Meta-analysis of risk factors for restenosis after stent implantation in patients with ischemic cerebrovascular disease.

OBJECTIVE: The aim of this study was to investigate the risk factors for restenosis after stent implantation in patients with ischemic cerebrovascular disease (ICVD), and to provide a reference for potential measures to prevent ICVD. MATERIALS AND METHODS: Relevant studies were identified by searching PubMed, ScienceDirect and Web of Science databases. Combined adjusted odds ratios and 95% confidence intervals were calculated. RESULTS: Seven case-control studies were identified in the end. Diabetes mellitus and residual stenosis were the two main risk factors for restenosis (OR = 0.59, 95% CI: 0.39-0.91, p = 0.01; OR = 36.73, 95% CI: 19.72-70.02, p < 0.001). Gender, smoking, hypertension, dyslipidemia, and stent type were not significantly associated with restenosis (OR = 0.85, 95% CI: 0.53-1.38, p = 0.52; OR = 1.30, 95% CI: 0.91-1.86, p = 0.15; OR = 0.86, 95% CI: 0.16-4.66, p = 0.86; OR = 1.30, 95% CI: 0.58-2.91, p = 0.53; OR = 1.34, 95% CI: 0.72-2.48, p = 0.35). CONCLUSIONS: The prevention of restenosis after stenting is particularly important for ICVD patients with diabetes or a high residual stenosis rate.

[Analysis of suspected occupational diseases cases and subsequent diagnosis follow-up investigation in Hubei Province from 2020 to 2021].

Objective: To understand the epidemiological characteristics of suspected occupational diseases cases, and to track the subsequent diagnosis of suspected cases in Hubei Province from 2020 to 2021, and to provide theoretical basis for the supervision of suspected occupational diseases. Methods: In April 2022, the data of suspected occupational diseases cases and occupational diseases in Hubei Province from 2020 to 2021 were collected by the Occupational Diseases and Health Risk Factors Information Surveillance System. The distribution and diagnosis of suspected occupational diseases cases were analyzed. We investigated undiagnosed suspected occupational diseases by telephone. Results: From 2020 to 2021, a total of 1872 cases of suspected occupational diseases in 6 categories and 18 species were reported in Hubei Province. The top three suspected occupational diseases were suspected occupational noise deafness (36.75%, 688/1872), suspected coal worker's pneumoconiosis (33.07%, 619/1872) and suspected silicosis (20.99%, 393/1872). The diagnosis rate of suspected occupational diseases was 33.60% (629/1872). The rate of confirmed diagnosis was 63.59% (400/629). The diagnosis rate (26.86%, 456/1698) and rate of confirmed diagnosis (55.48%, 253/456) of suspected occupational diseases detected by occupational health examination were the lowest. The diagnosis rate of suspected occupational diseases detected by comprehensive medical institutions and private medical institutions were lower than disease prevention and control institutions and occupational disease prevention center (P<0.05). The main reasons for not entering the diagnostic procedure included that workers were not informed that they were diagnosed as suspected occupational diseases (31.55%, 124/393), workers were unwilling to apply for occupational disease diagnosis (18.56%, 73/393), and some workers planned to apply for diagnosis but had not yet applied (10.69%, 42/393) . Conclusion: Occupational noise deafness, coal worker's pneumoconiosis and silicosis are the main diseases of suspected occupational diseases in Hubei Province. In order to increase the diagnosis rate and confirmed diagnosis rate of suspected occupational diseases, it is suggested to strengthen management and supervision from the aspects of case management, information warning and worker notification.

Microsomal glutathione S-transferase 1 targets the autophagy signaling pathway to suppress ferroptosis in gastric carcinoma cells.

OBJECTIVE: Ferroptosis is a newly discovered form of programmed cell death; however, the specific mechanisms that regulate ferroptosis have yet to be fully elucidated in gastric carcinoma. In this study, we aimed to investigate how microsomal glutathione S-transferase 1 (MGST1) regulates ferroptosis in gastric carcinoma cells. METHODS: Gastric adenocarcinoma (SGC7901) cells that overexpressed MGST1 or expressed only low levels of MGST1, were treated with specific compounds (erastin, sorafenib, RSL3, MK-2206 and SC79). Then, we detected the levels of malondialdehyde (MDA), glutathione (GSH), iron and reactive oxygen species (ROS). Protein expression levels of the non-classical autophagy and protein kinase B (Akt)/glycogen synthase kinase-3ß (GSK-3ß) pathways were determined by western blotting and cell viability was analyzed by Cell Counting Kit-8 (CCK-8) assays. The expressions of target genes were detected using qRT-PCR. RESULTS: We evaluated a range of ferroptosis-inducing compounds and found that MGST1 expression was down-regulated during ferroptosis in SGC7901 cells. The ferroptosis inducer RSL3 played a role in classical ferroptotic events while the overexpression of MGST1 impaired these effects. Interestingly, the overexpression of MGST1 resulted in the inactivation of autophagy by repressing the expression of ATG16L1 and the conversion of LC3-I to LC3-II. The upregulation of ATG16L1 eliminated the inhibitory action of MGST1 on ferroptosis. Notably, the overexpression of MGST1 induced the activation of the Akt/GSK-3ß pathway. An Akt inhibitor antagonized the inhibitory effects of MGST1 on autophagy and ferroptosis. CONCLUSION: Collectively, our findings demonstrate a novel molecular mechanism and signaling pathway for ferroptosis. We also characterized that the overexpression of MGST1 induces gastric carcinoma cell proliferation by activating the Akt/GSK-3ß signaling pathway.

Hearing Preservation and Spatial Hearing Outcomes After Cochlear Implantation in Children With TMPRSS3 Mutations.

OBJECTIVE: Investigate hearing preservation and spatial hearing outcomes in children with TMPRSS3 mutations who received bilateral cochlear implantation. STUDY DESIGN AND METHODS: Longitudinal case series report. Two siblings (ages, 7 and 4 yr) with TMPRSS3 mutations with down-sloping audiograms received sequential bilateral cochlear implantation with hearing preservation with low-frequency acoustic amplification and high-frequency electrical stimulation. Spatial hearing, including speech perception and localization, was assessed at three time points: preoperative, postoperative of first and second cochlear implant (CI). RESULTS: Both children showed low-frequency hearing preservation in unaided, acoustic-only audiograms. Both children demonstrated improvements in speech perception in both quiet and noise after CI activations. The emergence of spatial hearing was observed. Each child's overall speech perception and spatial hearing when listening with bilateral CIs were within the range or better than published group data from children with bilateral CIs of other etiology. CONCLUSION: Bilateral cochlear implantation with hearing preservation is a viable option for managing hearing loss for pediatric patients with TMPRSS3 mutations.

[A case of fungal conjunctivitis manifested by a conjunctival mass].

A 71-year-old man presented with a history of persistent redness and swelling in the left eye accompanied by an enlarging mass in the conjunctiva. He denied any history of trauma. Local anti-inflammatory treatment was ineffective. Slit lamp examination demonstrated a tough and immobile grayish broad basal mass at the corneal limbus and bulbar conjunctiva and a local bulge of 3 mm × 2 mm at the medial and lateral side of the upper palpebral conjunctiva near the eyelid margin. The excisional biopsy showed granulomatous inflammation with irregular and atypical squamous epithelial hyperplasia. Histopathology and immunohistochemical staining revealed a fungal infection. The secretion smear examination was performed to clarify the pathogen as Candida albicans, and chronic fungal maxillary sinusitis was found through imaging tests. Thus a diagnosis of conjunctival candidiasis was made. The conjunctival mass subsided after systemic and local antifungal therapy.

[Analysis of hepatic pathological inflammation and fibrosis condition and its influencing factors in 721 patients with chronic hepatitis B with normal ALT].

Objective: To analyze the hepatic pathological inflammation and fibrosis condition in order to explore the relationship with related clinical indicators in patients with chronic hepatitis B patients with normal alanine aminotransferase (ALT). Methods: 721 cases of chronic hepatitis B with normal ALT who were initially diagnosed in the Department of Infectious Diseases of Henan Provincial People's Hospital from August 2016 to December 2019 were retrospectively collected. Liver biopsy was performed in all patients. General data of patients such as gender, age, liver function indexes, blood routine indexes, HBsAg level, HBeAg status, HBV DNA level, spleen thickness and prothrombin time were collected. Univariate and multivariate analysis methods were used to determine the influencing factors of inflammation and fibrosis degree with liver biopsy. A receiver operating characteristic curve (ROC) was used to evaluate the established multi-factor prediction model. Alpha=0.05 was considered as a standard orientation of test. Results: The average age of 721 cases with chronic hepatitis B was 36.1±9.7 years, and the male to female ratio was 1.28/1, with inflammation and fibrosis grade mainly concentrated in G1S1 (349 cases), G1S2 (132 cases), G2S2 (119 cases), and G2S1 (57 cases). Among them, there were 349 (48.4%) cases of G1S1, and 372 (51.6%) cases of G/S≥2. The main manifestations were mild to moderate inflammation and fibrosis, and only 64 (8.88%) cases had severe G/S≥3. HBsAg level (stratified with 4 log10 IU/ml as the boundary) analyzed in 721 cases were correlated with the relevant clinical indicators stratification and liver pathological inflammation and fibrosis, and the difference was statistically significant (inflammation grade, χ2=6.182, P=0.013; Fibrosis grade, χ2=36.534, P=0.001). Univariate analysis of the relevant clinical indicators that may influence the patient's liver pathological G/S ≥2 showed the patient's age, albumin, γ- glutamyltransferase (GGT), platelet, prothrombin time (PT), spleen thickness and HBsAg level were all statistically significant (P<0.05), while multivariate analysis showed that age, GGT, PT, and spleen thickness had statistical differences (P<0.05). The prediction model was established in accordance to multivariate analysis, and the area under the ROC curve was 0.642. Maximization of the sum of sensitivity and specificity as cut-off value of Logit P=0.497, the diagnostic sensitivity, specificity, and Youden's index were 60.6%, 64.5%, and 0.252, respectively. Conclusion: More than half of patients with chronic hepatitis B with normal ALT have significant inflammation and fibrosis and require timely antiviral therapy. Age, GGT, PT and spleen thickness can help comprehensively evaluate the liver inflammation and fibrosis status among patients, but the lack of accurate prediction models suggests that more effective indicators that can help predict the inflammation and fibrosis status of such patients have yet to be discovered. Therefore, liver biopsy should still be actively performed in patients with normal ALT to confirm the diagnosis and timely treatment.

[Effects of sodium iodide symporter co-expression on proliferation and cytotoxic activity of chimeric antigen receptor T cells in vitro].

OBJECTIVE: To investigate the effects of co-expression of sodium iodide symporter (NIS) reporter gene on the proliferation and cytotoxic activity of chimeric antigen receptor (CAR)-T cells in vitro. METHODS: T cells expressing CD19 CAR (CAR-T cells), NIS reporter gene (NIS-T cells), and both (NIS-CAR-T cells) were prepared by lentiviral infection. The transfection rates of NIS and CAR were determined by flow cytometry, and the cell proliferation rate was assessed using CCK-8 assay at 24, 48 and 72 h of routine cell culture. The T cells were co-cultured with Nalm6 tumor cells at the effector-target ratios of 1∶2, 1∶1, 2∶1 and 4∶1 for 24, 48 and 72 h, and the cytotoxicity of CAR-T cells to the tumor cells was evaluated using lactate dehydrogenase (LDH) assay. ELISA was used to detect the release of IFN-γ and TNF-ß in the co-culture supernatant, and the function of NIS was detected with iodine uptake test. RESULTS: The CAR transfection rate was 91.91% in CAR-T cells and 99.41% in NIS-CAR-T cells; the NIS transfection rate was 47.83% in NIS-T cells and 50.24% in NIS- CAR-T cells. No significant difference in the proliferation rate was observed between CAR-T and NIS-CAR-T cells cultured for 24, 48 or 72 h (P> 0.05). In the co-cultures with different effector-target ratios, the tumor cell killing rate was significantly higher in CAR-T group than in NIS-CAR-T group at 24 h (P < 0.05), but no significant difference was observed between the two groups at 48 h or 72 h (P>0.05). Higher IFN-γ and TNF-ß release levels were detected in both CAR-T and NIS-CAR-T groups than in the control group (P < 0.05). NIS-T cells and NIS-CAR-T cells showed similar capacity of specific iodine uptake (P>0.05), which was significantly higher than that in the control T cells (P < 0.05). CONCLUSION: The co-expression of the NIS reporter gene does not affect CAR expression, proliferation or tumor cell-killing ability of CAR-T cells.

[Assessment of MS-Score and HScore in timeliness of diagnosis of macrophage activation syndrome associated with adult-onset Still's disease].

The data of 33 patients with adult-onset still's disease (AOSD)-associated macrophage activation syndrome (MAS) were retrospectively collected from January 2013 to December 2020 in Peking Union Medical College Hospital. Hemophagocytic lymphohistiocytosis (HLH)-2004 criteria, macrophage activation syndrome/juvenile idiopathic arthritis (MS-Score) and hemophagocytic syndrome diagnostic score (HScore) were used to diagnose AOSD-associated MAS, respectively. The time of diagnosis of AOSD-associated MAS by MS-Score was 19.0 (4.5, 31.0) days [M (Q1,Q3)] earlier than by HLH-2004 criteria, and 13.5 (0.5, 21.5) days earlier than by HScore (both P<0.05). The difference was not statistically significant between the time of diagnosis of AOSD-associated MAS by Hscore and by HLH-2004 criteria (P>0.05). There was significant difference among the three criteria (P<0.001). MS-Score can be used to diagnose AOSD-associated MAS earlier than HLH-2004 criteria, while the timeliness of HScore is not certain.

[Glucose-6 phosphatase catalytic subunit inhibits the proliferation of liver cancer cells by inducing cell cycle arrest].

Objective: To investigate the effects of glucose-6-phosphatase catalytic subunit (G6PC) recombinant adenovirus on proliferation and cell cycle regulation of liver cancer cells. Methods: Recombinant adenovirus AdG6PC was constructed. Huh7 cells and SK-Hep1 cells were set as Mock, AdGFP and AdG6PC group. Cell proliferation and clone formation assay were used to observe the proliferation of liver cancer cells. Transwell and scratch assay were used to observe the invasion and migration of liver cancer cells. Cell cycle flow cytometry assay was used to analyze the effect of G6PC overexpression on the proliferation cycle of liver cancer cells. Western blot was used to detect the effect of G6PC overexpression on the cell-cycle protein expression in liver cancer cells. Results: The recombinant adenovirus AdG6PC was successfully constructed. Huh7 and SK-Hep1 cells proliferation assay showed that the number of proliferating cells in the AdG6PC group was significantly lower than the other two groups (P < 0.05). Clone formation assay showed that the number of clones was significantly lower in AdG6PC than the other two groups (P < 0.05), suggesting that G6PC overexpression could significantly inhibit the proliferation of liver cancer cells. Transwell assay showed that the number of cell migration was significantly lower in AdG6PC than the other two groups (P < 0.05). Scratch repair rate was significantly lower in AdG6PC than the other two groups (P < 0.05), suggesting that G6PC overexpression can significantly inhibit the invasion and migration of liver cancer cells. Cell cycle flow cytometry showed that G6PC overexpression had significantly inhibited the Huh7 cells G(1)/S phase transition. Western blot result showed that G6PC overexpression had down-regulated the proliferation in cell-cycle related proteins expression. Conclusion: G6PC inhibits the proliferation, cell-cycle related expression, and migration of liver cancer cells by inhibiting the G(1)/S phase transition.

[Effectiveness of the "14 plus 7 day quarantine" and "nucleic acid plus total antibody testing" strategy for screening imported patients with COVID-19 in Xiamen].

Objective: To analysis effectiveness of the "14 plus 7 day quarantine" and "nucleic acid plus total antibody testing" strategy (combined screening strategy) for screenin the imported patients with COVID-19 in Xiamen. Methods: The study populations were overseas travelers arriving in Xiamen from March 17 to December 31, 2020, and overseas travelers who had quarantine outside Xiamen for less than 21 days from July 18 to December 31, 2020. Data were collected and analyzed on the timing of detection, pathways, and test results of the imported patients with COVID-19 after implementing combined screening strategy. Results: A total of 304 imported patients with COVID-19 were found from 174 628 overseas travelers and 943 overseas travelers from other cities. A total of 163 cases (53.6%) were diagnosed by multitime, multisite intensive nucleic acid testing after positive finding in total antibody testing. Among them, 27 (8.9%) were first positive for nucleic acid in 14 plus 7 day quarantine and 136 were first positive for nucleic acid in 14-day quarantine. Only 8 of these individuals were tested positive for nucleic acid after positive total antibody testing. The other 128 individuals were tested positive for nucleic acid after being negative for average 2.3 times (maximum of 6 times). Aditional 155 cases might be detected by using the combined "14 plus 7 day quarantine" and " nucleic acid plus total antibody testing" strategy compared with "14-day quarantine and nucleic acid testing" strategy, accounting for 51.0% of the total inbound infections. So the combined screening strategy doubled the detection rate for imported patients with COVID-19. No second-generation case caused by overseas travelers had been reported in Xiamen as of February 26, 2021. Conclusions: Xiamen's combined screening strategy can effectively screen the imported patients with COVID-19 who were first positive for nucleic acid after 14 day quarantine. Compared with "14 day quarantine and nucleic acid testing", the combined screening strategy improved detection rate and further reduced the risk of the secondary transmission caused by the imported patients with COVID-19.

[Occurrence and prediction on post-contrast acute kidney injury following endovascular interventions].

Objective: To investigate the incidence, risk factors and prognosis of post-contrast acute kidney injury (PC-AKI) and to evaluate the usefulness of serum cystatin C (sCysC) and serum creatinine (sCr) for the prediction of PC-AKI after endovascular interventions. Methods: The clinical data of 404 patients who underwent endovascular procedures from August 2014 to October 2018 in the Sixth People's Hospital South Campus, Shanghai Jiao Tong University were retrospectively analyzed. All patients received 0.9% sodium chloride through an angiographic catheter during the procedure. Patients with an estimated GFR (eGFR)<60 ml/(min·1.73m2) received a continuous intravenous hydration with isotonic saline from 6 hours before to 12 hours after an endovascular procedure. The level of sCr, eGFR and sCysC were measured at 1-2 days pre-procedure and at 48, 72 h, and 7 days post-procedure. Univariate and multivariate logistic regression analyses were used to identify risk factors of PC-AKI. A receiver operator characteristic (ROC) curve was used to evaluate the usefulness of various factors for the prediction of PC-AKI. Kaplan-Meier method was used for survival analysis. Results: Thirteen patients (3.2%) developed PC-AKI. All patients were divided into PC-AKI group and no PC-AKI group for statistical comparison. Wilcoxon signed rank sum test revealed that sCr levels at 7 days post-procedure [63.0 (56.0, 74.0) µmol/L] were significantly lower than pre-procedure sCr levels [65.6 (56.2, 77.0) µmol/L] in patients without PC-AKI (P<0.05). Meanwhile, eGFR levels were significantly higher at 72 h [114.9 (96.3, 135.0) ml/(min·1.73m2)] and 7 days [116.7 (98.5, 139.9) ml/(min·1.73m2)] post-procedure than eGFR levels before endovascular procedures [112.3 (94.1, 133.5) ml/(min·1.73m2)] in patients without PC-AKI (P<0.05). However, there was an increase in sCysC at 48 h [0.9 (0.8, 1.1) mg/L] after endovascular procedures than pre-operative sCysC [0.9 (0.8, 1.1) mg/L] in patients without PC-AKI (P<0.05). SCr, sCysC, levels were significantly increased at 48 h [108.0 (95.3, 125.0) µmol/L, 1.5 (1.2, 2.0) mg/L] and 72 h [123.4 (91.3, 143.0) µmol/L, 1.6 (1.1, 2.0) mg/L] post-procedure than SCr, sCysC, levels before endovascular procedures [81.6 (63.1, 111.0) µmol/L, 1.1 (1.0,1.7) mg/L] and eGFR levels were significantly decreased at 48 h [55.8 (48.9, 77.6) ml/(min·1.73m2)] and 72 h [52.7 (47.7, 63.9) ml/(min·1.73m2)] after endovascular procedures than eGFR levels before exposure to CM [88.8 (65.6, 100.7) ml/(min·1.73m2)] in patients with PC-AKI (P<0.05). SCr, sCysC and eGFR in PC-AKI group tended to levels before an endovascular procedure within 7 days. The receiver operator characteristic curve (ROC) analysis showed that preoperative sCysC and sCr levels had high discriminatory power for evaluating the risk of PC-AKI after an endovascular procedure. ROC analysis showed that sCysC before endovascular procedures was useful to predict the risk of PC-AKI with a satisfactory sensitivity of 69.2% (9/13), specificity of 77.5% (300/387), positive predictive value (PPV) of 9.3% (9/96) and negative predictive value (NPV) of 98.7% (300/304). The incidence of PC-AKI was low in patients with a pre-procedure sCysC<1.09 mg/L. The sCr was predictive of PC-AKI with a satisfactory sensitivity of 69.2% (9/13), specificity of 76.7% (300/391), PPV of 9.0% (9/100) and NPV of 98.7% (300/304). The incidence of PC-AKI was low in patients with a pre-procedure sCr<77.6 µmol/L. Results of univariate analysis and multiple logistic regression analysis indicated that sCysC before endovascular procedures was an risk factor for PC-AKI (OR=13.917, 95%CI:1.666-116.237, P=0.015). The one-year, three-year and five-year survival rate for patients diagnosed with PC-AKI was 50%, 30% and 30% respectively. The median survival time was 6 (0-26) months. Conclusions: The sCysC before endovascular procedures is an independent risk factor of PC-AKI. SCysC and SCr before an endovascular procedure with a cut-off value of 1.09 mg/L and 77.6 µmol/L may help to rule out patients at lower risk of PC-AKI.

[Impacts of incomplete revascularization following off-pump coronary artery bypass grafting on perioperative outcomes in octogenarians].

Objective: To assess the impacts of incomplete revascularization following off-pump coronary artery bypass grafting (OPCABG) on perioperative outcomes in octogenarians. Methods: A retrospective analysis of 242 octogenarian patients with coronary artery disease (CAD) hospitalized in Beijing Anzhen Hospital from June 2008 to July 2016 was performed. These patients were divided into the complete revascularization group (n=181) and the incomplete revascularization group (n=61) depending on whether they underwent complete revascularization. The impacts of incomplete revascularization following OPCABG on perioperative outcomes were summarized and compared between the two groups. Results: Among the 242 patients over 80 years who received OPCABG, there were 198 males (81.8%). Compared to the complete revascularization group, those in the incomplete revascularization group were older [(83.2±1.5) vs (81.5±1.1) years old, P=0.03], with more carotid stenosis (44.3% vs 25.4%, P=0.01), more involved in the diagonal and circumflex branch of coronary artery (49.2% vs 17.1%, P=0.01; 83.6% vs 70.2%, P=0.03), shorter operative time [(4.1±1.7) h vs (4.7±1.2) h, P=0.03), longer preoperative [(7.1±2.3) d vs (5.2±2.0) d, P=0.01] and total hospitalization time [(16.3±6.8) d vs (12.5±4.2) d, P=0.01], however, the differences of the in-hospital mortality and incidence of other perioperative complications were not statistically significant between the two groups (all P>0.05). Conclusion: Compared with complete revascularization, incomplete revascularization following OPCABG in CAD patients over 80 years old does not increase the perioperative mortality and the incidence of other complications, and it reduces the operative time. However, it increases the time of preoperative and total hospital stay.

Systematic investigation of metallosis associated with magnetically controlled growing rod implantation for early-onset scoliosis.

AIMS: To investigate metallosis in patients with magnetically controlled growing rods (MCGRs) and characterize the metal particle profile of the tissues surrounding the rod. METHODS: This was a prospective observational study of patients with early onset scoliosis (EOS) treated with MCGRs and undergoing rod exchange who were consecutively recruited between February 2019 and January 2020. Ten patients were recruited (mean age 12 years (SD 1.3); 2 M:8 F). The configurations of the MCGR were studied to reveal the distraction mechanisms, with crucial rod parts being the distractable piston rod and the magnetically driven rotor inside the barrel of the MCGR. Metal-on-metal contact in the form of ring-like wear marks on the piston was found on the distracted portion of the piston immediately outside the barrel opening (BO) through which the piston rod distracts. Biopsies of paraspinal muscles and control tissue samples were taken over and away from the wear marks, respectively. Spectral analyses of the rod alloy and biopsies were performed to reveal the metal constituents and concentrations. Histological analyses of the biopsies were performed with haematoxylin and eosin staining. RESULTS: Titanium (Ti), vanadium (V), and neodymium (Nd) concentrations in the biopsies taken near the wear marks were found to be significantly higher than those in the control tissue samples. Significantly increased Nd concentrations were also found in the tissues near the barrel of the MCGR. Chronic inflammation was revealed by the histological studies with fibrosis and macrophage infiltration. Black particles were present within the macrophages in the fibrotic tissues. CONCLUSION: Ti and V were generated mainly at the BO due to metal-on-metal contact, whereas the Nd from the rotor of the MCGR is likely released from the BO during distraction sessions. Phagocytotic immune cells with black particles inside raise concern regarding the long-term implications of metallosis. Cite this article: Bone Joint J 2020;102-B(10):1375-1383.

[Surgical selection and metastatic warning of splenic lymph node dissection in advanced gastric cancer radical surgery: a prospective, single-center, randomized controlled trial].

Objective: To investigate the surgical options for splenic lymph node dissection in patients with advanced gastric cancer undergoing radical total gastrectomy, and to evaluate the sentinel effect of No. 4s lymph node on splenic lymph node metastasis. Methods: A prospective, single-center, randomized and controlled study was carried out (Trial registration, No.NCT02980861). Enrollment criteria: (1) >18 years old and <65 years old; (2) gastric adenocarcinoma locating in the proximal or corpus; (3) preoperative clinical staging as cT2-4aN0-3M0; (4) D2 radical total gastrectomy feasible judged before operation; (5) physical ability score 0 to 1; (6) I to III of ASA classification. Pregnant or lactating women, patients with severe mental illness or previous history of upper abdominal surgery, those suffered from other malignant tumors in the past 5 years, or heart and lung system diseases judged to affect surgery before operation, those receiving preoperative chemotherapy, radiotherapy or targeted therapies, and distant metastases being found during surgery were excluded. According to above criteria, 222 patients at The First Medical Center of Chinese PLA General Hospital from December 2016 to December 2017 were enrolled prospectively and were randomly divided into the laparoscopic splenic hilar lymph node dissection group (laparoscopic group, n=114) and the open splenic hilar lymph node dissection group (open group, n=108). The result of rapid frozen immunohistochemistry of harvested No.4s lymph nodes was used to evaluate the sensitivity and specificity of sentinel effect on splenic hilar lymph node metastasis. The surgical parameters, postoperative recovery parameters, and complication rates were compared between the two groups. Results: There were 80 males and 34 females in the lapascopic group with a mean age of (56.1±10.2) years, and 69 males and 39 females in the open group with a mean age of (58.4±10.9) years. There were no significant differences in baseline data between the two groups (all P>0.05). Total blood loss was less in the laparoscopic group [(96.3±82.4) ml vs. (116.6±101.9) ml, t=1.124, P<0.001], and the amount of bleeding from the splenic hilar lymph nodes dissected was also less than that in the open group [(25.3±17.8) ml vs. (59.5±36.4) ml, t=1.172, P<0.001]. However, the operation time, the time of splenic hilar lymph node, the number of lymph node dissected and number of splenic hilar lymph node dissected were not significantly different between the two groups (all P>0.05). As compared to the open group, the laparoscopic group had shorter time to the first flatus [(1.3±1.2) days vs. (1.6±1.5) days, t=1.665, P=0.021], shorter time to fluid diet [(4.6±1.4) days vs. (4.9 ± 1.6) days, t=1.436, P=0.007], shorter time to remove nasogastric tube [(3.9±2.6) days vs. (4.3±2.4) days, t=0.687, P<0.001] and shorter hospital stay [(10.3±6.6) days vs. (12.1±7.2) days, t=0.697, P<0.001]. Complication rate was 14.0% (16/114) and (12.0%) ((1)3/108) in the laparoscopic group and the open group, respectively, without significant difference (χ(2)=6.723, P=0.331). The sensitivity of the No. 4s lymph node for the prediction of splenic hilar lymph node metastasis reached 89.5%, and the specificity reached 99.6%. Conclusions: Laparoscopic technique is safe and feasible in the treatment of splenic hilar lymph node dissection in advanced gastric cancer. The No.4s lymph node examination has good sentinel effect on predicting the metastasis of splenic hilar lymph nodes.

Prognostic alternative splicing regulatory network of splicing events in acute myeloid leukemia patients based on SpliceSeq data from 136 cases.

This study aimed to create prognostic signatures to predict AML patients' survival using alternative splicing (AS) events. The AS data, RNA sequencing data, and the survival statistics of 136 AML patients were obtained from The Cancer Genome Atlas (TCGA) and TCGA SpliceSeq databases. Total 34,984 AS events generated from 8,656 genes, 2,583 of which were survival-associated AS events, were identified using univariate Cox regression. The prognostic models constructed using independent survival-associated AS events revealed that low-risk splicing better predicted patients' survival. ROC analysis indicated that the predictive efficacy of the alternate terminator model was best in the area under the curve at 0.781. Enrichment analysis revealed several important genes (TP53, BCL2, AURKB, PPP2R1B, FOS, and BIRC5) and pathways, such as the protein processing pathway in the endoplasmic reticulum, RNA transport pathway, and HTLV-I infection pathway. The splicing network of splicing events and factors revealed interesting interactions, such as the positive correlation between HNRNPH3 and CALHM2-13010-AT, which may indicate the potential splicing regulatory mechanism. Taken together, survival-associated splicing events and the prognostic signatures for predicting survival can help provide an overview of splicing in AML patients and facilitate clinical practice. The splicing regulatory network may improve the understanding of spliceosomes in AML.

[Establishment of patient derived xenograft model of high-grade mucinous carcinoma peritonei accompanied with signet ring cells and identification of biological characteristics].

Objective: To establish the patient derived xenograft (PDX) model of pseudomyxoma peritonei (PMP), and identify the key characteristics of tumor biology of this model, in order to provide a reliable model for studying the pathological mechanisms and new therapeutic strategies of PMP. Methods: PMP tumor tissue was obtained from surgery and cut into pieces after washing. Then tumor pieces were implanted subcutaneously in BAL B/c-nu mice for 6 stable passages. In the 7th passage, tumor tissue was implanted orthotopically into abdomen. Subcutaneous tumor and orthotopic tumor were then homogenized to make tumor cell suspension, implanted into abdomen of 10 BAL B/c-nu mice through midline laparotomy, 100 µl for each. The key experimental parameters including body weight changes in the observation period, experimental peritoneal cancer index (ePCI) score at the autopsy, histopathological and immunohistochemical characteristics, and gene expression profiles by high-throughput whole-genome exon sequencing were detected and recorded. Results: The successful rate of established orthotopic PDX model of human PMP was 100% (10/10). The animals showed smooth body weight increases after tumor inoculation until day 27, then the body weight began to decrease steadily. Widespread tumor dissemination of PMP tumor through the whole abdomen was found by autopsy, including the diaphragm, liver, spleen, stomach, kidney, parietal peritoneum, bowel and mesenterium. Gelatinous ascites was also observed in abdominopelvic cavity. The ePCI score ranged from 5 to 9, with a 8 of median ePCI. Histopathological studies showed peritoneal mucinous carcinomatosis accompanied with signet ring cells (PMCA-S), obvious tumor cell atypia and parenchymal invasion.Immunohistochemistry showed the expressions of MUC1, MUC2, MUC5AC, CEA, CA199, CK20, CDX-2 and Ki-67 were positive, MUC6, CK7 and p53 were negative. Whole-exome sequencing identified that the most significant genetic alteration is the exon10 missense mutation c. 1621A>C of KIT gene, the mutation abundance was 89.7%. Conclusion: PDX model of PMCA-S is successfully established, which displays the characters of high-degree malignancy, high proliferation and strong aggressiveness.

[Clinical analysis of Langerhans cell histiocytosis originating in the base of nasal skull].

Objective:To summarize the clinical features, diagnosis and treatment of Langerhans histiocytosis（LCH） which first appeared in the nasal skull base. Method:Ten cases of LCH with nasal and skull base symptoms were analyzed retrospectively. The clinical characteristics of LCH with nasal and skull base symptoms were summarized. The correlation of other systems involved in LCH was analyzed. Result:Among the 10 patients, the youngest was 1 year and 5 months, and the oldest was 8 years, the average age was 3 years. The main imaging manifestations were osteolytic changes and soft tissue invasion. Seven patients were monofocal and three patients were multifocal. For localized lesions, radical resection and follow-up chemotherapy were performed, and conservative treatment was performed for patients with multiple system involvement and obvious systemic symptoms. Eight patients survived, 2 died. Conclusion:LCH occurs frequently in children and has certain clinical characteristics. Single system and single lesion surgery have a better therapeutic effect, and can achieve a greater survival rate with follow-up chemotherapy.

Genomic and transcriptional heterogeneity of multifocal hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) often presents with multiple nodules within the liver, with limited effective interventions. The high genetic heterogeneity of HCC might be the major cause of treatment failure. We aimed to characterize genomic heterogeneity, infer clonal evolution, investigate RNA expression pattern and explore tumour immune microenvironment profile of multifocal HCC. PATIENTS AND METHODS: Whole-exome sequencing and RNA sequencing were carried out in 34 tumours and 6 adjacent normal liver tissue samples from 6 multifocal HCC patients. Protein expression of Ki67, AFP, P53, Survivin and CD8 was detected by immunohistochemistry. Fluorescence in situ hybridization was carried out to validate the amplification status of sorafenib-targeted genes. RESULTS: We deciphered genomic and transcriptional heterogeneity among tumours in each multifocal HCC patient including mutational profiles, copy number alterations, tumour evolutionary trajectory and tumour immune microenvironment profiles. Of note, sorafenib-targeted alterations were identified in the trunk of phylogenetic tree in only one out of the six patients, which may explain the relative low treatment response rate to sorafenib in clinical practice. Moreover, we demonstrated RNA expression patterns and tumour immune microenvironment profiles of all nodules. We found that RNA expression pattern was associated with Edmondson-Steiner grading. Based on the differential expression of 66 reported immune markers, unsupervised hierarchical clustering analysis of 34 nodules identified immune subsets: one low expression cluster with seven nodules and one high expression cluster with 11 nodules. CD8+ T cells were more enriched in nodules of the high expression cluster. CONCLUSIONS: Our study provided a detailed view of genomic and transcriptional heterogeneity, clonal evolution and immune infiltration of multifocal HCC. The heterogeneity of druggable targets and immune landscape might help interpret the clinical responsiveness to targeted drugs and immunotherapy for multifocal HCC patients.