was the most common presenting symptom (19 of 22, 86.4%). 2) Filling defects in the right pulmonary artery were seen in 17 patients (77.3%) with computed tomography pulmonary angiography or magnetic resonance pulmonary angiography. Among those patients, 14 underwent positron emission tomography-computed tomography detection and 13 (92.9%) were found to have increased uptake value in the pulmonary artery. 3) The median survival (from diagnosis to death or January 2020) of the total series was 11.6 months (range, 0.7-68.5 months). The estimated cumulative survival rates at 1, 2, and 3 years were 52.6%, 32.8%, and 19.7%, respectively. Patients who received surgery and/or chemo-radiotherapy treatment had a better survival rate compared with patients without treatment (the estimated cumulative survival rates at 1, 2, and 3 years were 60.3%, 39.1%, and 29.3%, respectively, vs 33.3%, 16.6%, and 0, accordingly) and better survival time (median survival 17.02 vs 3.16 months, respectively) (p=0.025). CONCLUSIONS: Pulmonary artery sarcoma is easily misdiagnosed, as the symptoms and routine image detection are nonspecific. Positron emission tomography-computed tomography may be helpful in diagnosis. Surgery and/or chemo-radiotherapy offer a chance for better outcomes.

Relationship between total lesion glycolysis of primary lesions based on 18F-FDG PET/CT and lymph node metastasis in gastric adenocarcinoma: a cross-sectional preliminary study.

OBJECTIVES: We explored the relationship between lymph node metastasis (LNM) and total lesion glycolysis (TLG) of primary lesions determined by 18fluoro-2-deoxyglucose PET/computed tomography (18F-FDG PET/CT) in patients with gastric adenocarcinoma, and evaluated the independent effect of this association. METHODS: This retrospective study included 106 gastric adenocarcinoma patients who were examined by preoperative 18F-FDG PET/CT imaging between April 2016 and April 2020. We measured TLG of primary gastric lesions and evaluated its association with LNM. Multivariate logistic regression and a two-piece-wise linear regression were performed to evaluate the relationship between TLG of primary lesions and LNM. RESULTS: Of the 106 patients, 75 cases (71%) had LNM and 31 cases (29%) did not have LNM. Univariate analyses revealed that a per-SD increase in TLG was independently associated with LNM [odds ratio (OR) = 2.37; 95% confidence interval (CI), 1.42-3.98; P = 0.0010]. After full adjustment of confounding factors, multivariate analyses exhibited that TLG of primary lesions was still significantly associated with LNM (OR per-SD: 2.20; 95% CI, 1.16-4.19; P = 0.0164). Generalized additive model indicated a nonlinear relationship and saturation effect between TLG of primary lesions and LNM. When TLG of primary lesions was <23.2, TLG was significantly correlated with LNM (OR = 1.26; 95% CI, 1.07-1.48; P = 0.0053), whereas when TLG of primary lesions was ≥ 23.2, the probability of LNM was greater than 60%, gradually reached saturation effect, as high as 80% or more. CONCLUSIONS: In this preliminary study, there were saturation and segmentation effects between TLG of primary lesions determined by preoperative 18F-FDG PET/CT and LNM. When TLG of primary lesions was ≥ 23.2, the probability of LNM was greater than 60%, gradually reached saturation effect, as high as 80% or more. TLG of primary lesions is helpful in the preoperative diagnosis of LNM in patients with gastric adenocarcinoma.

Hepatic Artery Injection of 131I-Metuximab Combined with Transcatheter Arterial Chemoembolization for Unresectable Hepatocellular Carcinoma: A Prospective Nonrandomized, Multicenter Clinical Trial.

This prospective nonrandomized, multicenter clinical trial was performed to investigate the efficacy and safety of 131I-labeled metuximab in adjuvant treatment of unresectable hepatocellular carcinoma. Methods: Patients were assigned to treatment with transcatheter arterial chemoembolization (TACE) combined with 131I-metuximab or TACE alone. The primary outcome was overall tumor recurrence. The secondary outcomes were safety and overall survival. Results: The median time to tumor recurrence was 6 mo in the TACE + 131I-metuximab group (n = 160) and 3 mo in the TACE group (n = 160) (hazard ratio, 0.55; 95% CI, 0.43-0.70; P < 0.001). The median overall survival was 28 mo in the TACE + 131I-metuximab group and 19 mo in the TACE group (hazard ratio, 0.62; 95% CI, 0.47-0.82; P = 0.001). Conclusion: TACE + 131I-metuximab showed a greater antirecurrence benefit, significantly improved the 5-y survival of patients with advanced hepatocellular carcinoma, and was well tolerated by patients.

Anterior Cervical Discectomy and Fusion Combined with Foraminotomy Assisted by High-Definition 3-Dimensional Exoscope in the Treatment of Cervical Spondylotic Radiculopathy Secondary to Bony Foraminal Stenosis.

OBJECTIVE: To evaluate the outcomes of cervical spondylotic radiculopathy secondary to bony foraminal stenosis treated with anterior cervical discectomy and fusion (ACDF) combined with anterior cervical foraminotomy (ACF) assisted by High-Definition 3-Dimensional Exoscope. METHODS: In this retrospective study, a total of 19 consecutive patients (12 males and seven females, with an average of 49.2 years, range from 40 to 59 years) with spondylotic radiculopathy caused by bony foraminal stenosis underwent ACDF combined with ACF assisted by High-Definition 3-Dimensional Exoscope in our hospital between January 2019 and December 2019 were included in this study. All patients signed the consent form before the surgery. The patient baseline information such as gender, age, body mass index (BMI), surgery time, blood loss, hospital stay, lesion segment, side, follow-up time and postoperative complications were recorded. The Japanese Orthopedic Association (JOA), Neck Disability Index (NDI), and Visual Analogue Scale (VAS) were measured and compared before surgery, 1 months and final follow-up after surgery. The radiographic outcomes were evaluated using the C2 -C7 angel, disc height, foraminal height, superior diagonal distance, inferior diagonal distance, and foraminal area. RESULTS: The involved levels included C4 -C5 (six cases), C5 -C6 (10 cases), C6 -C7 (three cases). The mean duration of the surgery, mean blood loss, mean hospital stay, and mean follow-up were 100 ± 11.10 min, 19.4 ± 7.05 mL, 7.1 ± 0.99 days, and 12.1 ± 2.25 months, respectively. The average preoperative JOA score was 11.9 ± 1.31, then improved to 15.7 ± 0.73 (t = -13.45, P < 0.001) and 16.2 ± 0.74 (t = -14.39, P < 0.001) at 1 month after operation and at last follow-up, respectively. The average preoperative NDI score was 27.3 ± 3.36, then decreased to 5.1 ± 1.79 (t = 20.63, P < 0.001) and 4.5 ± 1.21 (t = 25.53, P < 0.001) 1 month after operation and at last follow-up, respectively. The average preoperative VAS score was 6.7 ± 0.93, then decreased to 2.4 ± 0.69 (t = 15.05, P < 0.001) and 1.9 ± 0.78 (t = 16.40, P < 0.001) 1 month after operation and at last follow-up, respectively. As compared with the condition before surgery, there was a significant improvement in the C2 -C7 angel, disc height, foraminal height, and foraminal area (P < 0.05). None of the patients developed postoperative vascular injury, nerve injury, loosening and rupture of the internal fixation, displacement of interbody fusion cage, and pseudarthrosis. CONCLUSION: ACDF combined with ACF assisted by High-Definition 3-Dimensional Exoscope is effective and safe for the treatment of CSR caused by secondary to bony foraminal stenosis.

Preoperative 18F-FDG SUVmax >6.3 or Size >2.3 cm of primary lesions predict lymph nodes metastasis with higher negative predictive value in peripheral cT1 non-small-cell lung cancer.

BACKGROUND: Sublobar resection is suitable for peripheral cT1N0M0 non-small-cell lung cancer (NSCLC). The traditional PET-CT criterion (lymph node size ≥1.0 cm or SUVmax ≥2.5) for predicting lymph nodes metastasis (LNM) has unsatisfactory performance. OBJECTIVE: We explore the clinical role of preoperative SUVmax and the size of the primary lesions for predicting peripheral cT1 NSCLC LNM. METHODS: We retrospectively analyzed 174 peripheral cT1 NSCLC patients underwent preoperative 18F-FDG PET-CT and divided into the LNM and non-LNM group by pathology. We compared the differences of primary lesions' baseline characteristics between the two groups. The risk factors of LNM were determined by univariate and multivariate analysis, and we assessed the diagnostic efficacy with the area under the receiver operating characteristic curve (AUC), sensitivity, specificity, positive predictive value and negative predictive value (NPV). RESULTS: Of the enrolled cases, the incidence of LNM was 24.7%. The preoperative SUVmax >6.3 or size >2.3 cm of the primary lesions were independent risk factors of peripheral cT1 NSCLC LNM (ORs, 95% CIs were 6.18 (2.40-15.92) and 3.03 (1.35-6.81). The sensitivity, NPV of SUVmax >6.3 or size >2.3 cm of the primary lesions were higher than the traditional PET-CT criterion for predicting LNM (100.0 vs. 86.0%, 100.0 vs. 89.7%). A Hosmer-Lemeshow test showed a goodness-of-fit (P = 0.479). CONCLUSIONS: The excellent sensitivity and NPV of preoperative of the SUVmax >6.3 or size >2.3 cm of the primary lesions based on 18F-FDG PET-CT might identify the patients at low-risk LNM in peripheral cT1 NSCLC.

Peripheral blood inflammation indices are effective predictors of anastomotic leakage in elective esophageal surgery.

BACKGROUND: This study investigated the predictive value of peripheral inflammatory indices, including neutrophil count, lymphocyte count, platelet count, neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR), in anastomotic leakage during elective esophageal surgery. METHODS: This retrospective study included all patients who underwent esophagectomy for esophageal squamous cell carcinoma from 2016 to 2020 in our institution. The peripheral blood inflammatory indices were obtained on preoperative days 1-7 (PRD 1-7), and postoperative days 1-3 (POD 1-3) and 4-7 (POD 4-7). Univariate, multivariate logistic, and receiver operating characteristic curve analyses were conducted to evaluate the diagnostic value of these peripheral blood inflammatory indices. RESULTS: A total of 198 patients were included in the study, and 25 (13%) patients experienced anastomotic leakage. Multivariate analyses identified diet, neutrophil count, and PLR on POD 1-3, and NLR on POD 4-7 as independent factors associated with anastomotic leakage. Using the receiver operating characteristic curve, the variable with the best area under curve was a neutrophil cutoff count of 4.1 [0.737; 95% CI: 0.639-0.835], with a sensitivity and specificity of 60.0% and 66.5%, respectively. This was followed by an NLR cutoff value of 9.5 on POD 4-7 (0.628; 95% CI: 0.505-0.752) and a cutoff PLR value of 220.1 on POD 1-3 (0.643; 95% CI: 0.536-0.750). Diet showed a poor result on the receiver operating characteristic curve analysis. CONCLUSIONS: Neutrophil count and PLR on POD 1-3 and NLR on POD 4-7 were shown to have predictive value for anastomotic leakage in elective esophageal surgery.

Tumor-to-liver standard uptake ratio using fluorine-18 fluorodeoxyglucose positron emission tomography computed tomography effectively predict occult lymph node metastasis of non-small cell lung cancer patients.

OBJECTIVES: We aimed to investigate predictive factors of occult lymph node metastasis and to explore the diagnostic value of various standardized uptake value (SUV) parameters using fluorine-18 fluorodeoxyglucose (F-FDG) positron emission tomography computed tomography (PET/CT) in predicting occult lymph node metastasis of clinical N0 non-small cell lung cancer patients. METHODS: We retrospectively analyzed PET/computed tomography parameters of tumor and clinical data of 124 clinical N0 non-small cell lung cancer patients who underwent both preoperative F-FDG PET/computed tomography and anatomical pulmonary resection with systematic lymph node dissections. The SUVmax, SUVmean, metabolic total volume, and total lesion glycolysis of the primary tumor was automatically measured on the PET/computed tomography workstation. Standardized uptake ratio (SUR) were derived from tumor standardized uptake value divided by blood SUVmean (B-SUR) or liver SUVmean (L-SUR), respectively. RESULTS: According to postoperative pathology, 19 (15%) were diagnosed as occult lymph node metastasis among 124 clinical N0 non-small cell lung cancer patients. On univariate analysis, carcinoembryonic antigen, cytokeratin 19 fragment, lobulation, and all PET parameters were associated with occult lymph node metastasis. The area under the receiver operating characteristic curve, sensitivity, and negative predictive value of L-SURmax were the highest among all PET parameters (0.778, 94.7%, and 98.4%, respectively). On multivariate analysis, carcinoembryonic antigen, cytokeratin 19 fragment, and L-SURmax were independent risk factors for predicting occult lymph node metastasis. Compared to L-SURmax alone and the combination of carcinoembryonic antigen and cytokeratin 19 fragment, the model consisting of three independent risk factors achieved a greater area under the receiver operating characteristic curve (0.901 vs. 0.778 vs. 0.780, P = 0.021 and 0.0141). CONCLUSIONS: L-SURmax showed the most powerful predictive performance than the other PET parameters in predicting occult lymph node metastasis. The combination of three independent risk factors (carcinoembryonic antigen, cytokeratin 19 fragment, and L-SURmax) can effectively predict occult lymph node metastasis in clinical N0 non-small cell lung cancer patients.

20(S)-Protopanaxdiol Suppresses the Abnormal Granule-Monocyte Differentiation of Hematopoietic Stem Cells in 4T1 Breast Cancer-Bearing Mouse.

Panax notoginseng (PN) has been used as a qi- and blood-activating (Huoxue) drug for thousands of years in China. It has also been widely used as an anticancer drug at present. As a Huoxue drug, the effect of PN on hematopoietic differentiation in tumor-bearing body has been paid more and more attention. Our research found that panax notoginseng saponins (PNS), especially panaxadiol saponins (PDS) and its aglucon 20(S)-Protopanaxdiol (PPD), could improve the immunosuppressive state by regulating the abnormal hematopoietic differentiation in a tumor-bearing body by multiple ways. An interesting phenomenon is that PDS reduced the neutrophil-lymphocyte ratio (NLR) via its inhibition effect on the granule-monocyte differentiation of spleen cells, which is associated with a decrease in the secretion of tumor MPO, G-CSF, PU.1, and C/EBPα. Otherwise, PDS increased the proportion of both hematopoietic stem cells and erythroid progenitor cells in the bone marrow, but inhibited spleen erythroid differentiation via inhibiting secretion of tumor EPO, GATA-1, and GATA-2. This study suggests that PNS regulated the tumor-induced abnormal granule-monocyte differentiation of hematopoietic stem cells, affecting the distribution and function of haemocytes in tumor-bearing mice.

Potential role of the compound Eucommia bone tonic granules in patients with osteoarthritis and osteonecrosis: A retrospective study.

BACKGROUND: Osteoarthritis is a major source of pain, disability, and socioeconomic cost worldwide. Osteonecrosis is a disabling disorder that frequently occurs in the younger population aged from 20-50 years. The compound Eucommia bone tonic granules, a traditional Chinese medicine, can alleviate the damage of osteoarthritis and osteonecrosis. AIM: To investigate the potential role of the compound Eucommia bone tonic granules (Eucommia) in the treatment of patients with osteoarthritis and osteonecrosis. METHODS: One-hundred forty osteoarthritis and osteonecrosis cases admitted to our hospital from January 2013 to December 2017 were selected. Patients were divided into two groups: Eucommia-meloxicam group and meloxicam group. Clinical efficacy and the Western Ontario and McMaster Universities Arthritis Index (WOMAC) score were evaluated according to the evaluation criteria of orthopedic diseases. The levels of bone-GLA protein, interleukin-17, recombinant human S100 calcium binding protein A12, sphingosine 1-phosphate, cystatin C, creatinine, and hemoglobin in peripheral blood were determined. RESULTS: The total effective rate in the two osteoarthritis groups was not different, but the total effective rate in the two osteonecrosis groups was significantly different. The overall efficacy of Eucommia-meloxicam group was superior to that of the meloxicam group. WOMAC showed that pain, stiffness, and dysfunction in the two groups of osteoarthritis and osteonecrosis before and after treatment were significantly different. The concentration of recombinant human S100 calcium binding protein A12, sphingosine 1-phosphate, cystatin C, creatinine, and hemoglobin before and after treatment in the Eucommia-meloxicam group and meloxicam group of osteoarthritis and osteonecrosis were significantly different, and the two treatment groups were significantly different from each other for osteoarthritis. CONCLUSION: Our findings indicate that Eucommia can effectively enhance the curative effect of meloxicam, and the combination of Eucommia and meloxicam is superior to meloxicam alone.

MicroRNA-34a inhibits bladder cancer cell migration and invasion, and upregulates PTEN expression.

MicroRNA-34a (miR-34a) serves as a tumor suppressor in a number of different types of cancer. The present study was performed to investigate the involvement of miR-34a in bladder cancer. In the present study, miR-34a was downregulated in patients with bladder cancer compared with the healthy controls in bladder biopsies and plasma. Downregulation of miR-34a distinguished between patients with bladder cancer and the healthy controls. miR-34a expression was associated with tumor metastasis; however, not with tumor size. Transfection of miR-34a mimics upregulated the expression of phosphatase and tensin homolog (PTEN) in bladder cancer cells, and decreased cell migration and invasion. miR-34a may inhibit bladder cancer cell migration and invasion by upregulating PTEN. miR-34a may additionally serve as a potential therapeutic target for bladder cancer.

[Evaluation and Comparison of SHA.LIN,S.T.O.N.E.Nephrolithometry Scoring System,and Clinical Research Office of the Endourological Society Nephrolithometry Nomogram for Predicting Stone Free Rate and Postoperative Outcomes after Percutaneous Nephrolithotomy].

To compare the accuracy of SHA.LIN,S.T.O.N.E.nephrolithometry scoring system,and Clinical Research Office of the Endourological Society(CROES)nephrolithometry nomogram in predicting percutaneous nephrolithotomy(PCNL)outcomes including stone free rate(SFR)and perioperative status. Methods The clinical data of 90 patients with nephrolithiasis undergoing PCNL in department of urology,China-Japan Friendship Hospital from January 2015 to March 2018 were retrospectively analyzed.The general data,stone characteristics,operation approaches,and perioperative variables were recorded.SHA.LIN,S.T.O.N.E.score,and CROES nomogram were assigned according to the computed tomography(CT)findings before surgery.Stone free status was evaluated by kidney-ureter-bladder one month after PCNL.The relationships of SHA.LIN score,S.T.O.N.E.score,and CROES score with SFR,postoperative complications,operation time(OT),length of hospital stay(LOS),estimated blood loss(EBL),and decrease of hemoglobin was evaluated.Receiver operating characteristic(ROC)curves were used to analyze the predictive accuracy. Results The SFR was 72.2%(65/90)and postoperative complications occurred in 33 cases(36.7%).The mean OT was(103.1±39.6)min,the mean EBL was(46.1±53.0)ml,the mean LOS was(15.3±5.2)d,the mean postoperative LOS was(8.5±3.4)d,and the mean decrease of hemoglobin was(16.1±10.2)g/L.Stone-free patients had significantly lower SHA.LIN score(8.23 vs. 10.36,P=0.000)and S.T.O.N.E.score(7.05 vs.8.16,P=0.000)and significantly higher CROES score(188.50 vs. 143.89,P=0.000)compared to patients with residual fragments.All these scores were not significantly associated with complications(P>0.05).On the other hand,all these scores were significantly correlated with OT,EBL,and decrease of hemoglobin(SHA.LIN:POT=0.006,PEBL=0.028,Pdecrease of hemoglobin=0.014;S.T.O.N.E.:POT=0.012,PEBL=0.047,Pdecrease of hemoglobin=0.011;and CROES:POT=0.040,PEBL=0.045,Pdecrease of hemoglobin=0.013).SHA.LIN(P=0.001)and S.T.O.N.E.(P=0.005)scores were associated with LOS.Logistic regression analysis revealed that SHA.LIN(OR=2.491),S.T.O.N.E.(OR=3.030),and CROES(OR=0.973)scores were significantly associated with stone-free status.ROC curves in predicting SFR showed that there was significant difference in the areas under the curves(AUC)for the SHA.LIN vs. S.T.O.N.E.score [0.808(95% CI=0.711-0.905)vs. 0.748(95% CI=0.632-0.864),P=0.047].AUC for the CROES score [0.770(95% CI=0.664-0.877)] showed no significantly different for the SHA.LIN score or the S.T.O.N.E.score(P>0.05). Conclusions All these three scoring systems have good predictive accuracy for SFR.SHA.LIN is more precise than S.T.O.N.E.in predicting SFR.However,they can not predict postoperative complications.

Hsp90ß interacts with MDM2 to suppress p53-dependent senescence during skeletal muscle regeneration.

Cellular senescence plays both beneficial and detrimental roles in embryonic development and tissue regeneration, while the underlying mechanism remains elusive. Recent studies disclosed the emerging roles of heat-shock proteins in regulating muscle regeneration and homeostasis. Here, we found that Hsp90ß, but not Hsp90α isoform, was significantly upregulated during muscle regeneration. RNA-seq analysis disclosed a transcriptional elevation of p21 in Hsp90ß-depleted myoblasts, which is due to the upregulation of p53. Moreover, knockdown of Hsp90ß in myoblasts resulted in p53-dependent cellular senescence. In contrast to the notion that Hsp90 interacts with and protects mutant p53 in cancer, Hsp90ß preferentially bound to wild-type p53 and modulated its degradation via a proteasome-dependent manner. Moreover, Hsp90ß interacted with MDM2, the chief E3 ligase of p53, to regulate the stability of p53. In line with these in vitro studies, the expression level of p53-p21 axis was negatively correlated with Hsp90ß in aged mice muscle. Consistently, administration of 17-AAG, a Hsp90 inhibitor under clinical trial, impaired muscle regeneration by enhancing injury-induced senescence in vivo. Taken together, our finding revealed a previously unappreciated role of Hsp90ß in regulating p53 stability to suppress senescence both in vitro and in vivo.

Immunohistochemical detection of PD-L1 among diverse human neoplasms in a reference laboratory: observations based upon 62,896 cases.

Targeting of the PD1/PD-L1 immune checkpoint pathway has rapidly gained acceptance as a therapeutic strategy for a growing number of malignancies. Testing for expression of PD-L1 in tumor cells and immune cells has been used as a companion or complementary test for drugs targeting the PD1/PD-L1 pathway. We evaluated the results of PD-L1 testing in a large reference lab cohort. Using Food and Drug Administration-approved methods and interpretive instructions for each individual test, 62,896 cases were evaluated for PD-L1 using antibody clone 22C3, 28-8, SP142, or SP263. Case data analyzed included test results and information on tumor location and clinical history. No clinical outcome information was available and no attempt was made to correlate PD-L1 results with any other tests performed. The following numbers of cases were evaluated: 22C3 with tumor proportion score [n = 52585], 22C3 with combined positive score [n = 2631], 28-8 [n = 4191], SP142 [n = 850], and SP263 [n = 70]. In 22C3/tumor proportion score cases, the general results were as follows: negative 33.1% (n = 17,405), (low) expression 33.9% (n = 17,822), and high expression 29.5% (n = 15,486). In cases identified as metastatic, the results were as follows: negative 35.9% (n = 1411), (low) expression 30.8% (n = 1211), and high expression 30.7% (n = 1208). We found broad ranges of expression in tumor types with increasing positivity, as adenocarcinomas were reported as poorly differentiated, whereas squamous cell carcinomas showed more positivity as tumors were described as well-differentiated. The results of many individual tumor types were evaluated and showed, in general, high levels of positive expression. Practical challenges and observations of PD-L1 stain results and interpretation are also discussed.

Simultaneous Detection of Eight Prohibited Flavor Compounds in Foodstuffs Using Gas Chromatography-Tandem Mass Spectrometry.

A multiflavor detection method, using gas chromatography-triple quadrupole tandem mass spectrometry (GC-MS/MS), has been developed for the simultaneous identification and quantification of eight prohibited flavor compounds in daily foods. Under the optimized extraction conditions, samples were purified directly through membrane filtration. Variables affecting the GC-MS/MS were optimized to obtain better separation. The excellent selectivity and sensitivity achieved in multiple reactions monitoring mode allowed satisfactory confirmation and quantitation. In this study, the linear ranges of the target compounds were 0.05 to 500 ng/L with good correlation coefficients ( R2 > 0.999). The limits of detection of target compounds ranged from 0.005 to 0.2 µg/kg. The average recoveries were in the range of 80.2 to 110.6% (beef jerky), 82.3 to 94.1% (cod liver oil), and 83.6 to 104.1% (candy).