Synthesis and evaluation for anti-HCoV-OC43 activity of novel aloperine derivatives with different core structures / 药学学报

In this study, we designed and synthesized 12 novel aloperine derivatives with different core structures. Among them, compound 3 with a ten-membered ring core was obtained through a special ring expansion reaction after γ-H Huffman elimination of quaternary ammonium salt, and the structure was verified by X-single crystal diffraction. Furthermore, their antiviral activity against human β-coronavirus HCoV-OC43 was evaluated by CCK-8 assay. Quaternary ammonium salt 2a and 3 had a good inhibitory effect against HCoV-OC43, and 2a had the highest anti-HCoV-OC43 activity with an EC50 values of 3.77 μmol·L-1 and a SI value of over 53.1. Schrӧdinger molecular docking results showed that both 2a and 3 might display their anti-HCoV-OC43 activity by directly acting on host TMPRSS2 and SR-B1. The results expanded the structural types of endocyclic aloperine and the function against coronavirus, and provided useful scientific data for the development of pharmaceutical applications of these compounds.

Synthesis and anti-SARS-CoV-2 activity and mechanism research of lycorine derivatives / 药学学报

We designed and synthesized eighteen lycorine derivatives with five different structural types, and evaluated their antiviral activities on a HCoV-OC43-infected H460 cell model. Structure-activity relationships suggested that the introduction of appropriate substituents on the 6N atom of lycorine was beneficial to activity. Compound 6a gave a good activity with the half effective concentration (EC50) and selectivity index (SI) values of 2.36 μmol·L-1 and 16.52, respectively. Surface plasmon resonance (SPR) result indicated that 6a might target the non-structural protein 12 (NSP12) subunit in RNA-dependent RNA polymerase (RdRp) of SARS-CoV-2 with the dissociation constant (KD) value of 1.36 μmol·L-1. Molecular docking indicated that 6a might act on nidovirus RdRp-associated nucleotidyltransferase (NiRAN) catalytic center of NSP12, distinct from the mechanism of nucleoside-like drugs such as remdesivir. This study provides scientific data for the development of lycorine derivatives into a new class of anti-SARS-CoV-2 small molecule inhibitors.

Clinical diagnosis and treatment of hereditary thrombocytopenia and purpura: a report of five cases and literature review / 中华血液学杂志

Objective: To report the clinical manifestations and laboratory features of five patients with congenital thrombotic thrombocytopenic purpura (cTTP) and explore its standardized clinical diagnosis and treatment along with a review of literature. Methods: Clinical data of patients, such as age of onset, disease manifestation, personal history, family history, and misdiagnosed disease, were collected. Treatment outcomes, therapeutic effects of plasma infusion, and organ function evaluation were observed. The relationship among the clinical manifestations, treatment outcomes, and ADAMTS13 gene mutation of patients with cTTP was analyzed. Additionally, detection of ADAMTS13 activity and analysis of ADAMTS13 gene mutation were explored. Results: The age of onset of cTTP was either in childhood or adulthood except in one case, which was at the age of 1. The primary manifestations were obvious thrombocytopenia, anemia, and different degrees of nervous system involvement. Most of the patients were initially suspected of having immune thrombocytopenia. Acute cTTP was induced by pregnancy and infection in two and one case, respectively. ADAMTS13 gene mutation was detected in all cases, and there was an inherent relationship between the mutation site, clinical manifestations, and degree of organ injury. Therapeutic or prophylactic plasma transfusion was effective for treating cTTP. Conclusions: The clinical manifestations of cTTP vary among individuals, resulting in frequent misdiagnosis that delays treatment. ADAMTS13 activity detection in plasma and ADAMTS13 gene mutation analysis are important bases to diagnose cTTP. Prophylactic plasma transfusion is vital to prevent the onset of the disease.

Advance on nitric oxide combined photothermal therapy for tumor treatment / 药学学报

Photothermal therapy (PTT) has attracted significant attention due to minimal side effects and high treatment specificity. However, it often requires very high temperature to achieve complete tumor ablation under a single PTT. Such high temperature brings obvious thermal damage and inflammatory response to the body, affecting the therapeutic effect. In recent years, nitric oxide (NO) has been used to significantly inhibit tumor growth and enhance the sensitivity of tumor cells of temperature and drugs, thus enhancing the therapeutic effect. However, compounds as NO donors often have some disadvantages such as poor biocompatibility and untargeted delivery, etc., therefore, this medical application based on NO therapy is limited. In conclusion, the organic combination of NO donors and photothermal agents (PTAs) is expected to overcome the shortcomings of single therapy and achieve the antitumor effect of "1 + 1 > 2". In view of the rapid development of NO combining with PTT in tumor therapy, this review firstly introduces the antitumor mechanisms of different types of NO donors. Then the treatment strategy based on NO combined with PTT is discussed. Finally, the prospects and challenges of this combination therapy strategy in the clinical treatment of cancer are discussed.

A combined regimen based on bortezomib and glucocorticoids for 6 patients with recurrent/refractory immune thrombotic thrombocytopenic purpura / 中华血液学杂志

Objective: To observe the efficacy and adverse reactions of a combination therapy regimen based on bortezomib and glucocorticoids in recurrent/refractory immune thrombocytopenic purpura (iTTP) . Methods: Six patients with recurrent/refractory TTP were included and treated with a glucocorticoid and two courses of bortezomib-based regimen. The clinical remission status of patients, changes in ADAMTS13 activity/ADAMTS13 inhibitor, and the occurrence of treatment-related adverse reactions were observed. Results: Of the 6 patients, 2 were males and 4 were females, with a median age of 21.5 (18-68) years. Refractory TTP was found in 1 case and recurrent TTP in 5 cases. Glucocorticoids were administered with reference to prednisone at 1 mg·kg(-1)·d(-1), and gradually reduced in dosage after achieving clinical remission. Bortezomib is subcutaneously administered at 1.3 mg/m(2) on days 1, 4, 8, and 11 with a 28-day treatment course consisting of 2 courses. Six patients achieved clinical remission after receiving bortezomib as the main treatment. ADMATS13 activity returned to normal in all patients with TTP after treatment, and the ADAMTS13 inhibitor turned negative. Thrombocytopenia is the most common adverse reaction after treatment, with other adverse reactions, including peripheral neuritis and abdominal pain, but ultimately all patients returned to normal. In a median follow-up of 26 (9-41) months, 5 patients maintained sustained remission, and 1 patient relapsed after 16 months of bortezomib treatment. Conclusion: Combination therapy of bortezomib and glucocorticoids has a satisfactory therapeutic effect and controllable adverse reactions for recurrent/refractory iTTP.

Escore Albumina-Bilirrubina para Predizer Desfechos em Pacientes com Cardiomiopatia Dilatada Idiopática / Albumin-Bilirubin Score to Predict Outcomes in Patients with Idiopathic Dilated Cardiomyopathy

Resumo Fundamento: A disfunção hepática é uma variável postulada de prognóstico desfavorável na cardiomiopatia dilatada (CMD). Objetivo: Este estudo teve como objetivo investigar o valor prognóstico do escore albumina-bilirrubina (ALBI), um modelo relativamente novo para a avaliação da função hepática, em pacientes com CMD idiopática. Métodos: Um total de 1.025 pacientes com CMD idiopática foram incluídos retrospectivamente e divididos em três grupos com base nos escores de ALBI: grau 1 (≤ −2,60, n = 113), grau 2 (−2,60 a −1,39, n = 835) e grau 3 (> −1,39, n = 77). Foi analisada a associação do escore ALBI com eventos clínicos adversos maiores (ECAM) intra-hospitalares e mortalidade a longo prazo. Valor de p inferior a 0,05 foi considerado estatisticamente significativo. Resultados: A taxa de ECAM intra-hospitalares foi significativamente maior nos pacientes com grau 3 (2,7% versus 7,1% versus 24,7%, p < 0,001). A análise multivariada mostrou que o escore ALBI foi um preditor independente para ECAM intra-hospitalares (odds ratio ajustada = 2,80, IC 95%: 1,63 - 4,80, p < 0,001). Após seguimento mediano de 27 meses, 146 (14,2%) pacientes morreram. A curva de Kaplan-Meier indicou que a taxa cumulativa de sobrevida a longo prazo foi significativamente menor em pacientes com grau mais alto de ALBI (log-rank = 45,50, p < 0,001). O escore ALBI foi independentemente associado à mortalidade a longo prazo (hazard ratio ajustada = 2,84, IC 95%: 1,95 - 4,13, p < 0,001). Conclusão: O escore ALBI, como modelo de risco simples, pode ser considerado uma ferramenta de estratificação de risco para pacientes com CMD idiopática.

Abstract Background: Liver dysfunction is a postulated variable for poor prognosis in dilated cardiomyopathy (DCM). Objective: This study aimed to investigate the prognostic value of the albumin-bilirubin (ALBI) score, a relatively new model for evaluating liver function, in patients with idiopathic DCM. Methods: A total of 1025 patients with idiopathic DCM were retrospectively included and divided into three groups based on ALBI scores: grade 1 (≤ −2.60, n = 113), grade 2 (−2.60 to −1.39, n = 835), and grade 3 (> −1.39, n = 77). The association of ALBI score with in-hospital major adverse clinical events (MACEs) and long-term mortality was analyzed. P-value less than 0.05 was considered statistically significant. Results: The in-hospital MACEs rate was significantly higher in the grade 3 patients (2.7% versus 7.1% versus 24.7%, p < 0.001). Multivariate analysis showed that ALBI score was an independent predictor for in-hospital MACEs (adjusted odds ratio = 2.80, 95%CI: 1.63 - 4.80, p < 0.001). After a median 27-month follow-up, 146 (14.2%) patients died. The Kaplan-Meier curve indicated that the cumulative rate of long-term survival was significantly lower in patients with higher ALBI grade (log-rank = 45.50, p < 0.001). ALBI score was independently associated with long-term mortality (adjusted hazard ratio = 2.84, 95%CI: 1.95 - 4.13, p < 0.001). Conclusion: ALBI score as a simple risk model could be considered a risk-stratifying tool for patients with idiopathic DCM.

Clinical analysis of 11 cases of lymphoma complicated with paraneoplastic neurological syndrome / 中华血液学杂志

Objective: To evaluate the clinical characteristics, treatment, and prognosis of patients with paraneoplastic neurological syndrome (PNS) associated with lymphoma. Methods: Between January 2012 and May 2021, the clinical data of 11 patients with lymphoma complicated with PNS treated at Peking Union Medical College Hospital were retrospectively reviewed. Results: Among the 11 patients (8 male and 3 female) , the median onset age was 61 (range, 33-78) years. The symptoms of PNS preceded lymphoma in 10 patients. The median time from the onset of PNS to the diagnosis of lymphoma was 4 months. Of the 11 patients, one had Hodgkin's lymphoma, 8 had B-cell non-Hodgkin's lymphoma, and 2 had peripheral T-cell lymphoma. Seven patients were evaluated for onconeural antibody, of whom 2 were positive (1 for anti-Ma2 antibody and 1 for anti-Yo antibody) . Of the 11 patients, the PNS symptoms of 3 patients were located in the central nervous system, 4 were located in the peripheral nervous system, and 3 were located in the muscle. Eight of the 11 patients were treated with glucocorticoid-based immunosuppressive therapy before the diagnosis of lymphoma. Patients with central nervous system involvement and dermatomyositis responded well to glucocorticoid, whereas patients with peripheral neuropathy did not significantly benefit. All 11 patients were treated with chemotherapy after the diagnosis of lymphoma. The efficacy of chemotherapy was assessed in 9 patients, 7 cases achieved complete remission, 1 case was evaluated as stable disease, and 1 case was evaluated as disease progression. The PNS symptoms of the patients who achieved complete response were almost completely recovered. The median follow-up time was 42 (range, 4-95) months. At the end of the follow-up period, 6 of the 11 patients survived, 3 were lost to follow-up, and 2 died. The median overall survival of the whole group was not reached. Conclusions: PNS can involve various parts of the nervous system and can be associated with different types of lymphoma. Through early diagnosis and treatment, the PNS symptoms could improve in most patients who achieve complete remission of lymphoma.

Synthesis and evaluation on triglyceride inhibitory activities of novel indole alkaloids / 药学学报

Three tricyclic [6,5,7] and six tetracyclic [6,5,5,5] novel indole alkaloids were synthesized and evaluated on triglyceride inhibitory activities for the first time. Among them, compound 4c showed the most potent activity with IC50 value of 6.35 μmol·L-1. Meanwhile, compound 4c also exhibited a good safety profile at the cellular level. Preliminary mechanism study indicated that 4c might increase intracellular lipid metabolism by activating AMPK. These results provide a novel family of lead compounds for the discovery of anti-NAFLD candidates.

Current status of thromboembolism risk assessment in patients hospitalized with non-valvular atrial fibrillation in tertiary hospitals in China / 中华心血管病杂志

Objective: To analyze the current status, trend and predictors of thromboembolism risk assessment in patients hospitalized with non-valvular atrial fibrillation (NVAF) in tertiary hospitals in China. Methods: The study was based on data from the Improving Care for Cardiovascular disease in China (CCC)-Atrial Fibrillation (AF) project. About 10% of the tertiary hospitals in each geographic-economic stratum were recruited. Participating hospitals reported the first 10 to 20 patients with a discharge diagnosis of atrial fibrillation monthly. From February 2015 to December 2019, a total of 49 104 NVAF patients from 151 tertiary hospitals in 30 provinces, municipalities and autonomous regions were enrolled. Clinical data of the patients was collected. The proportion of NVAF patients receiving thromboembolism risk assessment, variations in the proportion between different hospitals, the time trend of the application of thromboembolism risk assessment, and the predictors of the application of thromboembolism risk assessment were analyzed. Results: The age of the NVAF patients was (68.7±12.1) years, 27 709 patients (56.4%) were male. Only 17 251 patients (35.1%) received thromboembolism risk assessment. The proportion varied substantially between hospitals with the lowest value of 0 and the highest value of 100%. Among the hospitals, which enrolled more than 30 patients, no patients received thromboembolism risk assessment in 18.4% (26/141) of the hospitals, more than 50% of the patients received thromboembolism risk assessment in 21.3% (30/141) of the hospitals, and all the patients received thromboembolism risk assessment in only 1 hospital. The proportion of NVAF patients receiving thromboembolism risk assessment was 16.2% (220/1 362) in the first quarter of 2015, and significantly increased to 67.1% (1 054/1 572) in the last quarter of 2019 (P<0.001). Patients' characteristics were associated with the application of thromboembolism risk assessment. The odds of receiving thromboembolism risk assessment was lower in male patients compared to female patients(OR=0.94,95%CI 0.89-0.99), lower in patients with acute coronary syndrome or other cardiovascular diseases compared to those with AF as the primary admission reason (OR=0.59, 95%CI 0.55-0.63, OR=0.52, 95%CI 0.45-0.61, respectively), and lower in patients with paroxysmal, persistent and long-standing/permanent AF compared to those with first detected AF (OR=0.62, 95%CI 0.57-0.67, OR=0.72, 95%CI 0.66-0.79, OR=0.57, 95%CI 0.52-0.64, respectively). The odds was higher in patients with a history of hypertension, heart failure, stroke/TIA, and previous anticoagulant therapy compared to those without the above conditions (OR=1.17, 95%CI 1.11-1.23, OR=1.18, 95%CI 1.07-1.30, OR=1.17, 95%CI 1.08-1.27, OR=1.28, 95%CI 1.19-1.37, respectively) (P all<0.05). Conclusion: Thromboembolism risk assessment was underused in patients hospitalized with NVAF in tertiary hospitals in China, and there were substantial variations between hospitals in the application of thromboembolism risk assessment. The application of thromboembolism risk assessment in tertiary hospitals has been improved in recent years, but there is still plenty of room for future improvement. Patients' characteristics could affect the application of thromboembolism risk assessment in China.

Research and application of nanometer black phosphorus in phototherapy and drug carrier / 药学学报

The emerging nano-black phosphorus materials have created a new platform for biomedical research. Nano-black phosphorus has the following advantages: black phosphorus can produce singlet oxygen under near-infrared light irradiation, so it can be used as a photosensitizer for photodynamic therapy;black phosphorus has extensive light absorption in the long wavelength region, and this near-infrared photothermal property can be used in photothermal therapy. The high specific surface area and unique fold structure of the black phosphorus nanosheet make it have very high drug loading.This paper mainly reviews the applications of black phosphorus in biological imaging, photothermal therapy, photodynamic therapy, and as a drug carrier in recent years. Based on the photoelectric properties of black phosphorus nanomaterials combined with intelligent drug delivery platform, the synergistic effects of light/heat/chemistry, light/chemistry/gene, and light/chemistry/immunity can be produced, which has a broad application prospect.

Genetic Effect Analysis of β-globin Gene 3'UTR+101G>C (HBB:c. *233G>C) Variant / 中国实验血液学杂志

OBJECTIVE@#To investigate whether β-globin gene 3'UTR+101G>C (HBB:c.*233G>C) variant has genetic effect and provide basis for gene diagnosis and genetic counseling.@*METHOD@#Whole blood cell analysis and capillary zone electrophoresis (CZE) were used to analyze the hematological indexes. The most frequent 23 mutations in southern Chinese individuals were routinely measured by PCR-flow fluorenscence immunmicrobeads assay. Sanger sequencing was used to detect the other variants of β-globin gene (HBB).@*RESULTS@#In 463 cases, a total of 7 cases with HBB:c.*233G>C variant were detected, among them 4 cases carried other pathogenic variants of HBB gene (2 cases were in trans, 2 cases were in cis), who had typical hematological characteristics of mild β-thalassemia, and 3 cases also carried abnormal hemoglobin variation, but did not have hematological characteristics of β-thalassemia.@*CONCLUSION@#The study shows that HBB:c.*233G > C variant has no obvious genetic effect and should be a benign polymorphism.

Differential Diagnosis of Three Commonest Deletion β-Thalassemia in Chinese / 中国实验血液学杂志

OBJECTIVE@#To analyze the hematological characteristics of Chinese @*METHODS@#Hemoglobin electrophoresis and blood routine test were used to analyze the hematological indexes of all peripheral blood samples，PCR-Flow fluorescent hybridization and Gap-PCR were used to detect the globin gene mutations and the data were analyzed statistically.@*RESULTS@#The 3 types of deletion β- Thalassemia patients were showed as hypochromic small cell anemia. The MCH and MCV values of Taiwan type β-thalassemia patients were the lowest. The results of hemoglobin electrophoresis showed that the increasing of HbF was found in all of the 3 types. Except for the decreasing of Hb A2 in Chinese @*CONCLUSION@#Through analyze the hematological characteristics, it can be provide that the guidance for the differential diagnosis and genetic consultation of the three commonest deletion β-thalassemia in Chinese.

Content determination of six flavonoids in Dendrobium officinale stems from different producing areas,cultivation and processing methods by QAMS combined with dual-wavelength method / 中国中药杂志

A novel HPLC method with the quantitative analysis of multi-components by single marker( QAMS) combined with the dual-wavelength method was developed for simultaneous determination of six flavonoids in Dendrobium officinale stems from different producing areas,cultivation and processing methods to clarify the main factors contributing to the different composition of flavonoids.The separation of six flavonoids was performed on a Shiseido Capcell PAK MGⅡ C18 column( 4. 6 mm×250 mm,5 μm) using a linear gradient elution system of acetonitrile-0. 1% formic acid aqueous solution. Schaftoside,isoschaftoside,vicenin-2,and glucosylvitexin were simultaneously analyzed using rutin as a reference standard at detection wavelength of 340 nm,and naringenin was determined at290 nm. The credibility and feasibility of QAMS method were validated and the results demonstrated that no significant differences were observed as compared with the external standard method. Finally,a total of 82 batches of D. officinale samples were analyzed and principal component analysis( PCA) and discriminant analysis were applied to distinguish and compare D. officinale samples from different producing areas,cultivation and processing methods. The results showed that the total flavonoid content of D. officinale stems cultivated in the simulated wild( attached tree cultivation or attached stone cultivation) was significantly higher than that in greenhouse bed cultivation. The content of flavonoids in simulated-wild D. officinale stems was higher in Jiangxi,Guizhou,Zhejiang,and Fujian provinces,while that in greenhouse bed cultivation was higher in Fujian and Zhejiang provinces. The content of naringenin was positively correlated with processing temperature,and that of the other five flavonoids was negatively correlated with processing temperature. PCA showed that wild-simulated D. officinale and greenhouse bed-cultivated D. officinale could be roughly divided into two clusters. The samples cultivated in the greenhouse bed were divided into four categories according to the geographical habitats. Wild-simulated D. officinale samples from Guizhou gathered together,and there was no obvious rule in samples from other producing areas. The established method simplified the determination method of flavonoids in D. officinale,and could provide the basis for effective quality control,cultivation and processing of D. officinale.

Advances in small molecular inhibitors of IL-6/STAT3 signaling pathway / 药学学报

As a pleiotropic cytokine, interleukin-6 (IL-6) participates in many physiological activities in vivo. IL-6 plays an important role in the physiology and pathology of chronic inflammation, autoimmune diseases, tumors and other diseases through diverse mechanisms. At present, inhibitors targeting IL-6/IL-6R have been shown to improve treatments for some inflammatory diseases such as rheumatoid arthritis and systemic juvenile idiopathic arthritis. IL-6 binds to a specific receptor to activate the downstream JAK/STAT3 signaling pathway. However abnormally activated STAT3 often appears in various types of malignant tumors and participates in the occurrence and development of tumors. In addition, studies have shown that IL-6 is a key factor in the cytokine storm associated with COVID-19 patients. The physiological participation of IL-6/STAT3 pathway in complex diseases makes this pathway become a research hotspot for drug discovery. Therefore, we summarize the latest research progress of small molecular inhibitors on IL-6/STAT3 signaling pathway, in order to provide a reference for the development of IL-6/STAT3 related drug in the future.

Effect of repeated intranasal insulin on postoperative delirium in elderly patients undergoing general anesthesia / 中华麻醉学杂志

Objective:To evaluate the effect of repeated intranasal insulin on postoperative delirium (POD) in elderly patients undergoing general anesthesia.Methods:Seventy elderly patients, aged ≥65 yr, with body mass index ≤28 kg/m 2, of American Society of Anesthesiologists physical statusⅠ-Ⅲ, undergoing elective radical gastrectomy for gastric cancer under general anesthesia, were divided into 2 groups ( n=35 each) according to the random number table method: control group (group C) and insulin group (group I). In group C, normal saline 0.5 ml was administered intranasally twice a day from 2 days before surgery until the day of surgery.In group I, insulin 20 U (0.5 ml) was administered intranasally twice a day from 2 days before surgery until the day of surgery.The regional tissue oxygen saturation (rSO 2) was measured after entering the operating room (T 0), at intubation (T 1), at 1, 2 and 3 h after the start of operation (T 2-4), at the end of surgery (T 5) and at extubation (T 6). The insulin allergic reactions, nasal irritation and hypoglycemic reactions were recorded after intranasal administration of insulin or normal saline within 2 days before operation.The blood glucose concentrations were measured at T 0, T 3 and T 5.The occurrence of POD within 3 days after operation was recorded. Results:Compared with group C, the incidence of POD was significantly decreased within 3 days after operation, and the rSO 2 was increased at T 1-6 in group I ( P<0.05). The rSO 2 was significantly higher at T 1-6 than at T 0 in two groups ( P<0.05). There were no significant changes in blood glucose concentrations at T 0, T 3 and T 5 between the two groups ( P>0.05). No insulin allergic reactions, nasal irritation and hypoglycemic reactions occurred in two groups ( P>0.05). Conclusion:Repeated intranasal administration of insulin can increase the rSO 2 during operation and decrease the occurrence of POD in elderly patients undergoing radical gastrectomy for gastric cancer.

Different internal fixation methods of oblique lateral interbody fusion: a finite element analysis / 医学研究生学报

ObjectiveThere is still controversy about which internal fixation method should be used in oblique lateral interbody fusion (OLIF). This paper aims to compare the biomechanical stability of OLIF with different internal fixation methods.MethodsA 31-year-old healthy male volunteer was selected to have a 64-slice spiral CT scan of his lumbar spine. Mimics 19.0, Geomagic Studio 2013, SolidWorks 2017 and other software were used to build a three-dimensional model of L3-L5, and OLIF surgery was simulated to build OLIF finite element models with five different fixation methods: pedicle screw (PS), lateral single rod screw (LSRS), lateral double rod screw (LDRS), lateral single rod screw+ipsilateral translaminar facet screw (LSRS+ITLFS), lateral single rod screw+contralateral translaminar facet screw (LSRS+CTLFS). After validating the validity of the model, the motion modes of spinal flexion, extension, lateral bending and rotation were simulated, and the fixed segment activity and stress distribution characteristics of each model were compared.ResultsIn terms of fixed segment activity, PS had the best fixation effect, and its range of motion (ROM) was the smallest in all 6 modes. The ROM of the vertebral body was maximized when the LSRS was fixed in all directions. LSRS+ITLFS, LSRS+CTLFS and PS had the similar ROM. In terms of maximum stress of cage, PS had the minimum one except in the left bending. LSRS+ITLFS had little stress in all directions except in flexion; LSRS+CTLFS had little stress in all directions except in extension. In terms of the maximum stress in internal fixation, PS had the least one in all directions; LSRS+CTLFS followed, and the maximum stress appeared in extension and right bending (123.05MPA and 91.74MPA, respectively).ConclusionIn OLIF surgery, PS has the best biomechanical effect. LSRS+CTLFS has the similar effect and its clinical operation is simple with relatively small surgical injury, thus providing a reference for clinical choice.

Hematological Analysis and Diagnosis of Two Rare Abnormal Hemoglobin / 中国实验血液学杂志

OBJECTIVE@#To analyze the hematological characteristics of Hb Broomhill and Hb Hornchurch, and prenatal diagnosis should be carried out in two families.@*METHODS@#RBC parameters and hemoglobin electrophoretogram were analyzed on the peripheral blood of all patients, and amniotic fluid was collected for prenatal diagnosis. PCR-Flow fluorescent hybridization and Sanger sequencing were performed for gene diagnosis of thalassemia.@*RESULTS@#Three cases of Hb Broomhill were detected, including 2 cases with common SEA α-thalassemia, which was characterized by hypochromic microcytic mild anemia, the capillary electrophoregram revealed a tiny shoulder peak before the Hb A peak; 1 case was diagnosed as Hb Hornchurch combined with β-thalassemia, which also showed mild anemia. Hemoglobin electrophoretogram showed an abnormal hemoglobin variant peak at Hb A@*CONCLUSION@#The carriers of Hb Broomhill and Hb Hornchurch do not have microcytic hypochromic anemia, which do not aggravate the hematological symptoms, such as anemia when being combined with thalassemia of the same type.

Genetic Analysis, Prenatal Diagnosis and Preimplantation Genetic Diagnosis of Taiwanese Deletion β-Thalassemia / 中国实验血液学杂志

OBJECTIVE@#To perform genetic analysis, prenatal diagnosis and preimplantation genetic diagnosis (PGD) in a family with a rare deletional β- thalassemia.@*METHODS@#Hematological parameters of the peripheral blood collected from all the family members were analyzed by whole blood cell analysis and capillary zone electrophoresis (CZE). Polymerase chain reaction-reverse dot blot (PCR-RDB) was used to identify 17 common β- thalassemia gene mutations, the multiplex ligation-dependent probe amplification (MLPA) and gap-polymerase chain reaction (gap-PCR) were used to identify β- globin gene cluster deletions. Chorionic villus sample or umbilical cord blood was obtained for prenatal diagnosis. Oligo-cells from blastocyst biopsy were collected for preimplantation genetic diagnosis by whole genome amplification and next generation sequencing.@*RESULTS@#The proband was a carrier of Taiwanese deletion β- thalassemia, two fetuses were both thalassemia majors. The PGD results showed that 6 of 11 tested embryos could be choose for transplantation.@*CONCLUSION@#The Taiwanese deletion is a rare type deletion of β- globin gene cluster, and it can lead to thalassemia intermedia or thalassemia major when compounded with other β- globin gene mutation. PGD is another choice for thalassemia couples.

Anti-MRSA activities of cycloberberine derivatives with a novel chemical scaffold / 药学学报

Using CBBR as the parent core constructed in our lab, we designed and synthesized 15 novel compounds with diverse structures for evaluation of anti-bacterial activities. Structure activity relationship studies revealed that ① ring C was essential for the activity; ② 7,8- or 8,13-disubstituted CBBR derivatives showed ideal activities, weaker or similar to those corresponding to 7-, 8-, or 13-monosubstituted CBBR derivatives. Among those, compound 9a showed the most potential activity against MRSA/VISA isolates with MIC values of 1-2 μg·mL-1, much better than Lev. 9a also displayed higher stability in the plasma and liver microsomes. Molecular docking indicated that 9a might target bacterial DNA Topo IV ParE subunit, indicating a mode of action distinct from current antibacterial drugs on market. The results provided key scientific evidence for developing such compounds into a new family of anti-MRSA drugs.

Clinical Study on Middle-late Non-small Cell Lung Cancer Treated with Therapy of Strengthening Qi, Resolving Phlegm and Dissipating Mass / 广州中医药大学学报

Objective To observe the clinical effect of therapy of strengthening Qi, resolving phlegm and dissipating mass for middle-late non-small cell lung cancer. Methods Sixty patients with middle-late non-small cell lung cancer were randomly divided into 3 groups according to the results of intention-to-treat and genetic test. All of the 3 groups were given fundamental supportive and asymptomatic treatment, and additionally Group Ⅰ was mainly given oral use of Jinfuan Decoction with the actions of strengthening Qi, resolving phlegm and dissipating mass based on syndrome differentiation, group Ⅱ was treated with molecular targeted therapy with Gefitinib Tablets and /or Erlotinib Hydrochloride Tablets, and groupⅢ was only given the fundamental supportive and asymptomatic treatment. The 3 groups were treated for 3 cycles(84 days), and then we compared the tumor size, clinical symptoms, quality of life, distant metastasis, and the toxic and adverse effect in each group. Results (1) GroupⅠand group Ⅱhad stronger effect on relieving cough, shortness of breath and lassitude than groupⅢ(P<0.05); groupⅡand groupⅢwere more effective on relieving bloody sputum and chest pain than groupⅠ(P<0.05); groupⅠand groupⅢwere more effective on relieving fever than groupⅡ(P < 0.05). (2) In aspect of quality of life, KPS scores of groupⅠand group Ⅱwere much increased after treatment (P < 0.05), but the scores of group Ⅲ showed no obvious increase (P > 0.05). The improvement of KPS scores in groupⅠand groupⅡwas superior to that in groupⅢ(P<0.05). (3) GroupⅡhad a higher effective rate on stabilizing tumor size, the rate arrived to 65.0％, and was superior to that in groupⅠand groupⅢ(P <0.05) , and the effective rate in group Ⅰ was superior to that in group Ⅲ(P < 0.05). Group Ⅰ and group Ⅱhad a higher stabilizing rate than group Ⅲ(P < 0.05) , but the difference between group Ⅰ and group Ⅱ was insignificant (P>0.05). (4) GroupⅠhad less adverse reaction and higher safety. (5) The distant metastasis rate in groupⅠand groupⅡwas obviously lower than that in groupⅢ(P<0.05), but the difference of distant metastasis rate beetween group Ⅰ and group Ⅱ was insignificant (P > 0.05). Conclusion Therapy of strengthening Qi , resolving phlegm and dissipating mass is effective on relieving tumor-related symptoms , improving the quality of life, stabilizing the tumor, and controlling the distant metastasis in middle-late non-small cell lung cancer patients.