Development of a novel multi-functional integrated bioconjugate effectively targeting K-Ras mutant pancreatic cancer / 药物分析学报

Folate receptor(FR)overexpression occurs in a variety of cancers,including pancreatic cancer.In addi-tion,enhanced macropinocytosis exists in K-Ras mutant pancreatic cancer.Furthermore,the occurrence of intensive desmoplasia causes a hypoxic microenvironment in pancreatic cancer.In this study,a novel FR-directed,macropinocytosis-enhanced,and highly cytotoxic bioconjugate folate(F)-human serum albumin(HSA)-apoprotein of lidamycin(LDP)-active enediyne(AE)derived from lidamycin was designed and prepared.F-HSA-LDP-AE consisted of four moieties:F,HSA,LDP,and AE.F-HSA-LDP presented high binding efficiency with the FR and pancreatic cancer cells.Its uptake in wild-type cells was more extensive than in K-Ras mutant-type cells.By in vivo optical imaging,F-HSA-LDP displayed prominent tumor-specific biodistribution in pancreatic cancer xenograft-bearing mice,showing clear and lasting tumor localization for 360 h.In the MTT assay,F-HSA-LDP-AE demonstrated potent cytotoxicity in three types of pancreatic cancer cell lines.It also induced apoptosis and caused G2/M cell cycle arrest.F-HSA-LDP-AE markedly suppressed the tumor growth of AsPc-1 pancreatic cancer xenografts in athymic mice.At well-tolerated doses of 0.5 and 1 mg/kg,(i.v.,twice),the inhibition rates were 91.2％and 94.8％,respectively(P＜0.01).The results of this study indicate that the F-HSA-LDP multi-functional bioconjugate might be effective for treating K-Ras mutant pancreatic cancer.

Clinical characteristics of 83 patients with acute glyphosate herbicide poisoning / 中华急诊医学杂志

Objective:To analyze the clinical characteristics of patients with acute glyphosate herbicide poisoning and the differences in the severity of poisoning.Methods:A retrospective analysis was performed on patients with acute glyphosate herbicide poisoning admitted to the First Affiliated Hospital of Zhengzhou University from January 2014 to December 2020. The general information, exposure time, poisoning dose, poisoning cause, poisoning route, clinical manifestations, laboratory examination results during hospitalization, treatment measures, hospital stays and prognosis of the patients were collected. The patients were graded according to the poisoning severity scoring standard of Chinese Expert Consensus on Diagnosis and Treatment of Acute Poisoning in 2016. The highest severity score during hospitalization was used as the final grade. According to the final grade, asymptomatic and mild patients were included in the mild group, and moderate, severe and death patients were included in the severe group. The independent sample T test or Mann-Whitney U test was used for measurement data, and χ2 test or Fisher's exact test was used for counting data. The differences of general data and clinical data between the two groups were compared. Results:According to the inclusion and exclusion criteria, 83 patients with acute glyphosate herbicide poisoning were selected as the study subjects. All patients survived, mainly mild poisoning (56.6%), with a male to female ratio of 33∶50, and an average age of 39 years. The number of poisoning cases increased yearly (the highest in 2019), and most cases occurred in spring and summer. The main cause of poisoning was suicide (71.1%), direct oral administration (83.1%) was the primary route of poisoning, and the dominating clinical manifestations were digestive symptoms (71.1%). Laboratory tests showed increased white blood cell count (WBC), neutrophil percentage (NEUT %) and D-dimer, and decreased hemoglobin and potassium. Compared with the mild group, patients in the severe group were older [(51±17) years vs. (35±19) years], had a higher proportion of suicide and direct oral administration, a longer hospital stay [8.0 (4.8, 12.0) d vs. 3.0 (2.0, 5.5) d], a higher dose of poisoning [200.0 (50.0, 200.0) mL vs. 30.0 (11.3, 57.5) mL], and higher NEUT % within 24 h of admission [(83.4±10.4) vs. (73.2±12.8)]. The increase of WBC, NEUT %, aspartate aminotransferase, prothrombin time, D-dimer and the decrease of serum potassium were more common in the severe group than the mild group, with statistical significance (all P<0.05). Conclusions:The number of patients with acute glyphosate herbicide poisoning is increasing yearly. Generally, the condition is mild and the prognosis is satisfying. The severity is more serious in the middle-aged and elderly patients andthose with direct oral administration, high toxic dose, and high NEUT % within 24 h of admission. Severe poisoning is more likely to cause changes in laboratory indicators.

The prognostic value of platelet count related nomogram based on MIMIC-Ⅲ database for critically ill patients / 中华急诊医学杂志

Objective:To explore the relationship between platelet count (PLT) and organ dysfunction and prognosis in critically ill patients and its prognostic evaluation.Methods:A retrospective cohort study was conducted. The relevant records of 35 860 patients were extracted from the US Intensive Care Database (MIMIC-Ⅲ) from 2001 to 2012. According to the PLT count, patients were divided into the thrombocytopenia group (PLT<100×10 9/L), normal platelet group (100×10 9/L≤PLT≤300×10 9/L), and thrombocytosis group (PLT>300×10 9/L). This study included adult patients between 18 and 89 years old. Patients with survival time less than 24 h and lack of vital signs or PLT values were excluded. The outcome event was the hospital mortality of the patient. Survival was analyzed by the Kaplan-Meier method. The prognostic factors were identified by univariate and multivariate COX analyses. The nomogram to predict hospital mortality was built by the significant prognostic factors. In combination with the important prognostic factors, a nomogram was established to predict the prognosis of critically ill patients in hospital, and the AUC value under the ROC curve was used to assess the discriminative power of the nomogram. Results:Compared with the normal PLT group and the thrombocythemia group, organ dysfunction in the thrombocytopenia group was significantly worse; the SOFA score [3 (2, 5) vs. 2.0 (1, 5) vs. 7 (5, 9)], SAPS-Ⅱ score [31 (23, 41) vs. 32 (23, 42) vs. 38 (30, 50) ], hospital mortality (35.0% vs. 45.2% vs. 54.7%), the incidence of mechanical ventilation (50.3% vs. 41.4% vs. 62.8%), and renal replacement therapy (1.3% vs. 1.3% vs. 6.0%) were significantly higher (all P<0.05). COX regression analysis found that thrombocytopenia was an independent predictor of hospital mortality and was entered into a nomogram after final regressions ( HR=1.477, 95% CI: 1.347-1.691, P<0.01). When the above indicators were brought into the nomogram, the AUC of the nomogram was 0.744. Conclusions:Thrombocytopenia is an independent prognostic predictor of hospital mortality for critically ill patients. PLT-related nomograms have good discrimination, which may help clinicians evaluate the prognosis of hospitalized patients.

Changes of mitochondrial fission and fusion after myocardial injury in cardiac arrest rats / 中华急诊医学杂志

Objective:To investigate the dynamic changes of mitochondrial fission and fusion in the heart of cardiac arrest (CA) rats after return of spontaneous circulation (ROSC), and to explore the role of mitochondrial fission and fusion in the myocardial injury after ROSC.Methods:Healthy male SD rats were randomly random number assigned into the post-resuscitation (PR) 4 h ( n=12), PR 24 h ( n=12), PR 72 h ( n=12), and sham groups ( n=6). The rat CA model was induced by asphyxia, and cardiopulmonary resuscitation (CPR) was performed 6 min after CA. The protein expressions of mitochondrial Drp1, Fis1, Mfn1, and Opa1 were determined by Western blot in each group at 4, 24 and 72 h after ROSC. The mRNA expressions of Drp1, Fis1, Mfn1, and Opa1 were determined by RT-PCR. Myocardial ATP content and mitochondrial respiratory function were measured. The histopathologic changes of myocardial tissue were observed under light microscope. One-way analysis of variance (ANOVA) was use to compare quantitative data, and LSD- t test was used for comparison between groups. Results:Compared with the sham group, the protein and mRNA expressions of Drp1 and Fis1 were increased (all P<0.05) and the protein and mRNA expressions of Mfn1 and Opa1 were decreased (all P<0.05) in the PR 4 h and PR 24 h groups. However, there were no statistical differences in the protein and mRNA expressions of Drp1, Fis1, Mfn1, and Opa1 in the PR 72 h group compared with the sham group (all P>0.05). Compared with the sham group, the levels of ATP content [(4.53±0.76) nmol/g protein vs. (8.57±0.44) nmol/g protein and (5.58±0.58) nmol/g protein vs. (8.57±0.44) nmol/g protein] and mitochondrial respiratory control rate [(2.47±0.38) vs. (3.45±0.32) and (2.97±0.24) vs. (3.45±0.32)] were obviously decreased in the PR 4 h and PR 24 h groups (all P<0.05). There were no statistically significant differences in the ATP content [(7.73±0.95) nmol/g protein vs. (8.57±0.44) nmol/g protein] and mitochondrial respiratory control ratio [(3.39±0.34) vs. (3.45±0.32)] between the PR 72 h group and the sham group (all P>0.05). The pathological damage of myocardial tissue was obvious in the PR 4 h group, and was improved significantly in the PR 72 h group. Conclusions:The imbalance of mitochondrial fission and fusion is probably involved in the pathological process of myocardial injury after ROSC, which may be related to mitochondrial dysfunction.

Screening and identification of key genes ATP1B3 and ENAH in the progression of hepatocellular carcinoma: based on data mining and clinical validation / 南方医科大学学报

OBJECTIVE@#To explore the marker genes correlated with the prognosis, progression and clinical diagnosis of hepatocellular carcinoma (HCC) based on bioinformatics methods.@*METHODS@#The TCGA-LIHC, GSE84432, GSE143233 and GSE63898 datasets from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) were analyzed. The differentially expressed genes (DEGs) shared by different disease types were obtained using GEO2R and edge R packages, and Gene Ontology (GO) and Kyoto Gene and Genome Encyclopedia (KEGG) enrichment analyses of the DEGs were performed. The expression levels of these DEGs in normal and cancerous tissues were verified in TCGA-LIHC to identify the upregulated genes in HCC. Survival analysis, receiver-operating characteristic (ROC) curve analysis, and correlation analysis between the key genes and the clinical features of the patients were carried out using the R language. The differential expressions of 15 key genes were verified in clinical samples of HCC and adjacent tissues using RT-qPCR.@*RESULTS@#A total of 118 common DEGs were obtained in the database, and among them two genes, namely ATPase Na +/K + transport subunit beta 3 (ATP1B3) and actin regulator (ENAH), showed increased expressions with disease progression. Survival analysis combined with the TCGA-LIHC dataset suggested that high expressions of ATP1B3 and ENAH were both significantly correlated with a poor prognosis of HCC patients (P < 0.05), and their AUC values were 0.821 and 0.933, respectively. A high expression of ATP1B3 was correlated with T stage, pathological stage and pathological grade of the tumors (P < 0.05), while that of ENAH was associated only with an advanced tumor grade (P < 0.05). The results of RT-qPCR showed that ATP1B3 and ENAH were both significantly upregulated in clinical HCC tissues (P < 0.05).@*CONCLUSION@#ATPIB3 and ENAH are both upregulated in HCC, and their high expressions may serve as biomarkers of progression of liver diseases and a poor prognosis of HCC.

Total Flavones of Spatholobi Caulis Regulate Hippocampal Neuroplasticity in Depressed Rats Through CREB/BDNF Pathway / 中国实验方剂学杂志

ObjectiveTo investigate the effect and mechanism of total flavones of Spatholobi Caulis （TFSC） against depression in rats. MethodThe fifty KM mice were randomly divided into the normal group and high-， medium-， and low-dose （1， 0.5， 0.25 g·kg-1） TFSC groups and gavaged with the corresponding drugs for 12 successive days. One hour after the last administration， the immobility time in forced swimming test and tail suspension test was recorded. The SD rats were randomly divided into the normal group， model group， fluoxetine （5 mg·kg-1） group， and high- and low-dose （1， 0.25 g·kg-1） TFSC groups. Following the exposure of rats to two different kinds of stimuli daily for inducing chronic unpredictable stress， they were administered with the corresponding drugs for 21 d. After the experiment， the levels of serum neurotransmitters and inflammatory factors in rats were detected by enzyme-linked immunosorbent assay （ELISA）. The changes in hippocampal neurons of rats were observed by hematoxylin-eosin （HE） and Nissl staining. The mRNA expression levels of nuclear factor-κB （NF-κB） and tumor necrosis factor-α （TNF-α） in the hippocampus of rats were detected by real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）， and the protein expression levels of cAMP-response element binding protein （CREB）， phosphorylated CREB （p-CREB）， and brain-derived neurotrophic factor （BDNF） in hippocampal tissues by Western blot. ResultCompared with the normal group， TFSC significantly shortened the immobility time of mice in tail suspension and swimming tests （P<0.05）. Compared with the normal group， the model group exhibited reduced sucrose intake and wilderness activity （P<0.01）， decreased 5-HT， DA， NE （P<0.05， P<0.01）， MAO， IL-6， TNF-α （P<0.05， P<0.01）， damaged neurons， increased mRNA levels of TNF-α and NF-κB （P<0.01）， and down-regulated BDNF and CREB protein expression （P<0.05）. Compared with the model group， TFSC significantly enhanced sucrose intake and wilderness activity of rats （P<0.05）， increased the serum 5-HT， DA and NE （P<0.05， P<0.01）， and decreased the serum MAO， IL-6， and TNF-α （P<0.05， P<0.01） as well as NF-κB and TNF-α mRNA expression （P<0.01）， up-regulated the protein expression levels of BDNF and CREB （P<0.01）， and improved the pathological symptoms of hippocampus. ConclusionTFSC improved the hippocampal neurons of rats via CREB/BDNF signaling pathway and reduced depressive pathological damage， thus relieving depression.

Effect of Huangqisan Pellets on PI3K/Akt/mTOR Signaling Pathway and Autophagy in Kidney of Diabetic Nephropathy Rats / 中国实验方剂学杂志

ObjectiveTo investigate the effect of Huangqisan pellets （HQS） on the phosphatidylinositol-3 kinase/protein kinase B/mammalian target of rapamycin （PI3K/Akt/mTOR） signaling pathway and autophagy in the kidney of diabetic nephropathy （DN） rats. MethodDN rat model was established through high-fat diet combined with intraperitoneal injection of streptozotocin （35 mg·kg-1）. DN rats were randomly assigned into model group， irbesartan （0.027 g·kg-1） group， low-dose HQS （0.54 g·kg-1） group and high-dose HQS （1.08 g·kg-1） group. The levels of 24 h urinary total protein （UTP）， serum albumin （Alb）， serum creatinine （SCr）， urea nitrogen （BUN）， triglyceride （TG） and total cholesterol （TC） were measured after 12 weeks of continuous administration. The pathological changes of renal tissue were observed via hematoxylin-eosin （HE） staining. The expression of podocyte split diaphragm proteins nephrin and podocin in the renal tissue were detected by immunohistochemistry. The protein levels and phosphorylation of key proteins in PI3K/Akt/mTOR signaling pathway， as well as the expression of yeast Atg6 homolog （Beclin1） and microtubule-associated protein 1 light chain 3 （LC3） in the renal tissue were analyzed by Western blot. ResultCompared with the control group， the model group showcased increased 24 h UTP， SCr， BUN， TG， and TC levels and decreased Alb level （P<0.01）. After modeling， the rats showed granulosity of epithelial cells of renal tubules， thickening of capillary basement membrane， proliferation of mesangial cells， and sclerosis of glomerulus. Furthermore， modeling down-regulated the expression of nephrin and podocin in the podocyte hiatus of glomerulus （P<0.01） as well as the protein levels of p-PI3K， p-Akt， and p-mTOR and the autophagy markers LC3 and Beclin1 in renal tissue （P<0.01）. Compared with model group， irbesartan and HQS decreased the 24 h UTP， Cr， BUN， TG， and TC levels， increased the Alb level， and alleviated the pathological damage of kidney. Moreover， they up-regulated the expression of Nephrin and Podocin in the podocyte hiatus of glomerulus， as well as the protein levels of p-PI3K， p-Akt， p-mTOR， LC3， and Beclin1 in renal tissue （P<0.05， P<0.01）. ConclusionHQS may inhibit the PI3K/Akt/mTOR signaling pathway to enhance podocyte autophagy and protect the glomerulus， thus slowing down the development of DN.

Bioactive constituents of animal-derived traditional Chinese medicinal materials for breast cancer: opportunities and challenges / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Breast cancer is globally the most common invasive cancer in women and remains one of the leading causes of cancer-related deaths. Surgery, radiotherapy, chemotherapy, immunotherapy, and endocrine therapy are currently the main treatments for this cancer type. However, some breast cancer patients are prone to drug resistance related to chemotherapy or immunotherapy, resulting in limited treatment efficacy. Consequently, traditional Chinese medicinal materials (TCMMs) as natural products have become an attractive source of novel drugs. In this review, we summarized the current knowledge on the active components of animal-derived TCMMs, including Ophiocordycepssinensis-derived cordycepin, the aqueous and ethanolic extracts of O.sinensis, norcantharidin (NCTD), Chansu, bee venom, deer antlers, Ostreagigas, and scorpion venom, with reference to marked anti-breast cancer effects due to regulating cell cycle arrest, proliferation, apoptosis, metastasis, and drug resistance. In future studies, the underlying mechanisms for the antitumor effects of these components need to be further investigated by utilizing multi-omics technologies. Furthermore, large-scale clinical trials are necessary to validate the efficacy of bioactive constituents alone or in combination with chemotherapeutic drugs for breast cancer treatment.

Analgesic Effects of Two Types of Spinal Manipulation in Acute Lumbar Radiculopathy Model Rats / 中国结合医学杂志

OBJECTIVE@#To compare the analgesic effects of two types of spinal manipulation (SM) in acute lumbar radiculopathy (ALR) model rats induced by self-transplantation of autologous nucleus pulposus (ANP), and clarify the therapeutic mechanism.@*METHODS@#Totally 108 male Sprague-Dawley rats were randomly divided into 6 groups by a random number table (18 rats in each group), including a blank group with no interference, a sham operation group with a surgery by making a local soft tissue incision on the left side of L5-6 vertebral segment, a model group with ALR of L5 extraforaminal nerve by ANP self-transplantation without other interference, a sham manipulation (SMA) group with simulating physical rotation, as well as a mobilization (MOB) group with simulating low-velocity and variable-amplitude rotation and a manipulation (MAN) group with simulating high-velocity and low-amplitude rotation. The interventions in SMA, MOB, and MAN groups started 1 day after modeling followed by another 5 treatments at days 3, 5, 8, 10 and 12. Rats in the other 3 groups did not receive any special intervention. Behavioral pain tests of 50% mechanical pain withdrawal threshold (50% PWT) and paw withdrawal latency (PWL) were conducted 1 day before operation followed by another 10 tests on days 1-7, 10, 12 and 14. Immunohistochemical expression of nitric oxide synthase (NOS) was investigated on days 5 and 12 after operation.@*RESULTS@#After 3 experimental SM interventions, 50% PWT and PWL were higher in the MAN group than the SMA group on days 6 and 7, and higher on days 10, 12 and 14 postoperatively (P<0.05 or P<0.01), while the same indices were significantly higher in the MOB group than MAN group on days 1-4 (P<0.05 or P<0.01). The expression of NOS was lower in the MAN and MOB groups than SMA group on day 12 postoperatively (P<0.01).@*CONCLUSIONS@#Both manipulation and mobilization produced better results than sham interference in relieving pain by reducing neuroinflammation possibly. At the early period, compared with manipulation, mobilization presented less sensitive response to pain until later visit. SM may inhibit the overexpression of NOS, thereby alleviating severe radiculopathy.

Sleep quality and sleep disturbances in Chinese pregnant women: a multicenter cross-sectional study / 中华耳鼻咽喉头颈外科杂志

Objective: This study aims to investigate the sleep quality of pregnant women in Xuhui District, Shanghai, and the related factors of sleep disturbances during pregnancy. Methods: From February 2019 to February 2021, we used online integrated sleep questionnaire (including PSQI, BQ, ESS, AIS) in Shanghai Jiao Tong University School of Medicine Affiliated Sixth People's Hospital, The International Peace Maternity and Child Health Hospitals of China Welfare Institution, and Shanghai Eighth People's Hospital, to investigate the sleep quality across pregnancy. We also collected maternal physical examination results, childbearing history, sociodemographic, and other clinical data. The prevalences and related factors of various sleep disturbances in pregnant women were analyzed, including insufficient/excessive nighttime sleep, low sleep efficiency, difficulty falling asleep, poor sleep quality, insomnia, daytime sleepiness, and high risk of sleep-disordered breathing (SDB). Results: This study includes 1 898 cases in the first trimester (T1), 3 099 cases in the second trimester (T2), and 1 539 cases in the third trimester (T3). Poor sleep quality (38.6%), daytime sleepiness (mild 41.9%, moderate 17.7%, severe 2.1%), and suspicious insomnia (32.3%) are most prevalent among women in T1 (P<0.01). In comparison, short sleep time (2.7%), long sleep time (8.6%), difficulty falling asleep (12.2%), poor sleep efficiency (35.4%), very poor sleep quality (6.7%), clinical insomnia (21.8%), and high-risk SDB (6.4%) are most prevalent among women in T3 (P<0.05). During pregnancy, late gestation (OR=1.016, 95%CI: 1.006-1.025) and multiple induced/drug abortions (OR=1.329, 95%CI: 1.043-1.692) are risk factors for poor sleep quality (PSQI>5), while multiple full-term deliveries (OR=0.800, 95%CI: 0.675-0.949) is its protective factor. Advanced maternal age (OR=0.976, 95%CI: 0.956-0.997), multiple full-term deliveries (OR=0.808, 95%CI: 0.680-0.959), late gestation (OR=0.983, 95%CI: 0.974-0.992) and hypertension (OR=0.572, 95%CI: 0.401-0.814) are protective factors for daytime sleepiness (ESS>6). The high-risk pregnancy category (OR=9.312, 95%CI: 1.156-74.978) is a risk factor for insomnia (AIS≥4), while multiple full-term deliveries (OR=0.815, 95%CI: 0.691-0.961) is its protective factor. High BMI (OR=1.334, 95%CI: 1.270-1.402) and hypertension (OR=4.427, 95%CI: 2.539-7.719) are risk factors for high-risk SDB in pregnant women. Conclusions: The prevalences of various sleep disturbances are high throughout pregnancy. Noticeably, symptoms of maternal SDB develop along with pregnancy. Different types of sleep disturbances are associated with different factors. Women of high-risk pregnancy category, in late gestation, with high BMI, hypertension, a history of induced/drug abortion, or without a history of full-term delivery can be at high risk of sleep disturbances during pregnancy.

Effect evaluation of surgical plus radio(chemo)therapy and non-surgery chemoradiotherapy treatment strategies for advanced tonsillar squamous cell carcinoma / 中华耳鼻咽喉头颈外科杂志

Objective: Using propensity score matching method(PSM) to investigate the clinical effect of surgical plus radio(chemo)therapy and non-surgery chemoradiotherapy treatment strategies for advanced tonsillar squamous cell carcinoma. Methods: A retrospective analysis was conducted on the clinical data of 324 patients diagnosed with advanced tonsillar squamous cell carcinoma and treated in Peking Union Medical College Hospital from 2000 to 2018, confirmed by pathology and without distant metastasis. Survival analysis was performed using Kaplan-Meier estimates, the Cox proportional hazards model, and propensity score matching(PSM). Results: Of the 324 patients, 102 were treated with non-surgery chemoradiotherapy treatment strategies and 222 with surgical plus radio(chemo)therapy treatment. Cox multivariate analysis showed that the non-surgery treatment group had a favorable prognosis than the surgical treatment group, however, these outcomes were not significantly different [overall survival(OS): adjusted Hazard Ratios(aHR): 0.92, 95% confidence interval(CI): 0.60-1.42; disease-specific survival(DSS): aHR: 0.71, 95%CI: 0.43-1.20; disease-free survival(DFS): aHR: 0.82, 95%CI: 0.53-1.28]. The new patient cohort consisted of 102 subpairs after PSM. There were no significant differences between two groups(OS: aHR: 0.85, 95%CI: 0.51-1.40; DSS: aHR: 0.62, 95%CI: 0.35-1.11; DFS: aHR: 0.80, 95%CI: 0.49-1.33). Conclusion: Our findings indicate that patients with non-surgical treatment do not have significantly better survival outcomes compared to surgical treatment group, while non-surgical treatment has advantages in improving the quality of life of patients, so comprehensive treatment based on radiotherapy and chemotherapy may be recommended for advanced tonsillar squamous cell carcinoma.

Marginal features of CAD/CAM laminate veneers with different materials and thicknesses / 北京大学学报(医学版)

OBJECTIVE@#To analyze the marginal roughness and marginal fitness of chairside computer-aided design and computer-aided manufacturing (CAD/CAM) laminate veneers with different materials and thicknesses, and to provide a reference for the clinical application of laminate veneers.@*METHODS@#The butt-to-butt type laminate veneers were prepared on resin typodonts, the preparations were scanned, and the laminate veneers were manufactured by chairside CAD/CAM equipment. The laminate veneers were divided into four groups (n=9) according to the materials (glass-matrix ceramics and resin-matrix ceramics) and thickness (0.3 mm and 0.5 mm) of the veneers, with a total of 36. The marginal topo-graphies of each laminate veneer were digitally recorded by stereomicroscope, and the marginal rough-nesses of the laminate veneers were determined by ImageJ software. The marginal fitness of the laminate veneers was measured by a fit checker and digital scanning and measuring method. At the same time, the mechanical properties of glass-matrix ceramic and resin-matrix ceramic bars (n=20) were tested by a universal testing device.@*RESULTS@#The marginal roughness of 0.3 mm and 0.5 mm glass-matrix ceramic laminate veneers was (24.48±5.55) μm and (19.06±5.75) μm, respectively, with a statistically significant difference (P < 0.001). The marginal roughness of 0.3 mm and 0.5 mm resin-matrix ceramic laminate veneers was (6.13±1.27) μm and (6.84±2.19) μm, respectively, without a statistically significant difference (P>0.05). The marginal roughness of the glass-matrix ceramic laminate veneers was higher than that of the resin-matrix ceramic laminate veneers with a statistically significant difference (P < 0.001). The marginal fitness of 0.3 mm and 0.5 mm glass-matrix ceramic laminate veneers were (66.30±26.71) μm and (85.48±30.44) μm, respectively. The marginal fitness of 0.3 mm and 0.5 mm resin-matrix ceramic laminate veneers were (56.42±19.27) μm and (58.36±8.33) μm, respectively. There was no statistically significant difference among the 4 groups (P>0.05). For glass-matrix ceramics, the flexural strength was (327.40±54.25) MPa, the flexural modulus was (44.40±4.39) GPa, and the modulus of resilience was (1.24±0.37) MPa. For resin-matrix ceramics, the flexural strength was (173.71±16.61) MPa, the flexural modulus was (11.88±0.51) GPa, and the modulus of resilience was (1.29±0.27) MPa. The flexural strength and modulus of glass-matrix ceramics were significantly higher than those of resin-matrix ceramics (P < 0.001), but there was no statistically significant difference in the modulus of resilience between the two materials (P>0.05).@*CONCLUSION@#The marginal roughness of CAD/CAM glass-matrix ceramic laminate veneers is greater than that of resin-matrix ceramic laminate veneers, but there was no statistically significant difference in marginal fitness among them. Increasing the thickness can reduce the marginal roughness of glass-matrix ceramic laminate veneers, but has no effect on the marginal roughness of resin-matrix ceramic laminate veneers.

Clinical effects of free latissimus dorsi myocutaneous flap combined with artificial dermis and split-thickness skin graft in the treatment of degloving injury in lower extremity / 中华烧伤杂志

Objective: To observe the clinical effects of free latissimus dorsi myocutaneous flap combined with artificial dermis and split-thickness skin graft in the treatment of degloving injury in lower limbs. Methods: A retrospective observational study was conducted. From December 2017 to December 2020, 8 patients with large skin and soft tissue defect caused by degloving injury in lower extremity were admitted to Ningbo No.6 Hospital, including 5 males and 3 females, aged from 39 to 75 years, with wound area of 25 cm×12 cm-61 cm×34 cm. The free latissimus dorsi myocutaneous flap with latissimus dorsi muscle in the width of 12-15 cm and flap area of 20 cm×8 cm-32 cm×8 cm was used to repair the skin and soft tissue defect of bone/tendon exposure site or functional area. The other defect was repaired with bilayer artificial dermis, and the flap donor site was sutured directly. After the artificial dermis was completely vascularized, the split-thickness skin graft from thigh was excised and extended at a ratio of 1∶2 to 1∶4 and then transplanted to repair the residual wound, and the donor site of skin graft was treated by dressing change. The survival of latissimus dorsi myocutaneous flap, artificial dermis, and split-thickness skin graft after operation was observed, the interval time between artificial dermis transplantation and split-thickness skin graft transplantation was recorded, and the healing of donor site was observed. The appearance and function of operative area were followed up. At the last outpatient follow-up, the sensory recovery of flap was evaluated by British Medical Research Council evaluation criteria, the flap function was evaluated by the comprehensive evaluation standard of flap in Operative Hand Surgery, the scar of lower limb skin graft area and thigh skin donor area was evaluated by Vancouver scar scale, and the patient's satisfaction with the curative effects was asked. Results: The latissimus dorsi myocutaneous flap survived in 6 patients, while the distal tip of latissimus dorsi myocutaneous flap was partially necrotic in 2 patient and was repaired by skin grafting after resection at split-thickness skin grafting. The artificial dermis survived in all 8 patients after transplantation. The split-thickness skin graft survived in 7 patients, while partial necrosis of the split-thickness skin graft occurred in one patient and was repaired by skin grafting again. The interval time between artificial dermis transplantation and split-thickness skin graft transplantation was 15-26 (20±5) d. The donor site of latissimus dorsi myocutaneous flap healed with linear scar after operation, and the thigh skin graft donor site healed with scar after operation. The patients were followed up for 6-18 (12.5±2.3) months. The color and elasticity of the flap were similar to those of the surrounding skin tissue, and the lower limb joint activity returned to normal. There was no increase in linear scar at the back donor site or obvious hypertrophic scar at the thigh donor site. At the last outpatient follow-up, the sensation of the flap recovered to grade S2 or S3; 3 cases were excellent, 4 cases were good, and 1 case was fair in flap function; the Vancouver scar scale score of lower limb skin graft area was 4-7 (5.2±0.9), and the Vancouver scar scale score of thigh skin donor area was 1-5 (3.4±0.8). The patients were fairly satisfied with the curative effects. Conclusions: In repairing the large skin and soft tissue defect from degloving injury in lower extremity, to cover the exposed bone/tendon or functional area with latissimus dorsi myocutaneous flap and the residual wound with artificial dermis and extended split-thickness skin graft is accompanied by harvest of small autologous flap and skin graft, good recovery effect of functional area after surgery, and good quality of healing in skin grafted area.

Research progress on the low-temperature degradation of zirconia in prosthetic dentistry / 中华口腔医学杂志

Zirconia is widely used in the field of dentistry because of its superior mechanical and esthetic characteristics. However, the tetragonal zirconia polycrystal restorations commonly used in clinics will degrade at low temperatures in the oral environment, resulting in increased surface roughness, microcracks, and decreased mechanical properties. Low-temperature degradation of zirconia can be affected by grain size, stress, stabilizer content and type, surface treatment, sintering conditions, and other factors. Through a literature review and analysis, this review summarizes the research progress on the low-temperature degradation of zirconia in prosthetic dentistry to provide references for the improvement of zirconia in clinical and research applications.

Regulation of microRNA-126 on the polarization of human macrophages stimulated by Porphyromonas gingivalis lipopolysaccharide / 中华口腔医学杂志

Objective: To study the effect of microRNA-126 (miR-126) on the polarization of human monocyte-derived macrophages stimulated by Porphyromonas gingivalis (Pg) lipopolysaccharide (LPS). Methods: Macrophages derived from human myeloid leukemia mononuclear cells were stimulated by Pg-LPS (5 mg/L) and by Pg-LPS (5 mg/L) after 24 h-transfection of miR-126 mimic or negative control RNA for 48 h, respectively. Real-time quantitative-PCR (qRT-PCR), enzyme-linked immunosorbent assay (ELISA) and Western blotting were conducted to detect the changes in miR-126, pro-inflammatory factor tumor necrosis factor-α (TNF-α), anti-inflammatory factors interleukin-10 (IL-10), inducible nitric oxide synthase (iNOS), arginase-1 (Arg-1) and M1 polarization-related pathways such as nuclear factor kappa-B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways. Results: Compared with non-LPS stimulation group (TNF-α: 1.000±0.020, iNOS: 1.125±0.064, miR-126: 1.004±0.113, IL-10: 1.003±0.053, Arg-1: 1.130±0.061), the mRNA levels of TNF-α (3.105±0.278) and iNOS (4.296±0.003) increased significantly (t=6.53, P=0.003; t=42.63, P<0.001, respectively), while miR-126, IL-10 and Arg-1 expressions (0.451±0.038, 0.545±0.004 and 0.253±0.017) decreased significantly (t=7.95, P=0.001; t=7.36, P=0.002; t=11.94, P<0.001, respectively) after Pg-LPS stimulated by human-derived macrophages for 48 h. The protein expression of iNOS, TNF-α, Arg-1 and IL-10 were consistent at mRNA levels. Meanwhile, the expressions of phospho-NF-κB p65 (p-p65), phospho-extracellular signal-regulated kinase (p-ERK) and phospho-p38 MAPK (p-p38) increased significantly, while the expression of Arg-1 decreased significantly. Compared with the negative controls (scramble RNA) (TNF-α: 1.141±0.197, iNOS: 1.173±0.115, IL-10: 1.032±0.138, Arg-1: 0.933±0.044), the mRNA levels of TNF-α (0.342±0.022) and iNOS (0.588±0.085) expressions significantly decreased (t=5.35, P=0.006; t=5.05, P=0.007), while IL-10 (1.786±0.221) and Arg-1 expressions (2.152±0.229) significantly increased (t=3.71, P=0.021; t=6.21, P=0.003) after Pg-LPS stimulation with miR-126 mimic transfection. The relative protein expressions of iNOS, p-p65, p-ERK and p-p38 significantly decreased (t=13.00, P<0.001; t=6.98, P=0.002; t=10.86, P<0.001; t=8.32, P=0.001), while the protein level of Arg-1 significantly increased (t=12.08, P<0.001). Conclusions: Pg-LPS could promote M1 polarization of macrophages. miR-126 might inhibit the effect of Pg-LPS on the M1 polarization of macrophages through down-regulating NF-κB and MAPK signaling pathways.

The effects of robotic-assisted versus laparoscopic-assisted radical right hemicolectomy on short-term outcome and long-term prognosis based on propensity score matching / 中华外科杂志

Objective: To compare the short-term and long-term outcomes between robotic-assisted and laparoscopic-assisted radical right hemicolectomy in patients with adenocarcinoma of the right colon. Methods: Retrospective review of a prospectively collected database identified 288 right colon cancer patients who underwent either robotic-assisted (n=57) or laparoscopic-assisted right hemicolectomy (n=231) between October 2014 and October 2020 at Department of Gastrointestinal Surgery, the Affiliated Hospital of Qingdao University. There were 161 males and 127 females, aging (60.3±12.8) years (range: 17 to 86 years). After propensity score matching as 1∶4 between robotic-assisted and laparoscopic-assisted right hemicolectomy, there were 56 cases in robotic group and 176 cases in laparoscipic group. Perioperative outcomes and overall survival were compared between the two groups using t test, Wilcoxon rank sum test, χ2 test, Fisher exact test, Kaplan-Meier method and Log-rank test, respectively. Results: The total operative time was similar between the robotic and laparoscopic group ((206.9±60.7) minutes vs. (219.9±56.3) minutes, t=-1.477, P=0.141). Intraoperative bleeding was less in the robotic group (50 (20) ml vs. 50 (50) ml, Z=-4.591, P<0.01), while the number of lymph nodes retrieved was significantly higher (36.0±10.0 vs. 29.0±10.1, t=4.491, P<0.01). Patients in robotic group experienced significantly shorter hospital stay, shorter time to first flatus, and defecation (t: -2.888, -2.946, -2.328, all P<0.05). Moreover, the overall peri-operative complication rate was similar between robotic and laparoscopic group (17.9% vs. 22.7%, χ²=0.596,P=0.465). The 3-year overall survival were 92.9% and 87.9% respectively and the 3-year disease-free survival rates were 83.1% and 82.6% with no statistical significance between the robotic and laparoscopic group (P>0.05). Conclusions: Compared to laparoscopic-assisted right hemicolectomy, robot-assisted right hemicolectomy could improve some short-term clinical outcomes. The two procedures are both achieving comparable survival.

Discussion on the moral culture construction of medical and health industry in China based on the circular cases of violating the " nine prohibitions" / 中华医院管理杂志

Objective:To analyze the characteristics of the circular cases violating the " nine prohibitions" in recent years, so as to provide a basis for further strengthening the moral culture construction of the healthcare industry.Methods:Data came from the reported cases released on official websites of the discipline inspection committees, supervision committees and health committees at all levels in China from December 2013 to August 2021, which were identified by searching the keyword " case or report or moral culture and nine prohibitions" . Descriptive analysis and frequency analysis were conducted on the reported time, region and province, as well as the involved units, departments, persons, punishment results and case classification data of all the cases.Results:A total of 102 cases violating the " nine prohibitions" were included, of which the cases from 2014 to 2015 topped the rest, accounting for 51.96%(53 cases). Top three regions of these cases were central China, east China and southwest China, with 31 cases, 27 cases and 18 cases respectively. The units involved were mainly tertiary medical institutions, accounting for 44.12%(45 cases). More medical staff(134 people) than administrative staff(85 people) were involved in the cases. The largest number of cases was receiving kickbacks, with 52 cases(50.98%). The punishment results of cases included judicial procedures(76 people), Party discipline and government discipline punishment(67 people) and organizational punishment(76 people).Conclusions:Moral culture problem in China′s healthcare sector is characterized in wide coverage, complexity, comprehensiveness and long-term. Relevant authorities should keep up their efforts in enhancing the awareness of medical workers, improving the synergy mechanism in this regard, and strengthening the internal management of medical institutions.

Genome characterization and traceability analysis of SARS-CoV-2 in a local outbreak / 中华微生物学和免疫学杂志

Objective:To analyze the genome characteristics and variations in nucleotides and amino acids of SARS-CoV-2 causing an outbreak in Henan Province in November 2021 and perform the traceability analysis.Methods:In this study, throat swab specimens from cases in the acute phase were collected and tested for the nucleic acids of SARS-CoV-2 by real-time fluorescent RT-PCR. SARS-CoV-2 nucleic acid-positive samples were subjected to high-throughput genome sequencing and whole-genome alignment analysis.Results:The median Ct values of ORF1ab gene and N gene in 70 positive specimens was 26.41 (15.58 to 39.27) and 24.43 (12.04 to 39.74), respectively. Compared with the sequence of Wuhan-Hu(NC_045512) reference strain, 47 to 49 nucleotide mutations sharing 47 nucleotide mutation and 41 amino acid mutations were found in 63 strains of successfully sequenced SARS-CoV-2. Nine nucleotide mutations and 12 amino acid mutations were found in the spike protein. The index case shared 47 mutations with the Russian imported cases in Henan Province on October 14 and the local cases in Jiangxi Province in October. Moreover, their genomes were highly homologous and they all belonged to the Delta variant (AY.122 evolutionary branch).Conclusions:Continuous monitoring of imported COVID-19 cases and prolonging the period of quarantine were needed to reduce the risk of local outbreak and epidemic caused by imported COVID-19 cases. Analysis of the genomic characteristics of SARS-CoV-2 and the variations in nucleotides and amino acids was conducive to trace the origin of COVID-19 outbreak quickly and provide reference for precise control.

Clinical analysis of a case of central nervous system intravascular lymphoma with multiple intracerebral microbleeds and literature review / 中华神经科杂志

Objective:To investigate the clinicopathological features and imaging differential diagnosis of intravascular large B-cell lymphoma (IVLBCL) in the central nervous system (CNS).Methods:A case of CNS IVLBCL with multiple intracerebral microbleeds (CMBs) diagnosed in the Department of Neurology, Qilu Hospital of Shandong University in 2017 was reported. The clinical and imaging data, histological and immunohistochemical markers were retrospectively analyzed, and the relevant literature was reviewed.Results:The patient was a 31-year-old woman presented with headache and seizures. Cranial magnetic resonance imaging (MRI) showed multifocal lesions involving mainly the cortical and subcortical white matter (bilateral cerebral hemisphere and right cerebellar hemisphere), hyperintense signal on T 2-weighted and fluid-attenuated inversion recovery images, with hypointense signal on T 1-weigthed and diffusion-weighted images and contrast enhancement in some lesions. The susceptibility weighted imaging revealed multifocal cortical or subcortical hypointense lesions, involving mainly the subcortical white matter. Brain magnetic resonance angiography was normal. Brain magnetic resonance venography showed left side transverse sinus was hypoplastic. Cranial magnetic resonance spectroscopy showed decreased N-acetylaspartylglutamate peak, elevated choline peak and inverted lipid double peak. Her symptoms and the lesions once improved after starting steroid treatment. However, CNS recurrence occurred after 1 week of steroid withdrawal. She underwent the biopsy of the right frontotemporal lobe. The pathological examination showed multiple microscopic hemorrhages and edema scattered in the brain tissue. A large number of heterologous mononuclear cells were aggregated in small blood vessels in the parenchyma and meninges. Immunohistochemical analysis revealed that the tumor was negative for Epstein-Barr virus encoded small RNAs, CD 3, CD 10, cytokeratin and CD 138, and positive for CD 20, CD 79α, B-cell lymphoma (BCL)-2, BCL-6, myelocytomatosis oncogene (C-myc) and multiple myeloma oncogene-1 (MUM-1). The Ki67 proliferation index was about 70%. The diagnosis of IVLBCL was confirmed. Conclusions:IVLBCL in CNS is a rare and swiftly progressive disease with poor prognosis. Its clinical symptoms and imaging are nonspecific. Early diagnosis and treatment is critical. Biopsy is the gold standard for diagnosis. Random skin biopsy may be helpful for the early diagnosis. Furthermore, regarding the cause of multiple CMBs, the possibility of IVLBCL should be considered in the differential diagnosis, in addition to the common causes, such as primary angiitis of the CNS and cerebral amyloid angiopathy.

Free superficial iliac circumflex artery perforator flap with different arterial anastomosis methods for repairing soft tissue defects of limbs / 中华创伤杂志

Objective:To investigate the clinical effect of free superficial iliac circumflex artery perforator flap with different arterial anastomosis methods for repairing soft tissue defects of limbs.Methods:A retrospective cohort study was used to analyze the data of 60 patients with soft tissue defects of limbs treated in Ningbo No.6 Hospital from March 2017 to March 2020, including 38 males and 22 females, aged 21-57 years［(35.6±3.1)years］. The wounds were located on the upper limb in 33 patients and the lower limb wound in 27 patients. The defect area was 4.5 cm × 2.0 cm-17.0 cm × 8.0 cm. All patients received debridement and vacuum sealing drainage (VSD) in stage I, and free superficial iliac circumflex artery perforator flap transplantation in stage II. The flap area was 4.9 cm × 2.6 cm-17.0 cm × 8.0 cm. According to the different anastomotic vessels, the superficial iliac circumflex artery was anastomosed end-to- side to the radial artery in 25 patients, the ulnar artery in 8, the dorsalis pedis artery in 18 and the anterior tibial artery in 9. Flap healing and healing time were detected. Texture and appearance of the flap were observed at the last follow-up. The appearance of the donor area was evaluated by Vancouver scar scale (VSS), and the satisfaction rate of appearance of the recipient area was measured by numerical score.Results:All patients were followed up for 5-15 months［(7.1±1.3)points］. All flaps survived successfully after operation, including arterial crisis in 4 patients, among which 2 had flap perforator anastomosed with the radial artery, 1 with the ulnar artery and 1 with the dorsalis pedis artery. There was no significant difference in flap crisis after end-to-side arterial anastomosis in different recipient areas ( P>0.05). For patients with flap perforator anastomosed with the radial artery, the ulnar artery, the dorsalis pedis artery and the anterior tibial artery, the flap healing time was 15(14, 16)days, 15(14, 16)days, 14.5(14，16)days and 14(14，15.5)days, respectively (all P>0.05). The flaps showed sufficient elasticity and soft texture at the last follow-up. For patients with flap perforator anastomosed with the radial artery, the ulnar artery, the dorsalis pedis artery and the anterior tibial artery, the VSS of the donor area was (10.2±1.5)points, (10.9±1.6)points, (9.4±1.5)points and (9.8±1.5)points at the last follow-up (all P>0.05), and the satisfaction rate of appearance of the recipient area was 9 (8, 10)points, 9(8, 9)points, 9(8, 9)points and 8(8, 9.5)points at the last follow-up ( P>0.05), showing that all patients were satisfied with the appearance of the wound. Conclusions:The transplantation of free superficial iliac circumflex artery perforator flap with different arterial anastomosis methods is safe and reliable in repairing soft tissue defects of limbs with advantages of low occurrence of postoperative vascular crisis, good flap survival, no influence on flap healing by different anastomotic vessels, hidden donor area with small scar and satisfactory appearance of the recipient area. It can be used as one of the common vascular repair methods for free tissue flap transplantation.