Evaluation of clinical efficacy and safety on phacoemulsification combined with gonioscopy-assisted angle plasty for primary angle-closure glaucoma with cataract / 中华实验眼科杂志

Objective:To evaluate the efficacy and safety of phacoemulsification combined with gonioscopy-assisted angle plasty (Phaco-GAAP) for primary angle closure glaucoma (PACG) with cataract.Methods:A case series study was carried out.Twenty-five eyes of 22 patients with PACG and cataract were enrolled in Beijing Tongren Hospital from April 2022 to August 2022.All of the patients received Phaco-GAAP surgery.During the operation, viscoelastic-assisted goniosynechialysis was performed at first, followed by a secondary angle plasty for residual peripheral anterior synechiae (PAS) based on the quantified assessment by gonioscopy, and the extent of PAS was recorded intraoperatively.The operated eyes were followed at 1 day, 1 week, 1 month and 3 months after surgery to evaluate intraocular pressure (IOP), PAS range, the number of anti-glaucoma drugs application, operation-related complications, and success rate.The qualified success rate was defined as medicine-controlled IOP ≤21 mmHg after surgery, and complete success rate was defined as IOP ≤21 mmHg without any anti-glaucoma medication.This study complied with the Declaration of Helsinki and was approved by the Ethics Committee of Beijing Tongren Hospital (TRECKY2021-136). Written informed consent was obtained from each patient prior to entering the research cohort.Results:The extent of PAS was [270(225, 360)°], [165(110, 215)°] and [100(35, 175)°] at preoperation, first and secondary angle plasty, respectively, showing a significant difference among them ( χ2 =40.742, P<0.001). The PAS range was significantly reduced at first angle plasty in comparison with preoperation and was significantly reduced at secondary angle plasty in comparison with at first angle plasty (both at P<0.001), and the proportion of the angle PAS range ≥180° decreased from 48% to 24% after second angle plasty.In 13 eyes finished gonioscopy, the PAS range was [240(195, 305)°], [60(25, 182.5)°], [170(120, 275)°]and [180(140, 280)°]at preoperation, at the end of operation, postoperative 1 month and 3 months, respectively, with a significant difference ( χ2 =23.631, P<0.001). The PAS range was significantly smaller at postoperative 1 month, 3 months than that at preoperation (both at P=0.004) and larger than that at the end of operation ( P=0.011, P=0.003). The IOP was (40.19±17.23), (15.80±7.98), (13.89±5.09), (12.80±3.79) and(13.24±2.78) mmHg before operation and 1 day, 1 week, 1 month and 3 months after operation, respectively, showing a significant difference ( F=44.031, P<0.001), and the IOP was significantly reduced after operation (all at P<0.001). The PAS range at the end of operation was positively correlated with preoperation ( rs=0.409, P=0.042). The complete and qualified success rates were 95.8%, 95.8% for postoperative 1 month, 95.8% and 100% for postoperative 3 months, respectively.The primary complication was intraoperative anterior chamber angle hemorrhage, with an incidence of 68%. Conclusions:Phaco-GAAP can intraoperatively quantify PAS range and guide secondary angle plasty, therefore, it is an effective and safe surgical intervention for PACG with cataract.

The predicting indices for the outcome of refractory septic shock in preterm infants / 中国新生儿科杂志

Objective:To study the predictive value of vasoactive-inotropic score (VIS), fluid overload (FO) and lactate level for the outcome of preterm infants with refractory septic shock.Methods:Preterm infants diagnosed with refractory septic shock and required hydrocortisone treatment in our Department from January 2016 to December 2021 were analyzed retrospectively. Preterm infants were assigned into three gestational age groups (<28 weeks, 28-31 weeks, 32-36 weeks). According to the outcome of the disease, the children were further divided into good prognosis group and poor prognosis group. The relationship between the maximum VIS, FO and the mean lactic acid before hydrocortisone and the outcome of refractory septic shock was analyzed by receiver operating characteristic (ROC) curve, the cut-off point of ROC curve was calculated to obtain the predictive efficacy of the three indicators for the outcome of refractory septic shock in preterm infants.Results:A total of 50 preterm infants with refractory septic shock and received hydrocortisone treatment were enrolled, including 20 in the good prognosis group and 30 in the poor prognosis group. There were no significant differences in the maximum VIS, FO and mean lactic acid before hydrocortisone treatment between the two groups of gestational age of <32 weeks ( P> 0.05). The maximum VIS, FO and mean lactic acid of gestational age of 32-36 weeks in the poor prognosis group were higher than those in the good prognosis group, VIS: 56.1±15.7 vs. 37.1±12.9, FO (%): 108.2 (78.6,137.7) vs. 55.5 (10.3, 100.7), and mean lactic acid (mmol/L): 8.3 (4.6, 12.0) vs. 4.8 (-0.8, 10.5), all P<0.05. The area under the ROC curve of the mean lactic acid was the largest, the cut-off value was 4.1 mmol/L, and the Youden index was 1.732. Conclusions:VIS, FO and lactate level are difficult to be used for determining the outcome of refractory septic shock in preterm infants of <32 weeks. While the mean lactic acid has the best predictive performance in preterm infants of 32-36 weeks.

Research progress of palliative care for patients with lung transplantation / 中国实用护理杂志

This paper summarized the research progress of palliative care for lung transplantation patients, to summarize the necessity and influencing factors of palliative care for lung transplantation patients, and defined the research status of palliative care implementation mode for lung transplantation patients, with a view to providing ideas for further research of palliative care on lung transplantation patients in China.

Correlation between paroxysmal slow-wave events and cognitive impairment in patients with cerebral small vessel disease / 国际脑血管病杂志

Objective:To investigate the correlation between paroxysmal slow-wave events (PSWEs) and cerebral small vessel disease (CSVD) and CSVD-related cognitive impairment.Methods:Patients with CSVD visited Weihai Municipal Hospital from March 2021 to April 2022 were included, and sex- and age-matched healthy controls were recruited for cross-sectional analysis. The patients with CSVD were further divided into cognitive impairment group and non-cognitive impairment group. The self-developed Python script was used to detect the PSWE parameters in electroencephalogram records. Montreal Cognitive Assessment (MoCA) and Mini-Mental State Examination (MMSE) were used to evaluate cognitive function. Multivariate logistic regression analysis was used to determine whether PWSE parameters were the independent related factors of CSVD and CSVD-related cognitive impairment. Multiple linear regression analysis was used to determine the correlation between the PSWE parameters and overall cognitive function (MoCA total score) in patients with CSVD. Results:A total of 76 patients with CSVD (including 41 patients with cognitive impairment and 35 patients without cognitive impairment) and 45 healthy controls were included. Compared with the healthy control group, PWSEs in the F3 (left frontal area) and O1 (left occipital area) regions of the CSVD group occurred more frequently and lasted longer (all P<0.05). Multivariate logistic regression analysis showed that the frequency (odds ratio [ OR] 1.080, 95% confidence interval [ CI] 1.023-1.140; P=0.005) and duration ( OR 1.006, 95% CI 1.001-1.011; P=0.023) of PWSEs in the left frontal area, as well as the frequency ( OR 1.052, 95% CI 1.010-1.095; P=0.014) and duration ( OR 1.003, 95% CI 1.000-1.006; P=0.028) of PWSEs in the left occipital region were the independent related factors for CSVD. The frequency ( OR 1.106, 95% CI 1.033-1.183; P=0.004) and duration ( OR1.010, 95% CI 1.003-1.017; P=0.004) of PWSEs in the left frontal area were the independent risk factors for cognitive impairment in patients with CSVD. Multiple linear regression analysis showed that the frequency ( β= –0.242, P=0.045) and duration ( β= –0.235, P=0.046) of PWSEs in the left frontal region were negatively correlated with the overall cognitive function score in patients with CSVD. Conclusions:The frequency and duration of PSWEs in some brain regions of patients with CSVD increase, and there is an independent correlation between PSWEs and cognitive impairment, suggesting that the damage of blood-brain barrier may participate in the pathogenesis of cognitive impairment in patients with CSVD.

Progress on the impact of pathogenic gene mutations in epilepsy on treatment choices / 国际儿科学杂志

In the past decade, significant progress has been made in the study of epilepsy-causing genetic mutations and the molecular mechanisms of epilepsy clinical manifestations.A growing number of studies have shown that the mechanism of action of pathogenic genes related to clinical symptoms shows significant correlation.In the selection of antiepileptic drugs for patients with different gene mutation, early identification of pathogenic genes has guiding significance for the selection of antiepileptic drugs.This review summairzes common epilepsy pathogenic genes, including ion channels genes, cellular metabolism related genes and cell signaling pathway related genes, and research progress on therapeutic targets corresponding to pathogenic genes in recent years.As research deepens, specific gene defects and their machanisms of action provide a basis for studying new treatment methods.

Analysis of cytogenetic characteristics of primary childhood B-cell acute lymphoblastic leukemia and risk factors for first treatment response / 白血病·淋巴瘤

Objective:To investigate the cytogenetic characteristics and influencing factors associated with first treatment response in primary childhood B-cell acute lymphoblastic leukemia (B-ALL).Methods:The data of 49 children with primary B-ALL who were admitted to the First Hospital of Xiamen University from April 2019 to September 2021 were retrospectively collected, and the clinical characteristics, cytogenetic and molecular biology findings and other clinical indicators before and after treatment were obtained. Genotyping, clinical risk stratification after the first induction chemotherapy and chemotherapy regimen development were performed according to the pediatric ALL treatment specification (2018 version). The relationship between different genotypes and clinical indicators in children with B-ALL was analyzed, and the correlation between clinical risk stratification and each indicator was analyzed by Spearman rank correlation analysis.Results:The median age of 49 children was 3.0 years old (interquartile range: 3.2 years old), 32 cases (65.3%) were male and 17 cases (34.7%) were female, with a male-to-female ratio of 1.88∶1. Thirty-five cases (71.4%) had gene mutations before treatment and 14 cases (28.6%) had no mutations. Among the 35 cases with mutations, E2A-PBX1 was found in 5 cases (10.2%), including 1 case with Philadelphia chromosome (Ph)-like; IKZF1 deletion was found in 8 cases (16.3%), including 4 cases with Ph-like, 1 case with Ph-positive, and 1 case with MLL rearrangement; MLL rearrangement was found in 3 cases (6.1%); Ph-like alone was found in 12 cases (24.5%); TEL-AML1 was found in 6 cases (12.2%), including 2 cases with Ph-like; 1 case (2.0%) with Ph-positive alone. The clinical risk stratification showed that 7 cases (14.3%) had high risk, 28 cases (57.1%) had intermediate risk, and 14 cases (28.6%) had low risk. The proportions of patients with high and intermediate clinical risk before induction chemotherapy [20.0% (7/35) vs. 0.0% (0/14), 62.9% (22/35) vs. 42.9% (6/14)] and the proportion of patients with altered mutation status on day 33 of induction chemotherapy [42.9% (15/35) vs. 0.0% (0/14)] were higher in patients with mutations before induction chemotherapy than those in patients without gene mutations before treatment (all P < 0.01). The gene mutation or not before treatment was not correlated with gender, white blood cell count at first diagnosis, hormone sensitivity, minimal residual disease (MRD) from the 15th to the 19th day of induction chemotherapy, and MRD on the 33rd day of induction chemotherapy (all P > 0.05). Clinical risk stratification of children was associated with white blood cell count at first diagnosis ( r = 0.392, P = 0.005), neutrophil count ( r = 0.453, P = 0.001), lymphocyte count ( r = 0.418, P = 0.001), monocyte count ( r = 0.359, P = 0.017), blood uric acid level ( r = 0.378, P = 0.007), and proportion of bone marrow naive lymphocyte count before treatment ( r = 0.316, P = 0.027) and from 15th to the 19th day of induction chemotherapy ( r = 0.399, P = 0.005) and the 33rd day of induction chemotherapy ( r = 0.408, P = 0.028), proportion of children with bone marrow MRD ≥ 0.000 1 on the 33rd day of induction chemotherapy ( χ2 = 15.42, P < 0.001), and proportion of children with gene mutations before treatment ( χ2 = 9.10, P = 0.005). Conclusions:High levels of leukocytes, neutrophils, lymphocytes, monocytes, naive lymphocytes, blood uric acid, and naive lymphocytes from the 15th to the 19th day and the 33rd day of chemotherapy, MRD on the 33rd day of chemotherapy and genotype in children with B-ALL may be associated with poor response to treatment. Clinical risk stratification is associated with gene mutation status, and gene mutation may be an important indicator of treatment response in children with B-ALL.

Prediction of concentration immediately dangerous to life or health of benzene and its derivatives based on quantitative structure-activity relationship / 环境与职业医学

Background With the increasing exposure to hazardous chemicals in the workplace and frequency of occupational injuries and occupational safety accidents, the acquisition of occupational exposure limits of hazardous chemicals is imminent. Objective To obtain more unknown immediately dangerous to life or health (IDLH) concentrations of hazardous chemicals in the workplace by exploring the application of quantitative structure-activity relationship (QSAR) prediction method to IDLH concentrations, and to provide a theoretical basis and technical support for the assessment and prevention of occupational injuries. Methods QSAR was used to correlate the IDLH values of 50 benzene and its derivatives with the molecular structures of target compounds. Firstly, affinity propagation algorithm was applied to cluster sample sets. Secondly, Dragon 2.1 software was used to calculate and pre-screen 537 molecular descriptors. Thirdly, the genetic algorithm was used to select six characteristic molecular descriptors as dependent variables and to construct a multiple linear regression model (MLR) and two nonlinear models using support vector machine (SVM) and artificial neural network (ANN) respectively. Finally, model performance was evaluated by internal and external validation and Williams diagram was drawn to determine the scopes of selected models. Results The ANN model results showed that \begin{document}$ {R}_{\mathrm{t}\mathrm{r}\mathrm{a}\mathrm{i}\mathrm{n}}

Clinical Evidence of Oral Chinese Patent Medicines in Treatment of Chronic Kidney Disease： A Scoping Review / 中国实验方剂学杂志

ObjectiveTo review the information and clinical studies of oral Chinese patent medicines （CPMs） for chronic kidney disease （CKD）. MethodThe CPMs for treating CKD were retrieved from the Pharmacopoeia of the People's Republic of China， National Essential Drugs List， and Medicine List for National Basic Medical Insurance， Employment Injury Insurance and Maternity Insurance. China National Knowledge Infrastructure（CNKI）， VIP， Wanfang Data， SinoMed， PubMed， Embase， Cochrane， and Web of Science were searched for the clinical trials of the treatment of CKD by CPMs from their inception dates to September 25， 2022. A database was established with the collected CPMs， and then the general conditions of the clinical trials were analyzed and presented visually. ResultA total of 16 CPMs for CKD were included in this study， including 5 classical traditional Chinese medicine （TCM） prescriptions involving Rehmanniae Radix and 11 new CPMs. The indications of the TCM prescriptions did not mention the corresponding western disease names， and those of the new CPMs mainly included chronic renal insufficiency， chronic renal failure， and chronic nephritis. Four CPMs were prepared with single Chinese medicine or active components. Specifically， Bailing Preparation and Jinshuibao Preparation were mainly prepared with the powder of Cordyceps， and the main components of Haikun Shenxi capsules and Huangkui capsules were fucoidan sulfate and the flower extract of Abelmoschi Corolla， respectively. The CPMs mainly exerted tonifying and eliminating effects on the lung， spleen， and kidney. A total of 892 clinical trials were screened out， covering all the areas in China and presented an increasing trend. Bailing Preparation was the most studied， followed by Niaoduqing Preparation. Among the 892 studies， 475 focused on single CPMs without combination with other CPMs or therapies. These studies mainly compared between conventional intervention and conventional intervention + CPM， which accounted for 75.58%. The 475 studies covered different kidney diseases， such as chronic kidney disease， chronic renal failure， nephrotic syndrome， diabetic kidney disease， IgA nephropathy， and membranous nephropathy， and involved a variety of populations including the elderly and children. Thirty-six studies evaluated TCM syndromes， reflecting the characteristics and advantages of TCM treatment. ConclusionThere are abundant oral CPMs for CKD， with varied efficacy and characteristics for different kidney diseases. However， the instruction manuals of the oral CPMs are not detailed or standard. According to the clinical research evidence in this field， the research on oral CPMs for CKD is characterized by a wide scope， rich study types， and wide disease coverage， while the sample size and quality remain to be improved.

Metformin use and risk of ischemic stroke in patients with type 2 diabetes: A cohort study / 北京大学学报(医学版)

OBJECTIVE@#To explore the association between the use of metformin and the risk of ischemic stroke in patients with type 2 diabetes.@*METHODS@#A prospective cohort study was designed from the Fangshan family cohort in Beijing. According to metformin use at baseline, 2 625 patients with type 2 diabetes in Fangshan, Beijing were divided into metformin group or non-metformin group and the incidence of ischemic stroke between the different groups during follow-up was estimated and compared by Cox proportional hazard regression model. The participants with metformin were first compared with all the parti-cipants who did not use metformin, and then were further compared with those who did not use hypoglycemic agents and those who used other hypoglycemic agents.@*RESULTS@#The patients with type 2 diabetes were with an average age of (59.5±8.7) years, and 41.9% of them were male. The median follow-up time was 4.5 years. A total of 84 patients developed ischemic stroke during follow-up, with a crude incidence of 6.4 (95%CI: 5.0-7.7) per 1 000 person-years. Among all the participants, 1 149 (43.8%) took metformin, 1 476 (56.2%) were metformin non-users, including 593 (22.6%) used other hypoglycemic agents, and 883 (33.6%) did not use any hypoglycemic agents. Compared with metformin non-users, the Hazard ratio (HR) for ischemic stroke in metformin users was 0.58 (95%CI: 0.36-0.93; P = 0.024). Compared with other hypoglycemic agents, HR was 0.48 (95%CI: 0.28-0.84; P < 0.01); Compared with the group without hypoglycemic agents, HR was 0.65 (95%CI: 0.37-1.13; P=0.13). The association between metformin and ischemic stroke was statistically significant in the patients ≥ 60 years old compared with all the metformin non-users and those who used other hypoglycemic agents (HR: 0.48, 95%CI: 0.25-0.92; P < 0.05). Metformin use was associated with a lower incidence of ischemic stroke in the patients with good glycemic control (0.32, 95%CI: 0.13-0.77; P < 0.05). In the patients with poor glycemic control, and the association was not statistically significant (HR: 0.97, 95%CI: 0.53-1.79; P>0.05). There was an interaction between glycemic control and metformin use on incidence of ischemic stroke (Pinteraction < 0.05). The results of the sensitivity analysis were consistent with the results in the main analysis.@*CONCLUSION@#Among patients with type 2 diabetic in rural areas of northern China, metformin use was associated with lower incidence of ischemic stroke, especially in patients older than 60 years. There was an interaction between glycemic control and metformin use in the incidence of ischemic stroke.

Genotype-environment interaction on arterial stiffness: A pedigree-based study / 北京大学学报(医学版)

OBJECTIVE@#To utilized the baseline data of the Beijing Fangshan Family Cohort Study, and to estimate whether the association between a healthy lifestyle and arterial stiffness might be modified by genetic effects.@*METHODS@#Probands and their relatives from 9 rural areas in Fangshan district, Beijing were included in this study. We developed a healthy lifestyle score based on five lifestyle behaviors: smoking, alcohol consumption, body mass index (BMI), dietary pattern, and physical activity. The measurements of arterial stiffness were brachial-ankle pulse wave velocity (baPWV) and ankle-brachial index (ABI). A variance component model was used to determine the heritability of arterial stiffness. Genotype-environment interaction effects were performed by the maximum likelihood methods. Subsequently, 45 candidate single nucleotide polymorphisms (SNPs) located in the glycolipid metabolism pathway were selected, and generalized estimated equations were used to assess the gene-environment interaction effects between particular genetic loci and healthy lifestyles.@*RESULTS@#A total of 6 302 study subjects across 3 225 pedigrees were enrolled in this study, with a mean age of 56.9 years and 45.1% male. Heritability of baPWV and ABI was 0.360 (95%CI: 0.302-0.418) and 0.243 (95%CI: 0.175-0.311), respectively. Significant genotype-healthy diet interaction on baPWV and genotype-BMI interaction on ABI were observed. Following the findings of genotype-environment interaction analysis, we further identified two SNPs located in ADAMTS9-AS2 and CDH13 might modify the association between healthy dietary pattern and arterial stiffness, indicating that adherence to a healthy dietary pattern might attenuate the genetic risk on arterial stiffness. Three SNPs in CDKAL1, ATP8B2 and SLC30A8 were shown to interact with BMI, implying that maintaining BMI within a healthy range might decrease the genetic risk of arterial stiffness.@*CONCLUSION@#The current study discovered that genotype-healthy dietary pattern and genotype-BMI interactions might affect the risk of arterial stiffness. Furthermore, we identified five genetic loci that might modify the relationship between healthy dietary pattern and BMI with arterial stiffness. Our findings suggested that a healthy lifestyle may reduce the genetic risk of arterial stiffness. This study has laid the groundwork for future research exploring mechanisms of arterial stiffness.

Transient elastography technology role assessment during the diagnosis and treatment of patients with chronic hepatitis B virus infection / 中华肝脏病杂志

Objective: To explore the role of transient elastography technology in the assessment of disease staging and treatment in patients with chronic hepatitis B virus (HBV) infection. Methods: Patients who were clinically diagnosed with chronic HBV infection at Beijing Tsinghua Changgung Hospital from January 2018 to December 2021 was collected. Liver stiffness measurement (LSM) examination was performed more than once by transient elastography. The count data were expressed as cases (%) and the χ (2) test was made. Fisher's exact test was used with theoretical frequency less than 5. The measurement data between two groups was compared by t-test. Multiple groups were compared with an analysis of variance. Results: 1 055 patients were included in this study, including 669 (63.4%) males and 386 (36.6%) females. 757 (71.8%) patients were untreated. Among the untreated patients, the LSM value in the immune clearance (10.2 ± 3.8) kPa (187 cases, 40.4%), and the reactivation stages (9.1 ± 3.4) kPa (114 cases, 24.6%) was significantly higher than that in the immune tolerance (8.7 ± 3.6) kPa (78 cases, 16.8%) and immune control stages (8.4 ± 3.5) KPa (84 cases, 18.1%), and the difference between the four groups was statistically significant (F = 5.31 and P = 0.03). With ALT (male: 30 U/L, female: 19 U/L) as defined the normal value, the LSM value in the immune tolerance and the immune control stages were (5.8 ± 0.9) kPa and (7.1 ± 2.5) kPa, respectively, which were significantly lower than those of patients in the immune tolerance and immune control stages, and the difference was statistically significant (P < 0.01). There were 294 (38.8%) patients with uncertain period, excluding patients with fatty liver. Patients with uncertain periods were divided into four gray zone (GZ) groups: immune tolerance stage: LSM (5.1 ± 1.3) kPa was significantly lower than GZ-A (6.5 ± 2.4) kPa, t = 2.06, P = 0.03, and the difference was statistically significant; immune control stage: LSM was (5.6 ± 1.5) kPa, which was also lower than GZ-C (6.8 ± 1.3) kPa, t = 3.08, P = 0.02, and the difference was statistically significant; immune clearance stage: LSM > 8.0 kPa. LSM values showed a year-by-year reduction in patients with expanded indications who started antiviral treatment and were followed up for three years. Conclusion: The LSM value is significantly lower after the decrease of the defined high-normal ALT value in patients with the immune tolerance and immune control stages of chronic HBV infection. The LSM values of GZ-A and GZ-C in the uncertain periods of chronic HBV infection are higher than those of patients in the immune tolerance and immune control stages.

The role of the high-level public health school in the development of the Center for Disease Control and Prevention / 中华流行病学杂志

The Ministry of Education and other four departments jointly issued the Notice on the Construction of high-level schools of public Health, proposing that "it will take ten years to build a number of high-level schools of public health, and form a high-quality education development system to adapt to the construction of modern public health system". At present, the construction of high-level public health schools in various universities in China is in full swing. The high-level School of Public Health and the CDC have played an important role in constructing the national public health system and the human health community. The high-level public health schools are of strategic significance and important value to the development of the CDC. The review presents reflections and insights on the role of high-level public health schools in the development of the CDC and the challenges they might face.

Research progress on the relationship between COVID-19 and autoimmune diseases / 中华预防医学杂志

Different autoantibodies can be detected in patients with coronavirus disease 2019 (COVID-19). It is reported that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection could induce autoimmune diseases (AID), including children's multisystem inflammatory syndrome (MIS-C), Guillain Barre syndrome (GBS), Autoimmune hemolytic anemia (AIHA), immune thrombocytopenia (ITP) and thyroid autoimmune diseases. This article mainly reviews the similarities between COVID-19 and AID, the possibility of COVID-19 inducing AID, the risk of AID patients infected or vaccinated against COVID-19. The purpose is to provide strategies for the prevention, management and treatment of AID during the epidemic.

Effect of Xielitang on TLR4/NF-κB/HIF-1α Signaling Pathway in Mice with Ulcerative Colitis / 中国实验方剂学杂志

ObjectiveTo explore the protective effect of Xielitang on ulcerative colitis （UC） mice induced by dextran sodium sulfate （DSS） and its possible mechanism. MethodSixty C57BL/6 mice were randomly divided into normal group， model group， sulfasalazine group and and low-， medium-， and high-dose Xielitang groups. Free drinking DSS solution to build the chronic UC model mice. Except for normal group， other groups were given 1.5% DSS for 3 cycles of drinking （days 1-7， days 22-28 and days 43-49） and distilled water for the rest of the time （days 8-21， days 29-42 and days 50-63）. After the first cycle， corresponding drugs were given for 42 days. The changes of general condition， body weight and disease activity index （DAI） score of mice were daily recorded during the experiment. At the end of the treatment， serum and colon tissue samples were collected， colon length was measured， intestinal weight index and colonic mucosal injury （CMDI） score were calculated. The pathological status of colon tissue was observed by hematoxylin-eosin （HE） staining. The levels of interleukin-6 （IL-6）， interleukin-10 （IL-10） and tumour necrosis factor-α （TNF-α） were measured by enzyme-linked immunosorbent assay （ELISA）. The gene and protein expressions of Toll like receptor 4 （TLR4）， nuclear transcription factor-κB （NF-κB） and hypoxia inducible factor-1α （HIF-1α） in colon tissue was detected by Real-time quantitative polymerase chain reaction （Real-time PCR） and Western blot. ResultCompared with the normal group， the body weight， colon length and IL-10 content in the model group were significantly decreased （P<0.01）， DAI score， intestinal weight index， CMDI score， IL-6 and TNF-α contents， and mRNA and protein expression levels of TLR4， NF-κB and HIF-1α in the model group were significantly increased （P<0.01）. Moreover， the structure of colonic mucosa was destroyed and inflammatory cells infiltrated in the model group. Compared with model group， body weight， colon length and IL-10 content in each dose group of Xielitang were significantly increased （P<0.05， P<0.01）， DAI score， intestinal weight index and CMDI score， IL-6 and TNF-α contents， mRNA and protein expression levels of TLR4， NF-κB and HIF-1α were notably decreased （P<0.05， P<0.01）. The pathological injury of colon was obviously alleviated. ConclusionXielitang can significantly improve the inflammatory response of UC mice induced by DSS， and its mechanism may be related to the regulation of TLR4/NF-κB/HIF-1α signaling pathway.

Research progress of polymer self-healing mechanism and its application in biomedicine / 药学学报

Polymer self-healing is mainly based on the molecular structure and interaction of polymers, and some need external stimulation, such as light, heat, pH, etc. In recent years, many studies have found that the self-healing properties of polymers can prolong the life of materials, while maintaining the mechanical properties of polymers after healing. According to the different action modes of polymer materials, it can be divided into autonomous self-healing and non-autonomous self-healing. Among them, autonomous self-healing mainly works through reversible covalent bonds (Schiff base bond, Diels-Alder reaction, hydrazide bond), reversible non-covalent bonds (hydrogen bond, metal-ligand coordination bond, electrostatic interaction, π-π stacking interaction, hydrophobic interaction) and a combination of the two interactions. Drug carriers with unique self-healing properties play an important role in the encapsulation and stable release of biomacromolecules. In this review, the self-healing mechanism of polymers and their applications in the field of biomedicine were briefly summarized and discussed.

Establishment and characterization of bone marrow mesenchymal stem cell lines stably synthesizing high-level dopamine / 生物工程学报

A triple-transgenic (tyrosine hydroxylase/dopamine decarboxylase/GTP cyclohydrolase 1, TH/DDC/GCH1) bone marrow mesenchymal stem cell line (BMSCs) capable of stably synthesizing dopamine (DA) transmitters were established to provide experimental evidence for the clinical treatment of Parkinson's disease (PD) by using this cell line. The DA-BMSCs cell line that could stably synthesize and secrete DA transmitters was established by using the triple transgenic recombinant lentivirus. The triple transgenes (TH/DDC/GCH1) expression in DA-BMSCs was detected using reverse transcription-polymerase chain reaction (RT-PCR), Western blotting, and immunofluorescence. Moreover, the secretion of DA was tested by enzyme-linked immunosorbent assay (ELISA) and high-performance liquid chromatography (HPLC). Chromosome G-banding analysis was used to detect the genetic stability of DA-BMSCs. Subsequently, the DA-BMSCs were stereotactically transplanted into the right medial forebrain bundle (MFB) of Parkinson's rat models to detect their survival and differentiation in the intracerebral microenvironment of PD rats. Apomorphine (APO)-induced rotation test was used to detect the improvement of motor dysfunction in PD rat models with cell transplantation. The TH, DDC and GCH1 were expressed stably and efficiently in the DA-BMSCs cell line, but not expressed in the normal rat BMSCs. The concentration of DA in the cell culture supernatant of the triple transgenic group (DA-BMSCs) and the LV-TH group was extremely significantly higher than that of the standard BMSCs control group (P < 0.000 1). After passage, DA-BMSCs stably produced DA. Karyotype G-banding analysis showed that the vast majority of DA-BMSCs maintained normal diploid karyotypes (94.5%). Moreover, after 4 weeks of transplantation into the brain of PD rats, DA-BMSCs significantly improved the movement disorder of PD rat models, survived in a large amount in the brain microenvironment, differentiated into TH-positive and GFAP-positive cells, and upregulated the DA level in the injured area of the brain. The triple-transgenic DA-BMSCs cell line that stably produced DA, survived in large numbers, and differentiated in the rat brain was successfully established, laying a foundation for the treatment of PD using engineered culture and transplantation of DA-BMSCs.

Early prenatal exposure to air pollutants and congenital heart disease: a nested case-control study

BACKGROUND@#Congenital heart disease (CHD) is one of the most common congenital malformations in humans. Inconsistent results emerged in the existed studies on associations between air pollution and congenital heart disease. The purpose of this study was to evaluate the association of gestational exposure to air pollutants with congenital heart disease, and to explore the critical exposure windows for congenital heart disease.@*METHODS@#The nested case-control study collected birth records and the following health data in Tianjin Women and Children's Health Center, China. All of the cases of congenital heart disease from 2013 to 2015 were selected matching five healthy controls for each case. Inverse distance weighting was used to estimate individual exposure based on daily air pollution data. Furthermore, the conditional logistic regression with distributed lag non-linear model was performed to identify the association between gestational exposure to air pollution and congenital heart disease.@*RESULTS@#A total of 8,748 mother-infant pairs were entered into the analysis, of which 1,458 infants suffered from congenital heart disease. For each 10 µg/m3 increase of gestational exposure to PM2.5, the ORs (95% confidence interval, 95%CI) ranged from 1.008 (1.001-1.016) to 1.013 (1.001-1.024) during the 1st-2nd gestation weeks. Similar weak but increased risks of congenital heart disease were associated with O3 exposure during the 1st week and SO2 exposure during 6th-7th weeks in the first trimester, while no significant findings for other air pollutants.@*CONCLUSIONS@#This study highlighted that gestational exposure to PM2.5, O3, and SO2 had lag effects on congenital heart disease. Our results support potential benefits for pregnancy women to the mitigation of air pollution exposure in the early stage, especially when a critical exposure time window of air pollutants may precede heart development.

Analysis of GNAS gene variant in a Chinese pedigree affected with pseudohypoparathyroidism / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic etiology of a Chinese pedigree affected with pseudohypoparathyroidism.@*METHODS@#Peripheral blood samples of the proband and his parents were collected and subjected to trio-whole exome sequencing (trio-WES). Candidate variants were verified among the pedigree and 50 randomly selected healthy individuals through analysis of restriction fragment length polymorphism. Short tandem repeat (STR) linkage analysis was used to verify the parental origin of the pathogenic variants.@*RESULTS@#Trio-WES and Sanger sequencing showed that the proband and his mother had both harbored a c.121C>G (p.His41Asp) variant of the GNAS gene, which was not found in other family members and the 50 healthy controls. The variant was not found in international databases. Based on guidelines from the American College of Medical Genetics and Genomics, the variant was predicted to be likely pathogenic.@*CONCLUSION@#The novel c.121C>G variant of the GNAS gene probably underlay the disease in this pedigree. Above finding has enriched the spectrum of GNAS gene variants.

Clinical analysis of 11 patients with neuroendocrine carcinoma in maxillofacial region / 中华口腔医学杂志

Objective: To investigate the clinicopathological features, treatment and prognosis of maxillofacial neuroendocrine carcinoma. Methods: A total of 11 patients with maxillofacial neuroendocrine carcinoma diagnosed in the Department of Pathology of The First Affiliated Hospital of Zhengzhou University from December 2010 to July 2022 were retrospectively enrolled, including 8 males and 3 females, aged (65.2±9.5) years (ranged from 49 to 87 years), with a disease course of 0.5 to 6.0 months. The clinicopathological data including head and neck CT, MRI and treatment methods were analyzed. Results: Submandibular gland and maxilla were involved in 3 cases, parapharynx in 2 cases, and face, tongue root and soft palate in 1 case respectively. Clinically, the initial symptom is a rapidly growing painless or tender mass, which may be accompanied by restricted mouth opening, dysphagia, and local numbness after invasion of masticatory muscles and nerves. The tumors were all invasive and low-density, with unclear boundaries from the surrounding tissues. Among the patients, 9 received surgical treatment, and 5 received adjuvant treatment after surgery (2 received chemotherapy, 3 received radiotherapy+chemotherapy). According to the 5th edition of the World Health Organization classification of head and neck tumors in 2022, there were 1 case (1/11) with poorly differentiated large cells and 10 cases (10/11) with poorly differentiated small cells. Histologically, the macrocell type is composed of large cells with rough chromatin, obvious vacuolar nucleolus, protruding nucleolus, and necrosis. The small cell type is dominated by small blue round cells with neuroendocrine characteristics, with active growth and multifocal necrosis. Immunohistochemical staining showed that cytokeratin (CK), epithelial membrane antigen (EMA) and synaptophysin (Syn) were diffusively expressed, 10 cases expressed CD56, 8 cases expressed p63, 6 cases expressed weakly punctated chromograin-A (CgA), and S-100 was not expressed. The Ki-67 index ranges from 20 to 90 percent. By the end of follow-up (0.5 to 127.0 months), 3 patients were alive, and the mean progression-free survival (21.0 months) of postoperative chemoradiotherapy patients was significantly longer than that of surgery and/or chemotherapy alone (3.3 months). Conclusions: Maxillofacial neuroendocrine carcinoma is characterized by low differentiation of small cells, high degree of malignancy and poor prognosis. Radical surgery combined with chemoradiotherapy has better local control effect.

Optimization of ethanol reflux extraction process of Ziziphi Spinosae Semen- Schisandrae Sphenantherae Fructus based on network pharmacology combined with response surface methodology / 中国中药杂志

The present study optimized the ethanol extraction process of Ziziphi Spinosae Semen-Schisandrae Sphenantherae Fructus drug pair by network pharmacology and Box-Behnken method. Network pharmacology and molecular docking were used to screen out and verify the potential active components of Ziziphi Spinosae Semen-Schisandrae Sphenantherae Fructus, and the process evaluation indexes were determined in light of the components of the content determination under Ziziphi Spinosae Semen and Schisandrae Sphenantherae Fructus in the Chinese Pharmacopoeia(2020 edition). The analytic hierarchy process(AHP) was used to determine the weight coefficient of each component, and the comprehensive score was calculated as the process evaluation index. The ethanol extraction process of Ziziphi Spinosae Semen-Schisandrae Sphenantherae Fructus was optimized by the Box-Behnken method. The core components of the Ziziphi Spinosae Semen-Schisandrae Sphenantherae Fructus drug pair were screened out as spinosin, jujuboside A, jujuboside B, schisandrin, schisandrol, schisandrin A, and schisandrin B. The optimal extraction conditions obtained by using the Box-Behnken method were listed below: extraction time of 90 min, ethanol volume fraction of 85%, and two times of extraction. Through network pharmacology and molecular docking, the process evaluation indexes were determined, and the optimized process was stable, which could provide an experimental basis for the production of preparations containing Ziziphi Spinosae Semen-Schisandrae Sphenantherae Fructus.