Research progress on the regulation of intestinal flora and effect on intestinal absorption and transport by TCM components / 药学实践与服务

The domestic and international research progress on the regulation of gut microbiota by Traditional Chinese Medicine (TCM) ingredients and their impact on intestinal absorption and transportation were summarized, which provided assistance for subsequent clinical rational drug use targeting gut microbiota. Literature on the relationship between gut microbiota and intestinal absorption and transportation in recent years were reviewed and analyzed, and the mechanism of TCM ingredients regulating gut microbiota on drug absorption and transportation was elucidated. Research has found that TCM ingredients alter gut microbiota, thereby affecting intestinal barrier function and absorption of transport proteins, which is of great significance for rational clinical medication.

Hereditary pheochromocytoma/paraganglioma and associated syndromes:a clinical and genetic study / 陆军军医大学学报

Objective To summarize and analyze the clinical phenotypes,hereditary features and treatment and follow-up strategies of different hereditary pheochromocytoma/paragangliomas(PCC/PGL)and related syndromes.Methods Forty-four clinically diagnosed PCC/PGL patients admitted in our hospital from January 2000 to August 2022 were enrolled,and the clinical data of them and their family members were collected.Second-generation sequencing was performed on 43 patients for genetic detection,and Sanger sequencing was applied to verify the mutation of the probands and family members.Results There were 15 patients diagnosed with hereditary PCC/PGL,including 7 cases of von Hippel-Lindau(VHL)syndrome,3 cases of multiple endocrine neoplasia type 2(MEN2),and 5 cases of familial paraganglioma syndrome.Seven VHL syndrome families were diagnosed as VHL2A(c.500G＞A),VHL2B(c.239G＞T and c.444_457del),and VHL2C(c.293A＞G)according to their clinical manifestations.All probands received surgical treatment,and 2 cases of recurrent PCC and the patients with multiple renal cancer also received targeted therapy with sunitinib.Three MEN2 families carried c.1901G＞C,c.1832G＞A,and c.1901G＞A missense mutations,respectively,and were diagnosed with MEN2A clinically.All of them underwent adrenalectomy and thyroidectomy,including one for preventive thyroidectomy.Among the 5 familial paraganglioma syndrome families,4 patients carried SDHB mutations(SDHB:c.343C＞T,c.541-2A＞G,c.575G＞A,c.268C＞T)and 1 patient carried an SDHD mutation(SDHD:c.337_340del).Sporadic retroperitoneal PGL were most common.Conclusion More than 1/3 of PCC/PGL patients carry germline gene mutations,showing obvious genotype-phenotype correlation.Genetic diagnosis technology plays an important guidance role for clinical precision treatment and follow-up,and genetic counseling.

Analysis of factors related to sleep disorders in patients with chronic kidney disease / 安徽医科大学学报

Objective @#To evaluate the sleep quality of patients with chronic kidney disease (CKD) and to explore the related factors of sleep disorder in patients with CKD .@*Methods @#The basic data of hospitalization patients with CKD without renal replacement therapy were prospectively collected , and the Pittsburgh sleep quality index (PSQI) scale was used to evaluate the sleep quality of patients . Patients with a PSQI score of ≤5 were divided into the nor mal sleep group , and patients with a PSQI score of > 5 were divided into the sleep disorder group . Logistic regres sion analysis was used to explore the related factors of sleep disorder in patients with CKD .@*Results@#A total of 189 patients with CKD who did not receive renal replacement therapy were included , including 114 males (60.3% ) and 75 females (39.7% ) , aged 56.5 ±15.23 years . The PSQI score was 7.00 (5.00 , 8.00) , there were 58 ca ses in the normal sleep group and 131 cases in the sleep disorder group , and the prevalence of sleep disorder was as high as 69 3% . As the CKD stage progresses , the prevalence of sleep disorders gradually increases . There were differences between the sleep disorder group and the normal sleep group in subjective sleep quality , sleep latency , sleep duration , habitual sleep efficiency , sleep disorder superposition problems , and daytime dysfunction ( P < 0.05) , while there was no statistically significant difference in the scores of sleep medication use . Retirement or unemployed (OR = 6.509 , 95% CI:1.844 - 22.976) and women (OR = 4.561 , 95% CI: 1.241 - 16.767) were independent risk factors for sleep disorders , while e GFR (OR = 0.960 , 95% CI: 0.931 - 0.991) was a protective factor for sleep disorders , P < 0.05 . @*Conclusion @#The prevalence of sleep disorders in patients with chronic kidney disease without renal replacement therapy gradually increases with the decrease of e GFR and the increase of CKD stage , but they do not receive timely intervention with sleep improvement drugs . Clinicians need to focus on assess ing sleep quality in women versus unemployed or retired patients with CKD .

Expert consensus on the clinical diagnosis and treatment of scrub typhus / 中国人兽共患病学报

Scrub typhus is a type of natural focal disease caused by a bacteria called Orientia tsutsugamushi and mainly en-demic in East and Southeast Asia.The most common clinical symptoms of scrub typhus include fever,eschar,ulcer,lymph node enlargement and rash,which are not typical on early stage and could easily lead to misdiagnosis and missed diagnosis.By reviewing relevant guidelines and references at home and abroad,combining clinical diagnosis and treatment experiences in Chi-na,the experts from Biodiagnostic Technology Branch of China Medical Biotechnology Association and Chinese Society of Mi-crobiology Committee on Zoonotic Pathogens formed this consensus on the clinical diagnosis and treatment of scrub typhus.

Current application and prospect of accurate navigation technology in orthopaedic trauma / 中华外科杂志

In the past decades,a dramatic development of navigation technology in orthopaedic surgery has been witnessed. By assisting the localization of surgical region,verification of target bony structure,preoperative planning of fixation,intraoperative identification of planned entry point and direction of instruments or even automated insertion of implants,its ability and potential to reduce operation time,intraoperative radiation,surgical trauma,and improve accuracy has been proved. However,in contrast to the widespread use of navigation technology in arthroplasty,orthopaedic tumor,and spine surgery,its application in orthopaedic trauma is relatively less. In this manuscript,the main purpose is to introduce the technical principles of navigation devices,outline the current clinical application of navigation systems in orthopaedic trauma,analyze the current challenges confronting its further application in clinical practice and its prospect in the future.

Effective components and mechanism of Qijiao Shengbai Capsules based on fingerprinting and network pharmacology / 中国中药杂志

Qijiao Shengbai Capsules(QJ) can invigorate Qi and replenish the blood, which is commonly used clinically for adjuvant treatment of cancer and leukopenia due to chemoradiotherapy. However, the pharmacological mechanism of QJ is still unclear. This work aims to combine the high-performance liquid chromatography(HPLC) fingerprints and network pharmacology to clarify the effective components and mechanism of QJ. The HPLC fingerprints of 20 batches of QJ were established. The similarity evaluation among 20 batches of QJ was performed by using Similarity Evaluation System for Chromatographic Fingerprint of Traditional Chinese Medicine(version 2012), resulting in a similarity greater than 0.97. Eleven common peaks were identified by reference standard, including ferulic acid, calycosin 7-O-glucoside, ononin, calycosin, epimedin A, epimedin B, epimedin C, icariin, formononetin, baohuoside I, and Z-ligustilide. The "component-target-pathway" network was constructed by network pharmacy, and 10 key components in QJ were identified, such as ferulic acid, calycosin 7-O-glucoside, ononin, and calycosin. The components were involved in the phosphoinositide 3 kinase-protein kinase B(PI3K-Akt), mitogen-activated protein kinase(MAPK), and other signaling pathways by regulating potential targets, including EGFR, RAF1, PIK3R1, and RELA, to auxiliarily treat tumors, cancers, and leukopenia. The molecular docking conducted on the AutoDock Vina platform confirmed the high binding activity of 10 key effective components with core targets, with the binding energy less than-5 kcal·mol~(-1). In this study, the effective components and mechanism of QJ have been preliminary revealed based on HPLC fingerprint and network pharmacology, which provided a basis for quality control of QJ and a refe-rence for further study on its mechanism.

Migration characteristics among HIV/AIDS patients reported in Yiwu City from 2016 to 2020 / 预防医学

Objective@#To investigate the migration characteristics and follow-up treatment among HIV/AIDS patients after HIV confirmation in Yiwu City, Zhejiang Province from 2016 to 2020, so as to provide insights into the optimization of the HIV/AIDS control strategy among floating populations.@*Methods@#The reported HIV/AIDS patients' demographics, follow-up and treatment data in Yiwu City from 2016 to 2020 were captured from the HIV/AIDS Prevention and Control Information System of Chinese Disease Control and Prevention Information System. The migration characteristics, antiretroviral therapy and outcomes of HIV/AIDS patients were analyzed after HIV confirmation, and the factors affecting the migration of HIV/AIDS patients after HIV confirmation were identified using a Cox proportional hazard regression model.@*Results@#A total of 1 189 HIV/AIDS patients were enrolled, including 988 men (83.10%) and 806 cases without Zhejiang provincial household registration (67.79%). There were 441 patients (37.09%) migrating out of Yiwu City after HIV confirmation, with a migration rate of 17.73/100 person-years, and there were 366 patients migrating out of Zhejiang Province, with a cross-province migration rate of 30.78%. Among participants without Zhejiang provincial household registration, 395 patients (49.01%) migrated out of Yiwu City, including 337 patients (85.32%) returning to their household registration provinces, which mainly included Yunnan, Sichuan, Guizhou and Hunan. Cox proportional hazard regression analysis showed a high risk of migration among minority ethnic populations (HR=1.375, 95%CI: 1.044-1.811), retires (HR=3.605, 95%CI: 1.771-7.335), students (HR=8.969, 95%CI: 4.095-19.645), patients without Zhejiang provincial household registration (HR=4.545, 95%CI: 3.164-6.529) and patients identified through physical examination of floating populations or employees (HR=1.318, 95%CI: 1.006-1.727), and a low risk among married patients with spouses (HR=0.721, 95%CI: 0.569-0.913) and with an educational level of junior high school and above (HR: 0.428~0.753, 95%CI: 0.280-0.952). Among all floating HIV/AIDS patients, there were 26 cases lost to follow-up (5.90%) and 49 deaths (11.11%). In addition, the proportion of absence of antiretroviral therapy, HIV infection progressing into AIDS patients and failure in HIV inhibition were all greater among floating HIV/AIDS patients than among non-floating patients (P<0.05).@*Conclusions@#A high risk of migration was found among HIV/AIDS patients without Zhejiang provincial household registration, unmarried patients, patients with a low education level, retirees, students, and patients identified through physical examination of floating populations or employees in Yiwu City from 2016 to 2020, and migration does not facilitate the sustainability of antiretroviral therapy and follow-up, which may affect the prognosis of HIV/AIDS.

Combination immunotherapy of glioblastoma with dendritic cell cancer vaccines,anti-PD-1 and poly I:C / 药物分析学报

Glioblastoma(GBM)is a lethal cancer with limited therapeutic options.Dendritic cell(DC)-based cancer vaccines provide a promising approach for GBM treatment.Clinical studies suggest that other immu-notherapeutic agents may be combined with DC vaccines to further enhance antitumor activity.Here,we report a GBM case with combination immunotherapy consisting of DC vaccines,anti-programmed death-1(anti-PD-1)and poly I:C as well as the chemotherapeutic agent cyclophosphamide that was integrated with standard chemoradiation therapy,and the patient remained disease-free for 69 months.The patient received DC vaccines loaded with multiple forms of tumor antigens,including mRNA-tumor associated antigens(TAA),mRNA-neoantigens,and hypochlorous acid(HOCl)-oxidized tumor lysates.Furthermore,mRNA-TAAAs were modified with a novel TriVac technology that fuses TAAs with a destabilization domain and inserts TAAs into full-length lysosomal associated membrane protein-1 to enhance major histo-compatibility complex(MHC)class Ⅰ and Ⅱ antigen presentation.The treatment consisted of 42 DC cancer vaccine infusions,26 anti-PD-1 antibody nivolumab administrations and 126 poly I:C injections for DC infusions.The patient also received 28 doses of cyclophosphamide for depletion of regulatory T cells.No immunotherapy-related adverse events were observed during the treatment.Robust antitumor CD4+and CD8+T-cell responses were detected.The patient remains free of disease progression.This is the first case report on the combination of the above three agents to treat glioblastoma patients.Our results suggest that integrated combination immunotherapy is safe and feasible for long-term treatment in this patient.A large-scale trial to validate these findings is warranted.

Clinical characteristics of liver function injury in patients with coronavirus disease 2019 / 中华传染病杂志

Objective:To investigate the incidence of liver injury in patients with coronavirus disease 2019 (COVID-19), and to explore its impact on the condition and prognosis of patients.Methods:The medical records of 67 patients with COVID-19 who presented with pneumonia hospitalized at Tongji Hospital, Huazhong University of Science and Technology from February 11 to March 28, 2020 were collected. The results of liver biochemistry and coagulation function test at admission were analyzed. Data were compared by chi-square test, analysis of variance or Kruskal-Wallis H test. Results:Among 67 patients, total bilirubin increased in seven (10.4%) patients, which was slightly abnormal, albumin decreased in 36(53.7%) cases, and was below 30 g/L in 15(22.4%) cases, alanine transaminase (ALT) and aspartate transaminase (AST) were elevated in 19(28.4%) and 12(17.9%) cases, respectively. A total of 22(32.8%) cases had elevated ALT and (or) AST. The incidences with elevated ALT and (or) AST in moderate and severe patients were 33.3%(10/30) and 26.9%(7/26), respectively. Five of 11 critical patients had elevated ALT and (or) AST. There was no significant difference among the three groups ( χ2=1.21, P=0.546). Abnormal alkaline phosphatase and (or) γ-glutamyl transpeptidase were observed in 11(16.4%) cases. The prolongation of prothrombin time (PT) and activated partial thromboplastin time (APTT) occurred in 10(14.9%) and 17(25.4%) patients, respectively, while most of them were slightly abnormal. Only one patient presented with prolongation of PT and APTT meeting the standard of liver failure. A total of 61.2%(41/67) and 65.7%(44/67) of cases showed increase of fibrinogen and D-dimer, respectively, and 28.4%(19/67) and 19.4%(13/67), respectively increased to an obvious extent. The albumin levels in moderate, severe and critical patients were (37.85±6.19) g/L, (32.96±4.33) g/L and (33.02±3.63) g/L, respectively, which were significantly different ( F=7.36, P=0.001). There were significant differences in PT, APTT, fibrinogen and D-dimer among the three groups ( F=3.22, 3.31, 4.06 and H=17.63, respectively, all P<0.05). Conclusions:COVID-19 only leads to mild liver injury and has only mild impact on liver function. The decrease of albumin level and the increase of fibrinogen and D-dimer may be early predicting indexes for the disease severity.

Retrospective investigation on the normal range of serum alanine aminotransferase levels in healthy adults in Ningbo area / 中华传染病杂志

Objective:To reevaluate the upper limit of normal (ULN) of serum alanine aminotransferase (ALT) by retrospectively analyzing the ALT levels in healthy people in Ningbo area.Methods:A total of 56 140 people who underwent health examination and detection of liver biochemical indexes in the Affiliated Hospital of Medical School of Ningbo University and Yinzhou Huamao Hospital of Ningbo from 2018 to 2020 were enrolled. After excluding relevant factors that may lead to liver injury, 11 411 people were included to compare the difference of serum ALT levels among different genders and age groups (20 to 29 years, 30 to 39 years, 40 to 49 years and 50 to 59 years) to determine the ALT ULN in different gender groups. Statistical methods were performed using two independent samples t test and analysis of variance. Results:The serum ALT of males was (19.20±7.90) U/L, which was higher than that of females ((13.75±6.17) U/L), with statistical significance ( t=41.16, P<0.001). The serum ALT ULN in males and in females were 35 U/L and 26 U/L, respectively. The serum ALT levels of 20 to 29, 30 to 39, 40 to 49 and 50 to 59 years old groups were (15.48±7.61) U/L, (16.21±7.40) U/L, (17.36±7.52) U/L and (18.77±7.57) U/L, respectively.The difference was statistically significant ( F=71.51, P<0.001). Serum ALT level in 50 to 59 years old group was higher than that in 20 to 29 years old group, and the difference was statistically significant ( t=13.11, P<0.01). In males, the ALT ULN of 20 to 29 years old was the lowest of 34.43 U/L, and highest of 35.29 U/L in 40 to 49 years old. In females, the ALT ULN in the 20 to 29 years old group was the lowest of 23.01 U/L, and the ALT ULN in the 50 to 59 years old group was the highest of 30.79 U/L. ALT ULN increased with age in females. The serum ALT of males was higher than that of females in all age groups ( t=29.55, 26.91, 13.43 and 4.62, respectively, all P<0.05). Conclusions:The serum ALT level is significantly correlated to gender and age. The serum ALT ULNs of healthy adult are 35 U/L in males and 26 U/L in females in Ningbo area.

Development of a method for determination of osmotic pump controlled-release tablets of lorcaserin hydrochloride in beagle dog plasma and its application to pharmacokinetic study / 中国药理学通报

Aim To develop an UPLC-MS/MS method to determine the concentration of lorcaserin hydrochloride in beagle plasma, and study the pharmacokinetics of osmotic pump controlled-release tablets of lorcaserin hydrochloride. Methods A randomized crossover design was used, carbamazepine as the internal standard(IS), and plasma protein precipitation with acetonitrile. The chromatographic was Phenomenex Polar C18 column(100 mm×2. 1 mm, 3 μm), and acetonitrile - water(containing 10 mmol·L-1 ammonium acetate and 0.1% formic acid)(40:60, V/V)was mobile phase. Multiple reaction monitoring mode and electrospray positive ionization were used to detect lorcaserin hydrochloride. The MS/MS ion transitions were monitored at m/z 196.2→129.2 for lorcaserin hydrochloride and m/z 237→194.1 for carbamazepine, respectively. Results The linear range was 1 to 500 μg·L-1(r=0.999 2), the extraction recovery rate ranged from 87.70% to 89.70%, the precision RSD was 9.7%. The accuracy and matrix effect met the requirements, and the stability of lorcaserin hydrochloride was good in -20 ℃ refrigerator for 45 d, repeated freezing and thawing for three times, placed at room temperature for 24 h, and the disposed samples placed in automatsampler for 6 h were stable. The main pharmacokinetic parameters of the controlled-release tablet and immediate-release tablet were as follows:Tmax was(8.00±1.27)h and(1.00±0.13)h, Cmax was(70.56±3.73)μg·L-1 and(176.33±16.73)μg·L-1, and AUC0-t was(966.33±7.56)μg·h·L-1 and(973.05±69.09)μg·h·L-1, respectively. Conclusions The established UPLC-MS/MS method can be used to study the pharmacokinetics of lorcaserin hydrochloride in the plasma of beagle dogs, and osmotic pump controlled-release tablets has sustained release effect.

Efficacy and safety of various doses of hybutimibe monotherapy or in combination with atorvastatin for primary hypercholesterolemia: a multicenter, randomized, double-blind, double-dummy, parallel-controlled phase Ⅲ clinical trial / 中华心血管病杂志

Objective: To evaluate the efficacy and safety of hybutimibe monotherapy or in combination with atorvastatin in the treatment of primary hypercholesterolemia. Methods: This was a multicenter, randomized, double-blind, double-dummy, parallel-controlled phase Ⅲ clinical trial of patients with untreated primary hypercholesterolemia from 41 centers in China between August 2015 and April 2019. Patients were randomly assigned, at a ratio of 1∶1∶1∶1∶1∶1, to the atorvastatin 10 mg group (group A), hybutimibe 20 mg group (group B), hybutimibe 20 mg plus atorvastatin 10 mg group (group C), hybutimibe 10 mg group (group D), hybutimibe 10 mg plus atorvastatin 10 mg group (group E), and placebo group (group F). After a dietary run-in period for at least 4 weeks, all patients were administered orally once a day according to their groups. The treatment period was 12 weeks after the first dose of the study drug, and efficacy and safety were evaluated at weeks 2, 4, 8, and 12. After the treatment period, patients voluntarily entered the long-term safety evaluation period and continued the assigned treatment (those in group F were randomly assigned to group B or D), with 40 weeks' observation. The primary endpoint was the percent change in low density lipoprotein cholesterol (LDL-C) from baseline at week 12. Secondary endpoints included the percent changes in high density lipoprotein cholesterol (HDL-C), triglyceride (TG), apolipoprotein B (Apo B) at week 12 and changes of the four above-mentioned lipid indicators at weeks 18, 24, 38, and 52. Safety was evaluated during the whole treatment period. Results: Totally, 727 patients were included in the treatment period with a mean age of (55.0±9.3) years old, including 253 males. No statistical differences were observed among the groups in demographics, comorbidities, and baseline blood lipid levels. At week 12, the percent changes in LDL-C were significantly different among groups A to F (all P<0.01). Compared to atorvastatin alone, hybutimibe combined with atorvastatin could further improve LDL-C, TG, and Apo B (all P<0.05). Furthermore, there was no significant difference in percent changes in LDL-C at week 12 between group C and group E (P=0.991 7). During the long-term evaluation period, there were intergroup statistical differences in changes of LDL-C, TG and Apo B at 18, 24, 38, and 52 weeks from baseline among the statins group (group A), hybutimibe group (groups B, D, and F), and combination group (groups C and E) (all P<0.01), with the best effect observed in the combination group. The incidence of adverse events was 64.2% in the statins group, 61.7% in the hybutimibe group, and 71.0% in the combination group during the long-term evaluation period. No treatment-related serious adverse events or adverse events leading to death occurred during the 52-week study period. Conclusions: Hybutimibe combined with atorvastatin showed confirmatory efficacy in patients with untreated primary hypercholesterolemia, which could further enhance the efficacy on the basis of atorvastatin monotherapy, with a good overall safety profile.

Advances in the Regulation of Follicular Development by Extracellular Vesicles and Non-Coding RNAs / 中国医学科学院学报

Extracellular vesicles (EV),nanoscale vesicles encapsulated by phospholipid bilayers,are rich in biological molecules such as nucleic acids,metabolites,proteins,and lipids derived from parental cells.They are mainly involved in intercellular communication,signal transmission,and material transport and affect the functions of target cells.Ovulation disorders account for a higher proportion in the factors causing infertility which demonstrates increasing incidence year by year.Non-coding RNAs participate in a series of physiological and pathological processes of follicular development,playing a key role in female infertility.This review systematically introduces the types and biological roles of EV and elaborates on the regulation of follicular development from the effects of EV and non-coding RNAs on granulosa cell function,oocyte maturation,ovulation,luteal formation,and steroid hormone synthesis,providing a new idea and a breakthrough point for the diagnosis and treatment of infertility.

Clinical phenotype characteristics and genetic analysis in children with nephronophthisis and related syndromes caused by different gene mutations / 中国当代儿科杂志

OBJECTIVES@#To improve the understanding of the clinical phenotypes and genetic characteristics of nephronophthisis (NPHP) and related syndromes in children.@*METHODS@#A retrospective analysis was performed on the medical data of eight children with NPHP and related syndromes who were diagnosed and treated in the Department of Pediatrics of the Second Hospital of Hebei Medical University, from January 2018 to November 2022. The clinical characteristics and genetic testing results were analyzed.@*RESULTS@#Among these eight children, there were five boys and three girls, with an age of onset ranging from 15 months to 12 years. All 8 children exhibited different degrees of renal function abnormalities when they attended the hospital. Among the eight children, two had the initial symptom of delayed development, two had the initial symptom of anemia, and two were found to have abnormal renal function during physical examination. The extrarenal manifestations included cardiovascular abnormalities in two children, skeletal dysplasia in two children, liver dysfunction in one child, retinitis pigmentosa in one child, and visceral translocation in one child. All eight children had renal structural changes on ultrasound, and four children had mild to moderate proteinuria based on routine urine test. Of all eight children, five had NPHP1 gene mutations and one each had a gene mutation in the NPHP3, IFT140, and TTC21B genes, and four new mutation sites were discovered.@*CONCLUSIONS@#Children with NPHP and related syndromes often have the initial symptom of delayed development or anemia, and some children also have extrarenal manifestations. NPHP and related syndromes should be considered for children with unexplained renal dysfunction, and high-throughput sequencing may help to make a confirmed diagnosis.

Inhibitory Effect of Jinkui Shenqi Pills on Glucocorticoid-Enhanced Axial Length Elongation in Experimentally Myopic Guinea Pigs / 中国结合医学杂志

OBJECTIVE@#To explore the underlying mechanism of inhibition by Jinkui Shenqi Pills (JKSQP) on glucocorticoid-enhanced axial length elongation in experimental lens-induced myopia (LIM) guinea pigs.@*METHODS@#Sixty 2-week old male guinea pigs were randomly divided into 4 groups with 15 guinea pigs in each group, according to the random numbers generated by SPSS software: control, LIM, saline and JKSQP groups. The control group includes animals with no treatment, while the guinea pigs in the other 3 groups received lens-induced myopization on the right eyes throughout the experiment (for 8 weeks). The saline and JKSQP groups were given daily intraperitoneal injections of 10 mg/kg hydrocortisone for 2 consecutive weeks at the same time, and then orally administered either saline or JKSQP [13.5 g/(kg•d) for 6 consecutive weeks. Body weight, anal temperature and animal appearance were observed and recorded to evaluate the GC-associated symptoms. The ocular parameters, including refraction and axial length, were measured by streak retinoscopy and A-scan ultrasonography, respectively. The levels of plasma hormones associated with the hypothalamic-pituitary-adrenal axis (HPAA), including free triiodothyronine, free thyroxine, estradiol and testosterone, were measured by radioimmunoassay, and cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate were measured by enzyme-linked immunosorbent assay. In addition, the mRNA and protein expressions of retinal amphiregulin (AREG) was measured by quantitative real-time polymerase chain reaction and Western blotting, respectively.@*RESULTS@#JKSQP effectively increased body weight and anal temperature, improved animal appearance and suppressed axial length elongation in glucocorticoid-enhanced myopic guinea pigs with normalization of 4 HPAA-associated plasma hormones (all P<0.05). The plasma level of cAMP was significantly increased, whereas the plasma level of cGMP and the mRNA and protein expressions of retinal AREG were decreased after treatment with JKSQP (all P<0.05).@*CONCLUSION@#JKSQP exhibited a significant inhibitory effect on axial length elongation with decreased expression of AREG in the retina, and normalized 4 HPAA-associated plasma hormones and the expression of cAMP and cGMP in GC-enhanced myopic guinea pigs.

Genetic Architecture and Functional Implications of the CSF-Contacting Nucleus / 神经科学通报·英文版

We previously identified a unique nucleus, the cerebrospinal fluid (CSF)-contacting nucleus. This study aims to understand its gene architecture and preliminarily suggest its functions. The results showed that there were about 19,666 genes in this nucleus, of which 913 were distinct from the dorsal raphe nucleus (non-CSF contacting). The top 40 highly-expressed genes are mainly related to energy metabolism, protein synthesis, transport, secretion, and hydrolysis. The main neurotransmitter is 5-HT. The receptors of 5-HT and GABA are abundant. The channels for Cl-, Na+, K+, and Ca2+ are routinely expressed. The signaling molecules associated with the CaMK, JAK, and MAPK pathways were identified accurately. In particular, the channels of transient receptor potential associated with nociceptors and the solute carrier superfamily members associated with cell membrane transport were significantly expressed. The relationship between the main genes of the nucleus and life activities is preliminarily verified.

Establishment of a Patient-Derived T-Cell Acute Lymphoblastic Leukemia Xenograft Model in Novel Immunodeficient NCG Mice / 中国实验血液学杂志

OBJECTIVE@#The leukemia cells from patients with T-cell acute lymphoblastic leukemia (T-ALL) were inoculated into NCG mice to establish a stable human T-ALL leukemia animal model.@*METHODS@#Leukemia cells from bone marrow of newly diagnosed T-ALL patients were isolated, and the leukemia cells were inoculated into NCG mice via tail vein. The proportion of hCD45 positive cells in peripheral blood of the mice was detected regularly by flow cytometry, and the infiltration of leukemia cells in bone marrow, liver, spleen and other organs of the mice was detected by pathology and immunohistochemistry. After the first generation mice model was successfully established, the spleen cells from the first generation mice were inoculated into the second generation mice, and after the second generation mice model was successfully established, the spleen cells from the second generation mice were further inoculated into the third generation mice, and the growth of leukemia cells in peripheral blood of the mice in each group was monitored by regular flow cytometry to evaluate the stability of this T-ALL leukemia animal model.@*RESULTS@#On the 10th day after inoculation, hCD45+ leukemia cells could be successfully detected in the peripheral blood of the first generation mice, and the proportion of these cells was gradually increased. On average, the mice appeared listless 6 or 7 weeks after inoculation, and a large number of T lymphocyte leukemia cells were found in the peripheral blood and bone marrow smear of the mice. The spleen of the mice was obviously enlarged, and immunohistochemical examination showed that hCD3+ leukemia cells infiltrated into bone marrow, liver and spleen extensively. The second and third generation mice could stably develop leukemia, and the average survival time was 4-5 weeks.@*CONCLUSION@#Inoculating leukemia cells from bone marrow of patients with T-ALL into NCG mice via tail vein can successfully construct a patient-derived tumor xenografts (PDTX) model.

Auto-segmentation of high-risk clinical target volume and organs-at-risk for brachytherapy of cervical cancer based on nnUNet / 中国医学物理学杂志

Objective To develop an auto-segmentation model based on no new U-net for delineating high-risk clinical target volume(HR-CTV)and organs-at-risk(OAR)in CT-guided brachytherapy of cervical cancer,and to explore its clinical value.Methods The CT images of 63 patients with locally advanced cervical cancer who had completed image-guided brachytherapy were collected.The HR-CTV and OAR including bladder,rectum and sigmoid colon were delineated manually by a senior oncologist,and the results were taken as the gold standard.The automatic and manual segmentation results were compared,and Dice similarity coefficient was used to evaluate HR-CTV and OAR auto-segmentation accuracies.Results The Dice similarity coefficients of HR-CTV,bladder,rectum,and sigmoid colon were 0.903±0.015,0.948±0.011,0.903±0.008,and 0.803±0.024,respectively.Conclusion The established model can realize the accurate segmentations of HR-CTV,bladder,rectum and sigmoid colon,but the oncologist still needs to scrupulously check the results.

Effect of Celastrol Based on IRAK4/ERK/p38 Signaling Pathway on Proliferation and Apoptosis of Multiple Myeloma Cells / 中国实验血液学杂志

OBJECTIVE@#To investigate the effect of celastrol on the proliferation and apoptosis of human multiple myeloma (MM) cell lines, reveal the relationship between IRAK4/ERK/p38 signaling pathway and celastrol regulating the proliferation and apoptosis of H929 and ARP-1 cells, and explore whether celastrol combined with bortezomib has synergistic effect. @*METHODS@#CCK-8 method was used to detect the viability of MM cell lines H929 and ARP-1 treated by different concentrations of celastrol, bortezomib, and their combination, and the synergistic effect was determined by Kim's formula. The apoptosis rate of H929 cells and necrosis rate of ARP-1 were detected by Annexin V/PI method. The expression of key proteins and apoptosis proteins in IRAK4/ERK/p38 signaling pathway were detected by Western blot. @*RESULTS@#Celastrol could significantly inhibit the proliferation of H929 and ARP-1 cells (r=0.9018, r=0.9244) and induce apoptosis in a time-dependent manner. Compared with the control group, celastrol could significantly up-regulate the expression of PARP and cleaved caspase-3 while down-regulate the expression of p-IRAK4, p-ERK, and p-p38 in H929 and ARP-1 cells. Celastrol and bortezomib alone inhibited the proliferation of H929 and ARP-1 cells. Compared with celastrol and bortezomib alone, their combination had lower cell survival rate and higher apoptosis rate (P<0.05). @*CONCLUSION@#Celastrol can inhibit the proliferation and promote the apoptosis of H929 and ARP-1 cells, which may be related to inhibiting the phosphorylation of IRAK4 and blocking the activation of IRAK4/ERK/p38 signaling pathway. Celastrol combined with bortezomib has synergistic effect, which can more effectively inhibit the proliferation and induce apoptosis of H929 and ARP-1 cells.

Application of CBL in the teaching of knee MRI for orthopedic residents / 中华医学教育探索杂志

Objective:To study the effect of CBL on the teaching of knee magnetic resonance image (MRI) for orthopedic residents.Methods:From September 2015 to March 2018, CBL teaching method was applied in the teaching of knee MRI among 90 orthopedic residents of Arthritis Clinical & Research Center of Peking University People’s Hospital. The teaching effect of CBL was evaluated with questionnaire method. The scores of Knee MRI theoretical knowledge and image diagnosis were statistically compared after CBL teaching. SPSS 19.0 was performed for t test. Results:According to the questionnaire of 90 orthopedic residents, in the teaching of knee MRI, CBL teaching improved the residents' learning interest[77.8%(70/90)], fortified their theoretical knowledge[80.0%(72/90)], and enhanced their diagnosis ability of knee MRI[88.8%(80/90)], diagnosis ability of knee diseases[86.6%(78/90)], autonomous learning ability[84.5%(76/90)], expression ability[83.3%(75/90)], and the ability of creating active classroom atmosphere[51.1%(46/90)]. The performances of knee MRI theoretical knowledge and image analysis were significantly increased after CBL teaching, respectively from (65.35±10.36) points to (89.20±10.55) points and from (66.64±9.88) points to (89.50±10.06) points.Conclusion:CBL teaching can improve independent diagnostic ablity of knee MRI of orthopedic residents and lay a solid foundation of diagnosis and treatment for knee diseases, thus improving their clinical skills.