Curative Effect Observation of Burosumab for Children and Adults with X-Linked Hypophosphatemicrickets / 罕见病研究

We studied the patients diagnosed with X-linked hypophosphatemicrickets(XLH) and treated with burosumab in Peking Union Medical College Hospital from January 2021 to December 2022. In addition, we described the clinical characteristics of the patients, the changes of clinical indexes before and after burosumab treatment, and the adverse drug reactions during treatment. We also evaluated the efficacy and safety of burosumab for XLH. The results showed that three children XLH patients and one adult XLH patients received burosumab treatment. After treatment, the serum phosphorus level of all patients increased; the serum phosphorus of 3 children patients increased above the lower limit of the reference value range; the serum alkaline phosphatase(ALP) of all patients was lower than that of before treatment; the serum ALP of one adult patient was close to the normal range after 2.5 years of treatment. One child patient showed small crystals in kidney through ultrasound 48 weeks after treatment; one child and one adult showed increased serum parathyroid hormone(PTH)level before treatment and serum PTH continued increasing after treatment. Finally, it may be concluded that burosumab increased serum phosphorus levels in XLH patients, kept the level relatively stable, and reduced serum ALP levels. No serious adverse reactions occurred during treatment, in order to provide reference for the use of burosumab in patients with XLH.

Spatiotemporal roles of AMPK in PARP-1- and autophagy-dependent retinal pigment epithelial cell death caused by UVA.

BACKGROUND: Although stimulating autophagy caused by UV has been widely demonstrated in skin cells to exert cell protection, it remains unknown the cellular events in UVA-treated retinal pigment epithelial (RPE) cells. METHODS: Human ARPE-19 cells were used to measure cell viability, mitochondrial reactive oxygen species (ROS), mitochondrial membrane potential (MMP), mitochondrial mass and lysosomal mass by flow cytometry. Mitochondrial oxygen consumption rate (OCR) was recorded using Seahorse XF flux analyzer. Confocal microscopic images were performed to indicate the mitochondrial dynamics, LC3 level, and AMPK translocation after UVA irradiation. RESULTS: We confirmed mitochondrial ROS production and DNA damage are two major features caused by UVA. We found the cell death is prevented by autophagy inhibitor 3-methyladenine and gene silencing of ATG5, and UVA induces ROS-dependent LC3II expression, LC3 punctate and TFEB expression, suggesting the autophagic death in the UVA-stressed RPE cells. Although PARP-1 inhibitor olaparib increases DNA damage, ROS production, and cell death, it also blocks AMPK activation caused by UVA. Interestingly we found a dramatic nuclear export of AMPK upon UVA irradiation which is blocked by N-acetylcysteine and olaparib. In addition, UVA exposure gradually decreases lysosomal mass and inhibits cathepsin B activity at late phase due to lysosomal dysfunction. Nevertheless, cathepsin B inhibitor, CA-074Me, reverses the death extent, suggesting the contribution of cathepsin B in the death pathway. When examining the role of EGFR in cellular events caused by UVA, we found that UVA can rapidly transactivate EGFR, and treatment with EGFR TKIs (gefitinib and afatinib) enhances the cell death accompanied by the increased LC3II formation, ROS production, loss of MMP and mass of mitochondria and lysosomes. Although AMPK activation by ROS-PARP-1 mediates autophagic cell death, we surprisingly found that pretreatment of cells with AMPK activators (A769662 and metformin) reverses cell death. Concomitantly, both agents block UVA-induced mitochondrial ROS production, autophagic flux, and mitochondrial fission without changing the inhibition of cathepsin B. CONCLUSION: UVA exposure rapidly induces ROS-PARP-1-AMPK-autophagic flux and late lysosomal dysfunction. Pre-inducing AMPK activation can prevent cellular events caused by UVA and provide a new protective strategy in photo-oxidative stress and photo-retinopathy.

Predictive value of red blood cell distribution width and platelet-to-lymphocyte ratio for acute kidney injury in critically ill patients.

OBJECTIVES: The purpose of this study was to explore the value of red blood cell distribution width (RDW) and platelet-to-lymphocyte ratio (PLR) in predicting the occurrence of acute kidney injury (AKI) in critically ill patients. MATERIALS AND METHODS: Among 1,500 adult patients in the intensive care unit (ICU) between January 2016 and December 2019, we examined the associations of baseline RDW and PLR with the risk of AKI development using logistical analysis. In addition, we explored the value of RDW and PLR in predicting in-hospital mortality. RESULTS: Overall, 615 (41%) patients were diagnosed with AKI. We divided the groups into two subgroups each; the high-RDW (≥ 14.045%) group had a high risk of developing AKI (OR = 5.189, 95% CI: 4.088 - 6.588), and the high-PLR (≥ 172.067) group had a risk of developing AKI too (OR = 9.11, 95% CI: 7.09 - 11.71). The areas under the receiver operating characteristic curves (AUCs) for the prediction of AKI incidence based on RDW and PLR were 0.780 (95% CI: 0.755 - 0.804) and 0.728 (95% CI: 0.702 - 0.754) (all p < 0.001), with cut-off values of 14.045 and 172.067, respectively. Moreover, a higher RDW was associated with a higher rate of hospital mortality (OR: 2.907, 2.190 - 3.858), and the risk of in-hospital mortality related to PLR was 1.534 (95% CI: 1.179 - 1.995). CONCLUSION: A higher RDW was related to a higher risk of AKI occurrence and in-hospital mortality in the ICU.

15 and 30 min of immobilization after IUI: a randomized control trial.

The purpose of this study is to provide evidence for better guidance related to bed rest after intrauterine insemination (IUI). We conducted a randomized trial to compare the effect of 15 min versus 30 min of bed rest after IUI on pregnancy rate. A total of 204 couples were recruited from May 2021 to December 2021 and randomized to remain in the supine position for either 15 or 30 min after the procedure. The outcomes were the clinical pregnancy rate and comfort level after IUI. Ultimately, 198 couples were included in the analysis. The 15-min immobilization group consisted of 100 couples (226 cycles), and the 30-min immobilization group consisted of 98 couples (225 cycles). The clinical pregnancy rate per couple in the 15-min immobilization group (26 of 100) was not different from that in the 30-min immobilization group (23 of 98). With the use of discrete-time survival analysis, the cumulative probability of clinical pregnancy also showed no difference between these two groups. Based on the literature and on our study, the possible beneficial effect of 30-min immobilization after IUI is at least questionable, and a shorter time could be implemented depending on the results of a systematic review and the individual patient data from the currently executed trials.

Membrane Protein Modification Modulates Big and Small Extracellular Vesicle Biodistribution and Tumorigenic Potential in Breast Cancers In Vivo.

Extracellular vesicles (EVs) are released by cells to mediate intercellular communication under pathological and physiological conditions. While small EVs (sEVs; <100-200 nm, exosomes) are intensely investigated, the properties and functions of medium and large EVs (big EVs (bEVs); >200 nm, microvesicles) are less well explored. Here, bEVs and sEVs are identified as distinct EV populations, and it is determined that bEVs are released in a greater bEV:sEV ratio in the aggressive human triple-negative breast cancer (TNBC) subtype. PalmGRET, bioluminescence-resonance-energy-transfer (BRET)-based EV reporter, reveals dose-dependent EV biodistribution at nonlethal and physiological EV dosages, as compared to lipophilic fluorescent dyes. Remarkably, the bEVs and sEVs exhibit unique biodistribution profiles, yet individually promote in vivo tumor growth in a syngeneic immunocompetent TNBC breast tumor murine model. The bEVs and sEVs share mass-spectrometry-identified tumor-progression-associated EV surface membrane proteins (tpEVSurfMEMs), which include solute carrier family 29 member 1, Cd9, and Cd44. tpEVSurfMEM depletion attenuates EV lung organotropism, alters biodistribution, and reduces protumorigenic potential. This study identifies distinct in vivo property and function of bEVs and sEVs in breast cancer, which suggest the significant role of bEVs in diseases, diagnostic and therapeutic applications.

Evaluating the behavior and principle of deep eutectic solvent on ephedrine-type alkaloid extraction from Ephedrae Herba.

In this study, deep eutectic solvent (DES), as a new green solvent, was used to extract bioactive alkaloids from Ephedrae Herba using supersonic extraction. In a variety of tested hydrophilic and hydrophobic DESs, DES composed of choline chloride and xylitol was proved to be the most efficient solvent. Factors affecting extraction efficiency, including the mole ratio of hydrogen bond acceptor/hydrogen bond donor, water contention, and solid/liquid ratio, were optimized individually. Under optimal conditions, the yield of ephedrine (EP) and pseudoephedrine obtained using this new method was 14.24 and 4.32 mg/g, respectively, which was higher than that using the traditional solvent (acidified water and methanol). Furthermore, the extraction mechanism of DES and EP was investigated using molecular dynamics simulation study. Structural properties such as radial distribution functions and average number of hydrogen bonds were then computed. The results showed that hydrogen bonds and van der Waals forces are important driving forces of extraction; in addition, the hydrogen bonds between the Cl atom of choline chloride and N atom of EP played a dominant part in the extraction process. Based on the extraction principle, the extraction method using choline chloride as extraction solvent was also discussed.

Prevalence, risk factors and characteristics of delirium in intensive care unit patients: a prospective observational study / 中华危重病急救医学

OBJECTIVE@#To investigate the prevalence, risk factors, duration and outcome of delirium in intensive care unit (ICU) patients.@*METHODS@#A prospective observational study was conducted for critically ill patients admitted to the department of critical care medicine, the Affiliated Hospital of Guizhou Medical University from September to November 2021. Delirium assessments were performed twice daily using the Richmond agitation-sedation scale (RASS) and confusion assessment method of ICU (CAM-ICU) for patients who met the inclusions and exclusion criteria. Patient's age, gender, body mass index (BMI), underlying disease, acute physiologic assessment and chronic health evaluation (APACHE) at ICU admission, sequential organ failure assessment (SOFA) at ICU admission, oxygenation index (PaO2/FiO2), diagnosis, type of delirium, duration of delirium, outcome, etc. were recorded. Patients were divided into delirium and non-delirium groups according to whether delirium occurred during the study period. The clinical characteristics of the patients in the two groups were compared, and risk factors for the development of delirium were screened using univariate analysis and multivariate Logistic regression analysis.@*RESULTS@#A total of 347 ICU patients were included, and delirium occurred in 57.6% (200/347) patients. The most common type was hypoactive delirium (73.0% of the total). Univariate analysis showed statistically significant differences in age, APACHE score and SOFA score at ICU admission, history of smoking, hypertension, history of cerebral infarction, immunosuppression, neurological disease, sepsis, shock, glucose (Glu), PaO2/FiO2 at ICU admission, length of ICU stay, and duration of mechanical ventilation between the two groups. Multivariate Logistic regression analysis showed that age [odds ratio (OR) = 1.045, 95% confidence interval (95%CI) was 1.027-1.063, P < 0.001], APACHE score at ICU admission (OR = 1.049, 95%CI was 1.008-1.091, P = 0.018), neurological disease (OR = 5.275, 95%CI was 1.825-15.248, P = 0.002), sepsis (OR = 1.941, 95%CI was 1.117-3.374, P = 0.019), and duration of mechanical ventilation (OR = 1.005, 95%CI was 1.001-1.009, P = 0.012) were all independent risk factors for the development of delirium in ICU patients. The median duration of delirium in ICU patients was 2 (1, 3) days. Delirium was still present in 52% patients when they discharged from the ICU.@*CONCLUSIONS@#The prevalence of delirium in ICU patients is over 50%, with hypoactive delirium being the most common. Age, APACHE score at ICU admission, neurological disease, sepsis and duration of mechanical ventilation were all independent risk factors for the development of delirium in ICU patients. More than half of patients with delirium were still delirious when they discharged from the ICU.

Evaluation on the blocking effect of hepatitis B vaccine on mother-to-infant transmission in 302 cases and analysis of influencing factors / 公共卫生与预防医学

Objective To evaluate the effect of the current immunization strategy for hepatitis B virus (Hepatitis B) in blocking mother-to-infant transmission in Hubei Province, and to explore the mechanism and possible influencing factors of failure of mother-to-infant blockade. Methods A multi-stage random sampling method was used to select 2 counties or districts in Hubei Province. Through maternity hospital health handbook, neonatal health record or hospital medical record system, hepatitis B virus (HBV) surface antigen (HBsAg)-positive pregnant women in 2012-2018 years were included to retrospectively investigate their delivery status and the HBV infection status of their children. Results Among the 302 newborns, 32 were positive for HBsAg, and the success rate of blockade of mother-to-infant transmission of hepatitis B was 89.45%. Further analysis showed that 68.21% (206 / 302) of newborns were delivered in township hospitals, 66.23% (200 / 302) were delivered by caesarean section and 41.72% (126 / 302) were breastfed, while 16.89% (51/302) were positive for hepatitis B virus e antigen (HBeAg), and 41.06% (124/302) were positive for anti-HBe. The vaccination rate of hepatitis B immunoglobulin (HBIG) during pregnancy was 3.31% (10/302), and the newborn HBIG vaccination rate was 94.37% (285/302). There were 84.11% (254/302) of pregnant women taking protective measures in daily life. Logistic regression analysis showed that township hospitals (OR=2.82, P<0.05), HBeAg positivity during pregnancy (OR=8.68, P<0.05), and HBIG vaccination during pregnancy (OR=12.62 , P<0.05) were risk factors for failure of mother-to-infant blockade, while anti-HBe positivity during pregnancy (OR=0.22, P<0.05), vaccination of newborns with HBIG (OR=0.20, P<0.05), and protective measures taken in daily life (OR=0.28, P<0.05) were protective factors for mother-to-infant interruption. Conclusion Deliveries in township hospitals and HBeAg-positivity during pregnancy are more likely to fail in blocking of mother-to-infant transmission of hepatitis B. HBIG vaccination during pregnancy does not reduce the risk of blockade failure. Neonatal HBIG vaccination, anti-HBe positivity during pregnancy, and protective measures in daily life can reduce the risk of blockade failure of mother-to-infant transmission of hepatitis B.

Research and practice on integrated management of multi-campus in public hospitals / 中华医院管理杂志

The development of multi-campus is an effective way to expand and enlarge high-quality medical resources for public hospitals. In view of the problems in the relationship between power, responsibility and benefit, functional positioning, discipline layout, homogenization of medical quality and service, and management of human and financial resources in multi-campus, the authors introduced the integrated management system built by the Second Affiliated Hospital Zhejiang University School of Medicine in the process of multi-campus construction. The system included a standard-oriented quality system, a demand-oriented service system, a position-oriented personnel system, an efficiency-oriented financial system, a sharing-oriented information system and a mutual integration-oriented culture system, and formed an integrated management mode of " hospital-area synergy, differential positioning, and homogeneous development" , which significantly improved the management efficiency, service capacity and operational efficiency of the hospital, and could provide an effective reference for public hospital managers.

Correlation analysis between uranium exposure and renal injury / 中华放射医学与防护杂志

Objective:To analyze the relationship between plasma uranium concentration and renal injury.Methods:A case-control study was conducted in Hunan province, involving 102 renal injury cases and 102 matched controls. The association between plasma uranium concentration and renal injury was analyzed using conditional logistic regression models, and the dose-response relationship was analyzed through restricted cubic spline regression. The linear regression model and Spearman correlation were used to analyze the association between plasma uranium concentration and renal injury indicators.Results:The median of plasma uranium concentration was 8.94 ng/L in all subjects and 10.19 ng/L in the case group. The plasma uranium may be a risk factor for renal injury, with a dose-response relationship between the both representing nonlinear association ( χ2=5.15, P<0.05). The risk of renal injury was 4.21 times higher in the group exposed to highest uranium concentration than that in the group exposed to lowest uranium concentration. Plasma uranium concentration was closely related to glomerular filtration rate, serum creatinine and β 2-microglobulin ( r=0.211, -0.142, 0.195, P<0.05). Conclusions:The plasma uranium concentration is significantly associated with the renal injury, which may provide epidemiology evidence for the prevention of renal injury.

FERM domain-containing protein FRMD6 activates the mTOR signaling pathway and promotes lung cancer progression / 医学前沿

FRMD6, a member of the 4.1 ezrin-radixin-moesin domain-containing protein family, has been reported to inhibit tumor progression in multiple cancers. Here, we demonstrate the involvement of FRMD6 in lung cancer progression. We find that FRMD6 is overexpressed in lung cancer tissues relative to in normal lung tissues. In addition, the enhanced expression of FRMD6 is associated with poor outcomes in patients with lung squamous cell carcinoma (n = 75, P = 0.0054) and lung adenocarcinoma (n = 94, P = 0.0330). Cell migration and proliferation in vitro and tumor formation in vivo are promoted by FRMD6 but are suppressed by the depletion of FRMD6. Mechanistically, FRMD6 interacts and colocalizes with mTOR and S6K, which are the key molecules of the mTOR signaling pathway. FRMD6 markedly enhances the interaction between mTOR and S6K, subsequently increasing the levels of endogenous pS6K and downstream pS6 in lung cancer cells. Furthermore, knocking out FRMD6 inhibits the activation of the mTOR signaling pathway in Frmd6-/- gene KO MEFs and mice. Altogether, our results show that FRMD6 contributes to lung cancer progression by activating the mTOR signaling pathway.

Cross sectional, surveillance and longitudinal study of poor visual acuity in Gui an New Distinct of Guizhou Province / 中国学校卫生

Objective@#To understand the development trend of poor vision among primary students through cross sectional, surveillance and longitudinal analysis, so as to put forward some suggestions on adolescents growth and health.@*Methods@#Visual data of 3 753 pupils were inclucled for analysis from Gui an New Distinct, Guizhou Province in autumn semester 2021, and were compared with data collected during the year of 2016-2021. The curve, increment and contribution rate of poor vision from each grade of the three designs were contrasted.@*Results@#In 2021, poor vision rate among pupils in this town was 25.6%. The curve of poor vision rate in cross sectional data was U shaped with significant rise followed by decline which was different from monitoring and longitudinal tracking data, and the trend of poor vision rate of monitoring and longitudinal tracking data were linear with continued increases. The cross sectional data in 2021 showed that the highest contribution rate of poor vision rate of pupils was in grade 1(87.0% ), while other data showed that those were both in grade 4(45.0%, 33.9%).@*Conclusion@#The accuracy of the development trend of poor vision is lowest in cross sectional analysis and highest in longitudinal analysis. However, data acquisition and preservation is easy in cross sectional study and difficult in longitudinal study. It is necessary to improve the electronic information system based on cross sectional data to gradually form a complete monitoring and longitudinal tracking data, and combine different data to provide more accurate information.

Starting effect of highly active antiretroviral therapy on the incidence of anemia in HIV-infected patients / 上海预防医学

ObjectiveTo investigate the risk factors of anemia in HIV-infected patients receiving highly active antiretroviral therapy （HAART） in the Pudong New Area. MethodsA retrospective cohort study was conducted among HIV-infected patients who started HAART from 2005 to 2020 in Pudong New Area. Cox proportional hazards model was used to analyze the risk factors of anemia， moderate or severe anemia， and chronic anemia. The piecewise linear mixed-effect model was used to analyze the association between initial HAART classes and hemoglobin change in the follow-up. ResultsA total of 2 403 HIV-infected patients were included in the analysis. Among them， there were 357 cases of new onset anemia， 86 cases of chronic anemia and 102 cases of moderate or severe anemia， with the incidence density of 4.41/100 person years， 0.89/100 person years and 0.96/100 person years respectively. Multifactorial Cox regression analysis results showed that female， age >45 years， baseline CD4+ T lymphocyte count （CD4） <200 cells‧μL-1， opportunistic infections， glomerular filtration rate （eGFR） <60 mL‧min-1‧（1.73 m2）-1， and zidovudine （AZT） or protease inhibitor （PIs） based regimens were associated factors for the development of anemia. Female， age >45 years， CD4 <200 cells‧μL-1， opportunistic infections， and AZT-based regimens were associated with the development of chronic anemia. Mild anemia at baseline and AZT-based regimens were associated with the development of moderate or severe anemia. Linear mixed-effects model showed that the use of AZT （-7.87 g‧L-1， 95%CI： -9.42 to -6.32） or PIs （-3.43 g‧L-1， 95%CI： -5.57 to -1.30） was associated with lower Hb at follow-up. ConclusionInitial use of AZT and PIs is associated with progression to anemia and a lower follow-up hemoglobin level. Increased hemoglobin monitoring in users of AZT and PIs may be beneficial， especially during the first 6 months after initiation of HAART.

Research progress of sarcopenic obesity and chronic liver disease / 中华肝脏病杂志

Sarcopenia has attracted increasing attention with the study of nutrition in patients with liver disease. Sarcopenia is an independent risk factor for a poor prognosis of liver disease and is becoming increasingly common in patients with liver disease. Studies have shown that patients with liver disease and sarcopenic obesity have a worse prognosis than patients with liver disease and simple sarcopenia or obesity. In clinical practice, it is easy to recognize patients with malnutrition and decreased muscle mass, but we often ignore those patients with normal body weight or even obesity who will likewise experience muscle mass loss. Simply relying on the monitoring of body mass and body mass index to assess the nutritional and muscle status of patients with liver disease is not accurate. At present, our understanding of the relationship between chronic liver disease and sarcopenic obesity is still poorly understood. In this paper, the research progress on chronic liver disease, sarcopenia, and sarcopenic obesity in recent years is reviewed so as to provide a theoretical basis for improving the clinical prognosis of patients with liver disease.

Meta-analysis of Ac-SDKP inhibition of Pulmonary fibrosis in animal models / 中华劳动卫生职业病杂志

Objective: To systematically study the anti-fibrotic effect of N-acetyl-seryl-as partyl-lysyl-proline (Ac-SDKP) on pulmonary fibrosis. Methods: In May 2021, a computer search was performed on CNKI, Wanfang Knowledge Service Platform, VIP.com, China Biomedical Literature Database, Pubmed, OVID and other databases. The retrieval time was from January 2008 to May 2021. Randomized controlled experiments on the inhibition of pulmonary fibrosis by Ac-SDKP were screened. The control group was the pulmonary fibrosis model group and the experimental group was the Ac-SDKP treatment group. The quality of the literature was assessed using the syrcle risk of bias assessment tool, and data were extracted. Data analysis was Performed using revman 5.4 software. Results: 18 papers were included, with a total of 428 animal models. The results of meta analysis showed that the contents of α-smooth muscle actin (α-SMA), type I collagen, type Ⅲ collagen, transforming growth factor-β (TGF-β) and Nodule area in the exPerimental group were lower than those in the control grouP. [SMD=-2.44, 95%CI (-3.71--1.17), P=0.000][SMD=-5.36, 95%CI (-7.13--3.59), P=0.000] [SMD=-3.07, 95%CI (-4.13--2.02), P<0.000][SMD=-2.88, 95%CI (-3.63--2.14), P=0.000] [SMD=-1.80, 95%CI (-2.42--1.18), P=0.000], the content of hydroxy proline in the experimental group was higher than that in the control group [SMD=7.62, 95%CI (4.90-10.33), P=0.000], all indexes included in the literature were statistically significant. Conclusion: Ac-SDKP has obvious inhibitory effect on the process of pulmonary fibrosis, and may become a new clinical drug for the treatment of pulmonary fibrosis.

Short-term efficacy of empagliflozin in children with glycogen storage disease type Ⅰb / 中华儿科杂志

Objective: To analyze the short-time efficacy of empagliflozin in the treatment of glycogen storage disease type Ⅰb (GSD Ⅰb). Methods: In this prospective open-label single-arm study, the data of 4 patients were collected from the pediatric department in Peking Union Medical College Hospital from December 2020 to December 2022. All of them were diagnosed by gene sequencing and had neutropenia. These patients received empagliflozin treatment. Their clinical symptoms such as height and weight increase, abdominal pain, diarrhea, oral ulcer, infection times, and drug applications were recorded at 2 weeks, 1 month, 2 months, 3 months, 6 months, 9 months, 12 months, and 15 months after treatment to assess the therapeutic effect. The liquid chromatography-tandem mass spectrometry method was used to monitor the changes in 1, 5-anhydroglucitol (1, 5AG) concentration in plasma. At the same time, adverse reactions such as hypoglycemia and urinary tract infection were closely followed up and monitored. Results: The 4 patients with GSD Ⅰb were 15, 14, 4 and 14 years old, respectively at the beginning of empagliflozin treatment, and were followed up for 15, 15, 12 and 6 months, respectively. Maintenance dose range of empagliflozin was 0.24-0.39 mg/(kg·d). The frequency of diarrhea and abdominal pain decreased in cases 2, 3, and 4 at 1, 2 and 3 months of treatment, respectively. Their height and weight increased at different degrees.The absolute count of neutrophils increased from 0.84×109, 0.50×109, 0.48×109, 0.48×109/L to 1.48×109, 3.04×109, 1.10×109, 0.73×109/L, respectively. Granulocyte colony-stimulating factor was gradually reduced in 1 patients and stopped in 3 patient. Plasma 1, 5 AG levels in 2 children were significantly decreased after administration of empagliflozin (from 46.3 mg/L to 9.6 mg/L in case 2, and from 56.1 mg/L to 15.0 mg/L in case 3). All 4 patients had no adverse reactions such as hypoglycemia, abnormal liver or kidney function, or urinary system infection. Conclusion: In short-term observation, empagliflozin can improve the symptoms of GSD Ⅰb oral ulcers, abdominal pain, diarrhea, and recurrent infection, also can alleviate neutropenia and decrease 1, 5AG concentration in plasma, with favorable safety.

Pollution characteristics and health risk assessment of metals in farmland soil around the largest realgar mining area in Asia / 环境与职业医学

Background Heavy metal emissions from mining and smelting areas are a global problem, and health risks associated with heavy metal contamination of soils are of great concern. The long-term mining of the largest realgar mine in Asia has caused severe arsenic and other metal pollution to the surrounding rivers and soils. Objective To understand the levels of metal contamination and health risks in agricultural soils of villages surrounding the largest realgar mine in Asia, and to lay a good foundation for further necessary pollution control actions and decisions. Methods A field survey was conducted to collect soil samples according to the Technical rules for monitoring of environmental quality of farmland soil (NY/T 395-2012), and then inductively coupled plasma mass spectrometry was used to determine the contents of 28 heavy metals [cadmium (Cd), arsenic (As), lead (Pb), mercury (Hg), chromium (Cr), nickel (Ni), copper (Cu), zinc (Zn), beryllium (Be), selenium (Se), cobalt (Co), antimony (Sb), molybdenum (Mo), vanadium (V), barium (Ba), thallium (Tl), boron (B) , bismuth (Bi), lithium (Li), manganese (Mn), strontium (Sr), calcium (Ca), rubidium (Rb), iron (Fe), magnesium (Mg), aluminum (Al), kalium (K), and titanium (Ti)]. Geoaccumulation index, single factor pollution index, and Nemerow comprehensive index were used to evaluate the degree and characteristics of single metal pollution and combined pollution in soil, respectively. A health risk assessment model was used to evaluate the risks of metals in soil to human health. Results The results of geoaccumulation index calculation revealed that 22 heavy metals were enriched in the soil, and the indexes of target heavy metals from high to low were Cd > Se > Pb >Hg > As > Co> Ni > Cu > Zn > Bi > Sb > Mo > Be> Cr > Ba >V > Li > Sr> Mn> Rb > Ca> Tl . The single factor pollution indexes of 17 heavy metals from high to low were Be > Cd > B > Mo > V > As > Ni > Cu > Pb > Zn > Co > Se > Tl > Ba > Cr > Hg > Sb. The Nemerow comprehensive index indicated all sampling points were graded as severe pollution. The mean of total non-carcinogenic health risk values and the mean of carcinogenic health risk values for the target heavy metals in the area were higher than the threshold (1) and the maximum acceptable risk (1.0×10–4), respectively. The total carcinogenic health risks for adults and children reached 1.1×10–3 and 1.67×10–3, respectively. The mean non-carcinogenic health risk values of As, Co, Cr, and Pb pollution were greater than 1, and the maximum non-cancer risk value of Sb for children was greater than 1. The mean carcinogenic risk values of Ni, As, and Cu exceeded 1.0×10–4 for both adults and children, and the maximum carcinogenic risk values of Be and Cr for children were more than 1.0×10–4. Conclusion The farmland soil around the hugest realgar mine in Asia is contaminated by multiple metals. The study soil is seriously polluted by Cd, Se, Pb, As, Hg, Be, B, Mo, V, Ni, Cu, Pb, Zn, Co, and Ba. The pollution of Ni, As, Cu, Cr, and Be is considered as carcinogenic hazards to health, while the pollution of As, Co, Cr, Pb, and Sb poses non-carcinogenic health risks. Our study findings show that the soil is polluted by Co and Group 1 carcinogen Be, which could cause health risks; although Cr and Sb have not reached severe pollution levels, there are certain health risks and also need attention.

Advances in mechanism of traditional Chinese medicine in inhibiting angiogenesis in ovarian cancer / 中国中药杂志

Ovarian cancer is one of the three major cancers in gynecology. Ovarian cancer has insidious symptoms in its early stages and mostly has progressed to advanced stages when detected. Surgical treatment combined with chemotherapy is currently the main treatment, but the 5-year survival rate is still less than 45%. Angiogenesis is a key step in the growth and metastasis of ovarian cancer. The inhibition of ovarian cancer angiogenesis has become a new hotspot in anti-tumor targeted therapy, which has many advantages such as less drug resistance, high specificity, few side effects, and broad anti-tumor spectrum. Modern research has confirmed that traditional Chinese medicine(TCM) can inhibit tumor angiogenesis by inhibiting the expression of pro-angiogenic factors, up-regulating the expression of anti-angiogenic factors, inhibiting the proliferation of vascular endothelial cells, reducing the density of tumor microvessels, and regulating related signaling pathways, with unique advantages in the treatment of ovarian cancer. This paper presented a review of the role of TCM in inhibiting ovarian cancer angiogenesis in order to provide references for the optimization of clinical ovarian cancer treatment strategies.

Transcriptome-wide identification of walnut PP2C family genes in response to external stimulus.

Walnut is an important economic tree species while confronting with global environmental stress, resulting in decline in quality and yield. Therefore, it is urgent to elucidate the molecular mechanism for the regulation of walnut response to adversity. The protein phosphatase 2C (PP2C) gene family participates in cellular processes in eukaryotes through reversible phosphorylation of proteins and signal transduction regulation. However, the stress response function of PP2C genes was far to be clarified. Therefore, to understand the stress response mechanism of walnut tree, in this study, a total of 41 PP2C genes with complete ORFs were identified from Juglans regia, whose basic bio-information and expression patterns in response to multiple stresses and ABA were confirmed. The results showed that the ORFs of JrPP2Cs were 495 ~ 3231 bp in length, the predicted JrPP2C proteins contained 164 to 1076 amino acids and the molecular weights were 18,581.96 ~ 118,853.34 Da, the pI was 4.55 ~ 9.58. These JrPP2C genes were unevenly distributed on 14 chromosomes, among which Chr11 and Chr13 contained the most genes. Phylogenetic analysis found that these JrPP2C proteins were classed into 9 subfamilies, among which group F covered most JrPP2Cs. The JrPP2Cs in the same subfamily exhibited similarities in the composition of conserved domains, amino acid sequences of motifs and exon/intron organization in DNA sequences. Each JrPP2C includes 4 ~ 10 motifs and each motif contained 15 ~ 37 amino acids. Among the motifs, motif1, motif2, motif3 and motif8 were most abundant. Most of the JrPP2C genes diversely response to osmotic, cadmium, and Colletotrichum gloeosporioide stress as well as ABA treatments, among which JrPP2C28, JrPP2C17, JrPP2C09, JrPP2C36 were more obvious and deserves further attention. All these results indicated that JrPP2C genes play potential vital roles in plant response to multiple stimulus, and are possibly involved in ABA-dependent signaling pathway.

Analysis of clinical phenotype and genotype of Chinese children with disorders of sex development / 中华儿科杂志

Objective: To explore the heterogeneity and correlation of clinical phenotypes and genotypes in children with disorders of sex development (DSD). Methods: A retrospective study of 1 235 patients with clinically proposed DSD in 36 pediatric medical institutions across the country from January 2017 to May 2021. After capturing 277 DSD-related candidate genes, second-generation sequencing was performed to analyzed the heterogeneity and correlation combined with clinical phenotypes. Results: Among 1 235 children with clinically proposed DSD, 980 were males and 255 were females of social gender at the time of initial diagnosis with the age ranged from 1 day of age to 17.92 years. A total of 443 children with pathogenic variants were detected through molecular genetic studies, with a positive detection rate of 35.9%. The most common clinical phenotypes were micropenis (455 cases), hypospadias (321 cases), and cryptorchidism (172 cases) and common mutations detected were in SRD5A2 gene (80 cases), AR gene (53 cases) and CYP21A2 gene (44 cases). Among them, the SRD5A2 mutation is the most common in children with simple micropenis and simple hypospadias, while the AMH mutation is the most common in children with simple cryptorchidism. Conclusions: The SRD5A2 mutation is the most common genetic variant in Chinese children with DSD, and micropenis, cryptorchidism, and hypospadias are the most common clinical phenotypes. Molecular diagnosis can provide clues about the biological basis of DSD, and can also guide clinicians to perform specific clinical examinations. Target sequence capture probes and next-generation sequencing technology can provide effective and economical genetic diagnosis for children with DSD.