Research progress of endoplasmic reticulum targeting drug delivery system for anti-tumor immunotherapy / 药学学报

Endoplasmic reticulum (ER), a multifunctional organelle in eukaryotic cells, is responsible for protein synthesis and intracellular signal transduction, which dominates cell function, survival, and apoptosis. Disequilibrium of ER homeostasis may induce ER stress, which closely intertwines with tumor occurrence and progress. A few clinical-used drugs (such as anthraquinones and oxaliplatin) can mediate the immunogenic cell death of tumor cells through excessive ER stress, and sequentially stimulate anti-tumor immune responses as well as long-term immune memory. However, these drugs often exhibit poor targeting ability and extremely low ER accumulation in tumor cells, limiting their clinical efficacy. Therefore, the researches of ER-targeted delivery of these drugs will significantly benefit the efficient and precise anti-tumor immunotherapy. In this review, we introduce the relationship between ER and tumor immunity, and summarize the ER targeting strategies for anti-tumor immunotherapy in recent years. Furthermore, we discuss the problems of existing ER targeting strategies and look into its broad prospects of application.

Changes of subfoveal choroidal thickness and choroidal volume in different stages of diabetic retinopathy through automated choroid segmentation / 中华实验眼科杂志

Objective:To analyze the changes of subfoveal choroidal thickness (SFCT) and choroidal volume in type 2 diabetes patients with diabetic retinopathy (DR) through automated choroid segmentation.Methods:A cross-sectional study was conducted.Sixty-four patients (88 eyes) with type 2 diabetes diagnosed in The First Affiliated Hospital with Nanjing Medical University from May 2016 to May 2017 were enrolled, including 27 males (32 eyes) and 37 females (56 eyes), with an average age of (62.7±7.4) years and an average diabetes duration of (13.7±7.2) years.Best corrected visual acuity, slit lamp ophthalmoscopy, indirect ophthalmoscopy and spectral domain optical coherence tomography (SD-OCT) examination were carried out among all the patients.The patients were divided into non-DR (NDR) group (28 eyes), nonproliferative DR (NPDR) group (36 eyes) and proliferative DR (PDR) group (24 eyes) according to the Early Treatment Diabetic Retinopathy Study.Nineteen age-matched normal subjects (32 eyes) were enrolled as normal control group.SFCT and choroidal volume were measured through automated choroid segmentation based on SD-OCT with enhanced depth imaging.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of The First Affiliated Hospital with Nanjing Medical University (No.2017-SR-176).Results:Mean SFCT and choroidal volume of normal control group, NDR group, NPDR group and PDR group were (277.8±45.3)μm and (8.8±1.0)mm 3, (220.9±38.7)μm and (7.6±1.3)mm 3, (231.8±26.7)μm and (8.2±0.9)mm 3, (252.0±42.2)μm and (8.7±1.0)mm 3, respectively, with significant overall differences among the groups ( F=14.615, P<0.001; F=7.711, P<0.001). Mean SFCT and choroidal volume were significantly smaller in NDR and NPDR group than those in normal control group (both at P<0.05). Mean SFCT and choroidal volume of PDR group was greater than those of NDR group (both at P<0.05). Conclusions:SFCT and choroidal volume decrease during the early course of diabetes and increase significantly as DR worsens from NDR to PDR.

Study on knowledge, attitudes and practices of pulse oximetry among pediatric healthcare providers in China and their influencing factors / 中华实用儿科临床杂志

Objective:To investigate the knowledge, attitudes, and practices (KAP) of pulse oximetry among pediatric healthcare providers in China and analyze the factor influencing the KAP.Methods:A self-developed questionnaire was used for an online research on the KAP of 11 849 pediatric healthcare providers from 31 provinces, autonomous regions, and municipalities of China from March 11 to 14, 2022.The factors influencing the KAP of pulse oximetry among pediatric healthcare providers were examined by Logistic regression. Results:The scores of KAP, of pulse oximetry were 5.57±0.96, 11.24±1.25 and 11.19±4.54, respectively.The corresponding scoring rates were 69.61%, 74.95%, and 55.99%, respectively. Logistic regression results showed that the gender and working years of pediatric healthcare providers, the region they were located, and whether their medical institution was equipped with pulse oximeters were the main factors affecting the knowledge score (all P<0.05). Main factors influencing the attitude score of pediatric healthcare providers included their knowledge score, gender, educational background, working years, region, medical institution level, and whether the medical institution was equipped with pulse oximeters (all P<0.05). For the practice score, the main influencing factors were the knowledge score, gender, age, and whether the medi-cal institution was equipped with pulse oximeters (all P<0.05). Conclusions:Chinese pediatric healthcare providers need to further improve their knowledge about and attitudes towards pulse oximetry.Pulse oximeters are evidently under-used.It is urgent to formulate policies or guidelines, strengthen education and training, improve knowledge and attitudes, equip more institutions with pulse oximeters, and popularize their application in medical institutions.

Expert consensus on clinical application of pulse oximetry in children / 中华实用儿科临床杂志

Hypoxemia is a common complication of pneumonia, asthma, and bronchopulmonary dysplasia in children.Rapid identification of hypoxemia is of great significance for the disposal and management of critical children.Pulse oximetry is recognized by the World Health Organization as the best way to monitor hypoxemia in children, and it can monitor pulse oxygen saturation noninvasively and continuously.Based on the related literature at home and abroad, combined with the clinical needs of pediatrics, the " Expert consensus on clinical application of pulse oximetry in children" is formulated to improve the understanding of pediatricians and nurses on the application in pediatric clinical practice, principle, operation techniques, and limitations of pulse oximetry.

Effects of biofeedback dialysis mode of blood volume monitoring on cardiac function in the maintenance hemodialysis patients with intra-dialytic hypotension / 中国医师杂志

Objective:To discuss the effects of biofeedback dialysis mode of blood volume monitoring on cardiac function in the maintenance hemodialysis (MHD) patients with intra-dialytic hypotension (IDH).Methods:40 patients who underwent maintenance hemodialysis in Suzhou Hospital Affiliated to Nanjing Medical University from September 2018 to December 2020 and had IDH for many times were selected. They were divided into standard dialysis (SHD) group and biofeedback dialysis mode of blood volume monitoring (BVM) group, with 20 cases in each group. In the first 12 weeks of the first stage, the patients in both groups were treated with standard dialysis, and in the second 12 weeks, they were treated with maintenance hemodialysis according to standard dialysis and biofeedback dialysis mode of blood volume monitoring. The incidence of IDH and the changes of blood pressure before and after dialysis, body weight, ultrafiltration volume, B-type brain natriuretic peptide (BNP), left ventricular ejection fraction (LVEF), left ventricular end diastolic diameter (LVEDD), left ventricular posterior wall thickness (LVPW), inlet ventricular septal defect (IVSD), mitral valve flow spectrum E/A value (E/A) and left ventricular mass index (LVMI) were observed.Results:(1) In the second stage of treatment, the number of IDH requiring nursing intervention in BVM group was significantly lower than that in SHD group ( P<0.05). (2) The difference of blood pressure change in BVM group during the second stage of treatment was significantly lower than that in the first stage and SHD group ( P<0.05). (3) In the second stage of treatment, the ultrafiltration volume of patients in BVM group was significantly higher than that in the first stage, and the BNP and body weight were significantly lower than that in the first stage (all P<0.05). However, the body weight, BNP and ultrafiltration volume of patients in SHD group had no significan change in the two stages of treatment (all P>0.05). (4) After treatment, the LVID, LVPW, IVSD and LVMI in BVM group were significantly lower than those before treatment, and LVEF and E/A were significantly higher than those before treatment (all P<0.05). However, there was no significant change in echocardiographic indexes in SHD group before and after treatment (all P>0.05). Conclusions:The biofeedback dialysis mode of blood volume monitoring can significantly reduce the occurrence of IDH, and this dialysis mode can effectively improve the cardiac function of MHD patients with hypotension.

Identification of human LDHC4 as a potential target for anticancer drug discovery

One of the distinct hallmarks of cancer cells is aerobic glycolysis (Warburg effect). Lactate dehydrogenase A (LDHA) is thought to play a key role in aerobic glycolysis and has been extensively studied, while lactate dehydrogenase C (LDHC), an isoform of LDHA, has received much less attention. Here we showed that human LDHC was significantly expressed in lung cancer tissues, overexpression of Ldhc in mice could promote tumor growth, and knock-down of LDHC could inhibit the proliferation of lung cancer A549 cells. We solved the first crystal structure of human LDHC4 and found that the active-site loop of LDHC4 adopted a distinct conformation compared to LDHA4 and lactate dehydrogenase B4 (LDHB4). Moreover, we found that (ethylamino) (oxo)acetic acid shows about 10 times selective inhibition against LDHC4 over LDHA4 and LDHB4. Our studies suggest that LDHC4 is a potential target for anticancer drug discovery and (ethylamino) (oxo)acetic acid provides a good start to develop lead compounds for selective drugs targeting LDHC4.

A study of the effectiveness of nucleos(t)ide analogues in the treatment of HBeAg- positive chronic hepatitis B with normal alanine aminotransferase and high level of HBV DNA / 中华肝脏病杂志

Objective: To investigate the effectiveness of nucleos(t)ide analogues in the treatment of HBeAg-positive chronic hepatitis B with normal alanine aminotransferase and high level of HBV DNA. Methods: Treatment-naïve chronic hepatitis B patients who were followed up at the Center of Infectious Diseases, West China Hospital of Sichuan University from January 2019 to January 2020 were selected as subjects. Demographic characteristics, the results of laboratory examination before treatment and one year after treatment were retrospectively collected. Patients were divided into tenofovir dipivoxil (TDF) and propofol fumurate tenofovir (TAF) treatment group according to different types of medication. The changes of serum HBV DNA level, HBeAg serological conversion and HBsAg quantitative level were analyzed and compared between the two groups. Results: A total of 38 cases were enrolled. Among them, there were 16 and 22 cases in the TDF and TAF group, respectively. There was no statistically significant difference in demographic characteristics, baseline HBV DNA levels and HBsAg quantitative levels between the two groups. Virological response was achieved in 60.5% (23/38) of patients after one year of antiviral therapy. Serum HBV DNA levels below the lower limit of detection [68.2% (15/22) vs. 50.0% (8/16), P=0.258] and higher HBeAg seroconversion rate [18.2%] (4/22) vs. 6.3% (1/16), P=0.374] was obtained in TAF than TDF group; however, there was no statistically significant differences between the two. Serum HBsAg quantitative level was significantly reduced with TDF and TAF treatment. In addition, alanine aminotransferase elevation was reduced in TAF than TDF treated group. Multivariate logistic regression analysis showed that patient age was an independent predictor of a virological response to antiviral therapy. Conclusion: HBeAg-positive CHB patients with normal alanine aminotransferase, and high HBV DNA level can obtain better curative effect after TDF and TAF treatment.

Analysis on the industry characteristics of newly diagnosed occupational pneumoconiosis in Foshan City， 2007-2021 / 中国职业医学

@#Abstract: Objective To analyze the industry characteristics of new occupational pneumoconiosis in Foshan from 2007 to Methods 2021. The data of new cases of occupational pneumoconiosis in Foshan City from 2007 to 2021 were obtained from “ ” ， “ the China Disease Prevention and Control Information System subsystem the Occupational Disease and Health Hazardous ”， Results Factors Monitoring Information System and the industry characteristics of the cases were analyzed. From 2007 to ， ， （ ） 2021 there were 886 new cases of occupational pneumoconiosis in Foshan mainly include silicosis 68.3% in males （ ）， （ ） 94.2% and stage Ⅰ pneumoconiosis cases 75.9% . The median age of cases at the time of diagnosed disease was 47 years ， old and the median working age of dust exposure was 11.2 years. The enterprises where all cases are located involve eight top ， ； ， - industry categories of which manufacturing industry accounted for 97.6% and 30 major industry categories of which non （ ） ， metallic mineral products industry was the highest 60.5% . There were 554 sporadic cases and 332 cluster cases and the ， ， Conclusion industries were mainly non-metallic mineral products accounting for 55.0% and 69.6% respectively. ， - Occupational pneumoconiosis in Foshan is dominated by silicosis and the key industries are non metallic mineral products.

Research progress on the interactions between gut bacterial β-glucuronidases and Chinese herbal medicines / 药学学报

In traditional oral practice, the presystemic interactions with gut microbiota is an important mechanism underlying the holistic health benefits of Chinese herbal medicines (CHMs), making the study of CHMs distinct from the research of Western medicines of which the systemic exposure (level in blood) is the starting point and the core. Gut microbial metabolism complements host metabolism in maintaining metabolic homeostasis of many biologically important endogenous molecules and the disposition of numerous exogenous compounds. Among them, the widely distributed gut bacterial β-glucuronidases (BGUSs) coordinate with host UDP-glucuronosyltransferases (UGTs) to play a role in the occurrence and intervention of diseases by affecting the glucuronidation homeostasis and altering the intestinal local and/or systemic exposure of endogenous compounds and xenobiotics. On one hand, many ingredients of CHMs undergo enterohepatic circulation; On the other hand, CHMs can act on BGUSs directly or indirectly change the distribution and function of BGUSs through reprogramming gut microbiome. The multiple interactions between BGUSs and CHMs may play an important role in the overall therapeutic benefits of CHMs. This work firstly summarizes the latest research progress on BGUSs; then the physiological, pathological and pharmacological significance of BGUSs are exemplified with representative endogenous and exogenous compounds from the aspects of nutrient utilization, metabolic homeostasis, and therapeutic response based on the varied substrate spectra of BGUSs; finally, the scattered data in literature were integrated to summarize the multiple interactions between BGUSs and CHMs, highlighting the important role of BGUSs in the holistic actions of CHMs.

Comparative analysis of immunization effects before and after polio vaccine immunization schedule conversion / 中华微生物学和免疫学杂志

Objective:To compare the polio antibody level of healthy children in Jiangsu Province before and after the conversion of (inactivated poliovirus vaccine, IPV) immunization program.Methods:200 serum samples of healthy children under 5 years old in Jiangsu Province were collected before and after the vaccine conversion, and the neutralizing antibody against poliomyelitis was measured using the micro cell neutralization test. We compared the differences in the positive rate and geometric mean titer (GMT) of polio antibody before and after vaccine conversion.Results:Before vaccine conversion, positive rates of antibody against poliovirus type Ⅰ and Ⅲ were 98.50% and 92.00%, with GMTs of 1∶100.43 and 1∶23.34, respectively. After the conversion, positive rates of polio antibody type I and Ⅲ were 99.00% and 96.00%, GMT were 1∶213.04 and 1∶121.10.Conclusions:There is a difference in immunization effect before and after the polio vaccine conversion, and the antibody level of the population after vaccine conversion is higher than that before vaccine conversion. It is recommended to gradually increase the IPV dose in order to finally achieve the whole course of IPV inoculation.

Comparison of the effects between low-level assisted ventilation and T-piece method on respiratory mechanics during weaning of mechanically ventilated patients / 中华危重病急救医学

Objective:To compare the difference of low-level assisted ventilation and T-piece method on respiratory mechanics of patients with invasive mechanical ventilation during spontaneous breathing trial (SBT) within 3 days before extubation.Methods:A retrospective observational study was conducted. Twenty-five patients with difficulty in weaning or delayed weaning from invasive mechanical ventilation who were admitted to department of critical care medicine of the First Affiliated Hospital of Guangzhou Medical University from December 2018 to June 2020, and were in stable condition and entered the weaning stage after more than 72 hours of invasive mechanical ventilation were studied. A total of 119 cases of respiratory mechanical indexes were collected, which were divided into the low-level assisted ventilation group and the T-piece group according to the ventilator method and parameters used during the data collection. The different ventilation modes related respiratory mechanics indexes such as the esophageal pressure (Pes), the gastric pressure (Pga), the transdiaphragmatic pressure (Pdi), the maximum Pdi (Pdimax), Pdi/Pdimax ratio, the esophageal pressure-time product (PTPes), the gastric pressure-time product (PTPga), the transdiaphragmatic pressure-time product (PTPdi), the diaphragmatic electromyography (EMGdi), the maximum diaphragmatic electromyography (EMGdimax), PTPdi/PTPes ratio, Pes/Pdi ratio, the inspiratory time (Ti), the expiratory time (Te) and the total time respiratory cycle (Ttot) at the end of monitoring were recorded and compared between the two groups.Results:Compared with the T-piece group, Pes, PTPes, PTPdi/PTPes ratio, Pes/Pdi ratio and Te were higher in low-level assisted ventilation group [Pes (cmH 2O, 1 cmH 2O = 0.098 kPa): 2.84 (-1.80, 5.83) vs. -0.94 (-8.50, 2.06), PTPes (cmH 2O·s·min -1): 1.87 (-2.50, 5.93) vs. -0.95 (-9.71, 2.56), PTPdi/PTPes ratio: 0.07 (-1.74, 1.65) vs. -1.82 (-4.15, -1.25), Pes/Pdi ratio: 0.17 (-0.43, 0.64) vs. -0.47 (-0.65, -0.11), Te (s): 1.65 (1.36, 2.18) vs. 1.33 (1.05, 1.75), all P < 0.05], there were no significant differences in Pga, Pdi, Pdimax, Pdi/Pdimax ratio, PTPga, PTPdi, EMGdi, EMGdimax, Ti and Ttot between the T-piece group and the low-level assisted pressure ventilation group [Pga (cmH 2O): 6.96 (3.54,7.60) vs. 7.74 (4.37, 11.30), Pdi (cmH 2O): 9.24 (4.58, 17.31) vs. 6.18 (2.98, 11.96), Pdimax (cmH 2O): 47.20 (20.60, 52.30) vs. 29.95 (21.50, 47.20), Pdi/Pdimax ratio: 0.25 (0.01, 0.34) vs. 0.25 (0.12, 0.41), PTPga (cmH 2O·s·min -1): 7.20 (2.54, 9.97) vs. 7.97 (5.74, 13.07), PTPdi (cmH 2O·s·min -1): 12.15 (2.95, 19.86) vs. 6.87 (2.50, 12.63), EMGdi (μV): 0.05 (0.03, 0.07) vs. 0.04 (0.02, 0.06), EMGdimax (μV): 0.07 (0.05, 0.09) vs. 0.07 (0.04, 0.09), Ti (s): 1.20 (0.95, 1.33) vs. 1.07 (0.95, 1.33), Ttot (s): 2.59 (2.22, 3.09) vs. 2.77 (2.35, 3.24), all P > 0.05]. Conclusions:When mechanically ventilated patients undergo SBT, the use of T-piece method increases the work of breathing compared with low-level assisted ventilation method. Therefore, long-term use of T-piece should be avoided during SBT.

Renoprotective Effect of Sanjiao Qushi Prescription Against Cationic Bovine Serum Albumin Induced Membranous Nephropathy Mice Model and Its Influence on Nrf2/HO-1 Signaling Pathway / 中国实验方剂学杂志

Objective:To investigate the renoprotective effects that Sanjiao Qushi prescription ameliorates cationic bovine serum albumin （C-BSA） induced membranous nephropathy（MN） in mice model and its influence on nuclear factor erythroid-2-related factor-2（Nrf2）/heme oxygenase-1（HO-1） signaling pathway. Method:Sixty female BALB/c mice were randomly divided into the normal group（<italic>n</italic>=10） and the model group（<italic>n</italic>=50）. The mice in the model group received C-BSA injection via tail vein （6.5 mg·kg^-1）. The mice that were successfully modeled were randomized into the model group， the low dose Sanjiao Qushi prescription group（3.71 g·kg^-1）， the high dose Sanjiao Qushi prescription group（7.42 g·kg^-1） and benazepril hydrochloride group（1.3 mg·kg^-1）. And they were administered with the corresponding medicine by gavage once a day for four consecutive weeks. 24 hour-urine protein quantitation were performed before C-BSA injection and after C-BSA injection as well as the medicine gavage. When the treatment was finished， all of the mice were sacrificed and the biochemical indicators such as serum creatinine（SCr）， blood urea nitrogen（BUN）， triglyceride（TG）， total cholesterol（TC）， total protein（TP） and albumin（Alb） were measured. And the renal pathological morphology changes were observed by light microscope with hematoxylineosin（HE）， Masson and periodic acid-silver metheramine（PASM） staining. The deposition of immunoglobulin G（IgG） in the glomerulus was detected by fluorescence microscope. The expression of reactive oxygen species （ROS） of kidney was detected by fluorescence immunoassay. The protein expression levels of Nrf2 in cell nucleus and cytoplasm and the downstream protein factors HO-1 and NADH quinone acceptor oxidoreductase 1（NQO1） were detected by Western blot. Result:Compare to normal group， the levels of 24 hour-urine protein quantitation， TG and TC significantly increased in model group（<italic>P</italic><0.01）， while TP and Alb levels significantly decreased（<italic>P</italic><0.01）. The model group exhibited enlarged volume of glomerular， significantly thickened glomerular basement membrane（GBM）， fuchsinophilic protein deposition and spike formation through light microscope. Immunofluorescence staining for the model group exhibited granular deposition of IgG along the capillary wall. The expression of ROS in kidney significantly increased（<italic>P</italic><0.01）. The protein expression levels of Nrf2 in cell nucleus significantly increased（<italic>P</italic><0.01）， while Nrf2 in cytoplasm significantly decreased（<italic>P</italic><0.01）.The protein expression levels of HO-1 and NQO1 significantly increased（<italic>P</italic><0.01）. Compared to model group， the levels of 24 hour-urine protein quantitation， TG and TC significantly decreased in each treated group（<italic>P</italic><0.01）， TP and Alb levels significantly increased（<italic>P</italic><0.05，<italic>P</italic><0.01）. The pathological damages alleviated obviously. The expression of ROS in kidney significantly decreased（<italic>P</italic><0.01）. The protein expression levels of Nrf2 in cell nucleus significantly decreased（<italic>P</italic><0.01）， while Nrf2 in cytoplasm significantly increased（<italic>P</italic><0.05，<italic>P</italic><0.01）. The protein expression levels of HO-1 and NQO1 significantly increased（<italic>P</italic><0.01）. Conclusion:Sanjiao Qushi prescription worked on MN mice possibly by regulating related proteins in the Nrf2/HO-1 signaling pathway and relieving oxidative stress， thus decreasing 24 hour-urine protein and blood lipid， increasing serum protein， and alleviating the pathological damages to protect renal function and delay progress of the disease.

Optimization of a cucurbit6uril-based real-time label-free method for analyzing the activity of ornithine decarboxylase / 生物工程学报

Ornithine decarboxylase (ODC) is a key enzyme in the biosynthetic pathway of polyamines and catalyzes the decarboxylation of ornithine to produce putrescine. Inhibition of ODC activity is a potential approach for the prevention and treatment of many diseases including cancer, as the expression levels and the activities of ODC in many abnormal cells and tumor cells are generally higher than those of normal cells. The discovery and evaluation of ODC inhibitors rely on the monitoring of the reaction processes catalyzed by ODC. There are several commonly used methods for analyzing the activity of ODC, such as measuring the yield of putrescine by high performance liquid chromatography, or quantifying the yield of isotope labelled carbon dioxide. However, the cumbersome operation and cost of these assays, as well as the difficulty to achieve high-throughput and real-time detection, hampered their applications. In this work, we optimized a real-time label-free method for analyzing the activity of ODC based on the macromolecule cucurbit[6]uril (CB6) and a fluorescent dye, DSMI (trans-4-[4-(dimethylamino) styryl]-1-methylpyridinium iodide). Finally, the optimized method was used to determine the activities of different ODC inhibitors with different inhibition mechanisms.

Diagnosis and treatment of chronic suppurative lung disease in children / 中国小儿急救医学

Objective:To analyze the causes and clinical features of chronic suppurative lung disease(CSLD) in children.Methods:We retrospectivly analyzed the primary disease, imaging changes, electronic fiber bronchoscope changes, blood gas analysis, lung function, treatment outcome and other clinical data of CSLD in children hospitalized in our hospital from September 2018 to February 2020.Results:A total of 14 children with CSLD were collected, including six males and eight females, aged (5.9±2.7) years old.Among 14 cases of CSLD, six cases were diagnosed with upper airway cough syndrome, three cases with upper airway cough syndrome and bronchial asthma, two cases with cough variant asthma, and one case with combined immunodeficiency disease.There were different degrees of purulent inflammation under electronic fiber bronchoscopy, and three cases had airway inflammatory stenosis.The lavage fluid suggested neutrophil inflammation.Blood gas analysis was normal in ten cases and hypoxemia in four cases.In seven cases, pulmonary function examination was abnormal in six cases, and one case had emphysema on lung CT examination.After intravenous administration of antibiotics and sequential oral antibiotics, the symptoms of 14 children were relieved.Fourteen cases were followed up for 12 weeks.Among them, 12 cases had complete relief of clinical symptoms, one case had repeated cough with combined immunodeficiency disease, and one case was lost to follow-up.Conclusion:CSLD mostly has primary disease.Electronic fiber bronchoscopy is not only a necessary examination of CSLD, but also one of the important means for treatment.Purulent inflammation of the airways can lead to abnormal obstructive lung.Sufficient course of treatment and standardized use of antibiotics are the key to the treatment for CSLD.

Post-Marketing Surveillance of Qishe Pill () Use for Management of Neck Pain in a Chinese Patient Cohort to Determine its Safety, Tolerability and Effectiveness / 中国结合医学杂志

OBJECTIVE@#To evaluate the safety and effectiveness of Qishe Pill () on neck pain in real-world clinical practice.@*METHODS@#A multi-center, prospective, observational surveillance in 8 hospitals across Shanghai was conducted. During patients receiving 4-week Qishe Pill medication, Visual Analogue Scale (VAS) and Neck Disability Index (NDI) assessments have been used to assess their pain and function, while safety monitoring have been observed after 2 and 4 weeks.@*RESULTS@#Results from 2,023 patients (mean age 54.5 years) suggest that the drug exposure per unit of body mass was estimated at 3.41 ± 0.62 g/kg. About 8.5% (172/2,023) of all participants experienced adverse events (AEs), while 3.8% (78/2,023) of all participants experienced adverse reaction. The most common AEs were gastrointestinal events and respiratory events. The VAS score (pain) and NDI score (function) significantly decreased after 4-week treatment. An effect-quantitative analysis was also conducted to show that the normal clinical dosage may be consider as 3-4 g/kg, at which dosage the satisfactory pain-relief effect may achieve by 40-mm reduction in VAS.@*CONCLUSION@#These findings showed that patients with cervical radiculopathy who received Qishe Pill experienced significant improvement on pain and function. (Registration No. NCT01875562).

Association of different stages of histological chorioamnionitis with respiratory distress syndrome in preterm infants with a gestational age of < 32 weeks / 中国当代儿科杂志

OBJECTIVE@#To study the association of different stages of histological chorioamnionitis (HCA) with the incidence rate and severity of respiratory distress syndrome (RDS) in preterm infants.@*METHODS@#Related data were collected from the infants and their mothers who were treated in the Neonatal Intensive Care Unit of Qingdao Women and Children's Hospital, Qingdao University, from January 2018 to June 2020. According to the presence or absence of HCA and its stage, the infants were divided into four groups: control (@*RESULTS@#Compared with the control and late-stage HCA groups, the early-stage HCA group had a significantly lower incidence rate of placental abruption and a significantly higher rate of prenatal use of antibiotics (@*CONCLUSIONS@#Early-, middle-, and late-stage HCA can reduce the incidence rate of RDS in preterm infants. HCA stage may not be correlated with RDS severity in preterm infants, which needs to be verified by further research.

Preliminary study on effect of Gegen Qinlian Decoction on enzyme activity, gene expression and methylation level of FASN in adipose tissue of rats with insulin resistance / 中国中药杂志

To investigate the effect of Gegen Qinlian Decoction(GQD) on enzyme activity, gene expression and methylation level of fatty acid synthase(FASN) in adipose tissue from rats with insulin resistance induced by high-fat diet. The 60% fat-powered high-fat diet was continuously given to male SD rats to induce the insulin resistance model. Then, they were divided into five groups randomly and administrated by gavage every day for 16 weeks with following drugs respectively: 10 mL·kg~(-1)water for control group(C) and insulin resistance model control group(IR), 1.65 g·kg~(-1)GQD per day for low-dose group(GQDL), 4.95 g·kg~(-1)GQD per day for medium-dose group(GQDM), 14.85 g·kg~(-1)GQD per day for high-dose group(GQDH), and 5 mg·kg~(-1) rosiglitazone per day for rosiglitazone group(RGN). Epididymal adipose tissue was taken to determine enzyme activity of FASN by colorimetric method, mRNA expression level of Fasn by quantitative Real-time PCR(Q-PCR) and CpGs methylation level between +313 and +582 by bisulfite sequencing PCR(BSP). These results showed that Fasn expression was significantly lowered in IR model rats compared with the control rats(P<0.01). Enzymatic activity and CpGs methylation level of Fasn in IR group showed downward trends. Low and medium-dose GQD can increase enzyme activity of FASN(P<0.05). Moreover, low-dose GQD increased the total CpGs methylation level of Fasn fragment between +313 and +582 in insulin resistance rats(P<0.05). For GQDM group, the methylation frequency of CpGs at positions +506 and +508(P<0.01) as well as the methylation frequency of CpGs on the binding sites of transcription factorzinc finger protein 161(P<0.05) were significantly increased. The methylation frequency of CpG at +442 position was positively correlated with Fasn expression(P<0.01, r=0.735), and methylation frequencies of CpGs at +345 and +366 positions were positively associated to enzyme activity of FASN respectively(P<0.05, r=0.479; P<0.01, r=0.640). In conclusion, GQD can reverse enzyme activity of FASN and methylation level of Fasn in adipose tissue of insulin resistant rats, and CpG sites at positions +506 and +508 may be the targets of GQD. The methylation level of CpGs at + 345 and + 366 sites were possibly related to FASN activity, while methylation of CpG at + 442 site may be closely correlated with mRNA level of Fasn. In addition, GQD did not significantly change mRNA expression level of Fasn, but effectively reversed enzymatic activity, suggesting that GQD may regulate the post transcriptional expression of Fasn.

Thirty years of metabolic engineering for biosynthesis of polyhydroxyalkanoates / 生物工程学报

Polyhydroxyalkanoate (PHA) is a family of biodegradable polyesters synthesized by microorganisms. It has various monomer structures and physical properties with broad application prospects. However, its large-scale production is still hindered by the high cost. In the past 30 years, metabolic engineering approach has been used to tune the metabolic flux, engineer and introduce pathways. The efficiency of PHA synthesis by microorganisms has been significantly improved, and the diversity of PHA monomer, structure and substrate have also been enriched. Meanwhile, by changing cell morphology and PHA particle size, more efficient downstream production process has achieved and PHA production costs have been reduced. In recent years, "Next generation industrial biotechnology" (NGIB) based on extremophiles, especially halophilic Halomonas spp., has been rapidly developed. NGIB has achieved the opening and continuous production of PHA, which simplifies the production process and saves energy and fresh water. Combined with metabolic engineering, Halomonas spp. can be transformed into low-cost production platform of numerous PHA. It is expected to improve the market competitiveness and promote the commercialization of PHA.

Sevoflurane regulates cell activity and apoptosis of breast cancer via Circ_001589/miR-588 / 中华内分泌外科杂志

Objective:To explore the effects and molecular mechanism of circ_001598 on biological behavior of breast cancer (BC) cells.Methods:Sevoflurane in different concentrations were used to treat BC cells and the cell activity and apoptosis were detected. qRT-PCR was used to determine the relative expression of Circ_001598 and miR-588 in BC tissue and cells. The effects of Sevoflurane on Circ_001598, miR-588 expression was detected. Dual luciferase reporter gene assay was used to detect the relationship between Circ_001598 and miR-588. The expression of Circ_001598, miR-588 in BC cells was intervened, then cell activity and apoptosis level was detected by using MTT and flow cytometry individually.Results:Sevoflurane inhibited cell activity of BC cells, and promoted cell apoptosis. Circ_001598 was increased in BC tissue and cells, but Sevoflurane could down-regulate the expression of Circ_001598 (all P<0.05) . Overexpression of Circ_001589 partially saved the effects of Sevoflurane on cell viability and apoptosis. Circ_001598 negatively regulated miR-588 in BC cells. miR-588 expression was down-regulated in BC tissue and cells, but Sevoflurane up-regulated the expression level of miR-588 in BC cells (all P<0.05) . miR-588 transfection partially offseted the effects of Circ_001598 on Sevoflurane induced BC cells apoptosis. Conclusion:Sevoflurane affects BC cell viability and apoptosis via regulating Circ_001589/miR-588.

The anti-aging effects of different parts of Scutellaria baicalensis Georgi based on 1H NMR urine metabolomics / 药学学报

The effects of alcohol extracts from roots, stems, leaves, and flowers of Scutellaria Baicalensis Georgi (SBG) on endogenous metabolism in D-gal-induced aging-model rats were investigated by 1H NMR metabolomics. Results showed that 32 endogenous metabolites were identified in the urine. Combined with the VIP value and t-test, 14 different metabolites were found by multivariate statistical analysis of the spectrum. Compared with the control group, the content of α-ketoglutaric acid, hippuric acid and 3-hydroxybutyrate in the urine of rats in the model group was significantly decreased (P<0.05) and the content of trimethylamine oxide, glycine, alanine, lactic acid, dimethylglycine, acetate, pyruvate, taurine, allantoin, betaine, N-acetylated glycoprotein was significantly increased (P<0.05). The metabolites were mainly derived from taurine and hypo-taurine metabolism; glycine, serine and threonine metabolism; pyruvate metabolism; glycolysis/gluconeogenesis; glyoxylic acid and dicarboxylic acid metabolism; and the tricarboxylic acid cycle. The content of differential metabolites in urine samples was altered by the alcohol extracts from the different parts of SBG. Leaves extracts of SBG had the greatest effect on urine metabolites, and mainly affected taurine and hypo-taurine metabolism; glycine, serine and threonine metabolism; and pyruvate metabolism. This study provides a reliable experimental basis for the future development of SBG. This animal experiment was approved by the Committee on the Ethics of Animal Experiments of Shanxi University (SXULL2016036).