Pathogenesis and Differentiated Treatment Strategies of Childhood Tic Disorders Based on WANG Xugao's “Thirty Methods of Treating the Liver” / 中医杂志

Based on WANG Xugao's “thirty methods of treating the liver”， it is believed that the occurrence and development of childhood tic disorders follow the dynamic progression from liver qi disease to liver fire disease and then liver wind disease. The basic pathogenesis of three stages are characterized by binding constraint of liver qi， liver fire hyperactivity， and internal stirring of liver wind. Moreover， liver-blood deficiency and stagnation， and malnutrition of liver yin as the main point in terms of the imbalance of liver qi， blood， yin， and yang should be considered， as well as the imbalance relationship of the five zang organs such as the involvement of other organs and the gradually reach of the other organs. Guided by the principles of “thirty methods of treating the liver”， the treatment of tic disorders in liver qi stage should focus on soothing the liver and rectifying qi， soothing the liver and unblocking the collaterals， using Xiaochaihu Decoction （小柴胡汤） and Sini Powder （四逆散）. The treatment of tic disorders in liver fire stage involves clearing， draining and resolving liver heat， using Longdan Xiegan Decoction （龙胆泻肝汤）， Xieqing Pill （泻青丸）， Danggui Longhui Pill （当归龙荟丸）， and Huagan Decoction （化肝煎）. The treatment of tic disorders in liver wind stage involves extinguishing wind and subduing yang， using Lingjiao Gouteng Decoction （羚角钩藤汤） and Liuwei Dihuang Pill （六味地黄丸）. Throughout the treatment process， attention should be paid to harmonizing the liver's qi， blood， yin， and yang， as well as addressing the pathology of other organs.

Efficacy of Tiaogan Huaxian Pills in Prevention and Treatment of Hepatic Fibrosis in Hepatitis B and Its Effect on Diffusion-weighted Imaging / 中国实验方剂学杂志

ObjectiveTo investigate the preventive and therapeutic effects of Tiaogan Huaxian pills combined with entecavir on hepatic fibrosis in chronic hepatitis B with liver Qi stagnation， spleen deficiency， and blood stasis syndrome and its effect on diffusion-weighted imaging （DWI）. MethodClinical data of 117 patients with liver disease who visited the Department of Hepatology at the First Affiliated Hospital of Guangxi University of Chinese Medicine from January 2021 to April 2022 were retrospectively analyzed. According to different treatment plans， they were divided into a control group （59 cases） and a treatment group （58 cases）. Both groups of patients received entecavir-based etiology treatment， and the treatment group added Tiaogan Huaxian pills on the basis of basic treatment. Both groups were treated for 24 weeks. Before and after treatment， the two groups were compared in terms of alanine aminotransferase （ALT）， advanced surgical technologies （AST）， total bilirubin （TBil）， hepatitis B virus （HBV）-DNA conversion rate， liver stiffness measurement （LSM）， four items of liver fibrosis （hyaluronidase， type Ⅲ pro-collagen， type Ⅳ collagen， and laminin）， the fibrosis index based on four factors （FIB-4）， the aspartate aminotransferase to platelet ratio index （APRI）， the apparent diffusion coefficient （ADC） value in magnetic resonance imaging （MRI）， and traditional Chinese medicine symptom scores， so as to analyze the efficacy of the two groups. ResultBefore treatment， there was no significant difference in ALT， AST， TBil， LSM， four items of liver fibrosis， FIB-4， APRI， HBV-DNA conversion rate， ADC value， and traditional Chinese medicine symptom scores between the two groups. After treatment， both groups of patients showed significant reductions in ALT， AST， TBil， LSM， hyaluronidase， type Ⅲ pro-collagen， type Ⅳ collagen， laminin， FIB-4， and APRI （P<0.05） and a significant increase in ADC value （P<0.05） and HBV-DNA conversion rate （P<0.01）. The traditional Chinese medicine symptom score of the treatment group decreased significantly （P<0.05）. Compared with the control group after treatment， the effective rate of clinical traditional Chinese medicine in the treatment group was 91.38% （53/58）， which was significantly higher than that of the control group （54.23%， 32/59） （Z=-4.325， P<0.01）. In the treatment group， ALT， AST， TBil， LSM， hyaluronidase， type Ⅲ pro-collagen， type Ⅳ collagen， laminin， FIB-4， APRI， and traditional Chinese medicine symptom scores all decreased significantly （P<0.05）， and the increase in ADC values was more significant （P<0.05）， while the difference in HBV-DNA conversion rate was not statistically significant. There were no serious adverse reactions or events in either group. ConclusionTiaogan Huaxian pills combined with entecavir have significant clinical efficacy in the treatment of hepatic fibrosis in chronic hepatitis B， which can reduce liver inflammation activity， delay hepatic fibrosis progression， and reduce traditional Chinese medicine symptom scores. It is worthy of clinical promotion and application.

cAMP-Epac1 signaling is activated in DDAVP-induced endolymphatic hydrops of guinea pigs

Abstract Objective To explore whether Cyclic Adenosine Monophosphate (cAMP)-Epac1 signaling is activated in 1-Desamino-8-D-arginine-Vasopressin-induced Endolymphatic Hydrops (DDAVP-induced EH) and to provide new insight for further in-depth study of DDAVP-induced EH. Methods Eighteen healthy, red-eyed guinea pigs (36 ears) weighing 200-350 g were randomly divided into three groups: the control group, which received intraperitoneal injection of sterile saline (same volume as that in the other two groups) for 7 consecutive days; the DDAVP-7d group, which received intraperitoneal injection of 10 mg/mL/kg DDAVP for 7 consecutive days; and the DDAVP-14d group, which received intraperitoneal injection of 10 μg/mL/kg DDAVP for 14 consecutive days. After successful modeling, all animals were sacrificed, and cochlea tissues were collected to detect the mRNA and protein expression of the exchange protein directly activated by cAMP-1 and 2 (Epac1, Epac2), and Repressor Activator Protein-1 (Rap1) by Reverse Transcription (RT)-PCR and western blotting, respectively. Results Compared to the control group, the relative mRNA expression of Epac1, Epac2, Rap1A, and Rap1B in the cochlea tissue of the DDAVP-7d group was significantly higher (p< 0.05), while no significant difference in Rap1 GTPase activating protein (Rap1gap) mRNA expression was found between the two groups. The relative mRNA expression of Epac1, Rap1A, Rap1B, and Rap1gap in the cochlea tissue of the DDAVP-14d group was significantly higher than that of the control group (p< 0.05), while no significant difference in Epac2 mRNA expression was found between the DDAVP-14d and control groups. Comparison between the DDAVP-14d and DDAVP-7d groups showed that the DDAVP-14d group had significantly lower Epac2 and Rap1A (p< 0.05) and higher Rap1gap (p < 0.05) mRNA expression in the cochlea tissue than that of the DDAVP-7d group, while no significant differences in Epac1 and Rap1B mRNA expression were found between the two groups. Western blotting showed that Epac1 protein expression in the cochlea tissue was the highest in the DDAVP-14d group, followed by that in the DDAVP-7d group, and was the lowest in the control group, showing significant differences between groups (p< 0.05); Rap1 protein expression in the cochlea tissue was the highest in the DDAVP-7d group, followed by the DDAVP-14d group, and was the lowest in the control group, showing significant differences between groups (p< 0.05); no significant differences in Epac2 protein expression in the cochlea tissue were found among the three groups. Conclusion DDAVP upregulated Epac1 protein expression in the guinea pig cochlea, leading to activation of the inner ear cAMP-Epac1 signaling pathway. This may be an important mechanism by which DDAVP regulates endolymphatic metabolism to induce EH and affect inner ear function. Oxford Centre for Evidence-Based Medicine 2011 Levels of Evidence Level 5.

Characteristics and Differences of Household Fine Particulate Matter Pollution Caused by Fuel Burning in Urban and Rural Areas in China / 中国医学科学院学报

Objective To explore the overall level,distribution characteristics,and differences in household fine particulate matter (PM2.5) pollution caused by fuel burning in urban and rural areas in China. Methods The relevant articles published from 1991 to 2021 were retrieved and included in this study.The data including the average concentration of household PM2.5 and urban and rural areas were extracted,and the stoves and fuel types were reclassified.The average concentration of PM2.5 in different areas was calculated and analyzed by nonparametric test. Results The average household PM2.5 concentration in China was (178.81±249.91) μg/m3.The mean household PM2.5 concentration was higher in rural areas than in urban areas[(206.08±279.40) μg/m3 vs. (110.63±131.16) μg/m3;Z=-5.45,P<0.001] and higher in northern areas than in southern areas[(224.27±301.66) μg/m3 vs.(130.11±140.61) μg/m3;Z=-2.38,P=0.017].The north-south difference in household PM2.5 concentration was more significant in rural areas than in urban areas[(324.19±367.94) μg/m3 vs.(141.20±151.05) μg/m3,χ2=-5.06,P<0.001].The PM2.5 pollution level showed differences between urban and rural households using different fuel types (χ2=92.85,P<0.001),stove types (χ2=74.42,P<0.001),and whether they were heating (Z=-4.43,P<0.001).Specifically,rural households mainly used solid fuels (manure,charcoal,coal) and traditional or improved stoves,while urban households mainly used clean fuels (gas) and clean stoves.The PM2.5 concentrations in heated households were higher than those in non-heated households in both rural and urban areas (Z=-4.43,P<0.001). Conclusions The household PM2.5 pollution caused by fuel combustion in China remains a high level.The PM2.5 concentration shows a significant difference between urban and rural households,and the PM2.5 pollution is more serious in rural households.The difference in the household PM2.5 concentration between urban and rural areas is more significant in northern China.PM2.5 pollution in the households using solid fuel,traditional stoves,and heating is serious,and thus targeted measures should be taken to control PM2.5 pollution in these households.

Microfluidic Chip and Flow Cytometry for Examination of the Antiplatelet Effect of Ticagrelor / 中国医学科学院学报

Objective To examine the antiplatelet effect of ticagrelor by microfluidic chip and flow cytometry under shear stress in vitro. Methods Microfluidic chip was used to examine the effect of ticagrelor on platelet aggregation at the shear rates of 300/s and 1500/s.We adopted the surface coverage of platelet aggregation to calculate the half inhibition rate of ticagrelor.The inhibitory effect of ticagrelor on ADP-induced platelet aggregation was verified by optical turbidimetry.Microfluidic chip was used to construct an in vitro vascular stenosis model,with which the platelet reactivity under high shear rate was determined.Furthermore,the effect of ticagrelor on the expression of fibrinogen receptor (PAC-1) and P-selectin (CD62P) on platelet membrane activated by high shear rate was analyzed by flow cytometry. Results At the shear rates of 300/s and 1500/s,ticagrelor inhibited platelet aggregation in a concentration-dependent manner,and the inhibition at 300/s was stronger than that at 1500/s (both P<0.001).Ticagrelor at a concentration ≥4 μmol/L almost completely inhibited platelet aggregation.The inhibition of ADP-induced platelet aggregation by ticagrelor was similar to the results under flow conditions and also in a concentration-dependent manner.Ticagrelor inhibited the expression of PAC-1 and CD62P. Conclusion We employed microfluidic chip to analyze platelet aggregation and flow cytometry to detect platelet activation,which can reveal the responses of different patients to ticagrelor.

Identification and 3D architecture analysis of the LIPC gene mutation in a pedigree with familial hypercholesterolemia-like phenotype / 中华心血管病杂志

Objective: To identify and analyze 3D architecture of the mutational sites of susceptible genes in a pedigree with familial hypercholesterolemia-like phenotype (FHLP). Methods: This is a case series study. A pedigree with suspected familial hypercholesterolemia was surveyed. The proband admitted in Beijing Anzhen Hospital in April 2019. Whole-exome sequencing was performed to determine the mutational sites of susceptible genes in the proband. Polymerase chain reaction (PCR) sequencing was used to verify the pathogenic variant on proband's relatives. The structural and functional changes of the proteins were analyzed and predicted by Discovery Studio 4.0 and PyMol 2.0. Results: The patients in the pedigree showed abnormal lipid profiles, especially elevated levels of total cholesterol(TC). The genetic screening detected the c.1330C>T SNP in the exon 8 of lipase C (LIPC) gene, this mutation leads to an amino acid substitution from arginine to cysteine at position 444 (Arg444Cys), in the proband and proband's father and brother. In this family, members with this mutation exhibited elevated TC, whereas lipid profile was normal from the proband's mother without this mutation. This finding indicated that LIPC: c.1330C>T mutation might be the mutational sites of susceptible genes. The analysis showed that Arg444Cys predominantly affected the ligand-binding property of the protein, but had a limited impact on catalytic function. Conclusion: LIPC: c.1330C>T is a new mutational site of susceptible genes in this FHLP pedigree.

Clinical and gene mutation characteristics of patients with hereditary ellipsocytosis: nine cases report and literature review / 中华血液学杂志

Objective: To report gene mutations in nine patients with hereditary elliptocytosis (HE) and analyze the characteristics of pathogenic gene mutations in HE. Methods: The clinical and gene mutations of nine patients clinically diagnosed with HE at Institute of Hematology & Blood Diseases Hospital from June 2018 to February 2022 were reported and verified by next-generation sequencing to analyze the relationship between gene mutations and clinical phenotypes. Results: Erythrocyte membrane protein gene mutations were detected among nine patients with HE, including six with SPTA1 mutation, one with SPTB mutation, one with EPB41 mutation, and one with chromosome 20 copy deletion. A total of 11 gene mutation sites were involved, including 6 known mutations and 5 novel mutations. The five novel mutations included SPTA1: c.1247A>C (p. K416T) in exon 9, c.1891delG (p. A631fs*17) in exon 15, E6-E12 Del; SPTB: c.154C>T (p. R52W) ; and EPB41: c.1636A>G (p. I546V) . Three of the six patients with the SPTA1 mutation were SPTA1 exon 9 mutation. Conclusion: SPTA1 is the most common mutant gene in patients with HE.

Traditional Chinese Medicine Treats Chronic Atrophic Gastritis via Multiple Pathways / 中国实验方剂学杂志

ObjectiveTo mine the compatibility rules of patented traditional Chinese medicine (TCM) compound prescriptions for treating chronic atrophic gastritis (CAG) by systems pharmacology and molecular docking methods, and predict the targets and molecular mechanisms of Chinese medicinals with different efficacy in the treatment of CAG. MethodThe TCM compound prescriptions for treating CAG were extracted from the patent system of the China National Intellectual Property Administration. The active components and targets of the prescriptions were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), Traditional Chinese Medicine Integrative Database (TCMID), and UniProt. The candidate targets and pathways of CAG were obtained from GeneCards, DisGeNet, Online Mendelian Inheritance in Man (OMIM), MalaCards, Kyoto Encyclopedia of Genes and Genomes (KEGG) and Reactome. The gene ontology (GO) functional annotation and KEGG pathway enrichment were realized by R Studio 4.1.2. STRING11.0 was employed to build the protein-protein interaction (PPI) network, and AutoDock Vina 4.2.6 was used for the docking between key targets and components. ResultA total of 228 TCM compound prescriptions for treating CAG were extracted. The medicinals used in these prescriptions mainly had warm or cold nature, bitter or sweet taste, tropism to the spleen, stomach, and liver meridians, and the efficacy of tonifying Qi, regulating Qi movement, clearing heat, and activating and toniying blood. The prescriptions mainly treated CAG via p53, mitogen-activated protein kinase (MAPK), phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt), forkhead box protein O (FoxO), vascular endothelial growth factor (VEGF), and hypoxia-inducible factor-1 (HIF-1) signaling pathways. Molecular docking results confirmed that the active components in the prescriptions had docking activities with key receptor proteins. ConclusionThis study preliminarily analyzed the compatibility rules of TCM compound prescriptions in the treatment of CAG. The medicinals with different efficacy treat CAG by regulating cell proliferation, apoptosis, and oxidative stress response, preventing carcinogen production, promoting gastric acid secretion, and improving local microcirculation in a multi-target, multi-pathway, multi-link manner. The findings facilitate the research on the TCM treatment of CAG.

Value of dual-layer spectral detector CT in evaluating the intramedullary invasion of limb osteosarcoma / 中华放射学杂志

Objective:To explore the optimal keV value of the virtual monoenergetic image (VMI) for displaying the osteosarcoma by using the dual-layer spectral detector CT and to evaluate its application value in determining the extent of intramedullary invasion of osteosarcoma.Methods:From August 2021 to August 2022, 57 patients with conventional osteosarcoma of long bone confirmed by biopsy in Beijing Jishuitan Hospital, Capital Medical University were retrospectively analyzed. All patients completed dual-layer spectral CT enhanced examination before limb salvage surgery, and tumor segment resection specimens were obtained after surgery. Conventional 120 kVp image and VMI of 40, 50, 60, 70 and 80 keV were obtained by spectral CT examination, and the CT values of tumors, image noise were measured and the signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) of the corresponding images were calculated. The objective evaluation among the six groups of images were assessed with the Friedman test, and then determined the optimal keV value. The maximum distance between the intramedullary boundary of osteosarcoma and the adjacent articular surfaces was measured on the best keV VMI and the tumor segment resection specimens. The Wilcoxon signed rank test was used to find the differences and the Spearman correlation analysis was used to evaluate the correlation between the distance measured from the best keV VMI and the specimens.Results:There were significant differences in CT value, image noise, SNR and CNR between 40-80 keV VMI and 120 kVp conventional CT images ( P<0.05). The CT value, SNR and CNR of 40 and 50 keV VMI were better than 120 kVp ( P<0.001). The 50 keV VMI was chosen as the best keV VMI to measure the intramedullary extent of osteosarcoma. The distance measured from 50 keV VMI was 103.9 (80.4, 131.4) mm, while the distance measured from specimens was 113.5 (94.0, 142.0) mm, and the difference was statistically significant ( Z=-5.76, P<0.001). The 50 keV VMI measurements in 51 patients were smaller than the gross specimens, which underestimated the tumor intramedullary extent, with the difference was 11.1 (6.6, 13.8) mm. The Spearman correlation analysis demonstrated a high positive correlation of distance measured on gross specimens with the 50 keV VMI ( r s=0.960, P<0.001). Conclusions:Dual-layer spectral detector CT with 50 keV VMI is the best image to show the limb osteosarcoma. Compared with gross specimens, the distance measured from CT underestimated the intramedullary invasion range of limb osteosarcoma about 10 mm, but the two show a good correlation.

Research progress in extracorporeal shock wave therapy for rotator cuff injury / 中华创伤杂志

Rotator cuff injury often leads to shoulder pain and dysfunction. For the injured rotator cuff tendon without continuous interruption, conservative treatment is often used. However, the shoulder is used frequent in daily life, which makes that the rotator cuff injury generally shows gradual aggravation and eventually progresses to complete tear due to poor blood supply of the rotator cuff tendon tissue and weak repair ability. In order to reverse the pathophysiological changes after rotator cuff injury and promote the repair of injured rotator cuff tendon, a series of conservative treatments for rotator cuff injury have been explored. Extracorporeal shock wave therapy (ESWT) is one of the representative treatments, but its molecular biological mechanism in promoting rotator cuff repair is still unclear. Therefore, the authors review the progress of ESWT for rotator cuff injury from aspects of the molecular biological mechanism and clinical application status, so as to provide a reference for future researches and clinical application of ESWT.

Construction of core competence evaluation index system for in-service nurses in the imaging department / 中华医学教育探索杂志

Objective:To construct an evaluation index system for core competence of nurses in the imaging department.Methods:The literature research and the opinions of the research team were integrated to develop indicators for core competence of imaging nurses at all levels. Delphi method was used to conduct 2 rounds of consultation with 20 experts, and analytic hierarchy process (AHP) was used to determine the index weights at all levels. The indicators were converted into a self-assessment scale, and 31 imaging in-service nurses in a third-level hospital were selected for questionnaire survey. SPSS 21.0 software was used to analyze the consultation results.Results:Through 2 rounds of consultation, the evaluation index system for core competence of nurses in the imaging department was formed, including 5 first-level indicators, 18 second-level indicators, and 78 third-level indicators. The effective response rates of the two rounds of expert consultation were 100%, and the authority coefficients were 0.933 and 0.923. In the second round, the expert opinion coordination coefficients of the first, second and third grade indexes were 0.46, 0.53 and 0.47, respectively ( P < 0.01). The core competence scores of the 31 respondents ranged from 3.08 to 4.45 in each dimension. Conclusion:After 2 rounds of expert consultation, the expert opinions tended to be consistent and the degree of coordination was high. The constructed indicators can be used for the core competence training and teaching evaluation of in-service nurses in the imaging department.

Effect and reflection of WeChat official account teaching cases on the standardized residency training of nuclear medicine residents / 中华医学教育探索杂志

In order to help the standardized residency training of nuclear medicine residents, the standardized residency training base of nuclear medicine residents in Peking University People's Hospital, combined with forty-five nuclear medicine departments of teaching hospital, established the WeChat official account of "Standardized Residency Training of Nuclear Medicine" and submitted one teaching case per week. The appearance of the WeChat official account of "Standardized Residency Training of Nuclear Medicine" has made up for the shortcomings of insufficient teaching cases in a single training base, strengthened the training of residents' imaging diagnostic thinking, and promoted mutual learning among the bases. By writing teaching cases, instructors and residents have opened up ideas, increased knowledge, improved self-learning ability, and cultivated imaging diagnostic thinking. With the flexible and practical features of the WeChat official account, the consciousness and sustainability of residents' learning have been enhanced.

Evolutionary Law of Syndrome and Syndrome Elements during the Malignant Transformation of Chronic Hepatitis B / 中医杂志

ObjectiveTo clarify the evolutionary laws of syndromes and syndrome elements at different stages during the malignant transformation of chronic hepatitis B （CHB）. MethodsA total of 671 patients with hepatitis B virus infection， who were admitted to the outpatient and inpatient departments of Dongzhimen Hospital of Beijing University of Chinese Medicine and The Fifth Medical Center of Chinese PLA General Hospital from July 1st， 2020 to June 30th， 2021， were included， involving 120 cases of CHB， 340 cases of hepatitis B liver cirrhosis （HBLC）， 64 cases of precancerous lesions with hepatitis B liver cirrhosis （PLHC）， and 147 cases of hepatitis B liver cirrhosis with hepatocellular carcinoma （HCC）. A Survey form of traditional Chinese medicine syndrome during malignant transformation of chronic hepatitis B was designed， and the general information， auxiliary examination and the four examinations results were collected. Factor analysis and K-means clustering were used to determine and statistically analyze the syndrome and syndrome elements. ResultsFive traditional Chinese medicine （TCM） syndrome types were identified in CHB patients， while there were six TCM syndrome types in HBLC， PLHC and HCC stages. Among CHB patients， the main syndromes were liver constraint and spleen deficiency （53.33%） and liver-gallbladder damp-heat （21.67%）， and the dominant syndrome elements were qi stagnation （27.60%）， heat （17.71%） and qi deficiency （17.71%）. In the HBLC stage， the syndromes were mainly blood stasis obstructing the collaterals （23.83%） and liver constraint and spleen deficiency （22.35%）， with dominant syndrome elements being blood stasis （19.25%）， dampness （17.46%）， and qi deficiency （15.01%）. For the PLHC stage， the primary syndrome types were blood stasis obstructing the collaterals （29.68%） and liver-kidney yin deficiency （20.31%）， and the leading syndrome elements were blood stasis （22.12%）， yin deficiency （15.93%）， and qi deficiency （15.04%）. In the HCC stage， the syndrome was dominated by blood stasis obstructing the collaterals （33.34%） and liver-kidney yin deficiency （19.73%）， with the main syndrome elements being blood stasis （24.52%）， yin deficiency （16.09%）， and qi deficiency （15.33%）. During the progression of CHB to malignancy， there was a gradual decrease in excess syndromes including liver-gallbladder damp-heat and water-dampness internal obstruction from 21.67% to 19.04%. In contrast， deficiency syndromes including liver-kidney yin deficiency and spleen-kidney yang deficiency increased from 15.83% to 31.97%. Additionally， excess syndrome elements including qi stagnation， heat and dampness decreased from 59.89% to 34.48%， while deficiency syndrome elements including qi deficiency， yin deficiency and yang deficiency increased from 32.30% to 41.00%. ConclusionDuring the malignant transformation of CHB， there exists a progression of syndrome and syndrome elements， shifting from qi stagnation， heat and qi deficiency to blood stasis （predominantly excess）， dampness and qi deficiency， and then to blood stasis （predominantly deficiency）， yin deficiency and qi deficiency， characterized by “deficiency-excess complex， and shift from excess to deficiency”.

Novel strategy in Dengzhan Shengmai capsule metabolites analysis based on the prediction database / 药学学报

Dengzhan Shengmai capsule, as a compound Chinese patent medicine, consists of four herbs: Herba Erigerontis, Ginseng, Ophiopogon, and Schisandrae Chinensis Fructus, and contains significant components of flavonoids, lignans, saponins, and organic acids. It is widely used clinically to treat cerebrovascular diseases such as chronic cerebral hypoperfusion and dementia with remarkable efficacy. This study proposes a research strategy for multi-component traditional Chinese medicine metabolites based on prediction databases and unfolds the analysis using Dengzhan Shengmai capsule as an example. Using the UPLC-Q-TOF/MS method, the analytical method was established and detected biological samples such as urine, feces, and bile of rats before and after administration based on the prediction of theoretical metabolites of Dengzhan Shengmai capsule. The possible secondary fragment ion information of metabolites was identified by comparing the detected results with prediction databases. The metabolites were identified based on the archetypal component mass spectrometric cleavage law and multistage mass spectrometric data. 51 metabolites, mainly flavonoid, organic acid, and lignan constituents, were finally identified from rat biosamples based on 306 theoretical metabolites of Dengzhan Shengmai capsule. This study provides a new strategy for the identification of metabolites in vivo and the analysis of metabolic pathways of TCM. The study complied with the procedures established by the Animal Experiment Ethics Committee of the Institute of Materia Medica, Chinese Academy of Medical Sciences and passed the animal experiment ethics examine (No. 00003645).

Protective mechanism of Yinchenzhufu decoction against cholestatic liver injury induced by lithic acid based on network pharmacology / 药学学报

Yinchenzhufu decoction (YCZFD) is a classic formula for treating Yin Huang syndrome, which can improve liver injury caused by cholestasis. However, the mechanism of action of YCZFD still remains unclear. This article used network pharmacology, molecular docking, animal experiments, and molecular biology methods to explore the mechanism of YCZFD in treating liver injury caused by cholestasis. A mouse model of acute cholestasis induced by lithocholic acid was used to investigate the effects of YCZFD on liver injury. The experimental procedures described in this paper were reviewed and approved by the Ethical Committee at the Shanghai University of Traditional Chinese Medicine (approval NO. PZSHUTCM190823002). The results showed that YCZFD could reduce the levels of blood biochemical indicators and improve hepatocyte damage of cholestatic mice. Then, multiple databases were used to predict the corresponding targets of YCZFD active components on cholestatic liver injury. An intersection target protein-protein interaction (PPI) networks based on String database and Cytoscape software was used to demonstrate the possible core targets of YCZFD against cholestatic liver injury. The results indicated that core targets of YCZFD include tumor necrosis factor, interleukin-1β, non-receptor tyrosine kinase Src, interleukin-6, etc. GO (gene ontology) and KEGG (kyoto encyclopedia of genes and genomes) enrichment analysis indicated that YCZFD may regulate the tumor necrosis factor signaling pathway, nuclear factor-κB signaling pathway, bile secretion, and other related factors to ameliorate the cholestatic liver injury. AutoDockTools software was used to perform molecular docking verification on the core targets and components of YCZFD. To verify the results of network pharmacology, UPLC-MS/MS method was used to determine the effect of YCZFD on levels of bile acid profiles in mouse liver tissues. It was found that treatment with YCZFD significantly reduced the content of free bile acids, taurine bound bile acids, and total bile acids in the liver tissues of cholestatic mice. Then, results from real time PCR and Western blot also found that YCZFD can upregulate the expression of hepatic nuclear receptor farnesoid X receptor, metabolizing enzyme (UDP glucuronidase transferase 1a1), and efflux transporters (bile salt export pump, multidrug resistance-associated protein 2, multidrug resistance-associated protein 3, etc) in cholestasis mice, promote bile acid metabolism and excretion, and improve bile acid homeostasis. Moreover, YCZFD can also inhibit pyroptosis and inflammation by regulating NOD-like receptors 3 pathway, thereby inhibiting cholestatic liver injury.

Preparation of 3D printed metoprolol tartrate chewable tablets and optimization of printing process / 药学学报

With the growing demand of personalized medicine for children, it is especially important to develop medicines for children. In this study, using metoprolol tartrate as model drug, we developed 3D printed chewable tablets suitable for children with automated dosage distribution using semi-solid extruded (SSE) 3D printing technology. Based on the quality by design concept, this study prepared a semi-solid material with good printability using gelatin as the substrate, constructed 3D models and printed tablets with the aid of computer-aided design. The printing parameters were optimized and determined as follows: print temperature of 35-37 ℃, print speed of 25 mm·s-1, fill rate of 15%, and number of outer profile layers of 2. Subsequently, the printing process and the quality uniformity of the tablets were verified, and a linear relationship between the dose and the number of model layers was obtained. Finally, 3D printed chewable tablets were superior in terms of appearance, dose accuracy and compliance compared with traditional split-dose commercially available tablets. In this study, 3D printed metoprolol tartrate chewable tablets with good performance were successfully prepared to address the personalized medication needs of pediatric patients.

Left Ventricle Longitudinal Strain Parameters Are Effective for Differentiating Cardiac Amyloidosis from Primary Hypertensive Left Ventricular Hypertrophy / 中山大学学报(医学科学版)

ObjectiveTo clarify the value of the left ventricular longitudinal strain（LVLS）parameters in patients with cardiac amyloidosis （CA） and primary hypertension with left ventricular hypertrophy （HLVH）. MethodsForty-one patients confirmed with CA were selected and assigned to CA with hypertension group （n =14） and pure CA group （n=27） based on the initial diagnosis with or without hypertension. Twenty patients with primary hypertension-induced left ventricular hypertrophy （HLVH group） and twenty healthy controls were also selected， matching for gender， age， and body surface area. Clinical data， conventional echocardiography parameters were collected and LVLS parameters were measured. Within-group variations were compared among the four groups， and pairwise comparisons were conducted between groups. The sensitivity and specificity of each parameter in predicting CA were judged by the receiver operator characteristic （ROC） curvy in CA and HLVH patients with left ventricular ejection fraction （LVEF） preserved. ResultsAmong the conventional echocardiography parameters， LVEF and left ventricular end-diastolic diameter （LVEDD） were lower in the CA with hypertension group and pure CA group compared with the higher values in the HLVH group and control group. Whereas， left ventricular posterior wall thickness （LVPWT）， relative wall thickness （RWT）， and average E/e' were higher in the two CA groups compared with the HLVH group （all P＜0.05）.Among the LVLS parameters， Global longitudinal strain （GLS） was the worst in the CA with hypertension group so as pure CA group， modest in the HLVH group， and highest in the control group. On the contrary， relative longitudinal strain and ejection fraction strain ratio （EFSR） were the highest in the CA with hypertension group so as to pure CA group， modest in the HLVH group， and lowest in the control group （all P＜0.05）. ROC analysis showed that when LVEF was preserved， the absolute value of GLS less than 14.35% and EFSR higher than 4.28 could effectively distinguish CA from HLVH （all AUCs＞0.9，all P＜0.05）； meanwhile GLS showed high sensitivity（100%） and EFSR showed great specificity（95%）. There were not statistically significance in any parameter between CA with hypertension group and pure CA group（all P＞0.05）. ConclusionWhether CA was complicated with hypertension or not， there were statistically significance among routine echocardiography and LVLS parameters compared with HLVH. In particular， GLS and EFSR are accurate in predicting CA in patients with myocardial hypertrophy and preserved LVEF.

The first imported case of visceral leishmaniasis in Shenzhen City / 中国血吸虫病防治杂志

A patient with fever, chills, and pancytopenia as major clinical manifestations was presented. To investigate the cause, the patient’s peripheral blood was collected for pathogen screening using metagenomic next - generation sequencing (mNGS). The DNA sequence of Leishmania donovani was detected, and Leishmania amastigotes were found in bone marrow smears using microscopy. The case was therefore definitively diagnosed as visceral leishmaniasis, and was cured and discharged from hospital following treatment with liposomal amphotericin B for 14 days. This is the first imported case of visceral leishmaniasis since the founding of Shenzhen City in 1979.

Establishment of a new strategy to correct the interference of chyle blood on the detection of hemoglobin and mean red blood cell hemoglobin concentration / 中华检验医学杂志

Objective:To establish a new strategy for rapid correction of the interference of chyle blood on hemoglobin (HGB) and related indexes by reticulocyte (RET) channel research parameters (HGB-O, MCHC-O) from automatic hematological analyzer.Methods:With the diagnostic experimental design, a total of 90 impatient samples were sequential picked from Fuwai Hospital, which had routine blood testing from June 1 to July 31, 2021. The selected samples were free of hemolysis, jaundice, chylo. The age of the patients was (49.2±5.7) years, with 47 males and 43 females. Three different contents(25, 50, 75 μl) of fat emulsion injection were used to replace plasma in equal amounts to prepare chyle blood samples with mild, medium and heavy degrees of average red blood cell hemoglobin concentration (MCHC). The research parameters (HGB-O, MCHC-O) obtained by the RET channel detection of the automatic blood analyzer were used as the corrected HGB and its related index values (RET method), and the original values (the detection values before adding fat emulsion) and the formula correction values were paired with t-test or Wilcoxon signed rank test, single factor analysis of variance or Kruskal-Wallis rank-sum test, Bland-Altman and correlation analysis to evaluate the correction effect of RET method.Results:There was no significant difference ( H=0.035, P=0.983; H=0.097, P=0.953; H=0.112, P=0.945) between the RET correction values of HGB (g/L) [104.0(83.8, 132.8), 109.0(87.78, 128.25), 104.0(87.8, 131.8)] and the original values [104.0(83.0, 133.0), 107.5(86.75, 129.25), 103.5(85.8, 131.3)] and the formula correction values [104.0(84.0, 133.8), 106.0(86.75, 131.25), 102.5(86.8, 131.3)] in the samples of chythemia with varying degrees of MCHC (g/L) elevation; meanwhile, the RET correction values [366.5(325.8, 341.5), 333.5(323.8, 340.0), 333.5(327.0, 341.25)] and the original values [336.0(324.8, 342.0), 333.0(323.5, 342.3), 332.0(326.75, 340.5)] and the formula correction values [333.5(323.5, 343.3), 331.0(321.0, 338.3), 329.5(325.25, 337.25)] were also not statistically significant ( H=0.049, P=0.976; H=3.149, P=0.207; H=0.883, P=0.643). The detection values of HGB and related indexes corrected by RET method were in good agreement with the original values [96.7% (29/30) of the points were within the 95% consistency limit], and the two were positively correlated (the correlation coefficients were all higher than 0.919, P<0.01). Conclusion:The RET method based on the research parameters of RET channel of automatic hematological analyzer can serve as a new strategy to correct the interference of chyle blood on the detection of HGB and related indexes.

Mid-term follow-up of reconstruction with liquid nitrogen-inactivated autologous bone graft in patients with diaphyseal malignant tumours / 中华骨科杂志

Objective:To explore the mid-term efficacy of liquid nitrogen-inactivated autologous tumor segment bone replantation for repairing bone defects after resection of malignant tumors in the long bone shaft.Methods:A retrospective analysis was performed on the clinical data of 16 patients treated with liquid nitrogen-inactivated autologous bone graft at Beijing Jishuitan Hospital from July 2015 to June 2017 to repair defects caused by malignant tumour resection of the diaphysis. There were 10 males and 6 females with a mean age of 23.4±11.6 years (range, 8-44 years), including 8 classic osteosarcoma, 2 high-grade surface osteosarcoma, 4 Ewing's sarcoma, 1 periosteal osteosarcoma, and 1 undifferentiated pleomorphic sarcoma. Tumors were located in the humerus in 2 cases, in the femur in 8 cases and in the tibia in 6 cases. The mean length of tumor was 12.4±4.8 cm (range, 5.5-26 cm). Postoperative imaging examination was performed every 6 months, and the healing status of the transplanted bone-host bone was evaluated based on the imaging assessment method of the International Society of Limb Salvage (ISOLS) imaging assessment after allogeneic bone transplantation, and the complications were assessed using the Henderson classification. The five-year survival rate for patients and grafted bone was calculated using the Kaplan-Meier survival curve.Results:The median follow-up was 64 (60.3, 69.8) months. At the end of follow-up, 13 patients were tumour free and 3 patients died of multiple metastases at 19, 20 and 33 months after surgery. There were 32 osteotomy ends in 16 patients, of which 30 healed, including 11 metaphyseal osteotomy ends, and the healing time was 9 (6, 12) months after replantation of the tumour segment with liquid nitrogen-inactivated autologous bone; 19 osteotomy ends in the diaphysis took 13 (9, 21) months to heal, with a statistically significant difference in healing time between different sites ( Z=-2.25, P=0.025). Sixteen patients had six complications, including two cases of non-union at the diaphyseal site, one case of failure of internal fixation due to non-union, three cases of recurrence, and no soft tissue complications or infections. One patient with failed internal fixation was treated with a vascularized tip iliac bone graft that healed 6 months after surgery. Another patient died of multiple metastases with 1 unhealed diaphysis left. Three cases of recurrence were all located in the extracranial soft tissue of the autologous tumor segment inactivated by liquid nitrogen. Among them, one case underwent reoperation and local radiotherapy, and there was still no tumor survival after 65 months of surgery, and two cases died due to multiple metastases. The five-year survival rate of patients was 81% as calculated using the Kaplan-Meier survival curve, and the graft survival rate was 100%. There was no amputation and the limb salvage rate was 100%. Conclusion:The use of liquid nitrogen-inactivated autologous tumor segment bone replantation for reconstruction of bone defects after resection of malignant tumors in the shaft has advantages of higher healing rate, shorter healing time at the metaphyseal end compared to the osteotomy end, fewer complications, and higher survival rate of the replanted bone.