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”.

Diagnostic values of integrated evidence chain, Roussel Uclaf Causality Assessment Method, and Structured Expert Opinion Process method for drug-induced liver injury / 临床肝胆病杂志

Objective To investigate the clinical applicability and different characteristics of three commonly used diagnostic methods for drug-induced liver injury from the two aspects of liver injury induced by Western medicine and liver injury induced by traditional Chinese medicine. Methods A prospective cohort study was performed for 289 hospitalized patients with acute drug-induced liver injury who were admitted to The Fifth Medical Center of Chinese PLA General Hospital from January 2015 to December 2020 and did not receive integrated traditional Chinese and Western medicine therapy, among whom 187 patients had herb-induced liver injury and 102 had Western medicine-induced liver injury. The 289 patients were diagnosed by the integrated evidence chain (IEC), Roussel Uclaf Causality Assessment Method (RUCAM), and the Structured Expert Opinion Process (SEOP) method, and related data at acute onset were collected, including general information, latency period, detailed medication, and laboratory markers such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transpeptidase, alkaline phosphatase, and total bilirubin. A statistical analysis was performed to investigate the consistency between IEC, RUCAM, and SEOP in the diagnosis of Western medicine-induced liver injury and herb-induced liver injury and their own applicability. The Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data; the chi-square was used for comparison of categorical data. Results The hepatocellular type was the main type of clinical liver injury in both Western medicine-induced liver injury and herb-induced liver injury, accounting for 81.4% and 74.3%, respectively, and laboratory examination showed higher levels of ALT and AST. Western medicine-induced liver injury cases were diagnosed by IEC, RUCAM, and SEOP, with a clinical diagnosis rate of 65.7%, 100%, and 63.7%, respectively, and the constituent ratio of Western medicine-induced liver injury was 23.2%, 35.3%, and 22.5%, respectively. Herb-induced liver injury cases were diagnosed by these three methods, with a clinical diagnosis rate of 47.6%, 100%, and 29.9%, respectively, and the constituent ratio of herb-induced liver injury was 30.8%, 64.7%, and 19.4%, respectively. The consistency test of the three diagnostic methods showed that in the diagnosis of Western medicine-induced liver injury cases, there was good consistency between IEC and SEOP (Kappa=0.785, P 0.05) and between RUCAM and SEOP (Kappa=0.117, P > 0.05); in the diagnosis of herb-induced liver injury cases, there was poor consistency between RUCAM and SEOP (Kappa=0.066, P > 0.05), while there was good consistency between RUCAM and IEC (Kappa=0.026, P < 0.05) and between IEC and SEOP (Kappa=0.437, P < 0.05). Conclusion The IEC method shows good applicability for both Western medicine-induced liver injury and herb-induced liver injury, and there is good consistency between IEC and SEOP in the diagnosis of Western medicine-induced liver injury cases, while there is a relatively low level of consistency between IEC and SEOP in the diagnosis of herb-induced liver injury. There is poor consistency between RUCAM and the other two methods. In the clinical diagnosis of Western medicine-induced liver injury, IEC, RUCAM, and SEOP should be used in combination to accurately judge the causal relationship between drugs and liver injury.

Research on the Development of O 2O Pharmaceutical Care Mode in China under the Internet Plus Background / 中国药房

OBJECTIVE：To provide reference for improving the level of pharmaceutical care in hospitals and promoting the continuous transformation and upgrading of O 2O pharmaceutical care mode in medical institutions in China. METHODS ：Using “Internet”“Network”“O2O”“Pharmaceutical care ”“Medication education ”“Chronic disease management ”“Medication consultation ” “Science popularization and education ”as keywords ，related literatures were collected from CNKI ，VIP，Wanfang and other Chinese databases during Jan. 2012-Mar. 2020. The development process ，characteristics，service content ，advantages and disadvantages of O 2O pharmaceutical care mode in China were analyzed and summarized ，and relevant suggestions were put forward. RESULTS & CONCLUSIONS ：O2O pharmaceutical care in Chinese hospitals covers prescription review and dispensing ， drug distribution ，medication consultation after visiting ，medication education ，chronic disease management ，science popularization and education ，pharmacy clinic ，etc.，realizing the whole process of closed-loop management. At present ，O2O pharmaceutical care in Chinese hospital had gradually moved from stage 1.0 to stage 2.0. Artificial intelligence technology has also been widely integrated into all aspects of pharmaceutical care ，assisting hospital pharmacists to better practice the “patient-centered”service concept，not only improving the quality and value of pharmacists ’pharmaceutical care more efficiently and accurately ，but also promoting the sinking of high-quality pharmaceutical resources and serving the grassroots. O2O pharmaceutical care shows the advantage of optimizing the allocation of pharmaceutical care resources ，expanding the scope of pharmaceutical care ，improving the relationship between doctors and patients ，diverting patients with different needs ，and promote hierarchical diagnosis and treatment. However，there are still some problems ，such as the failure to effectively cover rural patients ，the risk of patient privacy leakage ， and the lack of special quality management standards ，which hinder the further development and improvement of scale advantage of O2O pharmaceutical care. It is suggested to further improve the pharmaceutical care function of the platform ，expand the consumer population，promulgate relevant laws and regulations as soon as possible ，carry out continuing education and training for pharmacists according to the needs of patients in grassroots areas ，establish and improve relevant laws and regulations ，and improve O 2O pharmaceutical care quality management standards， so as to promote the development of O 2O pharmaceutical care mode in the hospital in China.

Clinical features of Caroli disease: An analysis of 41 cases / 临床肝胆病杂志

ObjectiveTo investigate the clinical features of patients with Caroli disease. MethodsThe clinical data were collected from 41 patients who were diagnosed with Caroli disease in The Fifth Medical Center of Chinese PLA General Hospital from April 2015 to January 2020, and the patients were divided into type I group with 16 patients and type Ⅱ group with 25 patients. A retrospective analysis was performed for general information, laboratory markers, and clinical features. The independent samples t-test was used for comparison of normally distributed continuous data between groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between groups; the chi-square test was used for comparison of categorical data; a Spearman correlation analysis was also performed. ResultsThe type Ⅰ group had a significantly higher level of albumin (Alb) than the type Ⅱ group (t=0.976, P=0.048), and the type Ⅱ group had a significantly higher prothrombin time (PT) than the type I group (Z=3.115, P=0.001). Compared with the type I group, the type Ⅱ group had significantly higher incidence rates of esophageal and gastric varices, upper gastrointestinal bleeding and/or tarry stool, and portal hypertension (χ2=6.077, 5.468, and 2.403, P=0.002, 0.019, and 0.028). In the patients with type Ⅱ Caroli disease, the level of cholinesterase was negatively correlated with the incidence rates of esophageal and gastric varices and portal hypertension (r=-0.468 and -0.436, P=0.018 and 0.029); Alb level was negatively correlated with the incidence rate of esophageal and gastric varices (r=-0.561, P=0.004); red blood cell count was negatively correlated with the incidence rates of esophageal and gastric varices, upper gastrointestinal bleeding and/or tarry stool, and portal hypertension (r=-0.662, -0.566, and -0.436, P＜0.001, P=0.003, and P=0.029); hemoglobin count was negatively correlated with the incidence rates of esophageal and gastric varices, upper gastrointestinal bleeding and/or tarry stool, and portal hypertension (r=-0.605, -0.590, and -0.510, P=0.001, 0.002, and 0.009); PT was positively correlated with the incidence rates of esophageal varices and portal hypertension (r=0.488 and 0.520, P=0.013 and 0.008). ConclusionCompared with the patients with type I Caroli disease, the patients with type Ⅱ Caroli disease have a higher incidence rates of esophageal and gastric varices, upper gastrointestinal bleeding and/or tarry stool, and portal hypertension, with the changes in clinical indicators such as the decrease of Alb level and the increase of PT level, and they tend to have poor prognosis.

Clinical features and changing trend of elderly patients with drug-induced liver injury in The Fifth Medical Center of Chinese PLA General Hospital from 2009 to 2019 / 临床肝胆病杂志

ObjectiveTo investigate the features and changing trend of drug-induced liver injury (DILI) in the elderly from 2009 to 2019, and to provide a reference for clinical prevention and treatment of DILI in the elderly. MethodsA retrospective analysis was performed for the clinical data of 2107 elderly patients, aged ≥60 years, who were diagnosed with DILI in The Fifth Medical Center of Chinese PLA General Hospital from January 2009 to December 2019, and they were divided into groups according to age. Related clinical data were analyzed, including age, sex, clinical features, prognosis, and regional distribution. The Chi-square test was used for comparison of categorical data between groups. ResultsAmong the 2107 patients with DILI, there were 802 male patients and 1305 female patients, with a male/female ratio of 1∶1.63. Cholestasis type was the most common clinical type and was observed in 1439 patients (68.3%). There was the highest number of patients in the 60-64 years group (942 patients, 44.7%), among whom 618(65.6%) were female, 589(62.5%) had cholestasis type, 471(50.0%) had chronic DILI, 421(44.7%) had drug-induced liver cirrhosis, and 25(2.7%) had drug-induced liver failure. There were 187 patients in the 75-79 years group, among whom 110 (58.8%) patients were male, 137(73.3%) had cholestasis type, 114(60.9%) had liver cirrhosis, 4(2.1%) had drug-induced liver failure. The results showed that chronic DILI was more common in the 60-64 years group, and liver cirrhosis was more common in the 75-79 years group. As for prognosis, in the 60-64 years group, 27 patients (2.9%) were cured, 885 (93.9%) were improved, 30(32%) had no response or died; in the 65-69 years group, 16 (2.8%) were cured, 528 (92.0%) were improved, and 30(5.2%) had no response or died; in the 70-74 years group, 9(2.8%) were cured, 305(94.1%) were improved, and 10 (3.6%) had no response or died. The results showed that there was no significant difference in mortality rate between the different age groups (P＞0.05). The proportion of elderly DILI patients among hospitalized DILI patients increased from 15.90% in 2009 to 22.05% in 2013 and 27.51% in 2019, with a 1.73-fold increase in 11 years. As for regional distribution, the patients in North China accounted for the highest proportion of 47.08% (the patients from Hebei, Shanxi, and Inner Mongolia accounted for 24.92%, 10.96%, and 10.25%, respectively), followed by those in Northeast China who accounted for 17.85%. The patients in Beijing accounted for 11.53%. ConclusionThe proportion of elderly DILI patients among hospitalized DILI patients tends to increase in these years. Cholestasis type is the most common clinical type, and most of the patients with this clinical type progress to chronic DILI and drug-induced liver cirrhosis. Early diagnosis, early intervention, and standardized treatment of elderly DILI should be taken seriously.

Detection of the risk signals of drug-induced liver injury: Challenges and advances / 临床肝胆病杂志

Early detection and effective monitoring of the risk signals of drug-induced liver injury (DILI) are of great importance in the prevention and management of DILI in clinical practice. However, the lack of high sensitivity and strong specificity in the detection of risk signals brings great challenges to the identification and monitoring of risk signals and causes difficulties in establishing the strategies for the prevention and control of DILI. This article analyzes the challenges in the identification of DILI risk signals, summarizes the applicability and limitations of risk signals based on commonly used indices in early recognition, prediction, and early warning of DILI, proposes an identification and monitoring model for DILI risk signals based on specific biomarkers, and elaborates on their potential clinical values, so as to provide a scientific basis for developing targeted strategies for the prevention and control of the risk of DILI.

T cell--associated immunoregulation and antiviral effect of oxymatrine in hydrodynamic injection HBV mouse model

Although oxymatrine (OMT) has been shown to directly inhibit the replication of hepatitis B virus (HBV), limited research has been done with this drug. In the present study, the antiviral effect of OMT was investigated in an immunocompetent mouse model of chronic HBV infection. The infection was achieved by tail vein injection of a large volume of DNA solution. OMT (2.2, 6.7 and 20 mg/kg) was administered by daily intraperitoneal injection for 6 weeks. The efficacy of OMT was evaluated by the levels of HBV DNA, hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg) and hepatitis B core antigen (HBcAg). The immunoregulatory activity of OMT was evaluated by serum ELISA and flow cytometry. Results shows that OMT at 20 mg/kg inhibited HBV replication, and it was more efficient than entecavir (ETV) in the elimination of serum HBsAg and intrahepatic HBcAg. In addition, OMT accelerated the production of interferon-(IFN-) in a dose-dependent manner in CD4T cells. Our findings demonstrate the beneficial effects of OMT on the enhancement of immunological function and in the control of HBV antigens. The findings suggest this drug to be a good antiviral therapeutic candidate for the treatment of HBV infection.

Guiding significance of Guideline for diagnosis and treatment of herb-induced liver injury in clinical diagnosis: a retrospective analysis / 临床肝胆病杂志

ObjectiveTo investigate the clinical guiding significance of Guideline for diagnosis and treatment of herb-induced liver injury in the diagnosis of herb-induced liver injury (HILI). MethodsA retrospective analysis was performed for the clinical data of 595 hospitalized patients who were admitted to 302 Hospital of PLA from January 2009 to January 2014 and diagnosed with HILI according to HILI diagnostic strategies recommended by American College of Gastroenterology. The chi-square test was used for comparison of categorical data between groups. ResultsAccording to the Guideline for diagnosis and treatment of HILI, all 595 patients (100%) were diagnosed with suspected HILI, 234 (39.3%) were diagnosed with clinical HILI, and 52(8.7%) were diagnosed with definite HILI. Among the patients with clinical and definite HILI, 85.0% and 94.2%, respectively, had a clinical type of cell injury, and 52.6% and 423%, respectively, had a severe disease. There were no significant differences in prognosis between the patients with suspected, clinical, and definite HILI, and 81.5%, 82.5%, and 80.8%, respectively, were cured. ConclusionGuideline for diagnosis and treatment of HILI can effectively guide the diagnosis of HILI, avoid misdiagnosis in clinical practice, and guarantee the safe application of Chinese herbal medicine. Its clinical guiding significance in the diagnosis of HILI awaits more prospective studies.

Analysis of the preventive and therapeutic effects of Taohe Chengqi decoction on a rat model of hepatic encephalopathy / 中国比较医学杂志

Objective To analyze the preventive and therapeutic effects of a traditional Chinese medicine Taohe Chengqi decoction on a rat models of hepatic encephalopathy ( HE) induced by thioacetamide ( TAA) .Methods The rat model of HE was established by intraperitoneal injection of TAA,and the effects of Taohe Chengqi decoction were observed by neurobehavioral changes,neurological test,blood ammonia,serum biochemical indexes,and liver and brain pathological examination.Results The rat model of hepatic encephalopathy was successfully established.Low, medium and high dose Taohe Chengqi decoction markedly improved neuro-reflexes and liver and brain pathological damages, and significantly decreased the HE staging and serum biochemical indexes, and the results of high dose group was the best, similar to that of positive drug-treatment group.Conclusions Taohe Chengqi decoction exhibits promising preventive and therapeutic effects on the rat model of TAA-induced hepatic encephalopathy, and these results provide substantial experimetal evidence for its clinical application.

Microcalorimetric investigation on the interaction of six alkaloids from rhizoma coptidis / 药学学报

How to identify active constituents of traditional Chinese medicines (TCMs) and study their interactions are key problems in the development of TCMs. The inhibitory effect of six alkaloids from Rhizoma Coptidis (RC) on Shigella dysenteriae (S. dysenteria) growth had been investigated by microcalorimetry in this study. Main active constituents of RC were confirmed by comparing their contributions to the bacteriostatic effect, and the interactions among active constituents were further researched. According to the result, in 0.8 mg-mL-1 extract of RC, the contributions of six active alkaloids including berberine, coptisine, epiberberine, palmatine and the combination of jatrorrhizine and columbamine were 52.83%, 36.31%, 2.49%, 4.27% and 3.21%, respectively. Therefore, berberine and coptisine were the main active constituents of RC that inhibited the growth of S. dysenteria. The study of interactions among the six alkaloids indicated that, 1 there were some contstituents antagonizing the inhibitory effect of RC, 2 there was a synergy effect between berberine and coptisine, 3 there were additive effects between other four alkaloids and the main active constituents. These results may provide some useful references for the establishment of the quality standard for RC and the development of multi-component TCMs.

Effects of lamivudine on growth of intestinal characteristic bacteria by microcalorimetry in vitro / 药学学报

The study is aimed to investigate the effect of lamivudine on growth and metabolism of three intestinal characteristic bacteria (namely, Bifidobacterium adolescentis, Escherichia coli and Shigella dysenteriae). The growth condition of the three bacteria was quantitatively evaluated by microcalorimetry with four characteristic parameters of the thermal power-time curves, including the growth rate constant (k), thermal power (p), time to peak (t) and calorific value (Q). The results showed that the IC50 value of lamivudine on B. adolescentis was 200 microg x mL(-1), and the IC50 values of lamivudine on S. dysenteriae and E. coli were higher than 3 000 microg x mL(-1) and 6 000 microg x mL(1), respectively. Therefore, lamivudine made different inhibitory effects on the three bacteria, in which the B. adolescentis was most susceptible to lamivudine. This work showed that taking lamivudine chronically is likely to affect the balance of good flora in the intestinal tract, and might increase endotoxin release, leading to inflammation and disease progression in hepatopathy.

Genetic variants in the promoter of cyclooxygenase 2 interacting with Hp infection and the risk of esophageal cancer / 中国综合临床

Objective To evaluate the association of COX2 genetic variants with the risk of esophageal cancer and the interaction of COX2 genetic variants with Hp infection. Methods A total of 119 patients with esophageal cancer and 238 frequency-matched controls were genotyped by polymerase chain reaction-restriction fragment length polymorphism method. Odds ratios (OR) and 95% confidence intervals ( CI) were estimated by logistic regression. Results Case-control analysis showed an increased risk of developing esophageal cancer for 1195 GA(OR =2.69,95% CI= 1. 46-5. 14) and 1195AA ( OR = 2. 30,95% CI = 1.23-4. 89) genotype carriers,respectively, compared with non 1195 GG carriers. When stratified by Hp status, the significantly increased risk of esophageal cancer was found among Hp carrier with OR (95%CI) =2.74 (1.35-5.96) ,but not among Hp non-carriers. Conclusion Genetic polymorphism in COX2 promoter region may play an important role in esophageal cancer by Hp infection.

Clinical therapeutic effect of three-dimensional conformal radiation therapy combined with chemotherapy of paclitaxel on brain metastases from breast cancer in the elderly / 中华老年医学杂志

Objective To evaluate the efficacy and adverse reaction of three-dimensional conformal radiation therapy (3D-CRT) combined with chemotherapy of paclitaxel in treatment of brain metastases from breast cancer in the elderly.Methods The 50 patients were randomly divided into observation group (n=26,radiation combined with chemotherapy) and control group (n= 24,simple radiation).In the early stage,both groups received common two-dimesional conformal radiation therapy.The total dose (DT) of whole brain irradiation was 30-40 Gy.In the later stage,the reduced field for the local lesion of brain metastases would be altered to 3D-CRT for the post period with 2 Gy 5 times a week.DT was added from 10-24 Gy up to total DT of 50-64 Gy.The patients were given paclitaxel 65-85 mg/m2 by intravenous drip at 1st and 8th day with synchronization of 2-4 weeks,having paclitaxel chemotherapy of 2-4 circle,28 days a circle.After 2 month treatment,the efficacy and adverse effects of the two groups were observed.follow up for 2 years,the long-term efficacy and survival rate were evaluated.Results The effective rate was 76.9% in observation group and 45.8% in control group,respectively (x2 =5.120,P＜0.05) and the KPS score was 80.8% and 54.2%,respectively.The quality of life was improved in observation group versus control group (x2 =4.059,P＜0.05).Compared with control group,hypoleukemia was significant in observation group (P＜0.05).The complications such as nausea and vomiting,hepatic dysfunction were more in observation group than in control group,but there was no statistical significance between two groups.There was statistic ally significant difference in 2-year survival rate between two groups (x2= 4.7260,P＜0.05).Conclusions The 3D-CRT combined with paclitaxel chemotherapy is a prefered choice for locally advanced brain metastases from breast cancer.More side effects and adverse reaction are observed in observation group.However,all the patients could tolerate them.It is worthy of popularization and application.

The effect of endothelin-1 on the phagocytic function of human trabecular meshwork cells in vitro / 眼科研究

Background Endothelin-1 (ET-1) is an active regulator of intraocular pressure.The ET-1 level in aqueous humor is elevated in primary open-angle glaucoma,normal intraocular tension glaucoma and the animal model of glaucoma.There is now accumulating evidence for a role of ET-1 in the pathogenesis of glaucoma.However,the effect of ET-1 on the phagocytic function in trabecular meshwork cells (TMCs) is unclear.ObjectiveThis study is to observe the effect of ET-1 on the phagocytic function in cultured human TMCs.Methods Human trabecular meshwork tissue was obtained from healthy donator and cultured and subcultured in vitro by the explant culture method.The third passage of human TMCs were incubated with fluoresent red-labeled latex beads for 0,4,8,12,24,48 and 72 hours.The phagocytic kinetics of human TMCs were continuously evaluated by counting the number of latex beads in TMCs using a fluorescence microscope.Depending on the concentrations of ET-1 in culture medium,the TMCs were divided into control group (without ET-1),low-dose ET-1 (10~(-9)mol/L) treatment group,middle-dose ET-1 (10~(-8)mol/L) treatment group and high-dose ET-1 (10~(-7) mol/L) treatment group.In addition,based on the addition of endothelin receptor (ETAR) antagonist,the TMCs were divided into control group (without ETAR antagonist),ET-1 (10~(-8)mol/L) treatment group,ETAR antagonist (1×10~(-7)mol/L BQ123+10~(-8)mol/L ET-1) treatment group and ETBR antagonist(1×10~(-7) mol/L BQ788+10~(-8) mol/L ET-1)treatment group.TMCs of each group were incubated with latex beads,and the numbers of latex beads in TMCs were counted under a fluorescent microscope.Results Cultured HTM cells showed positive reactions for FN,LN,NSE and negative response for FⅧRag.The phagocytic kinetics test revealed that the latex beads were detected 4 hours after incubation.The density of latex beads was gradually increased with the delay of incubation duration and peaked at 24 hours.The number of the latex beads saturated after 48 hours of incubation.However,the number of latex beads in TMCs was significantly reduced after the addition of ET-1 in a dose-dependent manner (F=28.91,P＜0.05).The number of latex beads in the ET-1 group was less than that in the control group and the ETAR receptor antagonist group (q=13.7228,q=9.4312,P＜0.05).No significant difference was found in latex beads number between the ET-1 group and the ETBR antagonist group (q=1.1600,P＞0.05).Conclusion ET-1 inhibits the phagocytic function of human TMCs and ETAR plays a partial role in the phagocytic function of human TMCs.

The immunohistochemical analysis of AGEs, SP-A in the lung of diabetic rats / 中国医师杂志

Objective To approach the changes of advanced glycosylated end products (AGEs),surfactant proteins A (SP-A) in the lung of experimental diabetic rats and their relationship. Methods 48 male SD rats were divided into diabetes mellitus (DM) group and control group, each group with 24 rats.The DM rat model was made by injecting streptozocin (60mg/kg) into caudal vein. The rats were killed and the lung was individually taken out at the end of 4, 12 and 20 weeks after the models were established. The changes of AGEs, SP-A in rats lung were observed with immunohistochemical assay and the images were analyzed( black is minimum of gray, white is maximum of gray ). Results We observed a great quantity of AGEs positive cells in the alveolar epithelial cells, bronchial mucosal epithelium, angio-endothelial cell and smooth muscle cells of the DM rats. The average gray (AG) was inferior to that of the controls(4weeks 93.92 ± 7.92 vs 104. 75 ± 8. 20; 12 weeks 76. 25 ± 6. 76 vs 93.50 ± 7.56; 20 weeks 47.63 ± 7.96 vs 142. 38 ± 19. 76; P ＜0. 05) and decreased with the DM course. In the 4 weeks DM rats, there were a few SP-A positive cells in the type Ⅱ alveolar epithelial cells, Clara cells and alveolar macrophage cells. In the 12 and 20 weeks DM rats, there were a great many CTGF and TGF-β1 positive cells. The AG was inferior to that of the controls( 12 weeks 75.63 ± 6. 70 vs 110. 50 ± 13.20;20 weeks 47.38 ± 4. 84 vs 97. 25 ± 9. 87; P ＜ 0. 01 ). Conclusion With the progress of diabetes, DM rats' pulmonary alveolar type Ⅱ cells injury appeared, that might be related with the deposition of AGEs.

The relationship between retinoic acid receptor-β expression and chemotherapy response in esophageal squamous cell carcinoma / 中华内科杂志

Objective To observe the relationship between expression of retinoic acid receptor-β (RAR-β) in esophageal squamous cell carcinoma (ESCC) and chemotherapy response. Methods Fifty-two cases advanced ESCC patients treated by DDP and 5-FU, DDP 80 mg/m2, divided into 5 days;5-FU 375 mg/m2, dl-5. Immunohistochemistry was used to exmine the expression of RAR-β in ESCC. Fifty cases normal esophageal tissue were used as controls. Results RAR-β immunoreactivity was recognizd in both cytoplasm and nucleus, RAR-β positive rate was lower in ESCC compared with normal tissue (61.5%vs 92% ,P ＜0. 05 ). The 52 cases ESCC patients were treated 228 chemotherapy cycles, the overall response rate (OR) was 71.2%. The OR in RAR-β positive patients was 84. 4% (27/32), significant higher than RAR-β negative patients 50. 0% ( 10/20 ) ( P ＜ 0. 05 ). The time-to-progression ( TTP ) for RAR-β positive patients was 5.9 months, the median survival period was 12. 1 months, 2 years survival rate was 56. 7%;whereas TTP for RAR-β negative patients was 2. 1 months, the median survival period was 5.8 months,2 years survival rate was 32. 9%. There was signifcant difference between the 2 groups ( P ＜ 0. 05 ) .Conclusion RAR-β protein expression by immunohistochemistry may be a useful indicator to predict the chemotherapy response and clinical outcome for ESCC, meanwhile it may be an avenue for target therapy.

Pathological changes of diabetic rat thyroid ultrastructure and intervention effects of insulin and aminoguanidine / 解剖学报

Objective To investigate the thyroid ultrastructural pathological changes of diabetes mellitus (DM) rats as well as the intervention effects of insulin and aminoguanidine. Methods Totally 87 rats were treated with streptozotocin to establish DM animal models and divided into DM group(n=27),insulin intervention group(n=32) and aminoguanidine intervention group(n=28),25 rats were taken as normal controls. Twelve and 20 weeks after the animal model establishment, animals were sacrificed, thyroid tissue was taken and ultrastructure was observed. Results In the thyroid of DM rats, follicular epithelial cells present as applanate shape, microvilli were depleted, rough endoplasmic reticulum dilated to irregular vesicular. None pinocytotic vacuole and casual primary or secondary lysosome were seen. Follicular cavity was dilated, colloid in the cavity had higher electronic-density. Interstitial edema, capillary base lamian was thickened at different stage. Proteo-substance deposition with granulo-shape, cloud shape or homogeneity appeared. The number of thyroid parafollicular cells increased. But endocrine granule in parafollicular cells was few. When compared with DM group, the thyroid tissue injury of insulin intervention group and aminoguanidine intervention group were lessened to different degree. Conclusion The hypofunctional thyroid follicular cells, large quantity of proteo-substance deposition in the interstitium and increased parafollicular cells of DM rats may be related with hyperglycemia toxicity. Insulin and aminoguanidine treatment have some protection effects.

Short-term therapeutic effect of neoadjuvant chemotherapy with herceptin and docetaxel in patients with localized advanced breast cancer / 中国综合临床

Objective To investigate the efficacy and adverse effect of herceptin combined with docetaxel in patients with localized advanced breast cancer. Methods 16 patients with localized advanced breast cancer were treated with herceptin (8 mg/kg in the first cycle and 6 mg/kg from 2 to 4 cycles,d1) and docetaxel (75 mg/m2 ,d2) for 4 cycles. Three weeks were taken as a cycle. Following chemotherapy, the patients underwent improved radical operation of breast cancer or radical operation of preserving breast. Results The overall response rate (oRR) was 87.5%. The complete clinical remission rate (cCR) was 56. 3%. The complete pathologic remission rate (pCR) was 25.0%. The mainly adverse effects were bone marrow depression and gastrointestinal toxicity. Conclusion The regimen of herceptin combined with docetaxel is effective and can be well-tolerated by patients with localized advanced breast cancer. It shows promising prospect in clinical application.

Polymorphism profile of nine short tandem repeat Loci in the Han chinese / 基因组蛋白质组与生物信息学报·英文版

Nine short tandem repeat (STR) markers (D3S1358, VWA, FGA, THO1, TPOX, CSFIPO, D5S818, D13S317, and D7S820) and a sex-identification marker (Amelogenin locus) were amplified with multiplex PCR and were genotyped with a four-color fluorescence method in samples from 174 unrelated Han individuals in North China. The allele frequencies, genotype frequencies, heterozygosity, probability of discrimination powers, probability of paternity exclusion and Hardy-Weinberg equilibrium expectations were determined. The results demonstrated that the genotypes at all these STR loci in Han population conform to Hardy-Weinberg equilibrium expectations. The combined discrimination power (DP) was 1.05 x 10(-10) within nine STR loci analyzed and the probability of paternity exclusion (EPP) was 0.9998. The results indicate that these nine STR loci and the Amelogenin locus are useful markers for human identification, paternity and maternity testing and sex determination in forensic sciences.

Detection of the risk signals of drug-induced liver injury: Challenges and advances / 临床肝胆病杂志

Early detection and effective monitoring of the risk signals of drug-induced liver injury (DILI) are of great importance in the prevention and management of DILI in clinical practice. However, the lack of high sensitivity and strong specificity in the detection of risk signals brings great challenges to the identification and monitoring of risk signals and causes difficulties in establishing the strategies for the prevention and control of DILI. This article analyzes the challenges in the identification of DILI risk signals, summarizes the applicability and limitations of risk signals based on commonly used indices in early recognition, prediction, and early warning of DILI, proposes an identification and monitoring model for DILI risk signals based on specific biomarkers, and elaborates on their potential clinical values, so as to provide a scientific basis for developing targeted strategies for the prevention and control of the risk of DILI.