Clinical analysis of immunotherapy rechallenge in advanced gastric cancer / 中华肿瘤杂志

Objective: To evaluate the efficacy and influencing factors of programmed death protein 1 (PD-1) monoclonal antibody rechallenge therapy in advanced gastric cancer (GC). Methods: The clinical data of patients with advanced GC who were treated with anti-PD-1 rechallenge in Henan Cancer Hospital from January 2020 to December 2021 were collected retrospectively. The progression-free survival (PFS) was defined as the time from the first or second used of anti-PD-1 treatment to the date of disease progression or the last follow-up, named PFS(1) and PFS(2), respectively. Kaplan-Meier method and Log rank test were used for survival analysis, Cox proportional hazard model was used to analyze the influencing factors. Results: A total of 60 patients with anti-PD-1 rechallenge therapy were collected, the median follow-up time was 12.2 months. The median progression-free survival (PFS(2)) of anti-PD-1 rechallenge therapy was 2.9 months, the objective response rate (ORR) was 16.7%, and the disease control rate (DCR) was 55.0%. The median PFS(2) of the first and second anti-PD-1 identical and different rechallenge treatment was 3.5 months and 1.9 months (P=0.007) respectively. The median PFS(2) of positive PD-L1 expression in rechallenge therapy was 3.4 months, ORR was 22.7%, and DCR was 63.6%; the median PFS(2) was 4.5 months, ORR was 27.3%, and DCR was 54.5% in patients with median PFS(1)≥6 months. Multivariate analysis showed that peritoneal metastasis was independently associated with anti-PD-1 rechallenge therapy with PFS(2) (HR=2.327, 95% CI, 1.066-5.082, P=0.034). The incidence of adverse reactions in grade 1-2 and grade 3-4 of anti-PD-1 rechallenge therapy was 83.3%, and 35.0%, respectively, and the safety was controllable. Conclusion: Rechallenge therapy with anti-PD-1 is a feasible treatment in advanced GC, but the screening of suitable population for rechallenge therapy still needs prospective data analysis and verification.

Effect and Mechanism of Yishen Tongluo Prescription on miR-514a-5p/TNFSF15 Signaling Pathway in MN Rats / 中国实验方剂学杂志

ObjectiveTo explore the molecular mechanism of Yishen Tongluo prescription in inhibiting the apoptosis of glomerular podocytes in rats with membranous nephropathy （MN） based on the miR-514a-5p/tumor necrosis factor superfamily member 15 （TNFSF15） signaling pathway. MethodEighty SD rats were pre-immunized and injected with cationized bovine serum albumin （C-BSA） into the tail vein for inducing MN， and the successfully modeled MN rats were randomly divided into the model group， high-， middle-， and low-dose （26.44， 13.22， 6.61 g·kg-1） Yishen Tongluo prescription groups， and benazepril （10 mg·kg-1） group， with 10 rats in each group， and another 20 healthy rats were classified into the normal group. Rats in each group were gavaged with the corresponding drugs， once a day， for four successive weeks. After the administration， the 24-hour urine total protein （UTP） level， serum total cholesterol （TC）， triglyceride （TG）， albumin （ALB）， creatinine （SCr）， and urea nitrogen （BUN） levels were measured. The miR-514a-5p and TNFSF15 mRNA expression levels in the rat kidney tissue were detected by real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）， and the expression levels of podocyte marker proteins Nephrin， Podocin， Podocalyxin， Synaptopodin， TNFSF15， and podocyte apoptosis-related proteins B lymphocytoma-2 （Bcl-2）-related X protein （Bax）， Bcl-2-associated death promoter （BAD） protein， and B-cell lymphoma-extra large （Bcl-XL） by immunohistochemistry （IHC）. Western blot was used to detect the expression levels of TNFSF15， Bax， BAD， Bcl-2， and BCL-XL in the rat kidney tissue. The apoptosis rate of rat kidney tissue was measured using the in situ end labeling method （Tunnel）. ResultCompared with the normal group， the level of miR-514a-5p in the kidney tissue was significantly reduced （P<0.05）， and the TNFSF15 mRNA expression was significantly increased （P<0.05）. The expression levels of podocyte marker proteins Nephrin， Podocin， Podocalyxin， and Synaptopodin were down-regulated （P<0.05）. The protein expression levels of TNFSF15， Bax， and BAD were increased （P<0.05）， whereas the Bcl-2 and Bcl-XL protein expression levels were decreased （P<0.05）. The number of apoptotic cells diminished significantly （P<0.05）. Compared with the model group， the level of miR-514a-5p in the kidney tissue was significantly increased （P<0.05）， while the level of TNFSF15 mRNA was significantly decreased （P<0.05）. The expression levels of podocyte marker proteins Nephrin， Podocin， podocalyxin， and Synaptopodin were up-regulated （P<0.05）， whereas the TNFSF15， Bax， and BAD protein expression levels were down-regulated （P<0.05）. Bcl-2 and Bcl-XL protein expression levels rose （P<0.05）. The number of apoptotic cells significantly decreased （P<0.05）. ConclusionYishen Tongluo prescription reduces the apoptosis of rat kidney podocytes and alleviates the kidney injury of MN rats through the miR-514a-5p/TNFSF15 signaling pathway.

Study on Herpes Zoster Reactivation Induced by Arsenic in Patients with Acute Promyelocytic Leukemia / 中国实验血液学杂志

OBJECTIVE@#To investigate herpes zoster reactivation induced by arsenic in patients with acute promyelocytic leukemia (APL).@*METHODS@#The clinical data of 212 patients with APL treated in the Department of Hematology of the First Affiliated Hospital of Xi'an Jiaotong University from 2008 to 2019 were retrospectively analyzed to observe the activation of varicella zoster virus induced by arsenic. Kaplan-Meier analysis, chi-square test, and boxplot were used to analyze and describe the cumulative dose of arsenic and the time from the beginning of arsenic treatment to the occurrence of herpes zoster.@*RESULTS@#Excluding early death cases and early automatic discharge cases, 17 cases developed herpes zoster reactivation in 175 patients with APL treated with arsenic, and the cumulative median dose of arsenic was 6.2(2-12) mg/kg. Precise risk of reactivation of herpes zoster with 10 months in APL patients treated by arsenic was 9.7%.@*CONCLUSION@#Arsenic treatment can induce high reactivation rate of herpes zoster virus.

Retrospective analysis on 77 cases of T4b hypopharyngeal carcinoma treated by non-surgical treatments / 中华耳鼻咽喉头颈外科杂志

Objective: To analyze the effectiveness, safety and factors influencing the clinical prognosis of patients with hypopharyngeal carcinoma in T4b by nonsurgical treatments. Methods: The clinical data of 77 patients with T4b hypopharyngeal cancer treated in the College of Otolaryngology Head and Neck Surgery of the Chinese People's Liberation Army General Hospital from January 2010 to June 2021 were analyzed retrospectively. All were males, aged(57.0±8.0)years old. Patients were treated with induction chemotherapy plus concurrent chemoradiotherapy. Kaplan Meier survival analysis was used to compare the effects of different factors on prognosis. Adverse reactions during treatments and the causes of death were analyzed. Results: 98.7% of 77 patients with T4b hypopharyngeal cancer completed the chemotherapy plan and 94.8% completed the radiotherapy plan. The most common adverse reactions were grade 2 radiation oral mucositis (50/77, 64.9%) and grade 2 leukopenia (50/77, 64.9%). The incidence of grade 3 severe hoarseness was 7.8% (6/77), one patient (1.3%) underwent gastrostomy due to dysphagia, and pronunciation and swallowing function were effectively preserved in other patients. The overall survival rate was 71.9% at 1 year, 45.6% at 3 years and 29.7% at 5 years. The location of tumor, the presence of liquefaction necrosis in tumor, the use of molecular targeted drugs and the approach of radiotherapy were independent factors,each of which that affected the prognosis of T4b patients with advanced hypopharyngeal cancer [HR (95%CI) were 1.867(1.085-3.213), 3.018 (1.437-6.335), 0.372 (0.181-0.764) and 2.158 (1.015-4.588), respectively, P<0.05]. The two leading causes of death with high incidence were disease recurrence (12/32, 37.5%) and cervical large vessel rupture and hemorrhage (11/32, 34.4%). Conclusions: Non-surgical comprehensive treatment offers a high laryngeal preservation rate in patients with T4b hypopharyngeal cancer. The location of tumor, the liquefaction necrosis within tumor, the use of molecular targeted drugs, and the approach of radiotherapy are independent prognostic factors.

Pseudotyped SARS-CoV-2 Omicron variant exhibits significant escape from neutralization induced by a third booster dose of vaccination

The Omicron Variant of Concern (B.1.1.529) has spread internationally and is raising serious concerns about reduced vaccine efficacy and the increased risk of reinfection. We assessed the serum neutralizing activity using a pseudovirus-based neutralization assay in 292 healthcare workers who had received a homologous booster dose of BBIBP-CorV vaccine, 8 to 9 months after completing the priming two-dose vaccination schedule, to investigate whether the newly identified Omicron variant can escape serum antibody neutralization induced by the booster vaccination. The booster dose of BBIBP-CorV rapidly induced a significantly high level of humoral immune response, and the neutralization geometric mean titer (GMT) against the wild-type strain on day 28 after the booster dose was 294.85 (252.99-343.65), 6.1 times higher than the level on day 28 after the second dose. The neutralization against the Omicron variant was also improved by the booster vaccination, although the GMT showed an approximately 20.1-fold reduction to 14.66 (12.30-17.48) when compared with the wild-type strain. This study demonstrated that a booster dose of BBIBP-CorV led to a significant rebound in neutralizing immune response against SARS-CoV-2, while the Omicron variant showed partial resistance to neutralizing antibodies induced by the booster vaccination.

A Prospective Multicenter Study of the Chinese Scoring System for Hepatitis B Liver Failure.

Objective: To evaluate the clinical utility of a Chinese scoring system for hepatitis B liver failure in a prospective and multicenter study. Methods: Clinical data for 1,143 patients with hepatitis B liver failure who had been followed up for a minimum of 6 months were collected from seven liver disease centers across China. The disease severity and prognosis for the patients were predicted using the Chinese scoring system and compared to those predicted with the model for end-stage liver disease (MELD) score, MELD-Na score, and Child-Turcotte-Pugh (CTP) score. Results: The Chinese scoring system was more effective at predicting the outcomes of survival and mortality than the MELD score. In the peak disease stage, the area under the receiver operating characteristic curve for the Chinese scoring system was 0.954, significantly higher than that (0.896) for the MELD scoring system (P < 0.001). The positive prediction at 30, 90, and 180 days with the Chinese scoring system was 0.764 (95% CI: 0.714-0.808), 0.731 (95% CI: 0.694-0.769), and 0.724 (95% CI: 0.679-0.765), also significantly higher than that with the MELD, MELD-Na, and CTP scores (P < 0.001). In addition, the Chinese scoring system was superior to the MELD, MELD-Na, and CTP scores (P < 0.001) at predicting the prognosis of patients with hepatitis B liver failure at both 30 and 180 days. Conclusion: The Chinese scoring system demonstrated superior performance to the three established scoring systems in assessing the severity and outcomes of hepatitis B liver failure in this cohort.

Renal Protection of Yishen Tongluo Prescription in Rats with Membranous Nephropathy and Its Influence on AMPK/mTOR/ULK1 Signaling Pathway / 中国实验方剂学杂志

Objective:To observe the effects of Yishen Tongluo prescription （YTP） on autophagy-related proteins in rats with membranous nephropathy （MN） and explore its possible molecular mechanism in protecting the kidney. Method:Twenty of 80 Sprague-Dawley （SD） rats were randomly selected as the normal control， and the rest rats were pre-immunized and injected with cationized bovine serum albumin （C-BSA） through the tail vein to induce MN. The SD rats that were successfully modeled were randomized into the model group， benazepril hydrochloride group （10 mg·kg^-1）， and low- （6.61g·kg^-1）， medium- （13.22 g·kg^-1）， and high-dose （26.44 g·kg^-1） YTP groups， and administered with the corresponding drugs by gavage， once a day， for four consecutive weeks. Then the changes in such quantitative indicators as plasma albumin （ALB）， triglyceride （TG）， total cholesterol （TC）， serum creatinine （SCr）， blood urea nitrogen （BUN）， and 24-hour urinary total protein （UTP） were detected， followed by hematoxylin and eosin （HE） staining， Masson's trichrome staining， and periodic Schiff-methenamine （PASM） staining for observing the pathological changes in kidney under the transmission electron microscope （TEM）. The deposition of immunoglobulin G （IgG） and complement 3 （C3） in the glomerulus was detected by fluorescence immunoassay. The expression levels of autophagy marker proteins Beclin-1， microtubule-associated protein light chain 3Ⅱ （LC3Ⅱ）， and p62 were measured by immunohistochemistry （IHC）， and those of related proteins in the adenosine monophosphate-activated protein kinase / mechanisic target of rapamycin/Unc-51-like kinase 1 （AMPK/mTOR/ULK1） signaling pathway were determined by Western blot assy. Result:Compared with the normal group， the model group exhibited significantly increased UTP （<italic>P</italic><0.01） and serum TG and TC （<italic>P</italic><0.01）， decreased ALB （<italic>P</italic><0.01）， disordered glomerular structure， enlarged volume， thickened basement membrane， vacuolated renal tubules， excessively deposited collagen fibers and fuchsinophilic proteins， extensively fused podocyte foot processes， and diffusely deposited IgG and C3 in glomerular capillary loops. Besides， the expression levels of Beclin-1， LC3II， and phosphorylated AMPK （p-AMPK） decreased （<italic>P</italic><0.01）， while those of p62， phosphorylated mTOR （p-mTOR）， and phosphorylated ULK1 （p-ULK1） increased （<italic>P</italic><0.01）. The comparison with the model group revealed that the TG， TC， and UTP levels in the low-， medium-， and high-dose YTP groups and the benazepril hydrochloride group were reduced to varying degrees （<italic>P</italic><0.05， <italic>P</italic><0.01）， whereas the ALB level was increased （<italic>P</italic><0.01）. There was no statistically significant difference in SCr or BUN level. The pathological damages were alleviated. The expression levels of Beclin-1， LC3Ⅱ， and p-AMPK were up-regulated （<italic>P</italic><0.05， <italic>P</italic><0.01）， while those of p62， p-mTOR， and p-ULK1 were down-regulated （<italic>P</italic><0.05， <italic>P</italic><0.01）. Conclusion:YTP protects the kidney of rats with MN possibly by regulating related proteins in the AMPK/mTOR/ULK1 signaling pathway and activating the autophagy.

The feasibility of convalescent plasma therapy in severe COVID-19 patients: a pilot study

Currently, there are no approved specific antiviral agents for 2019 novel coronavirus disease (COVID-19). In this study, ten severe patients confirmed by real-time viral RNA test were enrolled prospectively. One dose of 200 mL convalescent plasma (CP) derived from recently recovered donors with the neutralizing antibody titers above 1:640 was transfused to the patients as an addition to maximal supportive care and antiviral agents. The primary endpoint was the safety of CP transfusion. The second endpoints were the improvement of clinical symptoms and laboratory parameters within 3 days after CP transfusion. The median time from onset of illness to CP transfusion was 16.5 days. After CP transfusion, the level of neutralizing antibody increased rapidly up to 1:640 in five cases, while that of the other four cases maintained at a high level (1:640). The clinical symptoms were significantly improved along with increase of oxyhemoglobin saturation within 3 days. Several parameters tended to improve as compared to pre-transfusion, including increased lymphocyte counts (0.65x109/L vs. 0.76x109/L) and decreased C-reactive protein (55.98 mg/L vs. 18.13 mg/L). Radiological examinations showed varying degrees of absorption of lung lesionswithin 7 days. The viral load was undetectable after transfusion in seven patients who had previous viremia. No severe adverse effects were observed. This study showed CP therapy was welltolerated and could potentially improve the clinical outcomes through neutralizing viremia in severe COVID-19 cases. The optimal dose and time point, as well as the clinical benefit of CP therapy, needs further investigation in larger well-controlled trials. Significance StatementCOVID-19 is currently a big threat to global health. However, no specific antiviral agents are available for its treatment. In this work, we explored the feasibility of convalescent plasma (CP) transfusion to rescue severe patients. The results from 10 severe adult cases showed that one dose (200 mL) of CP was welltolerated and could significantly increase or maintain the neutralizing antibodies at a high level, leading to disappearance of viremia in 7 days. Meanwhile, clinical symptoms and paraclinical criteria rapidly improved within 3 days. Radiological examination showed varying degrees of absorption of lung lesions within 7 days. These results indicate that CP can serve as a promising rescue option for severe COVID-19 while the randomized trial is warranted.

Coronavirus Disease 2019 Influenza A in Children: An Observational Control Study in China / 生物医学与环境科学（英文）

This study aimed to understand the differences in clinical, epidemiological, and laboratory features between the new coronavirus disease 2019 (COVID-2019) and influenza A in children. Data of 23 hospitalized children with COVID-19 (9 boys, 5.7 ± 3.8 years old) were compared with age- and sex-matched 69 hospitalized and 69 outpatient children with influenza A from a hospital in China. The participants' epidemiological history, family cluster, clinical manifestations, and blood test results were assessed. Compared with either inpatients or outpatients with influenza A, children with COVID-19 showed significantly more frequent family infections and higher ratio of low fever ( 39 °C), nasal congestion, rhinorrhea, sore throat, vomiting, myalgia or arthralgia, and febrile seizures. They also showed higher counts of lymphocytes, T lymphocyte CD8, and platelets and levels of cholinesterase, aspartate aminotransferase, lactate dehydrogenase, and lactic acid, but lower serum amyloid, C-reactive protein, and fibrinogen levels and erythrocyte sedimentation rate, and shorter prothrombin time. The level of alanine aminotransferase in children with COVID-19 is lower than that in inpatients but higher than that in outpatients with influenza A. Pediatric COVID-19 is associated with more frequent family infection, milder symptoms, and milder immune responses relative to pediatric influenza A.

UPLC Fingerprint Analysis of Acanthopanacix Cortex from Different Origins / 中国实验方剂学杂志

Objective::To established fingerprint of Acanthopanacix Cortex by UPLC method, in order to provide reference for quality control and evaluation. Method::UPLC method was performed on Waters BEH C18 (2.1 mm×100 mm, 1.7 μm), with acetonitrile-0.1% glacial acetic acid as the mobile phase for gradient elution.The detection wavelength was 282 nm, the flow rate was 0.3 mL·min-1, the column temperature was 25 ℃, and the injection volume was 2 μL.With syringin as reference substance, the fingerprint of 20 batches Acanthopanacix Cortex were analyzed under the same chromatographic conditions.The Similarity Evaluation System for Chromatographic Fingerprint of Chinese Materia Media (version 2012) was used to analyze the similarity of 20 batches of Acanthopanacix Cortex, and the SPSS 21.0 was applied for cluster analysis. Result::The UPLC fingerprint of the Acanthopanacix Cortex was established.The similarity results showed that the 7 batches of the 20 batches of Acanthopanacix Cortex was less than 0.800, and the remaining medicinal materials were similar within the range from 0.800 to 0.924.Besides, 12 common fingerprint peaks were calibrated and 4 components were identified, namely protocatechuic acid (peak 1), chlorogenic acid (peak 3), syringin (peak 4), and 4-methoxysalicylaldehyde (peak 12). The clustering results showed that the 20 batches of Acanthopanacix Cortex were divided into four groups.Among these batches, S1, S3, S9, S13 and S20 were clustered into one category, S11 was a category, S14 was a category, and the remaining samples belonged to a category. Conclusion::With a good precision, repeatability and stability, short analysis time as well as superior specificity, the method will provide a scientific basis to evaluate and control the quality of Acanthopanacix Cortex.

Etiology and Clinical Characteristics of Community-Acquired Pneumonia with Airway Malacia in Children.

Objective: The objective of this article is to study the etiology of community-acquired pneumonia in children with airway malacia. Methods: We retrospectively reviewed the medical records of 428 pneumonia patients. All patients underwent bronchoscopy, and bronchoalveolar lavage samples were processed for microbiological assessment. Results: In a total of 428 cases reviewed, 60 were found to have airway malacia. Pathogens were identified in 44 of the 60 specimens (73.3%), with 32 being single-pathogen infections. The most common pathogen was respiratory syncytial virus (RSV; 20%). Mixed-pathogen infections were observed in 12 patients. Airway malacia patients were younger than those without malacia (10.5 vs. 50 months, respectively; p < 0.001). Compared with those without airway malacia, wheezing, cyanosis and admission to the pediatric intensive care unit were more common in children with airway malacia and their hospital stay was longer. Conclusion: RSV was the most common pathogen in those with airway malacia. Airway malacia was found to aggravate infectious pneumonia.

Relationship between the Therapeutic Dose of Arsenic Trioxide and Relapse in Acute Promyelocytic Leukemia / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To analyze the correlation of ATO therapeutic dose with the relapse of patients with acute promyelocytic leukemia (APL) and to investigate the optimal dose and courses of ATO.</p><p><b>METHODS</b>The clinical data of 102 patients with APL from January 2008 to June 2015 were analyzed retrospectively. The clinical characteristics of APL patients in relapsed group and maintained remission group were compared. According to ATO dose in 2 years recommended in chinese guideline as criteria of grouping, the patients were divided into ATO high and low dose groups, then the relapse rate in groups was compared. The cut-off value of ATO dose was analyzed by ROC curve.</p><p><b>RESULTS</b>Univariate analysis showed that the relapse rate in high ATO and low ATO groups on 2 year treatment was 2.5% and 17.7% respectively (P<0.05); multiple variate analysis demonstrated that the ATO dose>22.4 mg/kg on 2 year treatment was independent preventive factor for the relapse of APL (OR=0.119, P<0.05). The ROC curve showed that the cut-off value of ATO dose on 2 year treatment was 8.765 mg/kg. The relapse rate of APL in group of ATO dose >8.765 mg/kg group was significantly lower than that in group of ATO dose <8.765 mg/kg.</p><p><b>CONCLUSION</b>The relapse of APL relates with used ATO dose, sufficient use of ATO dose can decrease the relapse rate of APL.</p>

A study on innovation incentive policy of pharmaceutical industry in China: A review / 中国卫生政策研究

Based on the typical characteristics of existing incentive and regulation in the pharmaceutical industry in China,the innovation incentive policy of the pharmaceutical industry can be divided into two types:incentive policy,and regulatory policy.This paper reviewed the research progress on the influence of price regulation policy,health insurance payment policy,centralized procurement regulation and incentive policy on the innovation of pharmaceutical industry.The present paper puts also forward the future research direction.Based on the literature review,it has been found that the futnre researches in this field should be based on the management practice situation in China,and make a breakthrough from the following three aspects-asymmetric information,comprehensive action mechanism from variable policy instruments,and introduction of new research paradigm.This research provides a theoretical reference for the research and decision-making of the innovation incentive policy in the pharmaceutical industry.

A study on innovation incentive policy of pharmaceutical industry in China: A review / 中国卫生政策研究

Based on the typical characteristics of existing incentive and regulation in the pharmaceutical industry in China,the innovation incentive policy of the pharmaceutical industry can be divided into two types:incentive policy,and regulatory policy.This paper reviewed the research progress on the influence of price regulation policy,health insurance payment policy,centralized procurement regulation and incentive policy on the innovation of pharmaceutical industry.The present paper puts also forward the future research direction.Based on the literature review,it has been found that the futnre researches in this field should be based on the management practice situation in China,and make a breakthrough from the following three aspects-asymmetric information,comprehensive action mechanism from variable policy instruments,and introduction of new research paradigm.This research provides a theoretical reference for the research and decision-making of the innovation incentive policy in the pharmaceutical industry.

Synthesis of functional phospholipids and preparation of shear-stress sensitive liposomes / 药学学报

This study aims to synthesize new phospholipids, 1,3-dipalmaminophospholipid(Pad-PC-Pad), and prepare shear-stress sensitive liposomes(SSSL). 1H NMR and MS indicated that Pad-PC-Pad were fully synthesized successfully. SSSL were prepared by filming-rehydration method with Pad-PC-Pad, which loaded calcein with aggregation-caused quenching(ACQ)characteristics to evaluate shear-stress sensitivity of liposomes and release behavior of liposomes in vitro. The results showed that the particle size of liposomes was 106.91 ± 1.24 nm and liposomes had lenticular morphology under transmission electron microscope. The release of calcein was increased with ultrasonic power, which suggests that the liposomes is shear-stress sensitive. Moreover, the liposomes exhibited a releasing effect for obstructed region under high shear-stress in a model system. Therefore, we synthesized quick functional phospholipid Pad-PC-Pad and the liposomes made from Pad-PC-Pad was shear-stress sensitive, which may be used for treatment of thrombosis.

Preliminary study of lipid bilayer-coated calcium phosphate nanoparticles as a drug carrier for antitumor drug / 药学学报

This study aims to prepare lipid bilayer-coated calcium phosphate core-shell nanoparticles (LCAPNs), which can dissolve in an acidic environment to improve the tumor cell toxicity of antitumor drug. Paclitaxel (PTX) loaded lipid coated calcium phosphate nanoparticles (PTX-LCAPNs) were prepared by thin-film dispersion method. The morphology, particle size and in vitro release behavior were characterized. Meanwhile, the intracellular uptake, intracellular dissolution, cell toxicity of PTX-LCAPNs and intracellular accumulation of PTX were evaluated in human HCC cell line (Huh-7). The results suggested that the mean diameter of the spherical LCAPNs was 124.73±6.41 nm. The PTX-LCAPNs demonstrated little drug leakage in simulated normal physiological conditions, while a rapid release was observed in simulated intracellular condition in vitro. Moreover, the PTX-LCAPNs achieved 1.7 fold improvement in the intracellular PTX concentration leading to 5-fold reduction in half maximal inhibitory concentration (IC50) values of PTX compared with calcium phosphate nanoparticles loaded with PTX (PTX-CAPNs), demonstrating a stronger cancer cell lethality.

Clinical analysis of serotretine combined with metformin in the treatment of senile diabetic patients with sulfonylurea failure / 中国生化药物杂志

Objective To investigate the clinical effect of sitagliptin combined with metformin in the treatment of sulfonylurea-deficient elderly patients with diabetes mellitus.Methods Sixty patients with diabetes mellitus were enrolled in our hospital from January 2013 to December 2016.The patients were divided into observation group(30 cases) and control group(30 cases) according to the random number method.The patients in the observation group were treated with sitagliptin and metformin.The patients in the control group were treated with gemcitabine, and the clinical treatment effect, fasting blood glucose, postprandial blood glucose, glycosylated hemoglobin, fasting C peptide and postprandial 2hC peptide Level of statistical comparison.Results The clinical effect of the observation group was significantly higher than that of the control group.Before and after treatment, the fasting blood glucose, 2h postprandial blood glucose, glycosylated hemoglobin, fasting C peptide and postprandial 2hC peptide level were not significantly different After fasting blood glucose, 2h postprandial blood glucose and glycosylated hemoglobin levels were significantly lower than before treatment, after treatment of fasting C peptide and postprandial 2hC peptide levels were significantly higher than before treatment.Conclusion The clinical efficacy of serotretine combined with metformin in the treatment of elderly patients with diabetes mellitus is similar to that of Yuxing, and the combination is more convenient and more suitable for clinical treatment.It is worthy to be popularized and applied in clinical practice.

Relationship between Peripheral Blood White Blood Cell Count and Early Death Rate in Patients with Acute Promyelocytic Leukemia / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the relationship between peripheral white blood cell count and early death rate of the patients with acute promyelocytic leukemia (APL).</p><p><b>METHODS</b>Through retrospective study, the relationship of early death rate in 116 cases newly diagnosed APL patients with maximum of peripheral blood white blood cell count should be analyzed before and after induction therapy as well as in the whole course of disease during the past 8 years.</p><p><b>RESULTS</b>There was a close relationship between the peripheral white blood cell count and the early death rate in APL patients. Peripheral blood white blood cell count in the early died patients was significantly higher than that of the survival patients (P<0.05). ROC analysis showed that the highest risk threshold of peripheral white cell count was 70×10/L (P<0.05) before treatment, while the highest risk threshold after treatment and in the whole course of disease were 96.4×10/L(P<0.05) and 91.5×10/L(P<0.01) respectively. The dealth rate of patients with highest risk threshold was significantly increased (P<0.05).</p><p><b>CONCLUSION</b>The highest peripheral blood white blood cell count closely relates with the early death rate of patients at different time points in the whole course of disease. Control of peripheral white blood cell count may effectively reduce the early death rate of APL patients.</p>

Echocardiographic Evaluation of Coronary Abnormalities and Cardiac Function in a Murine Model of Kawasaki Disease Using High-frequency Ultrasound / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Murine model of coronary arterial inflammation has been widely accepted as an animal model of and used in Kawasaki disease (KD). This study sought to evaluate the developmental changes of coronary arteries and cardiac function in a murine model of KD with a high-frequency ultrasound system and to provide evidence for the preparation of the model of KD.</p><p><b>METHODS</b>Lactobacillus casei cell wall extract was prepared and injected into C57BL/6 mice intraperitoneally (i.p.) to induce KD. A total of 120 mice were grouped into three groups. The intravenous immunoglobulin (IVIG) treatment group was i.p. injected with IVIG (2 g/kg), while the KD model and normal control groups were i.p. injected with 0.5 ml of phosphate buffered solution on day 5. All high-resolution echocardiography detection of mouse heart was performed by the same senior technician. Animal echocardiography was performed by measuring the coronary artery dimensions and cardiac function on days 0, 7, 14, 28, and 56 (high-resolution small animal ultrasound [Vevo770 pattern; VisualSonic, Canada] with broadband probe [RMVTM707B; frequency, 30 mHz; depth of focus, 1.2 cm]) which were measured and analyzed with Vevo770 software.</p><p><b>RESULTS</b>Pathological studies revealed focal inflammatory infiltrate asymmetrically distributed around the coronary artery trunk in the KD model group. Echocardiographic study including coronary dimension and cardiac function measurements was successfully performed in all subjects. The KD model and IVIG treatment groups showed left coronary artery dilation on days 7, 14, 28, and 56. The diameter of left coronary artery in the KD model group (0.53 ± 0.09 mm; 0.36 ± 0.07 mm; 0.34 ± 0.05 mm; 0.34 ± 0.04 mm) was significantly larger than those of IVIG treatment group (0.22 ± 0.02 mm; 0.28 ± 0.03 mm; 0.26 ± 0.03 mm; 0.27 ± 0.05 mm; 0.26 ± 0.03 mm; all P < 0.01) and the normal control group (0.21 ± 0.02 mm; 0.22 ± 0.03 mm; 0.22 ± 0.02 mm; 0.23 ± 0.02 mm; 0.27 ± 0.04 mm; all P< 0.01) on days 7, 14, 28, and 56. No significant differences were observed in the measurements of cardiac function among the groups on days 0, 7, 14, 28, and 56 (all P > 0.05).</p><p><b>CONCLUSIONS</b>Echocardiography could identify the consecutive changes of coronary artery in KD mice. Echocardiography is more convenient and direct in evaluating the coronary abnormalities in this animal model.</p>

Research on chemotaxis response of Alternaria panax to amino acid of ginseng root exudates / 中国中药杂志

Plate assay and spore germination method were used to study the chemotaxis response of Alternaria panax to arginine, glutamic acid, aspartic acid and threonine. The result showed that the optimum temperature of A. panax chemotaxis response to four amino acids were all 25 ℃. And chemotaxis responses of A. panax were different under conditions of different concentration and pH value. The chemotaxin reached to the highest under the condition of 2 mg•L⁻¹ and pH value was 7 for arginine, glutamic acid and threonine while 20 mg•L⁻¹ and pH value was 6 for aspartic acid . The data of chemotactic migration index (CMI) were 1.24, 1.38, 1.27, 1.31 and chemotactic growth rates(CGR) were 0.451 0, 0.353 0, 0.381 3, 0.228 8 and spores germination rates(SGR) were 57.33%，63%，56.67%，58% and the dry weight of mycelial (DWM) were 372.9, 348.5, 314.4, 390.2 mg•L⁻¹ respectively. It indicated that the low and middle concentration of amino acid had significant promoting effect on chemotaxis response of A. panax. As important substances generated in ginseng root, amino acids exhibited an efficient chemotactic effect on A. panax, and some even show inhibition effect under high concentration.