Expression and significance of pigment epithelium-derived factor and vascular endothelial growth factor in lens epithelial cells of diabetic patients with cataract / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To observe the expression levels of pigment epithelium-derived factor(PEDF)and vascular endothelial growth factor(VEGF)in lens epithelial cells(LECs)of diabetic patients with age-related cataract, and explore the pathogenesis of diabetic with age-related cataract.METHODS: Retrospectively study. A total of 30 patients with age-related cataract(ARC group)and 30 patients with type 2 diabetes mellitus combined with age-related cataract(DC group)who treated at the Department of Ophthalmology of the First Affiliated Hospital of Bengbu Medical College from August 2020 to April 2021 were collected. Anterior capsule specimens with a diameter of 5.5-6.0mm in the central region of the intraoperative eye were collected during phacoemulsification. The protein expression levels of PEDF and VEGF in LECs were detected by Western-blot. Quantitative real-time PCR(qRT-PCR)was used to detect the relative mRNA expression levels of PEDF and VEGF.RESULTS:PEDF and VEGF were expressed in LECs of both groups, and the relative expression of VEGF mRNA in DC group was 1.364±0.062, which was higher than that of ARC group(1.000±0.0; P<0.01). The relative mRNA expression level of PEDF was 0.398±0.053, which was significantly lower than 1.000±0.0 in the ARC group(P<0.001). The expression of VEGF protein in LECs was 2.053±0.026 in DC group and 1.680±0.064 in ARC group, respectively. Meanwhile, the expression of PEDF protein was 0.579±0.045 in DC group and 1.058±0.007 in ARC group(all P<0.01).CONCLUSION:The changes of PEDF and VEGF expression levels in LECs may be related to the occurrence and development of cataract in diabetic patients.

Application of artificial intelligence in the diagnosis of dry eye / 国际眼科杂志(Guoji Yanke Zazhi)

Dry eye(DE)is one of the most common eye diseases worldwide, with prevalence ranging from 5% to 50%. DE cannot be diagnosed timely and accurately due to its complex etiology and the limitations of testing equipment. In recent years, with the widespread use of artificial intelligence(AI)in the medical field, the application of machine learning and deep learning in the detection of dry eye has been deeply studied, such as interferometry, slit lamp examination and the classification and evaluation of meibomian gland images. Studies have found that the AI models can accurately analyze the measured data and images of patients with dry eye and with sensitivity and specificity of more than 90%. AI has great potential to assist clinicians in the objective diagnosis of dry eye and improve the quality of life of patients with dry eye. In this review, we summarized the current status of AI in dry eye, the potential challenges in clinical application, and look forward to the prospect of AI-assisted diagnosis of dry eye.

Effect of Loki Zupa on Airway Remodeling in Asthma Based on UPLC-MS Combined with Network Pharmacology and Experimental Verification / 中国实验方剂学杂志

ObjectiveTo investigate the effect of Loki Zupa on airway remodeling in asthma based on ultra-performance liquid chromatography-tandem mass spectrometry（UPLC-MS）combined with network pharmacology and experimental verification. MethodThe chemical constituents in Loki Zupa were identified by UPLC-MS. The potential active constituents of Loki Zupa were screened out based on literature retrieval， oral availability （OB） and drug-likeness （DL） in the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform（TCMSP） and Lipinski's rule of five in SwissADEM. The constituent targets of Loki Zupa were obtained through the SwissTargetPrediction. The relevant targets of airway remodeling in asthma were screened out from Online Mendelian Inheritance in Man（OMIM）， GeneCards， DrugBank， and DisGeNET. The STRING was used to conduct protein-protein interaction （PPI） among the main targets. Gene Ontology （GO） and Kyoto Encyclopedia of Genes and Genomes（KEGG） pathway enrichment analyses were carried out through DAVID. Finally， an asthmatic airway remodeling model was induced by ovalbumin （OVA） in mice， followed by hematoxylin and eosin（HE）， periodic acid Schiff（PAS）， and Masson staining for the observation of the pathological conditions of lung tissues. The inflammatory cells in the bronchoalveolar lavage fluid（BALF） of mice were detected. The protein expression levels in mouse lung tissues were detected by Western blot and key signaling pathways were further determined. ResultEighty-two constituents were detected in the negative ion mode and 74 in the positive ion mode by UPLC-MS. Thirty-six candidate constituents and 578 predicted targets of Loki Zupa were screened out through network pharmacology， and 173 common targets with airway remodeling in asthma were obtained， including key compounds such as sebacic acid， pectolinarigenin， naringenin， apigenin， and potential targets such as protein kinase B1（Akt）1 and hypoxia-inducible factor 1α（HIF-1α）. As predicted by KEGG enrichment analysis， Loki Zupa mainly exerted the effect against airway remodeling in asthma through phosphatidylinositol 3-kinase （PI3K）/Akt， HIF-1α， mitogen-activated protein kinase （MAPK）， and other signaling pathways. Animal experiments showed that the compound formula of Loki Zupa could reduce the proliferation of airway goblet cells in asthmatic mice， improve the deposition of collagen under the airway epithelium， and decrease the up-regulated relative expression levels of phosphorylate（p）-Akt/Akt and HIF-1α by OVA sensitization in mice （P<0.05， P<0.01）， which was consistent with the results of network pharmacology. ConclusionUPLC-MS combined with network pharmacology was used to preliminarily clarify the chemical composition of Loki Zupa and its underlying mechanism in intervention in airway remodeling in asthma. Specifically， Loki Zupa presumably synergistically intervened in airway remodeling in asthma through key targets represented by Akt1 and HIF-1α， and multiple pathways represented by the PI3K/Akt and HIF-lα pathways， which is expected to provide ideas for further research on Loki Zupa.

Investigation of a family cluster of COVID-19 in a district of Shanghai in 2021 / 上海预防医学

ObjectiveTo analyze the epidemiological characteristics of a family cluster of COVID-19 in a district of Shanghai， and to provide a scientific basis for prevention and control of cluster epidemic of COVID-19. MethodsField epidemiological survey was applied to study the cases and close contacts of a family cluster of COVID-19 in a district of Shanghai in 2021. Descriptive analysis of epidemiological survey data was conducted and real-time fluorescent quantification （RT-PCR） was used to detect new coronavirus nucleic acid for the collected specimens. ResultsCase A was the source of infection in the home aggregated epidemic. There were 2 second-generation cases infected in the whole incubation period. Case B and C were transmitted by case A through eating together. The PCR test results were negative both in the close contacts outside the family of primary contacts as well as in the close contacts to primary close contacts. ConclusionCOVID-19 is highly contagious and populations are generally susceptible. It is easy to cause family aggregated epidemic situation. Asymptomatic infection should be detected early and isolated. We should strengthen the tracking and management of close contacts of COVID-19 cases， and identify the second-generation cases as soon as possible.

Connotation and mitigation of polyphenolic astringency in Chinese medicine / 中国中药杂志

Taste is one of the important factors in the design of oral drug preparations. Polyphenols are the secondary metabolites produced in the growth process of Chinese medicine with a variety of physiological activities. However, astringency perceived from polyphenols tastes uncomfortable. As one of the true taste of Chinese medicine, astringency with drying, rough, and wrinkled sensation, seriously affects the texture of Chinese medicine and the compliance of patients. Due to the universality of polyphenolic astringency in Chinese medicine and the weakness of modern research, this study systematically reviewed and summarized the latest research on the mechanism of polyphenolic astringency, the astringency evaluation method, and the astringency-mitigation technology. Through comprehensively analyzing the quantification methods, such as sensory evaluation, animal preference evaluation, chemical evaluation, bionic evaluation, and polyphenol-protein interaction evaluation, the direction of overall astringency assessment with "unified dimension" was proposed. Since the characteristics of Chinese medicine and the mechanism of polyphenolic astringency did not reach a consensus, this study proposed the idea of astringency mitigation suitable for Chinese medicine. This study is intended to deepen the understanding of astringency associated with Chinese medicine, and establish a real and objective astringency evaluation method for Chinese medicine, thus promoting the technique of astringency mitigation of polyphenolic Chinese medicine preparations from trial and error to science.

Combined anti-bitterness strategy for extremely bitter characteristics of Andrographis Herba decoction and mechanism / 中国中药杂志

Three kinds of excipients were selected to investigate the anti-bitterness effect on the extremely bitter characteristics of Andrographis Herba decoction, and the optimal combined anti-bitterness formula was obtained. The preparation principle of different excipients was clarified by virtual screening and experimental verification to explore the advantages of the three kinds of excipients in the combined anti-bitterness effect. Sensory evaluation showed that mPEG_(2000)-PLLA_(2000), γ-cyclodextrin(γ-CD), and aspartame all had good anti-bitterness effect, which reduced the bitterness intensity of Andrographis Herba decoction by 0.5, 6, and 3 points, respectively. The anti-bitterness effect was superior when 0.15% mPEG_(2000)-PLLA_(2000), 1.60% γ-CD, and 0.04% aspartame were combined, and the taste score of the Andrographis Herba decoction decreased from 8 points(severe bitterness) to 1 point(almost no bitterness). Quantum chemistry calculations showed that mPEG_(2000)-PLLA_(2000) reduced the electrostatic potential of bitter groups, which spontaneously combined with it and formed a physical barrier, hindering the binding of bitter components to receptors. The interaction between γ-CD and bitter components was studied. It was found that the surface area and free energy of γ-CD decreased and the dipole moment increased, indicating that γ-CD included bitter components and self-assembled to form supramolecules. Molecular docking showed that hydroxy at position 14 and carbonyl at position 16 of andrographolide, and hydroxy at position 3 and 4, carbonyl at position 14, and five-membered lactone ring of dehydrated andrographolide were possibly the main bitter groups. The binding free energies of aspartame to bitter receptors TAS2 R10, TAS2 R14, and TAS2 R46 were-3.21,-1.55, and-2.52 kcal·mol~(-1), respectively, indicating that aspartame competed to inhibit the binding of bitter groups to bitter receptors. The results of content determination showed that the free amounts of andrographolide and dehydrated andrographolide in Andrographis Herba decoction were 0.23% and 0.28% respectively, while after adding flavor masking excipients, the dissociation amount of andrographolide and dehydrated andrographolide in the decoction decreased to 0.13% and 0.20%, respectively. The above results show that mPEG_(2000)-PLLA_(2000) involves some bitter components into it through micellar self-assembly to reconcile the entrance bitterness, and γ-CD includes the remaining bitter components in the real solution to control the main bitter taste. Aspartame further competes to inhibit the combination of bitter components and bitter receptors, and improves the taste to be sweet. Multi-excipients combined with anti-bitterness strategy significantly reduces the free concentration of bitter substances in Andrographis Herba decoction, and optimizes the taste of the decoction.

Late-onset hypogonadism in males: Guidelines and controversies / 中华内分泌代谢杂志

Late-onset hypogonadism (LOH) is an age-related testosterone deficiency syndrome. With the increasing aging of society, LOH results in impaired quality of life of middle-aged and elderly men. Although domestic and international guidelines have been issued in recent years, and the management of LOH became more standardized, numerous controversies still remained in the diagnosis of LOH, the benefits of testosterone replacement therapy (TRT) and therapeutic targets. Based on comparison of different guidelines, this review focuses on age cut-off , specific signs and symptoms of LOH, diagnostic cut-off level of testosterone, the advantages and disadvantages of TRT treatment, and non-testosterone therapy.

The application of transbronchial lung cryobiopsy guided by endobronchial ultrasound sheath in diagnosis of nonresolving pneumonias / 中国医师进修杂志

Objective:To explore the application of transbronchial lung cryobiopsy guided by endobronchial ultrasound sheath (EBUS-GS-TBCB) in diagnosis of nonresolving pneumonias.Methods:Sixty patients with nonresolving pneumonias from March 2019 to July 2020 in Dalian Municipal Central Hospital were selected. The patients were divided into EBUS-GS-TBCB group (31 cases) and transbronchial forcep lung biopsy guided by endobronchial ultrasound sheath(EBUS-GS-TBLB) group (29 cases) by random digits table method.Results:The diagnostic rate of nonresolving pneumonias in EBUS-GS-TBCB group was significantly higher than that in EBUS-GS-TBLB group: 87.10% (27/31) vs. 65.52% (19/29), and there was statistical difference ( χ2 = 3.90, P = 0.048). There were no statistical difference in sensitivity, specificity, accuracy, positive predictive value and negative predictive value between 2 groups ( P>0.05). There were no statistical difference inthe shortest distance from lesions to pleura, incidence of pneumothorax and incidence of bleeding between EBUS-GS-TBCB group and EBUS-GS-TBLB group: (27.42 ± 2.88) mm vs. (27.01 ± 2.37) mm, 6.45%(2/31) vs. 3.45%(1/29) and 22.58%(7/31) vs. 13.79% (4/29), P>0.05. Among the causes of nonresolving pneumonias, infectious factors accounted for 21.67% (13/60), non infectious factors accounted for 66.67% (40/60), and uncertain causes accounted for 11.67% (7/60). Conclusions:The diagnostic rate of EBUS-GS-TBCB in nonresolving pneumonias is significantly higher than EBUS-GS-TBLB, and the complications such as bleeding and pneumothorax do not increase significantly.

Clinical and laboratory diagnosis of indolent leukemic mantle cell lymphoma: report of one case and review of literature / 白血病·淋巴瘤

Objective:To improve the understanding of indolent mantle cell lymphoma (MCL).Methods:The data of a patient with indolent leukemic MCL in the Second Affiliated Hospital of Nanjing Medical University in May 2013 were collected. The cell morphology was analyzed by using cell smear, the flow cytometry was used to make immunophenotype analysis, the karyotype analysis was performed by usig cytogenetic technique, and polymerase chain reaction (PCR) was used to make the immunoglobulin gene analysis. At the same time, lymph node pathology and immunohistochemistry were also analyzed. The related articles published were reviewed to sum up the characteristics and the treatment of indolent MCL.Results:The male patient aged 60 years was obviously asymptomatic accompanied with slow disease progression, leukemic manifestation and without lymphadenopathy. He received pathological biopsy because of located lymphadenopathy in 2008. Small cell morphology, Kappa light chain immunophenotype, t(11;14) translocation showed after the cytogenetic examination, clonal immune globulin gene rearrangement and low Ki-67 positive index were identified. In situ MCL was diagnosed by retrospective pathology.Conclusions:Indolent MCL is extremely rare. It is typically asymptomatic with none or minimal nodal involvement, indolent disease course, leukemic phase with mild lymphocytosis, Kappa light chain expression, simple karyotype, classical or small cell morphology of tumor cells and the positive index of Ki-67 <10%. In situ MCL can be seen in pathology examination. IgVH gene mutation positive and SOX11 negative expression are notable in indolent MCL. International prognostic index of MCL is probably not appropriate in the prognostic analysis of leukemic indolent MCL. It is emphasized that initial observation and having therapies only after the disease progression can be suited for indolent MCL.

Analysis of dynamic image features of tear film in dry eye patients / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the image features of dynamic changes of tear film break-up after corneal fluorescein staining(FL)combined with tear film lipid layer(TFLL)dynamic changes in patients with dry eye and its value of diagnosis in dry eye. METHODS: A prospective study. A total of 66 patients(132 eyes)with dry eye admitted to our hospital during September 2019 to December 2020 were divided area break-up group(17 cases, 28 eyes), circle break-up group(20 cases, 27 eyes), line break-up group(25 cases, 28 eyes), spot break-up group(21 cases, 24 eyes)and random break-up group(20 cases, 25 eyes)according to the different fluorescein tear film break-up patterns(BUPs). The image features of tear film break-up dynamic changes and the image features of TFLL dynamic changes were compared in each group, and the differences in the first non-invasive tear film break-up time(NIBUTf), average non-invasive tear film break-up time(NIBUTav), tear meniscus height(TMH)and fluorescein staining scores were compare,RESULTS:A statistically significant differences were observed in NIBUTf among the groups of patients(P&#x003C;0.001). Except that there was no difference between spot break-up group and random break-up group(7.56±1.54s vs 8.02±1.86s, P=0.881), other groups had significant differences in pairwise comparisons(P&#x003C;0.05). There were statistically differences among the groups for NIBUTav(P&#x003C;0.001). Except that there was no difference between spot break-up group and random break-up group(9.54±2.12s vs 9.73±1.94s, P=0.997), other groups had significant differences in pairwise comparisons(P&#x003C;0.05). There was statistically difference among the groups for TMH(P&#x003C;0.001). Except that there was no difference between circle break-up group and line break-up group(0.16±0.03mm vs 0.17±0.03mm, P=0.986), there was no difference between spot break-up group and random break-up group(0.22±0.03mm vs 0.21±0.05mm, P=0.993), other groups had significant differences in pairwise comparisons(P&#x003C;0.05). There were statistically significant differences among the groups for FL scores and TFLL grading(P&#x003C;0.001).CONCLUSION:It is shown that different fluorescein BUPs intuitively reflects the tear film structure of the pathological changes according to evaluation and analysis of images feature of dynamic changes of FL tear film and TFLL combined with the results of static examination of tear film. It is helpful for clinicians to identify subtypes of dry eye, which has potential clinical value for the diagnosis and classification of dry eye.

Analgesic Effects of Two Types of Spinal Manipulation in Acute Lumbar Radiculopathy Model Rats / 中国结合医学杂志

OBJECTIVE@#To compare the analgesic effects of two types of spinal manipulation (SM) in acute lumbar radiculopathy (ALR) model rats induced by self-transplantation of autologous nucleus pulposus (ANP), and clarify the therapeutic mechanism.@*METHODS@#Totally 108 male Sprague-Dawley rats were randomly divided into 6 groups by a random number table (18 rats in each group), including a blank group with no interference, a sham operation group with a surgery by making a local soft tissue incision on the left side of L5-6 vertebral segment, a model group with ALR of L5 extraforaminal nerve by ANP self-transplantation without other interference, a sham manipulation (SMA) group with simulating physical rotation, as well as a mobilization (MOB) group with simulating low-velocity and variable-amplitude rotation and a manipulation (MAN) group with simulating high-velocity and low-amplitude rotation. The interventions in SMA, MOB, and MAN groups started 1 day after modeling followed by another 5 treatments at days 3, 5, 8, 10 and 12. Rats in the other 3 groups did not receive any special intervention. Behavioral pain tests of 50% mechanical pain withdrawal threshold (50% PWT) and paw withdrawal latency (PWL) were conducted 1 day before operation followed by another 10 tests on days 1-7, 10, 12 and 14. Immunohistochemical expression of nitric oxide synthase (NOS) was investigated on days 5 and 12 after operation.@*RESULTS@#After 3 experimental SM interventions, 50% PWT and PWL were higher in the MAN group than the SMA group on days 6 and 7, and higher on days 10, 12 and 14 postoperatively (P<0.05 or P<0.01), while the same indices were significantly higher in the MOB group than MAN group on days 1-4 (P<0.05 or P<0.01). The expression of NOS was lower in the MAN and MOB groups than SMA group on day 12 postoperatively (P<0.01).@*CONCLUSIONS@#Both manipulation and mobilization produced better results than sham interference in relieving pain by reducing neuroinflammation possibly. At the early period, compared with manipulation, mobilization presented less sensitive response to pain until later visit. SM may inhibit the overexpression of NOS, thereby alleviating severe radiculopathy.

Relationship between snoring and hypertension in middle-aged and elderly residents in Yangpu District， Shanghai / 上海预防医学

ObjectiveTo explore the relationship between snoring and hypertension in middle-aged and elderly residents in Yangpu District， Shanghai. MethodsThe data of this study were obtained from the project of “early screening and comprehensive intervention for high-risk of cardiovascular diseases” carried out by the National Cardiovascular Disease Center in Yangpu District in 2017. Questionnaire survey， physical examination and laboratory test were conducted among permanent residents aged 35‒75 years. Logistic regression model was used to analyze the influence of sleep snoring on hypertension. ResultsA total of 11 100 people with complete data were included in the analysis， The self-reported snoring rate of male was significantly higher than female （48.12% vs 36.21%， χ2=137.70， P<0.01）. The proportion of self-reported occasional snoring， frequent snoring and daily snoring were 14.67%（1 628/11 100）， 7.59%（843/11 100） and 17.50% （1 943/11 100）， respectively， and the prevalence of hypertension gradually increased with the increase of snoring frequency （≤60 years，male： χtrend2=51.83，P<0.01；female： χtrend2=95.01， P<0.01； >60 years， male： χtrend2=9.22， P<0.01； female： χtrend2=27.10， P<0.01）. Multivariate logistic regression analysis showed that in people aged ≤60 years， both men and women， snoring frequency was significantly associated with hypertension after adjusting for education， total family income， smoking， alcohol consumption， diabetes， body mass index （BMI） and waist circumference. In the males： occasional snoring OR （95%CI） was 1.95 （1.36，2.80）， frequent snoring OR （95%CI） was 1.55 （1.04，2.31）， daily snoring OR （95%CI） was 1.92 （1.43，2.59）. In the females： occasional snoring OR （95%CI） was 1.31 （1.08，1.59）， frequent snoring OR （95%CI） was 1.41 （1.07，1.88）， daily snoring OR （95%CI） was 1.63 （1.32，2.00）. But in people aged >60 years， the significant association between snoring frequencies and hypertension did not exist， after adjusting for education， total family income， smoking， alcohol consumption， diabetes， BMI and waist circumference. In the males： occasional snoring OR （95%CI） was 1.31 （0.97，1.78）， frequent snoring OR （95%CI） was 1.22 （0.87，1.73）， daily snoring OR （95%CI） was 1.19 （0.94，1.73）. In the females： occasional snoring OR （95%CI） was 1.06 （0.87，1.29）， frequent snoring OR （95%CI） was 1.30 （0.99，1.72）， daily snoring OR （95%CI） was 1.19 （0.97，1.46）. ConclusionIn people ≤60 years old， snoring is significantly associated with hypertension， so more attention should be paid to sleep snoring monitoring in middle-aged people for early detection of hypertension.

Epidemiological trend of notifiable infectious diseases in Yangpu District of Shanghai during 1950‒2020 / 上海预防医学

ObjectiveTo analyze the characteristics and trends of notifiable infectious diseases in Yangpu District of Shanghai， from 1950 to 2020， and to provide scientific basis for the formulation of control measures. MethodsDescriptive epidemiological method was used to collect and analyze the epidemiological data of notifiable infectious diseases. ResultsA total of 1 186 675 cases from 38 types of infectious diseases were reported. The annual morbidity of Class A and Class B infectious diseases fluctuated between 138.22/105 and 7 861.45/105， showing a decreasing trend. Among the 3 785 cases of death， the top five were measles， viral hepatitis， dysentery， tuberculosis and epidemic cerebrospinal meningitis. The high incidence diseases were intestinal infectious diseases， and the respiratory infectious diseases fluctuated in a wide range. Furthermore， blood-borne infectious diseases and sexual -transmitted diseases had continued to increase in recent years. As the result of normative vaccination， the incidence of associated infectious disease showed a downward trend. ConclusionThe incidence of infectious diseases in Yangpu District was on the drop from 1950 to 2020. Prevention and control work should focus on respiratory infectious diseases， blood-borne infectious diseases and sexual -transmitted diseases in the future. Furthermore， it is important to guarantee normative vaccination， especially， for prevention and control of infectious diseases.

MS2-RIP Assay for Identifying the Interaction Partners of lncRNA DANCR in Tumor Cells / 中山大学学报(医学科学版)

ObjectiveTo explore the functional mechanism of lncRNA DANCR in tumor cells， a MS2-RIP method was designed and conducted to identify the molecules that interact with DANCR. MethodsThe specific binding of MS2 bacteriophage capsid protein and MS2 binding site （MS2 BS）， a 19-base RNA stem-loop structure located at the 5′ terminus of the MS2 bacteriophage replicase gene， was applied to construct a plasmid for tandemly overexpressing DANCR and MS2 BS. DANCR was enriched and its associated molecules were further identified and analyzed. ResultsThe plasmid for tandemly overexpressing DANCR and MS2 BS was successfully constructed for the MS2-RIP experiment， which could significantly enrich DANCR and DANCR-binding protein EZH2 as a positive control. ConclusionBased on the high affinity binding between MS2 protein and MS2 BS， the MS2-RIP method was established for lncRNA DANCR， which could effectively capture DANCR as well as its associated molecules， providing a new technology for studying the functional mechanism of DANCR.

Clinical Analysis of Patients with MGUS, Primary Light Chain Amyloidosis, Multiple Myeloma or Multiple Myeloma with Concurrent Amyloidosis / 中国实验血液学杂志

OBJECTIVE@#To summarize and compare the clinical baseline characteristics of patients with monoclonal gammopathy of undetermined significance (MGUS), primary light chain amyloidosis (pAL), multiple myeloma (MM), or MM with concurrent amyloidosis, especially the differences in cytogenetic abnormalities.@*METHODS@#The clinical data of 15 cases of MGUS, 34 cases of pAL, 842 cases of MM and 23 cases of MM with concurrent amyloidosis were analyzed and compared retrospectively.@*RESULTS@#Cytogenetic statistics showed that the incidence of t (11; 14) in the four groups (MGUS vs pAL vs MM vs MM with concurrent amyloidosis) was 0%, 33.3%, 16.4%, and 15.8%, respectively (P=0.037); that of 13q deletion was 20.0%, 14.7%, 45.8% and 56.5%, respectively (P<0.001); gain of 1q21 was 50.0%, 12.5%, 47.4% and 40.9%, respectively (P=0.001). Proportion of pAL patients with 0, 1 and≥2 cytogenetic abnormalities (including 13q deletion, 17p deletion, 1q21 amplification and IgH translocation) accounted for 41.9%, 41.9% and 16.1%, respectively; while the proportion of the same category in MM was 17.6%, 27.3%, and 55.2% respectively; this ratio of MM with concurrent amyloidosis was more similar to MM. Subgroup analysis showed that genetic abnormalities (including 13q deletion, 17p deletion and 1q21 amplification) were comparable within t (11; 14) negative and positive groups. Compared with positive cases, t(11; 14) negative patients with MM or MGUS were more likely to have 13q deletions and multiple genetic abnormalities.@*CONCLUSION@#Clinical characteristics of pAL, especially cytogenetic abnormalities, are significantly different from MM with concurrent amyloidosis. It suggests that although the onset characteristics are similar, actually the two diseases belong to different disease subtypes which should be carefully predicted and identified.

Meta-analysis of effects of laparoscopic sleeve gastrectomy on vitamins and trace elements in obese patients / 中华临床营养杂志

Objective:To evaluate the changes in vitamins and trace elements in obese patients after laparoscopic sleeve gastrectomy (LSG).Methods:A systematic retrieval of the available literature was performed using Pubmed, Embase, Cochrane library, Web of Science, WanFang data and CNKI databases and studies were selected per predefined eligibility criteria. Statistical analysis was performed using Stata 13.0.Results:A total of 22 studies with 5320 individuals with obesity who underwent LSG were identified as eligible for inclusion. A significant increase was observed in serum 25(OH)D ( SMD = 0.59, 95% CI: 0.16 to 1.03, P = 0.007), phosphorus ( SMD = 0.28, 95% CI: 0.09 to 0.47, P = 0.004) and iron ( SMD = 0.46, 95% CI: 0.31 to 0.61, P < 0.01) after LSG. A significant decrease in serum zinc ( SMD = -0.41, 95% CI: -0.81 to -0.01, P = 0.044) was observed after LSG. But no significant changes in serum calcium ( SMD = 0.11, 95% CI: -0.14 to 0.36, P = 0.385), folate ( SMD = 0.27, 95% CI: -0.08 to 0.62, P = 0.133), vitamin B 12 ( SMD = 0.11, 95% CI: -0.25 to 0.47, P = 0.563) and magnesium ( SMD = 0.53, 95% CI: -0.08 to 1.14, P = 0.09) were observed. Conclusions:The changes of serum nutritional measurements in individuals with obesity who underwent LSG are uncertain. Therefore, it is recommended to monitor the nutritional laboratory values and add supplements when necessary to prevent postoperative malnutrition.

Research progresses in the biosynthesis of curcuminoids / 生物工程学报

Curcuminoids are rare diketone compounds in plants and can be found in the rhizome of Curcuma longa as well as other Zingiberaceae and Araceae. Curcuminoids have been widely used in food and medical area owing to the yellow colors, as well as the antioxidant and many other pharmacological activities. Curcuminoids are a mixture of compounds containing curcumin, demethoxycurcumin and bisdemethoxycurcumin, which have distinct benzene ring substituents. Currently, curcuminoids are exclusively produced through plant extraction, which do not satisfy the meeting of the market demand. Empowered with new synthetic biology tools and metabolic engineering strategies, there is renewed interest in production of curcuminoids using microorganisms. Heterologous production of curcuminoids has been achieved using Escherichia coli, Yarrowia lipolytica, Pseudomonas putida and Aspergillus oryzae via engineering of curcuminoids biosynthesis pathway. In this review, we first describe the biological activities and various applications of curcuminoids. Next, we summarize the biosynthetic pathway of curcuminoids in Curcuma longa and discuss the catalytic mechanisms of curcumin synthases. Then, we thoroughly explore recent advances in the use of distinct microorganisms for the production of curcuminoids with a special focus on metabolic engineering strategies. Finally, we prospect the microbial production of curcuminoids by highlighting some promising techniques and approaches.

PD-1/PD-L1 expression and its interaction with interferon-γ in Toxoplasma gondii-infected mice at middle and late pregnancy / 中国血吸虫病防治杂志

Objective To explore the dynamic expression of programmed cell death-1 (PD-1) and its ligand PD-L1 at the maternal-fetal interface of mice post-infection with Toxoplasma gondii at early pregnancy and examine its interaction with interferon-γ (IFN-γ). Methods A total of 20 mice at day 0 of pregnancy were randomly assigned into 4 groups, including the 12-day pregnancy control group (12 dpn group), 12-day pregnancy and infection group (12 dpi group), 18-day pregnancy control group (18 dpn group) and 18-day pregnancy and infection group (18 dpi group), respectively. On the 6th day of the pregnancy, mice in the 12 dpi and 18 dpi groups were injected intraperitoneally with 150 tachyzoites of the T. gondii PRU strain, while mice in the 12 dpn and 18 dpn groups were injected with the same volume of PBS. All mice in the four groups were sacrificed on 12th and 18th day of the pregnancy, and the number of placenta and fetus was counted and the weight of placenta and fetus was measured. Then, the placental and uterine tissues of the pregnant mice in each group were sampled for pathological examinations. The mRNA expression of PD-1, PD-L1, T. gondii surface antigen SAG-1 and IFN-γ genes was quantified using a quantitative real-time PCR (qPCR) assay, and the correlation between PD-1 and IFN-γ expression was examined. In addition, the 12 dpn group, 12 dpi group, 18 dpn group, 18 dpi group, PBS negative control of the 12 pdi group and PBS negative control of the 18 dpi group were assigned, and the PD-1 expression was determined in the uterine and placenta tissues of the pregnant mice. Results Adverse pregnant outcomes were seen in mice in the 12 dpi and 18 dpi groups, including placental dysplasia and fetal maldevelopment, and the placental weights and fetal body weights were significantly lower in mice in the 12 dpi and 18 dpi groups than those in the 12 dpn and 18 dpn groups (t = 5.52, 11.44, 12.63 and 11.67, all P < 0.01). The histopathological examinations showed that the decidua and junctional regions of the placental tissues were loosely connected in the 12 dpi and 18 dpi groups, and a large number of inflammatory cells infiltration and congestion were seen in the placental and uterine tissues. qPCR assay detected significant differences in PD-1, PD-L1, IFN-γ and SAG-1 expression in the placental and uterine tissues among the 12 dpn, 12 dpi, 18 dpn and 18 dpi groups (F = 22.48, 51.23, 9.61, 47.49, 16.08, 21.52, 28.66 and 238.90, all P < 0.05), and the PD-1, PD - L1, IFN - γ and SAG - 1 expression was all significantly higher in the placental and uterine tissues of mice in the 12 dpi group than in the 12 dpn group (all P values < 0.05). The PD-1 and PD-L1 expression was significantly lower in the placental tissues of mice in the 18 dpi group than in the 18 dpn group (all P values < 0.05), and the IFN-γ and SAG-1 expression was significantly higher in the placental and uterine tissues of mice in the 18 dpi group than in the 18 dpn group (all P values < 0.05), while the PD-1 and PD-L1 expression was significantly lower in the placental and uterine tissues of mice in the 18 dpi group than in the 12 dpi group (all P values < 0.05). Immunohistochemical staining showed PD-1 expression in the inflammatory cells of the placental tissues of mice in the 12 dpi group, and no apparent PD-1 expression in the 18 dpi group, while strongly positive PD-1 expression was found in the uterine epithelium of mice in the 12 dpi group, and mildly strong expression was in the 18 dpi group. In addition, the IFN-γ mRNA expression was positively correlated with the PD-1 mRNA expression in placental (rs = 0.99, P < 0.01) and uterine tissues of mice in the 12 dpi group (rs = 0.97, P < 0.01) and in placental (rs = 0.82, P < 0.01) and uterine tissues of mice in the 18 dpi group (rs = 0.81, P < 0.01). Conclusions Following T. gondii infection at early pregnancy, the PD-1 and PD-L1 expression shows a remarkable rise at middle pregnancy and a reduction at late pregnancy in placental and uterine tissues of mice, which appears the same tendency with IFN-γ expression during the same time period, and PD-1 expression positively correlates with IFN-γ expression. The dynamic expression of PD-1 and PD-L1 on the maternal-fetal interface of mice may be mutually mediated by IFN-γ induced by T. gondii infection.

Rutaecarpine exerted anti-osteroporosis / 药学学报

Osteoprotegerin (OPG), secreted by osteoblasts, is a marker of bone turnover. OPG can inhibit osteoclastic differentiation by binding receptor activator of nuclear factor-κB ligand (RANKL). In this study, we found that rutaecarpine (RUT) had the up-regulating OPG activity, and it could significantly increase OPG protein levels in both mouse embryonic osteogenic precursor MC3T3-E1 and human osteosarcoma U-2OS cells. Osteoblastogenic differentiation calcified nodules staining results showed that RUT significantly promoted the osteogenic differentiation of MC3T3-E1 cells. Osteoclastic differentiation tartrate resistant acid phosphatase (TRAP) staining results showed that RUT obviously inhibited the osteoclast differentiation of mouse macrophages RAW264.7 induced by RANKL. In vivo studies showed that low-dose RUT group (5 mg·kg-1·day-1) and high-dose RUT group (45 mg·kg-1·day-1) treatments for 3 months significantly increased bone density in ovariectomized (OVX) rats; calcein double labeling experiment and toluidine blue staining results indicated that low-dose RUT group promoted bone formation and decreased bone loss in vivo; immunohistochemistry results showed that low-dose RUT group increased the expression of OPG in rat femur. All animal procedures were performed in accordance with the regulations of the Institutional Animal Care and Use Committee of Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences. In summary, this study demonstrated that RUT could up-regulate OPG expression and had promoting osteoblastic differentiation and inhibiting osteoclastic differentiation effects in vitro and in vivo.

Preparation and enhanced photodynamic therapy of supramolecular nanoparticles to overcome tumor hypoxia / 药学学报

The therapeutic effect of tumor photodynamic therapy is severely limited by the hypoxic tumor microenvironment. Inhibiting tumor celloxygen consumption is a more effective way than increasing its oxygen supply to overcome the tumor hypoxia and enhance photodynamic therapy. To carry out this strategy, the supramolecular nanoparticles VER-ATO-SMN loaded with photosensitizer verteporfin (VER), oxygen-consuming inhibitor atovaquone (ATO), and stabilizer polyvinylpyrrolidone (PVP)-K30 were prepared by the nanoprecipitation method, and the optimal prescription was screened and optimized by single factor experiments. The results showed that the optimal prescription for VER-ATO-SMN was ATO∶VER (w/w) = 1∶1, PVP-K30 = 100 mg, N,N-dimethylformamide∶water (v/v) = 1∶10. The morphology, particle size, particle dispersion index and encapsulation efficiency of supramolecular nanoparticles were characterized. The VER-ATO-SMN showed a spherical morphology and was well dispersed. The hydrodynamic size of VER-ATO-SMN was 101.21 ± 4.30 nm as determined by dynamic light scattering (DLS). The encapsulation efficiencies of VER and ATO in VER-ATO-SMN prepared with the optimal prescription were 70.86% and 77.52%, respectively. The VER-ATO-SMN exhibited good laser stability and also showed high stability in conditions which simulated the physiological solution. Compared with free VER and VER liposome, VER-ATO-SMN performed enhanced therapeutic effect at the cell level. The mechanism was that VER-ATO-SMN could effectively incorporate into cells and improving the intracellular oxygen concentration by reducing the oxygen consumption of tumor cells could increase the amount of reactive oxygen species generated by VER mediated photodynamic therapy. The in vivo anticancer efficacy results of tumor-bearing mice suggested that VER-ATO-SMN could effectively inhibit the tumor growth or even completely eliminate the tumor. All animal experiments were performed in line with national regulations and approved by the Animal Experiments Ethical Committee of 900 Hospital of the Joint Logistics Team.