Objective:To investigate the arsenic metabolism pattern and possible influencing factors in the population in drinking-water-borne endemic arsenic poisoning (drinking-water-borne arsenic poisoning for short) areas.Methods:In December 2004, a cluster sampling method was used to select arsenic poisoning population (arsenic poisoning group) and healthy population (control group) in drinking-water-borne arsenic poisoning area of Bayannur City, Inner Mongolia Autonomous Region as the survey subjects. A questionnaire survey was conducted. Arsenic content in drinking water at home of survey subjects, the levels of urinary arsenic and its metabolites, including [trivalent arsenic (As Ⅲ), inorganic arsenic (iAs), monomethylarsenic acid (pentavalent, MMA V), dimethylarsenic acid (pentavalent, DMA V), total arsenic (tAs), percentage of inorganic arsenic (iAs%), percentage of monomethylarsenic acid (MMA%), percentage of dimethylarsenic acid (DMA%), primary methylation index (PMI), secondary methylation index (SMI)] were tested using high performance liquid chromatography-inductively coupled plasma mass spectrometry; nail arsenic and nail selenium levels were tested using atomic fluorescence spectrometer. The influencing factors of arsenic metabolism pattern were analyzed by multiple linear regression. Results:A total of 536 survey subjects were included, including 155 individuals in the arsenic poisoning group and 381 in the control group. The water arsenic level ranged from 0.0 to 825.7 μg/L. Compared with the control group, there was no significant difference in the distribution of gender, education level and dental fluorosis in the arsenic poisoning group ( P > 0.05), but there were significant differences in the distribution of age, marital status, smoking, drinking and water arsenic ( P < 0.05). Compared with the control group, the levels of urinary As Ⅲ, iAs, MMA V, DMA V, tAs, MMA%, MMA/DMA and nail arsenic in the arsenic poisoning group were higher ( P < 0.05), while the levels of urinary DMA%, SMI and nail selenium were lower ( P < 0.05); but there was no statistically significant difference in the levels of urinary iAs% and PMI ( P > 0.05). Gender, education level, depth of wells, water arsenic, total number of wells and nail arsenic were the influencing factors of urinary As Ⅲ (β = - 19.82, - 23.83, 0.61, 0.21, 7.26, 2.98, P < 0.05). Age, depth of wells, water arsenic and nail arsenic were the influencing factors of urinary tAs (β = 3.18, 3.25, 1.31, 15.59, P < 0.05). Gender, education level, depth of wells, water arsenic, total number of wells and nail arsenic were the influencing factors of urinary iAs (β = - 20.47, - 25.90, 0.64, 0.25, 7.87, 3.11, P < 0.05). Age, gender, education level, water arsenic and nail arsenic were the influencing factors of urinary MMA V (β = 0.52, - 17.07, - 21.84, 0.22, 2.77, P < 0.05). Age, depth of wells, water arsenic and nail arsenic were the influencing factors of urinary DMA V (β = 2.35, 2.47, 0.85, 9.22, P < 0.05). Conclusions:Compared with healthy individuals, there are differences in arsenic metabolism pattern among individuals with drinking-water-borne arsenic poisoning. Age, gender, education level, depth of wells, water arsenic, total number of wells and nail arsenic may be influencing factors of different arsenic metabolism patterns.

Objective:To investigate the relationship between the outcome of skin injury and urinary arsenic methylation metabolism levels in people exposed to arsenic through drinking water.Methods:Using cluster sampling method, permanent residents from drinking-water-borne endemic arsenic poisoning areas in Bayannur City, Inner Mongolia Autonomous Region were selected as survey subjects in 2004 (before water improvement). In 2017 (after water improvement), 74 survey subjects from 2004 were tracked and followed up. Urine samples were collected from survey subjects and high-performance liquid chromatography inductively coupled plasma mass spectrometry was used to detect the levels of arsenic methylation metabolites in urine. According to the "Diagnosis of Endemic Arsenic Poisoning" (WS/T 211-2015), the clinical grading (normal, suspicious, mild, moderate and severe) of skin injury of the survey subjects and the outcome of 2017 (improved, unchanged, aggravated) were assessed. A database was established and SPSS 25.0 software was used for statistical analysis.Results:The clinical grading ratios of skin injuries among survey subjects in 2004 and 2017 were compared, the differences were statistically significant (normal, suspicious, mild, moderate and severe: 38, 18, 4, 14 cases in 2004 and 27, 31, 3, 13 cases in 2017, χ 2 = 53.02, P < 0.001). Compared with 2004, in 2017, the levels of total arsenic (tAs), inorganic arsenic (iAs), monomethylarsenic (MMA), dimethylarsenic (DMA), percentage of inorganic arsenic (iAs%), and ratio of monomethylarsenic to dimethylarsenic (MMA/DMA) in the urine of survey subjects were low, and the differences were statistically significant ( Z = - 8.24, - 9.07, - 7.81, - 8.04, - 8.24, - 3.56, P < 0.001). The levels of dimethylarsenic percentage (DMA%), monomethylation rate (PMI) and dimethylation rate (SMI) were higher, and the differences were statistically significant ( Z = - 6.39, - 8.24, - 3.52, P < 0.001). In 2004, patients with different clinical grading of skin injuries had different outcomes in 2017 (χ 2 = 30.80, P < 0.001). There were statistically significant differences in tAs, iAs, MMA and DMA variation in urine among skin injury patients with different outcomes ( H = 10.62, 9.35, 8.80, 9.13, P < 0.05). Conclusions:Improving water can significantly reduce the levels of tAs, iAs, MMA, and DMA in the urine of arsenic exposed individuals. The outcome of skin injury in individuals exposed to arsenic through drinking water is related to the variation of urinary arsenic methylation metabolites tAs, iAs, MMA, and DMA.

p53 is an important tumor suppressor in the body,but research has found that p53 is one of the most frequent alterations in nearly half of human cancers.Mutant p53(mtp53)not only promotes tumor development but also serves as a pivotal factor in tumor immunity.Research has demonstrated that mtp53 participates in many aspects of tumor immune response through multiple mechanisms.We firstly describe the structure and function of mtp53,then the molecular mechanisms of mtp53 in tumor immuni-ty,including four aspects of promoting tumor immune escape,facilitating oxidative stress,regulating tumor-associated inflammatory signaling networks and tumor-infiltrating immune cell recruitment and dif-ferentiation.Finally,we summarize the effects of mtp53 on the immune micro-environment of lung canc-er,triple-negative breast cancer and colorectal cancer as well as the advances in the application of mtp53 in the treatment of cancers with PD-1/PD-L1 inhibitors,which may provide suitable directions and op-tions for the immunotherapy of mtp53-expressing cancers.

Objective:To study the effect of water improvement on urinary arsenic methylation metabolism in population exposed to arsenic through drinking water.Methods:A cluster sampling method was used to select drinking water type arsenism areas in Bayannur City, Inner Mongolia Autonomous Region. Permanent residents lived in the arsenism areas for more than 10 years were selected as the survey subjects. Urine samples ( n = 874, 111, 145) were collected in 2004 (before water improvement), 2014 (4 years after water improvement) and 2017 (7 years after water improvement), respectively, and some subjects were followed up in 2014 and 2017. High performance liquid chromatography-inductively coupled plasma mass spectrometry (HPLC-ICP-MS) was used to detect different forms of arsenic metabolites in urine [inorganic arsenic (iAs), monomethylarsonic acid (MMA), dimethylarsenic acid (DMA)], and total arsenic (tAs), the iAs percentage (iAs%), MMA percentage (MMA%), DMA percentage (DMA%), monomethylation rate (PMI), dimethylation rate (SMI), and the ratio of MMA to DMA (MMA/DMA) were calculated. The content and distribution of urinary arsenic metabolites in people exposed to arsenic before and after water improvement were compared and analyzed. Results:Compared with 2004, the levels of iAs, MMA, DMA, tAs and iAs% in urine of arsenic exposed population in 2014 were lower ( Z =-14.12,-12.79,-14.27,-14.21,-6.90, P < 0.001), the levels of MMA%, DMA% and PMI were higher ( Z =-3.22,-2.91,-6.90, P < 0.05); in the same drinking water arsenic exposed population, compared with 2004, the levels of iAs, MMA, DMA, tAs and iAs% in urine ( n = 48) were lower ( Z =-5.57,-5.53,-5.54,-5.55,-2.86, P < 0.05) in 2014, and PMI level was higher ( Z =-2.86, P = 0.004). Compared with 2014, the levels of iAs% and MMA/DMA in urine of arsenic exposed population in 2017 were lower ( Z =-4.97,-2.25, P < 0.05), the levels of MMA, DMA, tAs, DMA%, PMI and SMI were higher ( Z =-4.01,-5.39,-4.77,-4.61,-4.97,-2.25, P < 0.05); in the same drinking water arsenic exposed population, compared with 2014, the level of iAs% in urine ( n = 28) was lower ( Z =-2.87, P = 0.004) in 2017, the levels of DMA% and PMI were higher ( Z =-2.32,-2.87, P < 0.05). Conclusion:Water improvement could significantly reduce the levels of urinary arsenic metabolites iAs, MMA, DMA and tAs and increase the level of DMA% in arsenic exposed population.

Radiopharmaceuticals are radionuclide preparations or radiolabelled compounds used for clinical diagnosis or treatment. The targeted radionuclide therapy uses molecular carriers with high affinity for tumor cells to target radionuclides into specific tumor tissues to treat tumors. Compared with traditional radiotherapy and chemotherapy, it is more selective. With the development of nuclear medicine, the popularization of SPECT/CT, PET/CT, the discovery of new targets and the development of new radiopharmaceuticals, the targeted therapy with radiopharmaceuticals is playing an increasingly important role in the clinical treatment of tumors. This review briefly describes the classification, composition and characteristics of radiopharmaceuticals; the application of radioimmunodrugs targeting tumor-associated antigen in non-Hodgkin's lymphoma, colorectal cancer and prostate cancer; the clinical application of receptor-mediated radionuclide drugs in the treatment of neuroendocrine tumors, prostate cancer and breast cancer, and the research progress of radiopharmaceuticals based on gene modification in targeted tumor therapies. Finally, the application prospects and challenges of radiopharmaceuticals in cancer treatment are summarized in order to provide some references for the development and clinical application of radiopharmaceuticals for targeted tumor therapy.

Circular RNAs (circRNAs) are a class of non-coding RNAs that form closed rings in structure. They contain a high content in eukaryotic transcripts, and are characterized by richness, stability, high conservatism and tissue specificity. In recent years, it has been gradually revealed that circRNA can bind to some miRNAs or proteins and participate in the regulatory mechanisms of biogenesis and molecular functions, including the regulation of miRNAs molecular sponge, protein translation, gene transcription and RNA splicing. With the application of high-throughput sequencing and bioinformatics, circRNA has gradually become a new research hotspot in the field of non-coding RNA due to its special properties. The latest research evidence shows that circRNA plays a key role in the occurrence and development of tumors, and is inextricably linked with cell proliferation, apoptosis, angiogenesis, and metastasis, indicating that targeting circRNA will be attractive treatment strategies and potential biomarkers. In this paper, the characteristics and mechanism of circRNA were briefly described, the mechanism of action and regulation of circRNAs in human tumors were summarized, and the strategies and development prospects of circRNA in tumor research were further discussed. In sum, circRNA plays an important role in early diagnosis, precise treatment and prognosis prediction of tumors.

The solubility of nebivolol hydrochloride was determined in acidic aqueous media in the absence and presence of different concentration of NaCl, NaBr, or NaI at 37 ℃ in order to facilitate proper selection of dissolution media that have adequate discriminating power for enhancing the likelihood of a generic drug product to successfully pass in-vivo bioequivalence test. In the range of pH 5.0 to pH 1.0, the solubility of nebivolol hydrochloride decreased with the decrease in the pH of aqueous solution, and the solubility of nebivolol hydrochloride further decreased with the increase in the concentration of added sodium chloride. The solubility decrease of a few weakly basic drug molecules in acidic media and in higher concentration of added chloride was published previously by other researchers, and the observed decrease in the solubility in the presence of higher chloride concentration was interpreted in terms of common-ion effect. However, the results in this paper showed that the solubility of nebivolol hydrochloride also decreased when sodium chloride was replaced with sodium bromide or iodide. The approach described in this paper (i.e. substituting sodium chloride with sodium bromide or iodide) provides an effective method to verify whether common-ion effect is the true (or at least the sole) driving force behind the observed decrease in the solubility of nebivolol hydrochloride in the presence of sodium chloride. The solubility decrease reported in this paper can be interpreted in terms of salting-out effect of sodium chloride, bromide, and iodide. For hydrochloride salt of a weakly basic drug molecule like nebivolol hydrochloride, its solubility in an acidic dissolution medium can be purposely decreased to the lower end of sink condition by adding sodium chloride to make the resulting medium more discriminating. As shown in this paper, a medium at pH 1.2 with added sodium chloride is discriminating and this medium is shown to be bio-relevant to the in-vivo data collected under fasting condition (in-vivo study protocol was approved by Institutional Review Board).

Objective :To explore correlation between serum vitamin D level and cardiac diastolic function in patients with essential hypertension (EH) and normal left ventricular systolic function .Methods :A total of 177 EH patients with normal left ventricular systolic function in our department were divided into vitamin D no deficiency group (≥20ng／ml ,n＝62) and vitamin D deficiency group (＜20ng／ml ,n＝115) ,according to serum vitamin D level .The relationship between serum vitamin D level and cardiac diastolic function was analyzed .Results :(1) Compared with vitamin D no deficiency group , there were significant reductions in blood calcium level [ (2.38 ± 0.12) mmol／L vs.(2.32 ± 0.15) mmol／L] ,mitral early diastolic peak flow velocity [E ,(0.73 ± 0.15) m／s vs.(0.66 ± 0.14) m／s] ,ratio of E to late diastolic peak flow velocity (A) [E／A ,(0.86 ± 0.26) vs.(0.76 ± 0.20)] in vitamin D deficiency group , P＜0.05 or ＜0.01 ;(2) Among the total 177 patients ,serum vitamin D level was significant positively correlated with E and E／A ( r＝0.200 ,0.193 , P＝0.008 , 0.01) ;according to age stratification ,serum vitamin D level was significant positively correlated with E and E／A in ≥60 years patients (r＝0.175 ,0.223 ,P＝0.037 ,0.007) ;according to gender stratification ,serum vitamin D level was signifi‐cant positively correlated with E and E／A in male patients ( r＝0.268 ,0.221 , P＝0.003 ,0.014) ;(3) After correcting age and gender ,Logistic regression analysis indicated that serum vitamin D level was significant positively correlated with E and E／A (β＝3.418 ,1.738 , P＝0.002 ,0.023).Conclusion :Serum vitamin D level is significant positively correlated with cardiac diastolic function in EH patients with normal left ventricular systolic function .

Modified Da-chai-hu Decoction (MDD), a traditional Chinese medicinal formulation, which was empirically generated from Da-chai-hu decoction, has been utilized to treat severe acute pancreatitis (SAP) for decades. The aim of the present study was to explore its potential organprotective mechanism in SAP. In the present study, rat SAP model was induced by retrograde injection of 3.5% sodium taurocholate into the biliopancreatic duct, MDD (23.35 g/kg body weight, twelve times the clinical dose) were orally given at 2 h before and 10 h after injection. At 12 h after model induction, blood was taken from vena cava for analysis of amylase, diamine oxidase (DAO), pulmonary surfactant protein-A (SP-A), and C-reactive protein (CRP). Histopathological change of pancreas, ileum and lung was assayed by H&E staining, myeloperoxidase (MPO) activity were determinated using colorimetric assay, and the expressions of occludin and nuclear factor-κB (NF-κB) were detected by real-time RT-PCR and western blot, respectively. In addition, the tissue concentrations of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and monocyte chemoattractant protein-1 (MCP-1) were measured by enzyme-linked immunosorbent assay (ELISA). The results showed that in SAP rats, MDD significantly alleviated histopathological damage, depressed the MPO activity and the concentrations of TNF-α, IL-1β, and MCP-1 of pancreas, ileum and lung, and reduced the serum levels of amylase [(3283.4 ± 585.5) U·Lvs (5626.4 ± 795.1)U·L], DAO [(1100.1 ± 334.3) U·Lvs (1666.4 ± 525.3) U·L] and CRP [(7.6 ± 1.2) μg·mLvs (17.8 ± 3.8) μg·mL]. However, the serum SP-A concentration [(106.1 ± 16.6) pg·mLvs (90.1 ± 14.9) pg·mL] was elevated when treated SAP rats with MDD. Furthermore, MDD increased the occludin expression and reduced the NF-κB expression in pancreas, ileum and lung of SAP rats. Our findings suggested that MDD administration was an effective therapeutic approach for SAP treatment. It could up-regulate occludin expression to protect intercellular tight junction and down-regulate NF-κB expression to inhibit inflammatory reaction of pancreas, ileum and lung.

Objective: To evaluate the accuracy and clinical value of fractional lfow reserve (FFR) determined by CT coronary angiography (CTA) in relevant patients. Methods: A total of 43 patients treated in our hospitals from 2013-10 to 2015-10 were retrospectively studied. There were 29 (67.40%) with male gender, the average age was (60.2±10.1) years. The patients received CTA at 1 week prior coronary angiography (CAG), the interval between CTA and CAG was (5.4±1.6) days. FFR was measured by both CAG and CTA (FFRCT) in selected target vessel which was deifned as maximal diameter reduction 50% to 70%. The imaging data were recorded and compared, FFRCT was calculated. Results: 48 vessels from 43 patients were eligible for analysis as target vessels. FFRCT vas evaluated based on the gold criteria of FFR. FFRCT had the diagnostic accuracy at 83.3%, sensitivity 75.0%, speciifcity 89.3% and positive predictive value was 83.3%, negative predictive value was 83.3% respectively. FFR and FFRCT showed obvious correlation (r=0.704,P<0.001); Bland-Altman analysis presented good concordance with 95% limits of agreement for FFRCTand FFR value ranged from -0.12 to 0.16, and 95.8% of the points (46/48) fell in the 95% limit of agreement, Receiver operating characteristic curve indicated that AUC of FFRCT was 0.871 (95% CI 0.770-0.973). Conclusion: CTA could accurately assess FFR, and FFRCT might be used in guiding the treatment for patients with intermediate coronary stenosis in clinical practice.