Preparation and in vivo Distribution of Essential Oil from Alpinia zerumbet Fructus Encapsulated Nanoemulsions / 中国实验方剂学杂志

ObjectiveTo prepare oral nanoemulsions encapsulating essential oil from Alpinia zerumbet fructus（EOFAZ） and to investigate its pro-absorption effect in vitro and distribution in vivo. MethodThe proteoglycan conjugate polysaccharides of vinegar-processed Bupleuri Radix-bovine serum albumin（VBCP-BSA） was prepared by Maillard reaction of VBCP and BSA. Taking VBCP-BSA as emulsifier， vitamin B12（VB12） as absorption enhancer， and medium chain triglycerides mixed with EOFAZ as oil phase， the nanoemulsions loaded with EOFAZ was prepared by high energy emulsification method. The particle size， particle size distribution， surface Zeta potential， EOFAZ content and appearance and morphology of the nanoemulsions were characterized， and fluorescein tracer method was used to investigate the absorption effect of fluorescein-labeled EOFAZ nanoemulsions in vitro and their distribution in vivo. ResultVBCP-BSA was formed by Maillard reaction for 48 h with high grafting rate. Using VBCP-BSA as emulsifier， the homogeneous pink nanoemulsions was prepared and denoted as EOFAZ@VBCP-BSA/VB12. The particle size of the nanoemulsions was less than 100 nm and the particle size distribution was uniform. The surface of the nanoemulsions was a weak negative charge， and the shape was spherical. The encapsulation rate of the nanoemulsions for EOFAZ was greater than 80%， which had a good absorption effect in vitro and could enhance liver accumulation after oral administration. ConclusionThe designed proteoglycan nanoemulsions can effectively load EOFAZ， promote oral absorption and enhance liver distribution， which can provide experimental basis for the development of oral EOFAZ liver protection preparations.

Mechanism studies underlying the alleviatory effects of isoliquiritigenin on abnormal glucolipid metabolism triggered by type 2 diabetes / 药学学报

Isoliquiritigenin (ISL) is an active chalcone compound isolated from licorice. It possesses anti-inflammatory and anti-oxidative activities. In our previous study, we uncovered a great potential of ISL in treatment of type 2 diabetes mellitus (T2DM). Therefore, this study aims to reveal the mechanism underlying the alleviatory effects of ISL on T2DM-induced glycolipid metabolism disorder. High-fat-high-sugar diet (HFD) combined with intraperitoneal injection of streptozotocin (STZ) were used to establish T2DM mice model. All animal experiments were carried out with approval of the Committee of Ethics at Beijing University of Chinese Medicine. HepG2 cells were used in in vitro experiments, and sodium palmitate (SP) was applied to establish insulin resistance (IR) model cells. The effects of ISL on body weight, fasting blood glucose levels, and pathological changes in the livers of mice were examined. Enzyme-linked immune sorbent assay (ELISA) and real-time quantitative PCR (RT-qPCR) were applied to detect the regulatory effects of ISL on key targets involved in glucolipid metabolism. Additionally, molecular docking and analytical dynamics simulation methods were used to analyze the interaction between ISL and key target protein. The results indicate that ISL significantly downregulates the transcriptional levels and inhibits the activities of key enzymes involved in gluconeogenesis, including pyruvate carboxylase (PC), phosphoenolpyruvate carboxykinase (PEPCK), and fructose-1, 6-bisphosphatase (FBP). It also downregulates the transcriptional and protein levels of hepatocyte nuclear factor 4α (HNF4α) and cAMP response element binding protein (CREB), the two transcriptional factors involved in gluconeogenesis. Thus, ISL inhibits hepatic gluconeogenesis in T2DM mice. In addition, ISL reduces total cholesterol (TC) and triglyceride (TG) levels in the livers of T2DM mice. Moreover, ISL downregulates the mRNA levels of lipogenesis genes and upregulates those of genes involved in fatty acid oxidation, lipid uptake, and lipid export. In conclusion, ISL suppresses hepatic gluconeogenesis, promotes lipolysis, and restrains lipogenesis in T2DM mice, thereby improving the abnormal glycolipid metabolism caused by T2DM.

Research progress of nitrobenzoyl sesquiterpenoids as marine characteristic natural products / 药学学报

Sesquiterpenoids are widely found in nature, while nitrobenzoyl sesquiterpenoids are relatively rare. Twelve natural nitrobenzoyl sesquiterpenoids were all derived from marine Aspergillus fungi, which are typical natural products with marine characteristics. These natural products exhibit good antitumor, antiviral, and inhibition of osteoclast differentiation activity, especially in the treatment of osteoclast-related diseases, showing good medicinal development value. This article reviews the natural product sources, chemical structure, chemical synthesis, biosynthesis, bioactivity, and pharmacological mechanisms of nitrobenzoyl sesquiterpenoids and predicts and discusses their absorption, distribution, metabolism, excretion, toxicity (ADME/T), and drug-likeness, providing a comprehensive understanding of the natural products of nitrobenzoyl sesquiterpenoids from marine sources and their potential for pharmaceutical development.

Clinical study of Qinggan Bupi Jiangtang Decoction combined with western medicine in the treatment of adult type 2 diabetes mellitus with liver hyperactivity and spleen deficiency syndrome / 国际中医中药杂志

Objective:To evaluate the efficacy of Qinggan Bupi Jiangtang Decoction combined with western medicine in the treatment of adult type 2 diabetes mellitus (T2DM) with with liver hyperactivity and spleen deficiency syndrome.Methods:Prospective cohort study. A total of 103 T2DM patients with liver hyperactivity and spleen deficiency syndrome in the Department of endocrinology of Shanghai Municipal Hospital of Traditional Chinese Medicine from February 2020 to February 2021 were randomly divided into the observation group (52 cases) and the control group (51 cases) according to random number table method. Both groups were treated with conventional western medicine, the control group was treated with sitagliptin phosphate on the basis of routine treatment, and the observation group was treated with Qinggan Bupi Jiangtang Decoction on the basis of routine treatment. Both groups were treated for 12 weeks. TCM symptom scores were performed before and after treatment. The FPG, 2hPBG, HbA1c and fasting insulin (FINS) were detected by dry chemistry method and Roche electroluminescence method, and insulin resistance index (HOMA-IR) was calculated. The clinical efficacy was evaluated by dynamic blood glucose monitoring indexes TIR (percentage of time when glucose was in the range of 3.9-10.0 mmol/L), TAR (percentage of time when glucose was higher than the target range ≥ 11.1 mmol/L) and TBR (percentage of time when glucose was lower than the target range <3.9 mmol/L).Results:The total effective rate was 92.3% (48/52) in the observation group and 56.9% (29/51) in the control group ( χ2=15.32, P<0.01). The score of TCM syndrome in the observation group was significantly lower than that of the control group ( t=6.30, P<0.01). The compliance rate of HbA1c in the observation group was 46.2% (24/52) and that of the control group was 23.5% (12/51). There was significant difference between the two groups ( χ2=5.80, P=0.016). Compared with the groups before treatment, MAGE, TAR, TBR significantly decreased and TIR significantly increased in both groups after treatment ( P<0.01), but there was no significant difference between the two groups after treatment ( t values were 0.78, 1.06, 0.22 and 1.45, respectively, P>0.05). Compared with the groups before treatment, the levels of FPG, 2 hPBG and HbA1c in the two groups significantly decreased after treatment ( P<0.01), but there was no significant difference between the two groups after treatment ( t values were 1.32, 0.18,1.50, respectively, P>0.05). Compared with the groups before treatment, the levels of FINS and HOMA-IR in the two groups significantly decreased after treatment ( P<0.01), but there was no significant difference between the two groups after treatment ( t values were 1.25, 0.51, respectively, P>0.05). There were no adverse reactions in the observation group, 2 cases of mild nausea and 1 case of transient diarrhea in the control group. There was no significant difference between the two groups ( χ2=3.15, P=0.118). Conclusion:Qinggan Bupi Jiangtang Decoction combined with routine treatment can improve the blood glucose level, TIR and blood glucose standard rates of adult T2DM with liver hyperactivity and spleen deficiency syndrome, and the curative effect is equivalent to sitagliptin phosphate tablets.

Value of CT radiomic features in differential diagnosis of lung metastases / 国际肿瘤学杂志

Objective:To distinguish lung metastases of different origin by constructing a classification model according to CT radiomics features.Methods:A total of 226 patients with lung metastases of gastric cancer, breast cancer and kidney cancer attending Chongqing Red Cross Hospital from January 2015 to July 2020, with a total of 402 metastases, were randomly divided into a training cohort (training set, 136 patients, 280 metastases) and a validation cohort (validation set, 90 patients, 122 metastases) by the hold-out method. In addition, 68 patients with lung metastases (138 lung metastases in total) attending Chongqing Red Cross Hospital from August 2020 to April 2022 were matched as an external test cohort (test set). Region of interest segmentation was performed by two experienced radiologists independently and manually without clinical information to construct the model by using LASSO screening for the best radiomic features. Support vector machine (SVM) and random forest (RF) were selected to build dichotomous and trichotomous models respectively. The receiver operating characteristic curve was used to evaluate the classification efficiency of both models.Results:There were no statistically significant differences in age ( t=-0.06, P=0.534), gender ( χ2<0.01, P=0.961) and number of lung metastases ( χ2=0.71, P=0.703) between the validation and test sets. A total of 792 radiomic features were extracted, 703 of which had good agreement (intraclass correlation coefficient≥0.75), while 89 features being excluded for having poor agreement (intraclass correlation coefficient<0.75). The dichotomous model (SVM) screened 28 (lung metastases from gastric cancer vs. lung metastases from breast cancer), 25 (lung metastases from gastric cancer vs. lung metastases from kidney cancer) and 34 (lung metastases from kidney cancer vs. lung metastases from breast cancer) features, respectively; the trichotomous model (RF) screened 20 features (three types of lung metastases), in which Short Run Emphasis and Inverse Variance were significantly higher in lung metastases from kidney cancer than in the other two types, correlation was higher in lung metastases from gastric cancer than in the other two types, and there was no significant difference in the sphericity of the three lung metastases. For the dichotomous model, in the validation set, the area under the curve (AUC) of the 28 features selected to distinguish gastric cancer lung metastases from breast cancer lung metastases was 0.81, the AUC of the 25 features distinguishing gastric cancer lung metastases from kidney cancer lung metastases was 0.86, and the AUC of the 34 features distinguishing kidney cancer lung metastases from breast cancer lung metastases was 0.92, and the AUCs of the test set were 0.80, 0.79 and 0.86 respectively. For the trichotomous model, the AUC for predicting lung metastases from gastric cancer, breast cancer and kidney cancer in the validation set were 0.85, 0.82 and 0.91 respectively, and both macroscopic and microscopic AUC were 0.85; In the test set, the AUC for predicting lung metastases from gastric cancer, breast cancer, and kidney cancer were 0.77, 0.86 and 0.84 respectively, and both macroscopic and microscopic AUC were 0.81. Conclusion:The SVM and RF models based on CT radiomic features are helpful in distinguishing lung metastases derived from gastric cancer, breast cancer and kidney cancer.

Prognostic value of AST/ALT ratio combined with APTT regimen in NVAF patients receiving rivaroxaban anticoagulant therapy / 国际生物医学工程杂志

Objective:To investigate the prognostic value of the ratio of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) combined with activated partial thromboplastin time (APTT) in elderly patients with non-valvular atrial fibrillation (NVAF) treated with rivaroxaban.Methods:One hundred and twenty-two elderly patients with NVAF who were anticoagulated with rivaroxaban from June 2020 to June 2021 in the Third Central Hospital of Tianjin were enrolled and divided into four groups based on the median method. The patients in the Q1 group ( n = 32) have low AST/ALT/low APTT. The patients in the Q2 group ( n = 27) have low AST/ALT/high APTT. The patients in the Q3 group ( n = 29) have high AST/ALT/low APTT. The patients in the Q4 group ( n = 34) have high AST/ALT/high APTT. The efficacy endpoint events, and safety endpoint events were analyzed in the four groups, and univariate and multivariate Cox regression analyses were performed for the composite endpoint events. Results:The effectiveness endpoint events were mainly cardiovascular deaths, the number of which in the Q1 to Q4 groups was 0 (0), 1 (3.70%), 4 (13.79%), and 5 (14.71%), respectively. The safety endpoint events were mainly non-major bleeding events, the number of which in the Q1 to Q4 groups was 5 (15.62%), 2 (7.41%), 6 (20.69%), and 5 (14.71%), respectively. Compared to the Q1 group, the Q4 group had an increased risk of composite endpoint events after incorporating traditional risk factor correction ( HR: 3.851, 95% CI: 1.167 to 12.704). Conclusions:AST/ALT ratio combined with APTT can provide risk stratification for distant bleeding and cardiovascular adverse events in elderly NVAF patients treated with rivaroxaban anticoagulation and has some predictive value for their prognosis.

Co-occurrence trend of overweight,obesity and elevated blood pressure and its association with lifestyle factors among students in Inner Mongolia Autonomous Region / 中国学校卫生

Objective@#To explore the epidemiological trend of overweight and obesity, elevated blood pressure and their comorbidities in children and adolescents from Inner Mongolia Autonomous Region during 2016-2021, and to analyze its association with lifestyle, so as to provide reference for formulating prevention and control strategies of regional common comorbidities in schools.@*Methods@#A total of 8 908, 8 222, 9 448, 127 068, 100 778, and 138 540 students aged 10-18 years in Inner Mongolia were selected by stratified random cluster sampling in September each year from 2016 to 2021. Physical examination and questionnaire survey were conducted on the included students. The prevalence trends of overweight，obesity, elevated blood pressure and their co-occurrence were analyzed. Logistic regression was used to compare the prevalence of elevated blood pressure in different body mass index (BMI) groups. After excluding individuals without lifestyle information in 2021, Logistic regression analysis was used on 136 374 subjects to analyze the association between overweight，obesity, elevated blood pressure and their co-occurrence and lifestyle factors.@*Results@#During 2016 to 2021, the prevalence of comorbidity of overweight, obesity with elevated blood pressure among students in Inner Mongolia Autonomous Region were 5.04%，5.14%，4.99%，7.51%，7.60% and 9.45%， respectively . The prevalence of overweight and obesity was 26.94%, 28.07%, 29.62%, 34.19%, 36.71% and 37.53%, respectively. The prevalence of elevated blood pressure were 16.05%, 11.54%, 13.12%, 14.85%, 14.12% and 18.40%, respectively. Except for 2016, the risk of elevated blood pressure in overweight and obese people was higher than that in normal BMI group in other years, and there was a positive correlation between overweight and obesity and elevated blood pressure after gender and urban and rural areas ( P < 0.05 ). In 2021, the detection rate of comorbidity of overweight and obesity with elevated blood pressure among children and adolescents in urban areas was higher than that in suburban counties, and the reporting rate of healthy lifestyle was lower than that in suburban counties ( P <0.05).Skipping breakfast ( OR =1.11，95% CI =1.07-1.16) and non daily moderate and high intensity physical activity( OR =1.27，95% CI =1.20-1.34) were positively correlated with the co-occurrence of overweight，obesity and elevated blood pressure among children and adolescents in Inner Mongolia Autonomous Region. Non daily moderate and high intensity physical activity ≥60 min was positively correlated with elevated blood pressure ( OR =1.11，95% CI =1.07-1.16), and insufficient sleep was positively correlated with overweight，obesity ( OR =1.04, 95% CI =1.01-1.06)（ P ＜0.05）.@*Conclusion@#The prevalence of overweight，obesity, elevated blood pressure and their co-occurrence among children and adolescents in Inner Mongolia Autonomous Region is relatively high. Overweight/obesity is an important risk factor for elevated blood pressure, and unhealthy lifestyles are risk factors for co-occurrence of overweight，obesity and elevated blood pressure. Region specific lifestyle interventions are indispensable for the prevention and control of regional common comorbidities. Urban areas may be a key focus for lifestyle interventions.

Pharmacokinetic study of HMS-01 in mice / 药学实践杂志

Objective To study the pharmacokinetics of HMS-01 in mice and provide support for subsequent studies. Methods Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to establish a sensitive and specific method for the determination of the concentration of HMS-01 in plasma and other biological samples. The pharmacokinetics of HMS-01 in C57BL/6J mice were studied by the established method. To obtain the basic pharmacokinetic parameters, three doses of HMS-01 were given orally and one dose of HMS-01 was given intravenously. Results The pharmacokinetic results of mice showed that the intestinal absorption of HMS-01 was fast, the oral bioavailability of HMS-01 in mice was moderate (50% to 70%). The exposure levels (AUC and cmax) of HMS-01 in mice increased with the increase of dosage, while the AUC was linearly correlated with the increase of dosage. After intravenous administration of HMS-01, the half-life period in mice was about 1 h which was not long. The plasma clearance rate (CLtotal.p) was 2.8 L/h·kg, which was similar to the hepatic blood flow of mice. The apparent volume of distribution (VSS) was 5 L/kg, which was much larger than the total mouse fluid. There were significant differences in AUC and F (P<0.05), but no significant differences in parameters such as cmax,AUC0−∞,t1/2,CLtot,p,MRT,Vss in male and female mice which were given 30 and 60mg/kg HWS-01 orally. Conclusion The pharmacokinetic process of HMS-01 in mice showed gender differences, and the area under the curve of blood concentration time and bioavailability of female mice were higher than that of male mice. As oral bioavailability was reasonable, further in vivo studies on HMS-01 in mice with heart failure by oral administration could be considered to provide evidence.

Determination of 10 organophosphorus flame retardants in drinking water by On-line SPE-UPLC-MS/MS / 公共卫生与预防医学

Objective To establish a method for the determination of 10 organophosphorus flame retardants in drinking water by on-line solid phase extraction coupled with high performance liquid chromatography-tandem mass spectrometry (On-line SPE-UPLC-MS/MS). Methods After adding the internal standard, the water sample was filtered by Millipore filtration, and then concentrated and detected by Online SPE-UPLC-MS/MS. Samples were concentrated by C8 SPE column and separated by C18 column with acetonitrile-water-formic acid as the mobile phases gradient elution，and were detected by multiple reaction monitoring (MRM) acquisition under anion mode. Results The 10 organophosphorus flame retardants all displayed good linear relationships within a certain range of concentrations, with the correlation coefficients being more than 0.990. The method detection limits were 0.60-5.50 ng/L, and the spiked recoveries of low, medium and high concentrations were 64%-106% , 83%-104% and 85%-99%, respectively. Conclusion The method is simple, sensitive, rapid, accurate and reliable, so it is applicable for the determination of 10 organophosphorus flame retardants in drinking water.

Curcumin in Treatment of Osteosarcoma： A Review / 中国实验方剂学杂志

Osteosarcoma （OS） is the most common primary malignant bone tumor originating from mesenchymal stem cells， which features high degree of malignancy， strong invasiveness， easy early metastasis， and high recurrence rate. The clinical manifestations of OS are pain， local mass， limited movement， and pathological fracture. OS mainly occurs in children， adolescents， and the elderly， seriously threatening physical and mental health of patients， as well as their quality of life. The currently available therapies for OS are surgery， chemoradiotherapy， and the combination of the two. Although the therapeutic effect has been improved， tumor recurrence and metastasis and multidrug resistance still occur. Thus， the therapeutic effect is not satisfactory， especially in improving the overall survival rate of patients with metastatic OS. As a result， clinicians and researchers have been making efforts to find an effective therapy. In recent years， the mechanism of curcumin （CUR） against OS has attracted wide attention. CUR， a pigment extracted from the rhizomes or tubers of many plants， such as Curcuma longa， C. rcenyujin， and C. phaeocaulis， has a variety of pharmacological effects. Scholars have found that CUR has the effects of inhibiting proliferation， inducing apoptosis， and reversing multidrug resistance （MDR） of tumor cells， but also it has poor water solubility and low bioavailability， which limit the clinical application. This paper mainly discusses the mechanism of CUR against OS， the existing problems， new treatment methods， and future research directions， which is expected to provide new ideas for scientific researchers and provide a reference for the development and utilization of CUR in the future.

Technology and principle of improving solubility of Dioscoreae Rhizoma formula granules based on powder modification / 中国中药杂志

The powder modification technology was used to improve the powder properties and microstructure of Dioscoreae Rhizoma extract powder, thereby solving the problem of poor solubility of Dioscoreae Rhizoma formula granules. The influence of modifier dosage and grinding time on the solubility of Dioscoreae Rhizoma extract powder was investigated with the solubility as the evaluation index, and the optimal modification process was selected. The particle size, fluidity, specific surface area, and other powder properties of Dioscoreae Rhizoma extract powder before and after modification were compared. At the same time, the changes in the microstructure before and after modification was observed by scanning electron microscope, and the modification principle was explored by combining with multi-light scatterer. The results showed that after adding lactose for powder modification, the solubility of Dioscoreae Rhizoma extract powder was significantly improved. The volume of insoluble substance in the liquid of modified Dioscoreae Rhizoma extract powder obtained by the optimal modification process was reduced from 3.8 mL to 0 mL, and the particles obtained by dry granulation of the modified powder could be completely dissolved within 2 min after being exposed to water, without affecting the content of its indicator components adenosine and allantoin. After modification, the particle size of Dioscoreae Rhizoma extract powder decreased significantly, d_(0.9) decreased from(77.55±4.57) μm to(37.91±0.42) μm, the specific surface area and porosity increased, and the hydrophilicity improved. The main mechanism of improving the solubility of Dioscoreae Rhizoma formula granules was the destruction of the "coating membrane" structure on the surface of starch granules and the dispersion of water-soluble excipients. This study introduced powder modification technology to solve the solubility problem of Dioscoreae Rhizoma formula granules, which provided data support for the improvement of product quality and technical references for the improvement of solubility of other similar varieties.

Hedgehog pathway orchestrates the interplay of histone modifications and tailors combination epigenetic therapies in breast cancer

Epigenetic therapies that cause genome-wide epigenetic alterations, could trigger local interplay between different histone marks, leading to a switch of transcriptional outcome and therapeutic responses of epigenetic treatment. However, in human cancers with diverse oncogenic activation, how oncogenic pathways cooperate with epigenetic modifiers to regulate the histone mark interplay is poorly understood. We herein discover that the hedgehog (Hh) pathway reprograms the histone methylation landscape in breast cancer, especially in triple-negative breast cancer (TNBC). This facilitates the histone acetylation caused by histone deacetylase (HDAC) inhibitors and gives rise to new therapeutic vulnerability of combination therapies. Specifically, overexpression of zinc finger protein of the cerebellum 1 (ZIC1) in breast cancer promotes Hh activation, facilitating the switch of H3K27 methylation (H3K27me) to acetylation (H3K27ac). The mutually exclusive relationship of H3K27me and H3K27ac allows their functional interplay at oncogenic gene locus and switches therapeutic outcomes. Using multiple in vivo breast cancer models including patient-derived TNBC xenograft, we show that Hh signaling-orchestrated H3K27me and H3K27ac interplay tailors combination epigenetic drugs in treating breast cancer. Together, this study reveals the new role of Hh signaling-regulated histone modifications interplay in responding to HDAC inhibitors and suggests new epigenetically-targeted therapeutic solutions for treating TNBC.

A Retrospective Study on the Efficacy and Safety of Idarubicin Combined with High-Dose Cytarabine Consolidation in Patients with Acute Myeloid Leukemia over 60 Years of Age in First Remission / 中国实验血液学杂志

OBJECTIVE@#To evaluate the efficacy and safety of idarubicin combined with high-dose cytarabine as a post-remission therapy for elderly patients with acute myeloid leukemia (AML).@*METHODS@#From November 2017 to June 2021, 24 AML patients aged ≥60 years who were in complete remission for the first time were enrolled in consolidation chemotherapy with idarubicin (10 mg/m2 intravenously once for day 1) combined with high-dose cytarabine (1.5 g/m2 intravenously over 3 hours every 12 hours for day 1-3), and the efficacy and safety were observed.@*RESULTS@#Among the 24 patients, there were 12 males and 12 females, the median age was 65 (60-78) years old, and the median follow-up time was 23.3 (2-42.7) months. By the end of the follow-up, 15 patients relapsed and 11 patients died. The median disease-free survival (DFS) was 9 months and there were 3 cases of 2-year DFS. The median overall survival (OS) was 16.2 months, and there were 4 cases of 2-year OS. In terms of safety, 6 patients had grade 1-2 non-hematological adverse reactions, 12 patients had grade 3-4 hematological adverse reactions, and a total of 6 patients developed infection after consolidation chemotherapy. Multivariate analysis showed that two induction cycles and high-risk cytogenetic abnormalities were the adverse factors of DFS and OS in elderly patients with AML in this study.@*CONCLUSION@#For AML patients ≥60 years old in first complete remission, idarubicin combined with high-dose cytarabine as post-remission therapy has a better safety, but compared with other regimens does not improve the prognosis of elderly patients, which needs further exploration.

Content determination of seven active components of Eucommiae Cortex in aortic vascular endothelial cells of spontaneously hypertensive rats by UPLC-MS/MS / 中国中药杂志

In the present study, the contents of seven active components [genipinic acid(GA), protocatechuic acid(PCA), neochlorogenic acid(NCA), chlorogenic acid(CA), cryptochlorogenic acid(CCA),(+)-pinoresinol di-O-β-D-glucopyranosid(PDG), and(+)-pinoresinol 4'-O-β-D-glucopyranoside(PG)] of Eucommiae Cortex in aortic vascular endothelial cells of spontaneously hypertensive rats(SHR) were simultaneously determined by ultra-high liquid chromatography-triple quadrupole mass spectrometry(UPLC-MS/MS). The qualified SHR models were selected. The primary aortic endothelial cells(VECs) of rats were separated and cultured by ligation and adherence, followed by subculture. After successful identification, an UPLC-MS/MS method for simultaneously determining the contents of GA, PCA, NCA, CA, CCA, PDG, PG in seven components of Eucommiae Cortex in VECs was established, including specificity, linearity, matrix effect, recovery, accuracy, precision and stability. The established method had the lo-west limit of quantification of 0.97-4.95 μg·L~(-1), accuracy of 87.26%-109.6%, extraction recovery of 89.23%-105.3%, matrix effect of 85.86%-106.2%, and stability of 86.00%-112.5%. Therefore, the established accurate UPLC-MS/MS method could rapidly and simultaneously determine the contents of the seven active components of Eucommiae Cortex in VECs of SHRs, which provided a refe-rence for the study of cellular pharmacokinetics of active components of Eucommiae Cortex extract.

Study on static parameters of internal nasal valve in 3-dimensional model of nasal cavity space / 中华耳鼻咽喉头颈外科杂志

Objective: To identify the internal nasal valve (INV) and to evaluate its key parameters in the established 3D models of nasal cavity space via Mimics from CT images, in order to provide evidence for quantitative diagnosis of nasal valve compromise. Methods: A total of 32 Han adults without nasal diseases who underwent maxillofacial CT test in Shanghai Ninth People's Hospital from January 2015 to December 2018 were retrospectively recruited, including 16 males and 16 females, with the age ranged from 20 to 80 years (50% age<50 years old). Maxillofacial CT images were used to create 3D model of nasal cavity space. The INV was identified and the following parameters were measured: the angle between the INV and the nasal bone (θINV-B), unilateral cross-sectional area of the INV (AINV-R, AINV-L), total cross-sectional area of the INV (AINV), unilateral height of the INV (HINV-R, HINV-L), unilateral nasal valve angle (αINV-R, αINV-L), and the sum of nasal valve angle (αINV). The AINV in our study was compared with the results of the previously adopted planes (PlaneC, perpendicular to the hard palate and PlaneB, plane perpendicular to the nasal bone). The parameters above were compared among genders, age and race groups. SPSS 26 and GraphPad Prism 9 software were used for statistical analysis and mapping of data. Results: The AINV in our study was (214.87±52.94) mm², which was significantly less than that of PlaneC (254.97±47.80) mm² and PlaneB (226.07±57.36) mm². The measured parameters were as follows: θINV-B was (82.07±7.06)°; AINV-R was (112.66±31.39) mm²; AINV-L was (102.21±27.14) mm²; AINV was (214.87±52.94) mm²; HINV-R was (24.87±4.62) mm; HINV-L was (24.35±4.86) mm; αINV-R was (20.48±2.99)°; αINV-L was (19.65±3.82)°; αINV was (40.13±6.24)°. The AINV-R was larger than AINV-L (t=2.33, P<0.05); The HINV, AINV-R, AINV-L and AINV of males were more than those of females (t value was 5.77, 3.21, 2.91 and 3.52, respectively, all P<0.01). The AINV of the young group (<50 years) was larger than that of the old group (t=2.83, P<0.01); The θINV-B was different between the Han people and the Caucasian (t=2.92,P<0.01). The αINV of the Han people was larger than that of Caucasians (Z=-6.92, P<0.01), but the HINV was smaller (Z=-3.89, P<0.01). Conclusion: The AINV carried out in 3D models of nasal cavity space is significantly smaller than that obtained by the previous methods of CT evaluation. INV static parameters differ among genders, age and race groups.

Clinical experience of REcanalisation and balloon-oriented puncture for Re-insertion of long- term dialysis catheter in nonpatent central veins / 中华肝脏病杂志

It is difficult to insert long-term dialysis catheters after severe stenosis or occlusion of the internal jugular vein and innominate vein. We used REcanalisation and balloon-oriented puncture for Re-insertion of dialysis catheter in nonpatent central veins (REBORN) in seven patients with severe central venous lesions, and all patients were inserted with long-term dialysis catheters successfully. None had severe complications such as pneumothorax, hemothorax, or pulmonary embolism during operation. All catheters functioned well after postoperative follow-up of 2 months. REBORN provides a novel approach to establish difficult dialysis pathways.

Genetic analysis of two Chinese pedigrees affected with Hereditary hypofibrinemia due to missense variants / 中华医学遗传学杂志

OBJECTIVE@#To retrospectively analyze the clinical phenotypes and genetic variants in two Chinese pedigrees affected with Hereditary hypofibrinemia (IFD) and explore their molecular pathogenesis.@*METHODS@#Two probands and their pedigree members were admitted to the First Affiliated Hospital of Wenzhou Medical University on March 30, 2021 and May 27, 2021, respectively. Clinical phenotypes of the probands were collected, and blood clotting indexes of the probands and their pedigree members were determined. Variants of the FGA, FGB and FGG genes were analyzed by Sanger sequencing, and candidate variants were verified by sequence comparison. Bioinformatic software was used to analyze the conservation of the amino acids and pathogenicity of the proteins. Alteration in protein structure and intermolecular force before and after the variant was analyzed by simulating the protein model.@*RESULTS@#Proband 1, a 18-year-old male, had significantly low plasma fibrinogen activity (Fg:C) and plasma fibrinogen antigen (Fg:Ag), respectively at 0.80 g/L and 1.00 g/L. Proband 2, a 43-year-old male, had slightly low Fg:C and Fg:Ag at 1.35 g/L and 1.30 g/L, respectively. The Fg:C and Fg:Ag of proband 1's father, proband 2's father and son were also below the normal level. Genetic testing showed that proband 1 had harbored a heterozygous missense variant of c.688T>G (p.Phe230Val) in exon 7 of the FGG gene, which was inherited from his father. Proband 2, his father and son all had harbored a heterozygous variant of c.2516A>C (p.Asn839Thr) in exon 6 of the FGA gene. Homology analysis showed that the Phe230 and Asn839 residues were highly conserved among homologous species. Bioinformatic analysis predicted that both p.Phe230Val and p.Asn839Thr were pathogenic variants.@*CONCLUSION@#Analysis of protein simulation model showed that the p.Asn839Thr variant has changed the hydrogen bo`nd between the amino acids, thus affecting the stability of the protein structure. The heterozygous missense variants of p.Phe230Val and p.Asn839Thr probably underlay the IFD in the two pedigrees.

Clinical application of a quantitative method of atlantoaxial reduction angle in basilar invagination / 中华外科杂志

Objectives: To investigate the clinical application effect of a quantitative method of atlantoaxial reduction angle in basilar invagination. Methods: A retrospective analysis of clinical and radiographic data was conducted of 38 patients with complicated atlantoaxial dislocation and basilar invagination admitted to the Department of Neurosurgery, First Affiliated Hospital of Chongqing Medical University from May 2020 to May 2022. There were 5 males and 33 females, aged (53.5±9.9) years (range: 38 to 80 years). All patients underwent C1-2 interarticular fusion cage implantation+occipital-cervical fixation by pressing rob with the cantilever technique. The atlantoaxial reduction model of previous studies by our team was used to calculate the reduction angles before surgery. Then titanium rods of prebending angle were prepared according to the calculation before the operation. After that quantitative reduction of angle was performed during the operation. The paired t-test was used to compare the difference between the theoretical and actual reset value. Results: The theoretical reduction angle of all patients was (10.62±1.78)° (range: 6.40° to 13.20°), the actual reduction angle was (10.53±1.63)° (range: 6.70° to 13.30°) and there was no statistical difference between them (t=1.688, P=0.100). The theoretical posterior occipitocervical angle after the operation of all patients was (117.37±5.88)° (range: 107.00° to 133.00°), the actual posterior occipitocervical angle after the operation was (118.25±6.77)° (range: 105.40° to 135.80°) and there was no statistical difference between them (t=-0.737, P=0.466). The postoperative follow-up time of the patients was more than 6 months and the symptoms of all patients were relieved. All patients had satisfactory fusion between small joints without incision infection, internal fixation fracture, displacement, atlantoaxial redislocation, and other long-term complications. Conclusion: The quantitative method of atlantoaxial reduction angle in basilar invagination can calculate the theoretical reduction angle of the clivus axis angle and guide the preparation of the pre-bending titanium rod before surgery, so as to realize the quantification of the atlantoaxial reduction angle.

Pulmonary granular cell tumors: a clinicopathological analysis of five cases / 中华病理学杂志

Objective: To investigate the clinicopathological features of pulmonary granular cell tumors (pGCTs) and to improve the diagnostic accuracy of the tumor. Methods: A total of 5 pGCTs were diagnosed from February 2016 to January 2022 at Shanghai Pulmonary Hospital, Tongji University School of Medicine and Fudan University Shanghai Cancer Center, China. Immunohistochemical staining, and analysis of the clinicopathological characteristics were performed. Results: The average age of the pGCTs patients was 46 years (ranging from 24 to 54 years), with 3 females and 2 males. One case occurred in the bronchus with multiple nodules in the lung, 2 cases occurred in the bronchial opening, and 2 cases were solitary nodules in the lung. The maximum diameter of the tumors ranged from 12 to 15 mm (mean size 14 mm). Microscopically, the tumor showed infiltrative growth and consisted of round, oval or polygonal cells. Abundant eosinophilic cytoplasm was noted, and the nucleoli were prominent. None of the 5 cases showed any mitosis or necrosis. Immunohistochemical and histochemical study showed positive staining for S-100 (5/5), SOX10 (5/5), Vimentin (5/5), TFE3 (4/5), PAS (3/5), and amylase-digested-PAS (3/5), while 4 cases were negative for CD68. TFE3 FISH analyses on 2 cases showed that no signal abnormality was detected in these 2 cases. The average proliferation index of Ki-67 was 2.2% (range 0-5%). There was no recurrence in 4 cases of pGCTs with a follow-up time ranging from 2 months to 60 months. Conclusions: pGCTs are very rare tumors, most likely originating from Schwann cells. Immunohistochemical staining is the conventional diagnostic tool for pGCTs diagnosis. Recognition of this entity is essential for pathologists to avoid misdiagnosis and unnecessary treatments.

Roles of alternative splicing in infectious diseases: from hosts, pathogens to their interactions / 中华医学杂志(英文版)

Alternative splicing (AS) is an evolutionarily conserved mechanism that removes introns and ligates exons to generate mature messenger RNAs (mRNAs), extremely improving the richness of transcriptome and proteome. Both mammal hosts and pathogens require AS to maintain their life activities, and inherent physiological heterogeneity between mammals and pathogens makes them adopt different ways to perform AS. Mammals and fungi conduct a two-step transesterification reaction by spliceosomes to splice each individual mRNA (named cis -splicing). Parasites also use spliceosomes to splice, but this splicing can occur among different mRNAs (named trans -splicing). Bacteria and viruses directly hijack the host's splicing machinery to accomplish this process. Infection-related changes are reflected in the spliceosome behaviors and the characteristics of various splicing regulators (abundance, modification, distribution, movement speed, and conformation), which further radiate to alterations in the global splicing profiles. Genes with splicing changes are enriched in immune-, growth-, or metabolism-related pathways, highlighting approaches through which hosts crosstalk with pathogens. Based on these infection-specific regulators or AS events, several targeted agents have been developed to fight against pathogens. Here, we summarized recent findings in the field of infection-related splicing, including splicing mechanisms of pathogens and hosts, splicing regulation and aberrant AS events, as well as emerging targeted drugs. We aimed to systemically decode host-pathogen interactions from a perspective of splicing. We further discussed the current strategies of drug development, detection methods, analysis algorithms, and database construction, facilitating the annotation of infection-related splicing and the integration of AS with disease phenotype.