Preparation and in vitro evaluation of polylactic acid nanoparticles containing arginine and glucose oxidase / 药学学报

Hydrogen peroxide (H2O2) and nitric oxide (NO) has a short half-life, low bioavailability, poor tumor targeting and systemic adverse reactions in the physiological environment. In this study, phacoemulsification and nano-precipitation were used to synthesize didecyl dimethyl ammonium bromide (DDAB)/polylactic acid nanoparticles (PLA), then L-arginine (L-Arg) and glucose oxidase (GOx)-loaded nanoparticles (GADP) were prepared, and the in vitro antitumor activity was investigated．The particle size, potential, embedding rate and the ability to produce H2O2/NO of the nanoparticles were investigated. Meanwhile, in vitro cell cytotoxicity against human hepatoma cells (HepG2) was evaluated．The results showed that the prepared L-Arg-DDAB/PLA (ADP) nanoparticles were spherical particles. And the particle size and zeta potential were (225.7 ± 6.33) nm and (+23.5 ± 0.12) mV, respectively. The adsorption rate of GOx was 87.23% ± 0.02%. The drug loading of L-Arg was 15.6% ± 0.22%. The pH value of glucose solution and the amount of H2O2 showed that GADP had good catalytic activity. In vitro cytotoxicity experiments showed that blank nanoparticles were nontoxic, while the drug-loaded nanoparticles presented enhanced antitumor effect on HepG2 cells. And can inhibit tumor cell migration. The low dose nano-scale NO delivery system GADP can effectively inhibit the migration of tumor cells and kill tumor cells, thus producing therapeutic benefits.

Study on cerebral oxygen metabolism of healthy volunteers at three altitude areas by MR quantitative susceptibility mapping combined with three-dimensional arterial spin labeling sequence / 中华放射学杂志

Objective:To investigate the differences in cerebral oxygen metabolism in healthy volunteers at three altitude areas by MR quantitative magnetic susceptibility imaging (QSM) combined with three-dimensional arterial spin labeling (3D-ASL).Methods:From March 2019 to October 2020, Zhengzhou Han Chinese volunteers recruited from the First Affiliated Hospital of Zhengzhou University, Xining Han Chinese volunteers recruited from the Fifth People′s Hospital of Qinghai Province, Lhasa Han Chinese volunteers and Tibetan volunteers recruited from Lhasa People′s Hospital were collected. They were divided into 21-30 age group, 31-40 age group, and 41-50 age group. All the volunteers underwent MR QSM combined with 3D-ASL sequence imaging, and oxygen extraction fraction (OEF) and cerebral blood flow (CBF) images of gray matter, and white matter were collected, OEF and CBF values were obtained, and cerebral metabolic rate of oxygen (CMRO 2) values were calculated. The comparison of various indicators among multiple groups was conducted using one-way ANOVA, and pairwise comparisons were conducted using LSD- t test. Results:A total of 132 volunteers were included, including 38 Han Chinese volunteers in Zhengzhou, 9 in the 21-30 age group, 13 in the 31-40 age group and 16 in the 41-50 age group; 27 Han Chinese volunteers in Xining, including 9 in the 21-30 age group, 8 in the 31-40 age group and 10 in the 41-50 age group; 34 Han Chinese volunteers in Lhasa, including 13 in the 21-30 age group, 11 in the 31-40 age group and 10 in the 41-50 age group; and 33 Tibetan volunteers in Lhasa, including 10 in the 21-30 age group, 10 in the 31-40 age group and 13 in the 41-50 age group. In the group aged 21-30 years, the overall difference in brain gray matter OEF values among volunteers from different altitudes was statistically significant ( P<0.05), with statistically significant differences in OEF values between Tibetans in Lhasa and Han Chinese in Xining, Han Chinese in Lhasa ( P<0.05). The overall difference in CMRO 2 values in the gray matter of volunteers at different altitudes was statistically significant ( P<0.05), with significant differences in CMRO 2 values between Lhasa Tibetan and Han Chinese in Zhengzhou, Han Chinese in Xining, Han Chinese in Lhasa ( P<0.05). In the 31-40 age group, there were statistically significant differences in the overall CBF values of gray and white matter among volunteers from different altitudes ( P<0.05). Among them, there were statistically significant differences in the CBF values of gray and white matter between Han Chinese in Zhengzhou and Han in Xining, Han Chinese in Lhasa, Lhasa Tibetan ( P<0.05). The overall differences in OEF values of gray matter and white matter among volunteers at different altitudes were statistically significant ( P<0.05). Among them, there were statistically significant differences in OEF values of gray matter and white matter between the Han Chinese in Zhengzhou and the Han Chinese in Xining, the Han Chinese in Lhasa ( P<0.05). There was also a statistically significant difference in OEF values of gray matter and white matter between the Han Chinese in Lhasa and the Tibetan in Lhasa ( P<0.05). The overall difference in CMRO 2 values in gray and white matter among volunteers from different altitudes was statistically significant ( P<0.05). Among them, there was a statistically significant difference in CMRO 2 values of cerebral gray matter between Lhasa Tibetans and Zhengzhou Han, Xining Han, Lhasa Han ( P<0.05), and there was a statistically significant difference in CMRO 2 values of cerebral white matter between Lhasa Tibetans and Zhengzhou Han, Lhasa Han ( P<0.05). Conclusions:The cerebral oxygen metabolism of Tibetan living in the plateau is characterized by low oxygen consumption, low blood oxygen dependence and high tissue oxygen utilization. The CMRO 2 of the Han people who migrated to the plateau for a long time is maintained at a certain level, similar to that in the plain area. The effects of age factors on CBF, OEF and CMRO 2 are small.

Performance evaluation of nucleic acid testing system for blood screening in high-altitude areas / 中国输血杂志

【Objective】 To validate the performance of a nucleic acid testing(NAT) system for blood screening in the high-altitude Nagqu region of Tibet, in order to assess the capability of NAT in high-altitude areas and further enhance blood safety. 【Methods】 Various methods were employed to evaluate the analytical sensitivity, reproducibility, ability to prevent cross-contamination, and comparison between different NAT systems. 【Results】 The NAT system in the Nagqu region of Tibet achieved a 100% detection rate for high-concentration HBV DNA and HIV-1 RNA samples, and over 90% for medium-concentration samples. PROBIT analysis revealed the lower limits of detection (LOD) for HBV DNA and HIV-1 RNA to be 8.29 IU/mL (95% CI, 5.88~20.55 IU/mL) and 40.52 IU/mL (95% CI, 30.26~85.92 IU/mL), respectively. For HCV RNA genotype 2a, the LOD was 97.14 IU/mL (95% CI, 71.00~182.67 IU/mL), all of which were lower than the declared minimum detectable concentrations in the instructions. Reproducibility analysis demonstrated a 100% level of consistency within the system. Cross-contamination performance verification showed a strong ability to resist cross-contamination. Comparative analysis of repeated testing of low-concentration HBV DNA samples and multi-system testing in plain areas revealed consistency rates of 77.78%(14/18) and 77.27%(17/22), respectively, indicating certain differences between the NAT system in Nagqu region and other systems. 【Conclusion】 The NAT system exhibited excellent performance in blood screening at high altitudes. The results of performance validation in high-altitude blood screening NAT systems were largely consistent with those in plain areas, providing a reliable basis for enhancing blood safety in high-altitude regions.

Follow-up study on newly diagnosed occupational pneumoconiosis patients in Guizhou Province, 2006-2021 / 中国职业医学

Objective To analyze the survival status, distribution characteristics and social security of newly diagnosed occupational pneumoconiosis patients in Guizhou Province from 2006 to 2021. Methods The newly diagnosed pneumoconiosis cases reported in Guizhou Province from 2006 to 2021 were collected from the “Occupational Diseases and Hazards Monitoring Information System” under “National Health Insurance Disease Prevention and Control Information System”. Telephone or face-to-face surveys were conducted to investigate these patients. Results A total of 12 413 newly diagnosed pneumoconiosis patients were reported in Guizhou Province from 2006 to 2021, with 11 192 cases included in the follow-up, and 10 631 cases were followed-up successfully. According to the follow-up study, 10 565 cases (accounting for 99.4%) were survived, and 66 cases (accounting for 0.6%) died. The number of pneumoconiosis showed an increasing trend followed by a sharp decline from 2006 to 2021, reaching its peak in 2016. The main industry of the newly pneumoconiosis cases was concentrated in the mining industry (accounting for 90.6%). The top three regions with surviving cases in the follow-up were Bijie City, Zunyi City, and Qiannan Prefecture, accounting for 34.0%, 25.4% and 12.0%, respectively. The main types of pneumoconiosis were coal workers' pneumoconiosis and silicosis, accounting for 67.1% and 30.8%, respectively. Most cases were in the age group of 50 to <60 years old, accounting for 59.1%, and the majority of the workers had worked in dusty environments for 5 to <25 years, accounting for 91.5%. In terms of social security, about 89.5% of cases were in the basic medical insurance for urban and rural residents which was the most popular social security. The employer's compensation rate was 67.7%, and the work-related injury insurance participation rate was 51.5%. Conclusion Pneumoconiosis cases in Guizhou Province exhibit significant regional disparities. It has a high concentration in the industry, a younger age profile, and limited social security coverage. It is necessary to strengthen the special management of dust and industry supervision in mining industry, intensify follow-up work for pneumoconiosis cases, reinforce the construction of pneumoconiosis rehabilitation station in key regions, and improve the quality of life of pneumoconiosis cases.

Quality of life and influencing factors in lung cancer patients after video-assisted thoracic surgery / 中国胸心血管外科临床杂志

@#Objective    To investigate the short-term quality of life in patients after single-direction video-assisted thoracic surgery (VATS) for lung cancer, and explore the related influencing factors. Methods    Patients who underwent single-direction VATS for lung cancer in the Department of Thoracic Surgery, West China Hospital, Sichuan University from July 2020 to August 2021 were continuously selected. The QLQ-C30 and QLQ-LC13 were used to evaluate the quality of life of the patients after the surgery, and the influencing factors were analyzed. Results    A total of 193 patients were collected. There were 73 males aged 59.44±11.40 years, and 120 females aged 53.73±11.15 years. The QLQ-C30 score of the patients after single-direction VATS for lung cancer was 69.09±20.21 points. Univariate analysis and Pearson correlation analysis showed that age, occupation, anesthesia time, postoperative complications, postoperative antibiotic use time, postoperative hospital stay, insomnia, economic stress, hemoptysis, chest pain, dysphagia, arm or shoulder pain were associated with the quality of life (P≤0.05). The results of multiple regression analysis showed that anesthesia time, economic pressure, insomnia and chest pain had a significant impact on the overall quality of life 30 days after the surgery (P≤0.05). Conclusion    The anesthesia time, economic pressure, insomnia and chest pain are independent influencing factors for the quality of life after the VATS lung cancer surgery.

Failure mode and effect analysis for risk management of unplanned extubation after esophageal cancer surgery / 中国胸心血管外科临床杂志

@#Objective 聽 聽 To explore the application value of failure mode and effect analysis (FMEA) in the risk management of unplanned extubation after esophageal cancer surgery. Methods 聽 聽 A total of 1 140 patients who underwent esophageal cancer surgery in our department from January 2015 to May 2017 were selected as a control group, including 948 males and 192 females with an average age of 64.45卤4.53 years. FMEA was used to analyze the risk management process of unplanned extubation. The potential risk factors in each process were found by calculating the risk priority number (RPN) value, and the improvement plan was formulated for the key process with RPN>125 points. Then 1 117 patients who underwent esophageal cancer surgery from June 2017 to December 2019 were selected as a trial group, including 972 males and 145 females with an average age of 64.60卤5.22 years, and the FMEA risk management mode was applied. Results 聽 聽 The corrective measures were taken to optimize the high-risk process, and the RPN values of 9 high-risk processes were reduced to below 125 points after using FMEA risk management mode. The rate of unplanned extubation in the trial group was lower than that in the control group (P<0.05). Conclusion 聽 聽 The application of FMEA in the risk management of unplanned extubation after esophageal cancer surgery can reduce the rate of unplanned extubation, improve the quality of nursing, and ensure the safety of patients.

Time series analysis and prediction model of percentage of influenza-like illness （ILI） cases in Shanghai / 上海预防医学

ObjectiveTo predict the incidence trend of influenza-like illness proportion （ILI%） in Shanghai using the seasonal autoregressive integrated moving average model （SARIMA）， and to provide an important reference for timely prevention and control measures. MethodsTime series analysis was performed on ILI% surveillance data of Shanghai Municipal Center for Disease Control and Prevention from the 15th week of 2015 to the 52nd week of 2019， and a prediction model was established. Seasonal autoregressive integrated moving average （SARIMA） model was established using data from the foregoing 212 weeks， and prediction effect of the model was evaluated using data from the latter 36 weeks. ResultsFrom the 15th week of 2015 to the 52nd week of 2019， the average ILI% in Shanghai was 1.494%， showing an obvious epidemic peak. SARIMA（1，0，0） （2，0，0） 52 was finally modeled. The residual of the model was white noise sequence， and the true values were all within the 95% confidence interval of the predicted values. ConclusionSARIMA（1，0，0） （2，0，0） 52 can be used for the medium term prediction of ILI% in Shanghai， and can play an early warning role for the epidemic and outbreak of influenza in Shanghai.

A survey of symptoms after thoracoscopic lung cancer resection based on patient-reported outcomes / 中国胸心血管外科临床杂志

@#Objective     To analyze the changes of perioperative symptoms of lung cancer patients by using patient-reported outcomes at different time points. Methods    A total of 109 patients who underwent thoracoscopic lung cancer resection in the department of thoracic surgery of our hospital from March to April 2021 were selected, including 55 (50.46%) males and 54 (49.54%) females. The mean age was 55.19±12.12 years. The postoperative symptom scale for lung cancer patients was used to investigate the changes of symptoms before surgery, 1 day after surgery, the day of discharge, and 30 days after surgery. Results     The mean hospital stay was 6.89±2.25 days. None of the patients reported any clinical symptoms related to lung cancer before surgery. The most prominent symptoms 1 day after surgery were pain (3.33±0.96 points), nausea (2.81±1.18 points), dizziness (2.00±0.85 points), fatigue (1.89±0.79 points) and shortness of breath (1.79±1.37 points). The patients with dizziness, nausea, fatigue and other symptoms gradually decreased, and the symptoms were relieved significantly (P<0.05). However, the symptoms of conscious pain, cough and shortness of breath lasted for a long time. At 30 days after surgery, 70.64%, 64.22% and 33.03% of patients felt pain, cough and shortness of breath, respectively, and the degree of cough was aggravated (P<0.001). Conclusion     Pain, cough, dizziness, shortness of breath and fatigue are the core postoperative symptoms of lung cancer patients. Most postoperative adverse symptoms can be effectively controlled in a short period of time, but pain, cough and shortness of breath still present persistent characteristics, which deserve further study.

Relation of perceived social support to mental health in prison police： a moderated mediating analysis / 四川精神卫生

BackgroundThe mental health level of the prison police is relatively low， so finding innovative ways to improve the mental health of them is of great significance for the safety of prison supervision and the implementation of peaceful China initiative. ObjectiveTo explore the relationship between perceived social support， perceived stress and psychological resilience with mental health of prison police， and to provide references for improving their mental health. MethodsIn March 2022， 424 policemen working in a male prison in a western province were selected by cluster sampling method， and investigated with the Perceived Social Support Scale （PSSS）， Chinese Perceived Stress Scale （CPSS）， Connor-Davidson Resilience Scale （CD-RISC） and General Health Questionnaire 20 （GHQ-20）， then Process 4.2 was used employed to verify the mediating role of perceived stress as well as the moderating role of psychological resilience in the relationship between perceived social support and mental health. Results①Male subjects scored higher on GHQ-20 than female subjects （t=2.095， P<0.05）. ②CPSS score was negatively correlated with PSSS and GHQ-20 scores （r=-0.670， -0.703， P<0.01）， and GHQ-20 score showed a positive correlation with PSSS and CD-RISC scores （r=0.580， 0.693， P<0.01）. ③Perceived social support positively predict mental health （β=0.154， 95% CI： 0.133~0.175， P<0.01）. ④Perceived stress played a mediating role in the relationship between perceived social support and mental health， and the mediation effect size was 0.087， accounting for 88.78% of the total effect （95% CI： 0.064~0.112， P<0.01）. ⑤Psychological resilience played a moderating role in the second half （perceived stress→mental health） of the mediating path of "perceived social support→perceived stress→mental health"（β=0.074， 95% CI： 0.046~0.102， P<0.01）. ⑥Psychological resilience also regulated the mediation effect of perceived stress on the relationship between perceived social support and mental health ［three regression coefficients tested in turn are significant： a=-0.537 （95% CI： -0.594~-0.480， P<0.01）， b1=-0.162 （95% CI： -0.197~-0.127， P<0.01）， b3=0.074 （95% CI： 0.046~0.102， P<0.01）］. ConclusionPerceived social support of prison police has an impact on their mental health both directly and indirectly through perceived stress. In addition， perceived social support of prison police has a moderated mediation effect on mental health， and it is partially moderated by psychological resilience.［ Funded by General Project of Sichuan Prison Administrative Bureau in 2022］

Cardiac amyloidosis: pathological classification and clinical analysis of 48 cases / 中华病理学杂志

Objective: To investigate the histological features and clinical manifestations in different types of cardiac amyloidosis to improve diagnostic accuracy. Methods: The histopathological features and clinical manifestations of 48 patients diagnosed with cardiac amyloidosis by Congo red stain and electron microscopy through endomyocardial biopsy were collected in West China Hospital of Sichuan University from January 2018 to December 2021. Immunohistochemical stains for immunoglobulin light chains (κ and λ) and transthyretin protein were carried out, and a review of literature was made. Results: The patients age ranged from 42 to 79 years (mean 56 years) and the male to female ratio was 1.1 to 1.0. The positive rate of endomyocardial biopsy was 97.9% (47/48), which was significantly higher than that of the abdominal wall fat (7/17). Congo red staining and electron microscopy were positive in 97.9% (47/48) and 93.5% (43/46), respectively. Immunohistochemical stains showed 32 cases (68.1%) were light chain type (AL-CA), including 31 cases of AL-λ type and 1 case of AL-κ type; 9 cases (19.1%) were transthyretin protein type (ATTR-CA); and 6 cases (12.8%) were not classified. There was no significant difference in the deposition pattern of amyloid between different types (P>0.05). Clinical data showed that ATTR-CA patients had less involvement of 2 or more organs and lower N-terminal pro-B-type natriuretic peptide (NT-proBNP) than the other type patients (P<0.05). The left ventricular stroke volume and right ventricular ejection fraction of ATTR-CA patients were better than the other patients (P<0.05). Follow-up data of 45 patients was obtained, and the overall mean survival time was 15.6±2.0 months. Univariate survival analysis showed that ATTR-CA patients had a better prognosis, while cardiac amyloidosis patients with higher cardiac function grade, NT-proBNP >6 000 ng/L, and troponin T >70 ng/L had a worse prognosis (P<0.05). Multivariate survival analysis showed that NT-proBNP and cardiac function grade were independent prognostic factors for cardiac amyloidosis patients. Conclusions: AL-λ is the most common type of cardiac amyloidosis in this group. Congo red staining combined with electron microscopy can significantly improve the diagnosis of cardiac amyloidosis. The clinical manifestations and prognosis of each type are different and can be classified based on immunostaining profile. However, there are still a few cases that cannot be typed; hence mass spectrometry is recommended if feasible.

Immunogenicity and safety of revaccination of 23-valent pneumococcal polysaccharide vaccine in people aged 60 years and above / 中华流行病学杂志

Objective: To evaluate the immunogenicity and safety of revaccination of 23-valent pneumococcal polysaccharide vaccine (PPV23) in elderly people aged ≥60 years. Methods: The elderly aged ≥60 years with 1 dose of PPV23 vaccination were selected as revaccination group and those without history of pneumococcal vaccine immunization were selected as the first vaccination group. One dose of PPV23 was administered to both groups, and the first blood samples were collected before vaccination while the second blood samples were collected on day 28-40 after vaccination. ELISA was used to detect the concentrations of anti-specific serotype Streptococcus pneumoniae podocyte polysaccharide immunoglobulin G, and the safety of the vaccination was evaluated after 30 days. Results: The geometric mean concentration (GMC) of antibody to 23 serotypes before the vaccination (0.73-13.73 μg/ml) was higher in revaccination group than in the first vaccination group (0.39-7.53 μg/ml), the GMC after the vaccination (1.42-31.65 μg/ml) was higher than that before the vaccination (0.73-13.73 μg/ml) in the revaccination group, and the GMC after the vaccination (1.62-43.76 μg/ml) was higher than that before the vaccination (0.39-7.53 μg/ml) in the first vaccination group; the geometric mean growth multiple in revaccination group (2.16-3.60) was lower than that in the first vaccination group (3.86-16.13); The mean 2-fold antibody growth rate was lower in revaccination group (53.68%, 95%CI: 52.30%-55.06%) than in the first vaccination group (93.16%, 95%CI: 92.18%- 94.15%), all differences were significant (P<0.001). After the vaccination, 13 serotypes of GMC were higher in the first vaccination group than in revaccination group (P<0.001), the differences were not significant for 10 serotypes of GMC (P>0.05). The incidence of local adverse reaction was 19.20% and 13.27% in revaccination group and the first vaccination group, respectively (P=0.174). Conclusions: The antibody level in ≥60 years people who received one dose of PPV23 after a 5-year interval was still higher than that in unvaccinated people. The antibody level decreased after 5 years of the first vaccination, and the antibody level could be rapidly increased by one more dose vaccination, but the overall immune response was lower than that of the first vaccination; revaccination with PPV23 has a good safety.

Association between muscle mass and quality of life in Shaanxi adults / 中华流行病学杂志

Objective: To investigate the association between muscle mass and quality of life in adults in Shaanxi adults. Methods: The data in this analysis were part of the baseline survey of the Regional Ethnic Cohort Study in Northwest China from June 2018 to May 2019 in Shaanxi Province. The participants' quality of life, including physical component summary (PCS) and mental component summary (MCS), was assessed by the 12-Item Short Form Survey, and the Body Fat Determination System measured muscle mass. A logistic regression model with adjustment for confounding factors was established to analyze the association between muscle mass and quality of life in different genders. Further, sensitivity and subgroup analyses were conducted to explore its stability. Finally, a restricted cubic spline was employed to investigate the dose-response relationship between muscle mass and quality of life in different genders. Results: A total of 20 595 participants were included, with an average age of 55.0, and 33.4% were male. After controlling for potential confounders, compared with the Q1 group, the risk of low PCS was reduced by 20.6% (OR=0.794, 95%CI: 0.681-0.925) and the risk of low MCS was lower reduced by 20.1% (OR=0.799, 95%CI: 0.689-0.926) in female Q5 groups. Compared with the Q1 group, the risk of low PCS was reduced by 24.4% (OR=0.756, 95%CI: 0.644-0.888) in the male Q2 group. However, no significant association between muscle mass and MCS in males has been found. In females, restricted cubic spline analysis showed a significant linear dose-response relationship between muscle mass and PCS and MCS. Conclusions: There is a positive association between muscle mass and quality of life in Shaanxi adults, especially females. With the increase in muscle mass, the physical and mental functions of the population continue to improve.

Proposal and thoughts on establishing and improving multi-level dental insurance in China / 中华口腔医学杂志

Oral diseases are highly prevalent in China, while oral health services are generally underutilized and public health resources are wasted. Lacking oral insurance may be one of the leading causes. The basic medical insurance of China does not cover dental care in most cities, which is worthy to further discuss. To better understand the experience of dental insurance from international dental care practice, the dental coverage scope, content, co-pay ratio, and effects of oral insurance on oral health improvement from the abroad countries with typical health insurance systems were summarized by using scoping review. Then, we discussed the coverage scope for dental health of basic medical insurance and private insurance in China. We also analyzed the current issues of dental care coverage and cost-share. At last, we proposed thoughts and suggestions to establish and improve a multi-level oral health insurance system with Chinese characteristics under the basic medical insurance frame. In particular, we gave suggestions on increasing the coverage for high dental care xpenditure by ebasic medical insurance, supplying children and teenagers with preventive dental care, and encouraging private insurance companies to cover dental care expenditure.

Mechanism of active ingredients in Periploca forrestii compound against rheumatoid arthritis based on integrative metabolomics and network pharmacology / 中国中药杂志

In this study, an ultra-performance liquid chromatography-quadrupole time-of-flight high resolution mass spectrometer(UPLC-Q-TOF-HRMS) was used to investigate the effects of the active ingredients in Periploca forrestii compound on spleen metabolism in rats with collagen-induced arthritis(CIA), and its potential anti-inflammatory mechanism was analyzed by network pharmacology. After the model of CIA was successfully established, the spleen tissues of rats were taken 28 days after administration. UPLC-Q-TOF-HRMS chromatograms were collected and analyzed by principal component analysis(PCA), orthogonal partial least squares discriminant analysis(OPLS-DA), and MetPA. The results showed that as compared with the blank control group, 22 biomarkers in the spleen tissues such as inosine, citicoline, hypoxanthine, and taurine in the model group increased, while 9 biomarkers such as CDP-ethanolamine and phosphorylcholine decreased. As compared with the model group, 21 biomarkers such as inosine, citicoline, CDP-ethanolamine, and phosphorylcholine were reregulated by the active ingredients in P. forrestii. Seventeen metabolic pathways were significantly enriched, including purine metabolism, taurine and hypotaurine metabolism, glycerophospholipid metabolism, and cysteine and methionine metabolism. Network pharmacology analysis found that purine metabolism, glycerophospholipid metabolism, and cysteine and methionine metabolism played important roles in the pathological process of rheumatoid arthritis. This study suggests that active ingredients in P. forrestii compound can delay the occurrence and development of inflammatory reaction by improving the spleen metabolic disorder of rats with CIA. The P. forrestii compound has multi-target and multi-pathway anti-inflammatory mechanism. This study is expected to provide a new explanation for the mechanism of active ingredients in P. forrestii compound against rheumatoid arthritis.

Clinical manifestations and genetic analysis of 4 patients with variants of FBN1 gene / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic basis for four patients suspected for Marfan syndrome (MFS).@*METHODS@#Four male patients with suspected MFS and their family members who were treated at West China Second Hospital of Sichuan University from September 12, 2019 to March 27, 2021 were selected as the study subjects. Peripheral venous blood samples were collected from the patients and their parents or other pedigree members for the extraction of genomic DNA. Whole exome sequencing was carried out, and candidate variants were validated by Sanger sequencing. The pathogenicity of the variants was determined based on the guidelines from the American College of Medical Genetics and Genomics (ACMG).@*RESULTS@#Genetic testing revealed that all four patients have harbored variants of the FBN1 gene, including c.430_433del (p.His144fs) deletional variant in exon 5, c.493C>T (p.Arg165*) nonsense variant in exon 6, c.5304_5306del (p.Asp1768del) deletional variant in exon 44 and c.5165C>G (p.Ser1722Cys) missense variant in exon 42. According to the ACMG guidelines, the c.430_433del and c.493C>T were classified as pathogenic variants (PVS1+PM2_Supporting+PP4; PVS1+PS1+PS2+PM2_Supporting+PP4). c.5304_5306del and c.5165C>G were classified as likely pathogenic variants (PS2+PM2_Supporting+PM4+PP4; PS2_Moderate+PS1+PM1+PM2_Supporting).@*CONCLUSION@#The c.430_433del and c.5304_5306del variants of the FBN1 gene identified in this study were unreported previously. Above results have enriched the variation spectrum of the FBN1 gene and provided a basis for genetic counseling and prenatal diagnosis of patients with MFS and acromicric dysplasia.

Research progress of EGFRvIII targeted immunotherapy in the treatment of glioblastoma / 药学学报

Glioblastoma (GBM) is the most common primary brain tumor, which is prone to recurrence and metastasis with poor prognosis. In recent years, immunotherapy has prolonged the survival of patients with GBM, providing a new option for the treatment of GBM. Target selection is very important for immunotherapy. Epidermal growth factor receptor variant III (EGFRvIII) is highly expressed on the surface of GBM cells in some patients, and EGFRvIII was not expressed in normal tissues. EGFRvIII are pivotal for the occurrence and progression of GBM, various targeted therapy including immunotherapy is promising to improve the efficacy of GBM. Currently, there are various approaches to target EGFRvIII, including humanized monoclonal antibodies, adoptive cell therapies and therapeutic vaccines. In this review, we focus on the preclinical and clinical findings of targeting EGFRvIII for GBM.

Study of the effects of long-term outcomes of autologous peripheral blood stem cell reinfusion in patients with decompensated cirrhosis / 中华肝脏病杂志

Objective: Autologous peripheral blood stem cells (PBSC) derived from bone marrow can promote liver regeneration and improve the liver function of patients, but there are few studies on its effect on the long-term outcomes in patients with decompensated cirrhosis. Based on previous work, this study observed the clinical outcomes of PBSC treatment in patients with decompensated cirrhosis for 10 years, in order to provide more data support for the safety and efficacy of stem cells in clinical applications. Methods: Data of patients with decompensated liver cirrhosis who completed PBSC treatment in the Department of Gastroenterology of the First Affiliated Hospital of Air Force Military Medical University from August 2005 to February 2012 were included. The follow-up endpoint was death or liver transplantation, and patients who did not reach the follow-up endpoint were followed-up for at least 10 years. The patients with decompensated liver cirrhosis who met the conditions for PBSC treatment but did not receive PBSC treatment in our hospital during the same period were used as controls. Results: A total of 287 cases with decompensated liver cirrhosis had completed PBSC treatment, and 90 cases were lost to follow-up within 10 years after surgery. A total of 151 cases with complete survival follow-up data were included in the control group. There were no statistically significant differences in baseline information such as gender, age, etiological composition and liver function score between the two groups. The 10-year survival rate was higher in PBSC than control group (37.56% vs. 26.49%, P<0.05). Cholinesterase, albumin, international normalized ratio, Child-Turcotte-Pugh score, model for end-stage liver disease score, and other indicators were gradually recovered within 3 months to 1 year after PBSC treatment, and stabilized at a more desirable level in the long-term after follow-up for up to 10 years. There was no statistically significant difference in the incidence of liver cancer between the two groups (25.22% vs.31.85%, P=0.267). The age of onset of hepatocellular carcinoma was later in PBSC than control group [(56.66±7.21) years vs. (52.69±8.42) years, P<0.05]. Conclusions: This long-term observational follow-up study of more than ten years confirms that PBSC treatment can bring long-term benefits to patients with decompensated cirrhosis, with good long-term safety, thus providing more data support on the safety and efficacy of stem cells for clinical applications.

Anti-tumor activity of novel targeting HER2 antibody-drug conjugates / 药学学报

Antibody-drug conjugates (ADCs) are widely used in cancer treatment. Human epidermal growth factor receptor-2 (HER2) is overexpressed in various types of solid tumors and is a validated therapeutic target for cancers. To develop a more effective therapy, we generated a novel anti-HER2 humanized monoclonal antibody MIL40 and MIL40 drug conjugates as novel cancer therapies. The MIL40 was conjugated with small molecule cytotoxic agents DM1 [emtansine, N2'-deacetyl-N2'-(3-mercapto-1-oxopropyl)-maytansine] or monomethylauristatin E (MMAE) to generate ADCs, which were evaluated for their in vitro and in vivo anti-cancer activities. Experimental results show that MIL40-DM1 and MIL40-MMAE can effectively identify and bind to HER2-positive tumor cells. The binding capabilities of MIL40-DM1 and MIL40-MMAE with HER2 extracellular domain (ECD) antigens were not different after conjugation with DM1 or MMAE. The ADCs showed potent cytotoxicity in HER2-positive ovarian cancer cells SKOV3, breast cancer cells SKBR3 and stomach cancer cells N87 in vitro. MIL40-DM1 can effectively inhibit the volume and weight growth of SKOV3 transplant tumors in mice. The mice in this study were used and treated by following the international guidelines for the care and use of laboratory animals, and approved by Animal Ethics Committee of Institute of Military Cognitive and Brain Sciences.

Bioinformatics and expression analysis on MYB-related family in Angelica dahurica var. formosana / 中国中药杂志

In recent years, the MYB-related gene family has been found pivotal in plant growth and development. MYB-related gene family in Angelica dahurica var. formosana was systematically investigated based on "Chuanzhi No. 2" through transcriptome database search and bioinformatics and the temporal and spatial expression patterns were analyzed through real-time fluorescence-based quantitative polymerase chain reaction(PCR). The results showed that 122 MYB-related proteins family were identified, mainly including the unstable hydrophilic proteins with good thermal stability. Most of the proteins were located in nuclei. The majority of the proteins had the structures of random coil and α-helix. Five MYB-related proteins family of A. dahurica var. formosana had membrane-binding domains. The conserved domain analysis of MYB-related proteins family of A. dahurica var. formosana showed that the MYB domains of genes in five subgroups, similar to 2 R-, 3 R-, and 4 R-MYB proteins, contained three evenly distributed Trp(W) residues in the MYB repeat sequence. The phylogenetic analysis of MYB-related proteins family in A. dahurica var. formosana and Arabidopsis thaliana showed that the MYB-related members were unevenly distributed in five subgroups, and A. thaliana and A. dahurica var. formosana had almost the same number of genes in the CCA1-like subgroup. There were differences in the number, type, and distribution of motifs contained in 122 encoded proteins. Transcription factors with similar branches had similar domains and motifs. The expression pattern analysis showed that the transcription factors AdMYB53, AdMYB83, and AdMYB89 responded to hormones to varying degrees, and they were highly expressed in leaves and responded quickly in roots. This study lays a foundation for further investigating the function of MYB-related transcription factors of A. dahurica var. formosana and solving the corresponding biological problems such as bolting early.

Laparoscopic Common Bile Duct Exploration for Treatment of Common Bile Duct Stones:Clinical Analysis of 158 Cases / 中国医学科学院学报

Objective To evaluate the safety and effectiveness of laparoscopic common bile duct exploration in the treatment of common bile duct stones. Methods A retrospective analysis was conducted for 158 patients with cholecystolithiasis and choledocholithiasis admitted to the Number One Hospital of Zhangjiakou from January 2015 to December 2019.The patients were assigned into three groups according to the diameters of cystic duct and common bile duct,degrees of abdominal infection and tissue edema,and operation method.Group A(16 cases):laparoscopic cholecystectomy,transcystic choledochoscopic exploration for stone removal;Group B(94 cases):laparoscopic cholecystectomy,common bile duct incision exploration combined with choledochoscopy for stone removal,T tube drainage;Group C(48 cases):laparoscopic cholecystectomy,common bile duct incision exploration combined with choledochoscopy for stone removal,primary closure of the common bile duct.The operation time,residual rate of stones,and complication(bleeding,bile leakage,and wound infection) rate were compared between groups. Results The operation time of groups A,B,and C was(95.1±14.7),(102.2±18.1),(110.1±16.4) minutes,respectively,which showed no statistical difference between each other(F=0.020,P=0.887).One case in group A had residual stones,while no residual stone appeared in groups B and C.The overall stone clearance rate was 99.4% and the overall complication rate was 1.9%.There was no perioperative death. Conclusion It is generally safe and effective to carry out laparoscopic cholecystectomy and common bile duct exploration for stone removal in suitable populations.