Auranofin reverses acquired resistance to osimertinib in non-small cell lung cancer / 中国药理学通报

Aim To investigate the role of auranofin in reversing acquired resistance to osimertinib in non-small cell lung cancer. Methods Osimertinib-sensi-tive NSCLC cell lines HI975 and PC9 were used to establish osimertinib-resistant NSCLC cell lines HI975/OR and PC9/OR. An FDA approved library of 1470 FDA drugs was used to high-throughput screen the reversal agents of acquired resistant of osimertinib by CCK-8. Compusyn was used to calculate the combination index of osimertinib and auranofin to determine the optimal dose of drug combination. CCK-8, EdU, flow cytometry and Transwell experiments were used to detect osimertinib, auranofin and the combination drug effect on proliferation, apoptosis, migration and invasion of osimertinib acquired NSCLC cell lines. RNA-sequencing was applied to screen differentially expressed mRNAs in osimertinib treatment alone and osimertinib combined with auranofin treatment group. qRT-PCR and western blot were employed to validate the selected gene expression and protein expression. Results Compared with osimertinib sensitive cell lines H1975 and PC9, H1975/OR and PC9/OR showed significantly higher cell viability and lower apoptosis rate after osimertinib treatment. The resistance index was 70. 31 and 136. 99, respectively. In FDA approved 1470 drug library, only auranofin could enhance the sensitivity of osimertinib in H1975/OR and PC9/OR. When 1 μmol • L

Molecular characteristics and drug resistance of non-O1non-O139 Vibrio cholerae in Zhongshan City, Guangdong Province / 中国热带医学

@#Abstract: Objective　To investigate the molecular characteristics and drug resistance of non-O1/non-O139 Vibrio cholerae in Zhongshan City, and to provide laboratory basis for cholera prevention and control. Methods　The strains of non-O1/non-O139 Vibrio cholerae isolated from sporadic patients and aquatic products from 2015 to 2021 in Zhongshan city were collected. The identification and cluster analysis of the strains were analyzed by matrix assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF-MS), the ctxA virulence gene of strains were detected by real-time fluorescence quantitative PCR, the cluster analysis of the strains was analyzed by pulsed-field gel electrophoresis (PFGE), and the drug resistance of the strains were analyzed by microbroth dilution method. Results　From 2015 to 2021, 33 strains of non-O1/non-O139 Vibrio cholerae were isolated from Zhongshan City, including 28 strains from sporadic patients and 5 strains from aquatic products. Through MALDI-TOF-MS identification, 33 strains of non-O1/non-O139 Vibrio cholera can be identified to the level of species, and the identification results were all Vibrio cholerae. Among 33 non-O1/non-O139 Vibrio cholerae strains, 1 strain carried the ctxA virulence gene. The drug-resistant strains accounted for 69.7% (23/33), and the multidrug resistant strains accounted for 18.2% (6/33). A total of 7 kinds of drug resistance spectrum were produced, including 3 kinds of multidrug resistant spectrum, and showed drug resistance to 8 antibiotics, among which the resistance rates to streptomycin, cefazolin and compound sulfamethoxazole were above 30%. The 33 strains of non-O1/non-O139 Vibrio cholerae were divided into 32 PFGE fingerprints with a similarity ranging from 61.7% to 100%. MALDI-TOF-MS cluster analysis divided 33 non-O1/non-O139 Vibrio cholerae strains into two clusters. Conclusions The results of molecular typing of non-O1/non-O139 Vibrio cholerae in Zhongshan City presented diversity, and no significant correlation was found between PFGE and MALDI-TOF-MS cluster analysis. The strains demonstrated various degrees of resistance to certain antibiotics, and there were multidrug-resistant and toxigenic strains. Therefore, it is necessary to alert to the harmfulness of non-O1/non-O139 Vibrio cholerae and enhance monitoring.

Lnc-TMEM132D-AS1 overexpression reduces sensitivity of non-small cell lung cancer cells to osimertinib / 南方医科大学学报

OBJECTIVE@#To screen the differentially expressed long non-coding RNAs (lncRNAs) in non-small cell lung cancer (NSCLC) cells with acquired resistance to osimertinib and explore their roles in drug resistance of the cells.@*METHODS@#The cell lines H1975_OR and HCC827_OR with acquired osimertinib resistance were derived from their osimertinib-sensitive parental NSCLC cell lines H1975 and HCC827, respectively, and their sensitivity to osimertinib was assessed with CCK-8 assay, clone formation assay and flow cytometry. RNA sequencing (RNA-seq) and real-time quantitative PCR (qPCR) were used to screen the differentially expressed lncRNAs in osimertinib-resistant cells. The role of the identified lncRNA in osimertinib resistance was explored using CCK-8, clone formation and Transwell assays, and its subcellular localization and downstream targets were analyzed by nucleoplasmic separation, bioinformatics analysis and qPCR.@*RESULTS@#The resistance index of H1975_OR and HCC827_OR cells to osimertinib was 598.70 and 428.82, respectively (P < 0.001), and the two cell lines showed significantly increased proliferation and colony-forming abilities with decreased apoptosis (P < 0.01). RNA-seq identified 34 differentially expressed lncRNAs in osimertinib-resistant cells, and among them lnc-TMEM132D-AS1 showed the highest increase of expression after acquired osimertinib resistance (P < 0.01). Analysis of the TCGA database suggested that the level of lnc-TMEM132D-AS1 was significantly higher in NSCLC than in adjacent tissues (P < 0.001), and its high expression was associated with a poor prognosis of the patients. In osimertinib-sensitive cells, overexpression of Lnc-TMEM132D-AS1 obviously promoted cell proliferation, colony formation and migration (P < 0.05), while Lnc-TMEM132D-AS1 knockdown partially restored osimertinib sensitivity of the resistant cells (P < 0.01). Lnc-TMEM132D-AS1 was localized mainly in the cytoplasm, and bioinformatics analysis suggested that hsa-miR-766-5p was its candidate target, and their expression levels were inversely correlated. The target mRNAs of hsa-miR-766-5p were mainly enriched in the Ras signaling pathway.@*CONCLUSION@#The expression of lnc-TMEM132D-AS1 is significantly upregulated in NSCLC cells with acquired osimertinib resistance, and may serve as a potential biomarker and therapeutic target for osimertinibresistant NSCLC.

New model of PIRADS and adjusted prostatespecific antigen density of peripheral zone improves the detection rate of initial prostate biopsy: a diagnostic study / 亚洲男科学杂志(英文版)

This study explored a new model of Prostate Imaging Reporting and Data System (PIRADS) and adjusted prostate-specific antigen density of peripheral zone (aPSADPZ) for predicting the occurrence of prostate cancer (PCa) and clinically significant prostate cancer (csPCa). The demographic and clinical characteristics of 853 patients were recorded. Prostate-specific antigen (PSA), PSA density (PSAD), PSAD of peripheral zone (PSADPZ), aPSADPZ, and peripheral zone volume ratio (PZ-ratio) were calculated and subjected to receiver operating characteristic (ROC) curve analysis. The calibration and discrimination abilities of new nomograms were verified with the calibration curve and area under the ROC curve (AUC). The clinical benefits of these models were evaluated by decision curve analysis and clinical impact curves. The AUCs of PSA, PSAD, PSADPZ, aPSADPZ, and PZ-ratio were 0.669, 0.762, 0.659, 0.812, and 0.748 for PCa diagnosis, while 0.713, 0.788, 0.694, 0.828, and 0.735 for csPCa diagnosis, respectively. All nomograms displayed higher net benefit and better overall calibration than the scenarios for predicting the occurrence of PCa or csPCa. The new model significantly improved the diagnostic accuracy of PCa (0.945 vs 0.830, P < 0.01) and csPCa (0.937 vs 0.845, P < 0.01) compared with the base model. In addition, the number of patients with PCa and csPCa predicted by the new model was in good agreement with the actual number of patients with PCa and csPCa in high-risk threshold. This study demonstrates that aPSADPZ has a higher predictive accuracy for PCa diagnosis than the conventional indicators. Combining aPSADPZ with PIRADS can improve PCa diagnosis and avoid unnecessary biopsies.

MicroRNA-22-3p Regulates the Expression of Kruppel-like Factor 6 to Affect the Cardiomyocyte-like Differentiation of Bone Marrow Mesenchymal Stem Cell / 中国医学科学院学报

Objective To explore the effect of microRNA-22-3p (miR-22-3p) regulating the expression of Kruppel-like factor 6 (KLF6) on the cardiomyocyte-like differentiation of bone marrow mesenchymal stem cell (BMSC). Methods Rat BMSC was isolated and cultured,and the third-generation BMSC was divided into a control group,a 5-azacytidine(5-AZA)group,a mimics-NC group,a miR-22-3p mimics group,a miR-22-3p mimics+pcDNA group,and a miR-22-3p mimics+pcDNA-KLF6 group.Real-time fluorescent quantitative PCR (qRT-PCR) was carried out to determine the expression of miR-22-3p and KLF6 in cells.Immunofluorescence staining was employed to detect the expression of Desmin,cardiac troponin T (cTnT),and connexin 43 (Cx43).Western blotting was employed to determine the protein levels of cTnT,Cx43,Desmin,and KLF6,and flow cytometry to detect the apoptosis of BMSC.The targeting relationship between miR-22-3p and KLF6 was analyzed by dual luciferase reporter gene assay. Results Compared with the control group,5-AZA up-regulated the expression of miR-22-3p (q=7.971,P<0.001),Desmin (q=7.876,P<0.001),cTnT (q=10.272,P<0.001),and Cx43 (q=6.256,P<0.001),increased the apoptosis rate of BMSC (q=12.708,P<0.001),and down-regulated the mRNA (q=20.850,P<0.001) and protein (q=11.080,P<0.001) levels of KLF6.Compared with the 5-AZA group and the mimics-NC group,miR-22-3p mimics up-regulated the expression of miR-22-3p (q=3.591,P<0.001;q=11.650,P<0.001),Desmin (q=5.975,P<0.001;q=13.579,P<0.001),cTnT (q=7.133,P<0.001;q=17.548,P<0.001),and Cx43 (q=4.571,P=0.037;q=11.068,P<0.001),and down-regulated the mRNA (q=7.384,P<0.001;q=28.234,P<0.001) and protein (q=4.594,P=0.036;q=15.945,P<0.001) levels of KLF6.The apoptosis rate of miR-22-3p mimics group was lower than that of 5-AZA group (q=8.216,P<0.001).Compared with the miR-22-3p mimics+pcDNA group,miR-22-3p mimics+pcDNA-KLF6 up-regulated the mRNA(q=23.891,P<0.001) and protein(q=13.378,P<0.001)levels of KLF6,down-regulated the expression of Desmin (q=9.505,P<0.001),cTnT (q=10.985,P<0.001),and Cx43 (q=8.301,P<0.001),and increased the apoptosis rate (q=4.713,P=0.029).The dual luciferase reporter gene experiment demonstrated that KLF6 was a potential target gene of miR-22-3p. Conclusion MiR-22-3p promotes cardiomyocyte-like differentiation of BMSC by inhibiting the expression of KLF6.

Short-term efficacy of digitally-assisted traditional Chinese medicine manual reduction combined with 3D printed splint in the treatment of AO type-A distal radius fractures / 中国骨伤

Objective To explore the short-term efficacy of digitally-assisted traditional Chinese medicine manual reduction combined with 3D printed splint in the treatment of AO type-A distal radius fractures, and explore the quantification of traditional Chinese medicine manual reduction and personalized improvement of splinting. Methods The clinical data of 50 patients with AO type-A distal radius fractures, who received treatment at the outpatient department of Cangzhou Integrated Traditional Chinese and Western Medicine Hospital in Hebei Province, were retrospective analyzed. The patient cohort included 22 females and 28 males, with ages ranging from 25 to 75 years old. Among them, 27 cases presented with distal radius fractures on the left side, and 24 cases on the right side. The patients were categorized into two groups: treatment group (n=25) and control group(n=25). There were 13 males and 12 females in the treatment group, with an average age of (56.2±5.5) years old. Treatment approach for this group involved several steps. Initially, Mimics Research software was used to conduct comprehensive analysis of complete CT data from the affected limb, resulting in the creation of a three-dimensional model. Subsequently, 3D models of the bones and skin contours, stored as STL format files, were imported into the Materialise Magics 23.0 software for model processing and repair. This facilitated the simulation of reduction and recording of displacement data, effectively generating a "digital prescription" to guide and quantify traditional Chinese medicine manipulation procedures. Finally, a personalized 3D printed splint was applied for fixation treatment. There were 15 males and 10 females in the control group, with an average age of (53.32±5.28) years old. These patients were treated with manualreduction combined with traditional splinting. The clinical efficacy of the two groups was assessed in terms of fracture reduction quality, fracture healing time, Gartland-Werley wrist joint score and X-ray parameters (palminclination angle, ulnar deviation angle, radius height) at 6 weeks post-operatively. Results The treatment group exhibited a shorter duration for achieving clinical healing compared to the control group (P<0.05). Six weeks post-operatively, the treatment group demonstrated higher wrist joint function scores, and a higher proportion of excellent and good outcomes than the control group(P<0.05). The treatment group was superior to the control group in terms of imaging parameters 6 weeks post-operatively (P<0.05). Conclusion By quantifying skin contours through digital simulation prescription reduction, a personalized 3D printed splint is developed to effectively stabilize fractures, enhancing localized fixation while ensuring greater adherence, stability, and comfort. This innovative approach offers personalized treatment for AO type-A distal radius fractures and presents a novel, precise treatment strategy for consideration.

Prenatal diagnosis and genetic analysis of a fetus with partial deletion of Yq and mosaicism of 45,X / 中华医学遗传学杂志

OBJECTIVE@#To carry out prenatal diagnosis and genetic analysis for a fetus with disorders of sex development (DSDs).@*METHODS@#A fetus with DSDs who was identified at the Shenzhen People's Hospital in September 2021 was selected as the study subject. Combined molecular genetic techniques including quantitative fluorescence PCR (QF-PCR), multiplex ligation-dependent probe amplification (MLPA), chromosomal microarray analysis (CMA), quantitative real-time PCR (qPCR), as well as cytogenetic techniques such as karyotyping analysis and fluorescence in situ hybridization (FISH) were applied. Ultrasonography was used to observe the phenotype of sex development.@*RESULTS@#Molecular genetic testing suggested that the fetus had mosaicism of Yq11.222qter deletion and X monosomy. Combined with the result of cytogenetic testing, its karyotype was determined as mos 45,X[34]/46,X,del(Y)(q11.222)[61]/47,X,del(Y)(q11.222),del(Y)(q11.222)[5]. Ultrasound examination suggested hypospadia, which was confirmed after elective abortion. Combined the results of genetic testing and phenotypic analysis, the fetus was ultimately diagnosed with DSDs.@*CONCLUSION@#This study has applied a variety of genetic techniques and ultrasonography to diagnose a fetus with DSDs with a complex karyotype.

Clinical Features of Multicenter Autoimmune Glial Fibrillary Acidic Protein Astrocytosis / 罕见病研究

  Objective  To investigate the clinical features of autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy.  Methods  We collected and analyzed the clinical and laboratory data and obtained the clinical characteristics of diagnosis and treatment from fifteen patients with positive GFAP antibody tested by cerebrospinal fluid and diagnosed autoimmune GFAP astrocytopathy by the multi-centers.  Results  The mean age of the first onset of autoimmune GFAP astrocytopathy was 39.73 years old (range 4-65 years), with no significant gender difference. In terms of clinical manifestations, we found the whole brain symptoms including abnormal mental behavior, disturbance of consciousness, epileptic attack accounting for more than 50, , meningitis accounting for 66.7%, myelitis (53.3%), limb tremor (53.3%), vision loss (33.3%); systemic symptoms including fever(100%) and fatigue(86.7%). 46.7% of patients were initially diagnosed with tuberculous meningoencephalitis and were treated with diagnostic antituberculous therapy. The MRI showed 46.7% of patients showed brain linear perivascular radial gadolinium enhancement in the white matter perpendicular to the ventricle.  Conclusions  Autoimmune GFAP astrocytopathy are acute or subacute dieases and the main clinical features include encephalitis, meningitis, myelitis and optic neuritis. They are likely to be misdiagnosed as tuberculous meningoencephalitis and can manifest progressive loss of consciousness in early phase, which is even life threatening.

Macrophage Activation Induced by TMAO through CD147 / MMPs / 中国生物化学与分子生物学报

Trimethylamine N-oxide (TMAO), a metabolite of intestinal flora, can promote Atherosclerosis (AS) in various ways. Current studies have found that it has a close relationship with plaque stability in clinical practice, but its molecular mechanism remains unclear at present. Extracellular matrix metalloproteinase inducers (CD147) / matrix metalloproteinases (MMPs) regulate a signal pathway highly related to plaque stability, which can promote plaque instability and lead to cardiovascular adverse events by weakening the thickness of the fibrous cap. Therefore, in this study, the mouse macrophageRAW264. 7 was stimulated by TMAO to establish a cell model to observe the effects on CD147, MMP2, and MMP9, and the CD147 gene silencing model was further constructed by using the siRNA transfection method to explore the interaction between CD147 and MMP2 and MMP9. Rt-qPCR and Western blotting results showed that there was no significant change in the gene expression level of CD147 in mouse macrophage RAW264. 7, but significantly increased in protein levels (P < 0. 05), while MMP2 andMMP9 were increased in mRNA and protein levels (P<0. 05). The expression of CD147, MMP2, andMMP9 was significantly inhibited in CD147 siRNA transfected cells (P<0. 05). In conclusion, TMAO significantly increases the expression of MMP2 and MMP9 in mouse macrophages RAW264. 7, and this effect may be partially realized through the CD147/ MMP pathway.

Resibufogenin suppresses human hepatocellular carcinoma cell proliferation, migration and invasion in vitro / 药学学报

This manuscript aims to investigate the effects of resibufogenin on the proliferation, migration and invasion of human hepatocellular carcinoma cells and its related mechanisms. MTT assay was used to determine the inhibitory effect of resibufogenin on the growth of four hepatocellular carcinoma cells in vitro. Wound-healing assay and Transwell assay were used to evaluate the migration and invasion ability of resibufogenin on MHCC-97H cells. Western blot assay was used to detect the expression of migration and invasion related proteins in MHCC-97H cells treated with different concentrations of resibufogenin. The results showed that resibufogenin significantly inhibited the proliferation of hepatocellular carcinoma cells in vitro. The half maximal inhibitory concentration (IC50) values on MHCC-97H, HepG2, SK-Hep-1 and Huh-7 cells were 0.55 ± 0.06, 2.83 ± 0.24, 5.25 ± 0.49, 14.89 ± 2.28 μmol·L-1, respectively. Resibufogenin also suppressed the migration and invasion of MHCC-97H cells in a concentration-dependent manner. The protein expression of integrin α2, integrin α6, integrin β1, N-cadherin, matrix metalloproteinase 2 (MMP2) and transcription factor Twist in MHCC-97H cells were decreased significantly with the increase of the concentration of resibufogenin, while the protein expression of E-cadherin increased. In addition, we found that p-PI3K/PI3K and p-AKT/AKT ratios were significantly reduced after treatment with resibufogenin. In conclusion, resibufogenin can inhibit the proliferation, migration and invasion of hepatocellular carcinoma MHCC-97H cells in vitro, which is related to the regulation of intracellular migration and invasion protein expression and PI3K/AKT signaling pathway.

A cohort study on the influence of the chronic diseases on falls among middle-aged and older Chinese / 中华流行病学杂志

Objective: To analyze the influence of chronic diseases on falls among middle-aged and older Chinese. Methods: Baseline data of 13 670 middle-aged and older adults recruited from China Health and Retirement Longitudinal Study (CHARLS) in 2011 were used and followed up to 2018, among those were 7 443 (54.45%) middle-aged people aged 45-59 and 6 227 (45.55%) older adults aged 60 and above. The Cox proportional hazards model was used to analyze the effects of different types, the number of chronic diseases and the interaction between chronic illness and other factors on the fall risk of middle-aged and older people. Results: After adjusting for confounding factors, respiratory diseases increased the risk of falls by 21% (HR=1.21, 95%CI:1.02-1.45), and arthritis increased the risk of falls by 27% (HR=1.27,95%CI: 1.12-1.43) in the group aged 45-59, kidney disease increased the risk of falls by 26% (HR=1.26, 95%CI: 1.03-1.53) in the group aged 60 and above. A linear dose-response relationship between the number of chronic diseases and fall risk (χ2=133.61, P<0.001) was found in all the age groups. The interaction between having chronic diseases and the factors of females (HR=1.64, 95%CI: 1.43-1.89), impaired activities of daily living (ADL) (HR=1.66, 95%CI: 1.39-1.99), and having a fall history (HR=2.58, 95%CI: 2.24-2.97) increased the risk of falls. Conclusions: There is a positive linear relationship between the number of chronic diseases and the fall risk among Chinese aged 45 and above. The female middle-aged and elderly patients with chronic diseases and the middle-aged and elderly patients with impaired ADL or a history of falls are the high-risk groups for falls that need to be focused on intervention. The window of fall injury prevention should be moved forward to the middle-aged stage in time.

Analysis of monitoring results of chronic diseases of island residents who have drunken desalinated seawater for a long time / 上海预防医学

Objective To study the current situation of chronic diseases among island residents who have drunken desalinated water for a long time， and to reveal the relationship between drinking desalinated water and water from other sources and the prevalence of chronic diseases among the population. Methods According to the different drinking water sources of island residents， the research subjects were divided into seawater desalination group （residents of Gouqi Township， Shengsi County）， mixed water source group （residents of Shengshan Town， Shengsi County） and freshwater group （residents of Huanglong Township， Shengsi County）. Through the chronic disease network report and resident health file system， the current situation of chronic diseases in different water groups was investigated and analyzed. Results There were significant differences in the prevalence of malignant tumor among drinking water sources （ χ 2=23.867， P <0.001）， with the prevalence of mixed water group >desalination group >fresh water group. There were significant differences in the prevalence of coronary heart disease （ χ 2=194.883， P <0.001）， with the prevalence of mixed water group >desalination group >fresh water group. There were significant differences in the prevalence of stroke （ χ 2=35.637， P <0.001）， with the prevalence of fresh water group > mixed water group > desalination group. There was no significant difference in the prevalence of diabetes mellitus （ χ 2=2.808， P =0.246）， but there was significant difference in the age of onset of diabetes mellitus （ χ 2=7.368， P =0.001）， and significant difference in the prevalence of diabetes mellitus in the age group ≥55 （ χ 2=17.144， P <0.001）， and the onset age and prevalence were all in the order of fresh water group > desalination group > mixed water source group. There was no significant difference in the prevalence of hypertension （ χ 2=3.962， P =0.138）， but there was significant difference in the prevalence of hypertension in the age group ≥55 （ χ 2=20.734， P <0.001）， with the prevalence of fresh water group > desalination group > mixed water source group. Conclusion Long-term consumption of desalinated water by residents is correlated with malignant tumors， coronary heart disease and stroke， and has no correlation with diabetes and hypertension.

Analysis of monitoring results of chronic diseases of island residents who have drunken desalinated seawater for a long time / 上海预防医学

Objective To study the current situation of chronic diseases among island residents who have drunken desalinated water for a long time， and to reveal the relationship between drinking desalinated water and water from other sources and the prevalence of chronic diseases among the population. Methods According to the different drinking water sources of island residents， the research subjects were divided into seawater desalination group （residents of Gouqi Township， Shengsi County）， mixed water source group （residents of Shengshan Town， Shengsi County） and freshwater group （residents of Huanglong Township， Shengsi County）. Through the chronic disease network report and resident health file system， the current situation of chronic diseases in different water groups was investigated and analyzed. Results There were significant differences in the prevalence of malignant tumor among drinking water sources （ χ 2=23.867， P <0.001）， with the prevalence of mixed water group >desalination group >fresh water group. There were significant differences in the prevalence of coronary heart disease （ χ 2=194.883， P <0.001）， with the prevalence of mixed water group >desalination group >fresh water group. There were significant differences in the prevalence of stroke （ χ 2=35.637， P <0.001）， with the prevalence of fresh water group > mixed water group > desalination group. There was no significant difference in the prevalence of diabetes mellitus （ χ 2=2.808， P =0.246）， but there was significant difference in the age of onset of diabetes mellitus （ χ 2=7.368， P =0.001）， and significant difference in the prevalence of diabetes mellitus in the age group ≥55 （ χ 2=17.144， P <0.001）， and the onset age and prevalence were all in the order of fresh water group > desalination group > mixed water source group. There was no significant difference in the prevalence of hypertension （ χ 2=3.962， P =0.138）， but there was significant difference in the prevalence of hypertension in the age group ≥55 （ χ 2=20.734， P <0.001）， with the prevalence of fresh water group > desalination group > mixed water source group. Conclusion Long-term consumption of desalinated water by residents is correlated with malignant tumors， coronary heart disease and stroke， and has no correlation with diabetes and hypertension.

Epidemiological charactristics of cancer in Zhoushan City / 预防医学

Objective@#To investigate epidemiological characteristics of cancers in Zhoushan City in 2018, so as to provide the evidence for the formulation of cancer control strategies.@*Methods@#The cancer data in Zhoushan City in 2018 were captured from Zhejiang Provincial Information Management System for Chronic Disease Surveillance. The gender- and age-specific incidence of cancers was descriptively analyzed. The cancer incidence was standardized to the data of the Sixth National Population Census in China in 2010 ( Chinese standard population ) and Segi's world standard population.@*Results@#The crude incidence rate, age-standardized incidence rate by Chinese standard population ( ASR China ), and age-standardized incidence rate by world standard population ( ASR world ) of cancers were 468.65/105, 300.12/105 and 232.79/105 in Zhoushan City in 2018, and the cumulative cancer incidence rate was 26.91% among residents at ages of 0 to 74 years, while the truncated-age cancer incidence rate was 431.90/105 among residents at ages of 35 to 64 years. The crude incidence rate, ASR China, and ASR world of cancers were 473.00/105, 285.67/105 and 229.03/105 in men, and 464.43/105, 317.66/105 and 241.30/105 in women in Zhoushan City in 2018, respectively. In addition, the mean age of new cases with cancers in 2018 was ( 61.34±13.19 ) years in Zhoushan City in 2018, and the highest crude cancer incidence was seen in residents at ages of 70 to 74 years ( 1 327.50/105 ). The crude cancer incidence rate was higher in new female cases at ages of 25 to 54 years than in new male cases, and the crude cancer incidence rate was higher in new male cases at ages of 60 to 84 years than in new female cases ( P<0.05 ). The 10 most common cancers included lung cancer, female breast cancer, thyroid cancer, gastric cancer, colorectal cancer, liver cancer, cervical cancer, prostatic cancer, pancreatic cancer and bladder cancer, which accounted for 80.20% of all cancers in Zhoushan City in 2018.@*Conclusions@#High cancer incidence was found in Zhoushan City in 2018, and elderly populations are at high risk of developing cancers. The management of lung cancer, female breast cancer, thyroid cancer, gastric cancer and colorectal cancer should be given a high priority.

Risk factors for lymph node metastasis in T1 colorectal cancer and application value of its nomogram prediction model / 中华消化外科杂志

Objective:To investigate the risk factors for lymph node metastasis in T1 colorectal cancer and application value of its nomogram prediction model.Methods:The retrospective case-control study was conducted. The clinicopathological data of 914 patients with T1 colorectal cancer who underwent radical resection in the Zhongshan Hospital of Fudan University from June 2008 to December 2019 were collected. There were 528 males and 386 females, aged from 25 to 87 years, with a median age of 63 years. Observation indicators: (1) clinicopathological data of patients with T1 colorectal cancer; (2) follow-up; (3) analysis of influencing factors for lymph node metastasis; (4) development and internal validation of a nomogram predition model. Patients were regularlly followed up once three months within postoperative 2 years and once six months thereafter to detect tumor recurrence and survival. The endpoint of follow-up was at postoperative 5 years. Measurement data with normal distribution were represented as Mean±SD, and comparison between groups was analyzed using the t test. Measurement data with skewed distribution were represented as M (range). Count data were described as absolute numbers or percentages, and comparison between groups was analyzed using the chi-square test. The Kaplan-Meier method was used to calculate survival rates and draw survival curves. The Log-rank test was used for survival analysis. Univariate and multivariate analyses were performed using the Logistic regression analysis. Based on results of multivariate analysis, a Logistic regressional nomogram for prediction of lymph node metastasis probability was constructed using R language software. The calibration curve was used to evaluate the consistency between probability predicted by the nomogram model and actual observation probability, which was reprensented by a consistency index. The Bootstrap method was used for evaluation of the model performance to receive the calibration curve. The Hosmer-Lemeshow test was used to calculate the goodness of fit in model. Results:(1) Clinicopathological data of patients with T1 colorectal cancer: 687 of 914 patients underwent direct surgery and 227 underwent remedial operation after endoscopic resection. All the 914 patients were confirmed as pT1NxM0 colorectal cancer by pathological examination. The tumor diameter was (2.3±1.2)cm. The pathological catogaries of 914 patients included 865 cases of adenocarcinoma and 49 cases of mucinous adenocarcinoma. The tumor differentiation degree of 914 patients included 727 cases of high or middle differentiation and 187 cases of low differentiation or undifferentiation. Of the 914 patients, 633 cases had submucosal infiltration depth ≥1 000 μm and 281 cases had submucosal infiltration depth <1 000 μm. There were 110 cases with nerve vessel invasion and 804 without nerve vessel invasion. The number of intraoperative lymph node dissection was 13 (range, 1-48). There were 804 cases in stage N0 of N staging, 98 cases in stage N1 and 12 cases in stage N2. There was no perioperative death. (2) Follow-up: 886 of 914 patients were followed up for 25 months (range, 1-129 months). During the follow-up, 24 patients had tumor recurrence or metastasis. The 5-year cumulative tumor recurrence rate of 914 patients was 4.8% and the median recurrence time was 17.0 months. Liver was the main site of tumor recurrence, accounting for 58.3%(14/24). The 5-year recurrence-free survival rate of 914 patients was 95.2%. The 5-year recurrence-free survival rate was 96.3% of 804 patients without lymph node metastasis, versus 86.6% of 110 patients with lymph node metastasis, showing a significant difference between the two groups ( χ2=6.83, P<0.05). (3) Analysis of influencing factors for lymph node metastasis: results of univariate analysis showed that preoperative carcinoembryonic antigen (CEA), preoperative CA19-9, tumor differentiation degree, submucosal infiltration depth, nerve vessel invasion were related factors for lymph node metastasis in T1 colorectal cancer ( odds ratio=2.56, 3.25, 2.21, 2.68, 3.39, 95% confidence interval as 1.41-4.67, 1.22-8.66, 1.43-3.41, 1.56-4.88, 2.10-5.48, P<0.05). Results of multivariate analysis showed that preoperative CEA ≥5 μg/L, preoperative CA19-9 ≥37 U/mL, poor differentiation or undifferentiation, submucosal infiltration depth ≥1 000 μm and nerve vessel invasion were independent risk factors for lymph node metastasis in T1 colorectal cancer ( odds ratio=2.23, 3.47, 2.01, 2.31, 2.91, 95% confidence interval as 1.02-4.15, 1.08-10.87, 1.03-3.27, 1.40-4.47, 1.64-5.13, P<0.05). (4) Development and internal validation of a nomogram predition model: based on results of multivariate Logistic analysis, a nomogram prediction model for lymph node metastasis in T1 colorectal cancer was developed. The nomogram score was 59 for preoperative CEA >5 μg/L, 100 for preoperative CA19-9 ≥37 U/mL, 48 for poor differentiation or undifferentiation, 67 for submucosal infiltration depth ≥1 000 μm and 92 for nerve vessel invasion, respectively. The total of different scores for different clinicopathological factors corresponded to the probability of lymph node metastasis. The receiver operating characteristic curve was drawed to evaluate the predictive performance of nomogram for lymph node metastasis in T1 colorectal cancer, with the area under curve of 0.70(95% confidence interval as 0.64-0.75, P<0.05). The Bootstrap internal validation of predictive performance in the nomogram predition model showed a consistency index of 0.70 (95% confidence interval as 0.65-0.75). The calibration chart showed a good consistency between the probability predicted by the nomogram model and actual probability of lymph node metastasis. The Hosmer-Lemeshow test showed a good fitting effect in model ( χ2=1.61, P>0.05). Conclusions:Preoperative CEA ≥5 μg/L, preoperative CA19-9 ≥37 U/mL, poor differentiation or undifferentiation, submucosal infiltration depth ≥ 1 000 μm and nerve vessel invasion are independent risk factors for lymph node metastasis in T1 colorectal cancer. The constructed nomogram model can help predict the probability of lymph node metastasis in T1 colorectal cancer.

Qualitative study on the real psychological experience of family members of patients in neurological intensive care unit / 中国实用护理杂志

Objective:To deeply understand the real experience of family members of patients in the neurosurgery intensive care unit during the period of accompanying them, and to provide reference for managers to formulate nursing countermeasures to improve the coping ability of family members.Methods:Descriptive phenomenological research method in qualitative research was adopted to conduct in-depth interviews with family members of 12 patients admitted to a neurosurgery intensive care unit in Shanghai, manage the interview data with Nvivo11 software, and use Colaizzi's seven-step analysis method to summarize and analyze the topic.Results:There were four themes: adhere to and do not give up, adhere to was due to the trust and affirmation of the medical care, do not give up was because it was difficult to give up blood kinship, adhere to the hope of life because of patients; timing change of emotional experience, first aid period: helpless to rescue and expecting the condition to stabilize, complication peak: understanding the characteristics of the disease and paying attention to the treatment progress, stable period: uncertain prognosis and desire for emotional companionship.The powerlessness of the future; learn to self psychological adjustment.Conclusions:The family members of patients with severe neurological diseases have both negative experience and positive feelings, and the accompanying experience and needs at different stages of the disease are changing dynamically. According to the cognition and needs of the family members, exploring and developing palliative medicine, tapping the potential of the family members from a positive perspective and improving coping ability are one of the ways to maintain the stable mental health of the family members.

Research progress on correlation between lncRNAs and pathogenesis of vascular diseases / 中国职业医学

Occupational hand-arm vibration diseases(HAVD) is a legitimate occupational disease in China, and the mechanism of its pathogenesis is vibration-induced vascular injury. Once HAVD occurs, it is difficult for the patients to recover and can cause great harm to workers exposed to hand-arm vibration. It is difficult to detect and evaluate the occurrence and progress of the disease at an early stage using existing technology, which is disadvantageous to the early prevention and treatment of the disease. Long noncoding RNAs(lncRNAs) play an important role in regulating the development, growth, and remodeling of blood vessels and other biological processes. This article reviews the role and mechanism of lncRNAs in vascular injury, and provides scientific theoretical basis for early diagnosis and treatment of HAVD.

Micheliolide enhances the sensitivity of colorectal cancer cells to oxaliplatin by promoting autophagy / 中国肿瘤生物治疗杂志

@#[Abstract] Objective: To study the effect of micheliolide (MCL) on the sensitivity of colorectal cancer cells to oxaliplatin (OxP) and its possible mechanism. Methods: HCT116 and LoVo cells were treated with 2 μmol/L MCL and 100 μmol/L OxP alone or in combination. The cell viability and colony forming ability in vitro were detected by CCK-8 and plate cloning formation assay, respectively. After being transfected with GFP-LC3 lentivirus, HCT116 cells were respectively treated with 2 μmol/L and 5 μmol/L MCL for 24 h. The aggregation of autophagy bodies in HCT116 cells induced by MCL was observed under fluorescence microscope. The effects of MCL on the expressions of LC3B-Ⅰ, LC3B-Ⅱ, p62 and STAT3 were detected by WB assay; the molecular docking model of MCL and STAT3 was constructed by Autodock version. Results: After the treatment of 2 μmol/L MCL combined with 100 μmol/L OxP, the activity of HCT116 and LoVo cells as well as the colony forming ability of HCT116 cells significantly decreased (all P < 0.01). After HCT116 cells were treated with 2 and 5 μmol/L MCL, the autophagy rate of cells in the treatment groups was significantly higher than that of the control group (all P < 0.01), the LC3B Ⅱ/Ⅰ ratio was 3.25 and 5.78 times that of the control group, the expression level of p62 was 25.5% and 9.8% of the control group, and the phosphorylation level of STAT3 was 2.18 and 3.87 times that of the control group. Molecular docking results showed that MCL might directly bind to STAT3 protein in vivo. Conclusion: MCL may enhance the sensitivity of colorectal cancer cells to OxP by promoting autophagy through STAT3 pathway.

Review of taste masking techniques in Chinese patent medicine / 中国中药杂志

Single herbs and Chinese patent medicine preparations often have bad taste, such as bitterness and astringency, which is one of the key factors affecting patients' medication compliance, and would affect the therapeutic effect and restrict the extensive application in clinical practice. Therefore, how to make use of taste masking techniques to improve the bad taste of traditional Chinese medicines has become an important project. Through the collection and summarization of Chinese and foreign journals and papers in recent years, this paper discussed the generation mechanism of bitter taste, the new methods of masking bitter taste and the evaluation me-thods of bitter taste, in order to provide references for the taste masking of Chinese patent medicines preparations.

Analysis on Quality Transmitting of Substance Benchmarks of Yihuangtang / 中国实验方剂学杂志

Objective:To explore the quality transmitting relationship between decoction pieces and substance benchmarks with the fingerprint， index component content and dry extract rate as evaluation indexes， and investigate the key quality attributes of 15 batches of substance benchmarks of Yihuangtang， and establish the quality standard of this substance benchmarks. Method:Fifteen batches of Yihuangtang substance benchmarks freeze-dried powder samples were prepared， the fingerprint and index component content of 15 batches of decoction pieces and substance benchmarks were determined by high performance liquid chromatography （HPLC）， the mobile phase was acetonitrile （A）-0.1% phosphoric acid aqueous solution （B） for gradient elution （0-6 min， 97%B； 6-12 min， 97%-92%B； 12-25 min， 92%-90%B； 25-35 min， 90%-89%B； 35-50 min， 89%-82%B； 50-75 min， 82%-72%B； 75-85 min， 72%-35%B）， the detection wavelength was set at 230 nm， combined the dry extract rate to clarify the attribution of characteristic peaks and the range of similarity with the control chromatogram， the content range and transfer rate range of geniposidic acid and berberine hydrochloride， the dry extract rate range and the variation range of the substance benchmarks. Result:The established HPLC fingerprint had good precision， repeatability and stability， and could be used for the simultaneous determination of decoction pieces and substance benchmarks of Yihuangtang. The similarities between the control chromatogram and fingerprint of substance benchmarks were >0.99. A total of 15 characteristic peaks were assigned， and 8 characteristic peaks were identified by the reference substances， of which 6 were from Phellodendri Chinensis Cortex processed with salt， 1 was from Plantaginis Semen processed with wine， and 1 was from stir-fried Dioscoreae Rhizoma. The content ranges of geniposidic acid and berberine hydrochloride in 15 batches of substance benchmarks of Yihuangtang were 0.10%-0.16% and 0.63%-1.05%， the transfer rate ranges of them were 20.91%-32.65% and 19.60%-29.59%， respectively. The dry extract rate range of the substance benchmarks was 8.45%-9.92%. Conclusion:The quality standard of Yihuangtang substance benchmarks can be preliminarily formulated by the combination of fingerprint， dry extract rate and determination of index component， which can provide the basis for the quality control of Yihuangtang and the development of related preparations.