Clinical effect of Ranibizumab combined with 577nm micropulse laser in the treatment of severe diabetic macular edema / 国际眼科杂志(Guoji Yanke Zazhi)

AIM:To observe the clinical effect of ranibizumab combined with 577nm micropulse laser in the treatment of severe diabetic macular edema(DME). METHODS:There were 52 eyes of 52 patients diagnosed with severe DME who admitted to the People's Hospital of Guangxi Zhuang Autonomous Region from June 2016 to September 2019. The patients were randomly divided into the observation group(26 patients with 26 eyes, treated with ranibizumab combined with 577nm micropulse laser)and the control group(26 patients with 26 eyes, treated with ranibizumab alone). Patients in both groups received intravitreal injection of ranibizumab with “3+PRN” regimen. Followed up at 9mo after treatment to observe the central macular thickness(CMT), the best corrected visual acuity(BCVA)and the times of intravitreal injection of ranibizumab in the two groups.RESULTS:Compared with before treatment, the CMT and BCVA of the two groups were significantly improved at each time point after treatment(all P<0.001), but there was no difference between the two groups(P>0.05). During the follow-up period, the times of vitreous injection of ranibizumabin the observation group was significantly less than that in the control group(5.88±1.24 times vs 7.12±1.24 times, P=0.001). CONCLUSION:Both ranibizumab combined with 577nm micropulse laser and ranibizumab alone are effective in reducing edema and improving vision in patients with severe DME, but the combination therapy reduces the times of injection.

Efficacy and safety of roxadustat in the treatment of renal anemia in calciphylaxis dialysis patients / 中华肾脏病杂志

Objective:To observe the efficacy and safety of roxadustat in the treatment of renal anemia in calciphylaxis dialysis patients who had poor response to recombinant human erythropoietin (rHuEPO).Methods:This study was a prospective cohort study. The dialysis patients who were diagnosed with calciphylaxis and had previous regular use of rHuEPO≥3 months with hemoglobin (Hb) levels<110 g/L in the Department of Nephrology of Zhong Da Hospital affiliated to Southeast University from January 1, 2019 to March 28, 2021 were recruited. The effect of oral roxadustat in calciphylaxis dialysis patients with renal anemia was analyzed by self-comparison method.Results:There were totally 18 calciphylaxis dialysis patients with renal anemia enrolled in the study and the age was (49.7±16.2) years old, including 11 males and 7 females, and 14 cases on hemodialysis and 4 cases on peritoneal dialysis. The high-sensitivity C-reactive protein level was 27.3(15.6, 48.5) mg/L(reference value 0-3 mg/L) at baseline. The baseline Hb level was (85.4±11.6) g/L, and after 3 months of oral roxadustat, the Hb level was (105.8±15.2) g/L ( t=-9.282, P<0.001). The Hb compliance rate was 44.4%(8/18). Ferritin decreased significantly at 3 months compared with the baseline level [208.0(59.0, 306.3) μg/L vs 229.0(127.3, 385.2) μg/L, Z=-3.637, P<0.001]. The total iron binding capacity level increased significantly compared with the baseline level [127.0(65.0, 211.5) μmol/L vs 105.5(43.8, 153.7) μmol/L, Z=-2.156, P=0.031]. Transferrin saturation level at 3 months was lower than that at baseline, but there was no significant difference [20.2%(14.2%, 27.7%) vs 20.5%(18.7%, 34.9%), Z=-1.546, P=0.122]. No adverse reactions occurred during the observation period. Conclusion:The application of roxadustat can effectively correct Hb level and improve iron metabolism with high safety in calciphylaxis dialysis patients with renal anemia under inflammatory status.

Herbal Textual Research on Coptidis Rhizoma in Famous Classical Formulas / 中国实验方剂学杂志

Through the combing of ancient books of Chinese herbal medicine in the past dynasties， a textual research of Coptidis Rhizoma involved the name， origin， medicinal parts， producing area， quality evaluation， harvesting and processing methods in famous classical formulas was conducted in this paper. After textual research， the mainstream varieties of Coptidis Rhizoma in the Ranunculaceae family before Tang and Song dynasties were Coptis chinensis and C. chinensis var. brevisepala， after the Ming and Qing dynasties， C. deltoidea， C. teeta and C. omeiensis were gradually praised. In ancient times， the authentic producing area of Coptidis Rhizoma has the characteristics of gradually moving to the west. The eastern Coptidis Rhizoma was highly praised in the early stage， while in the later stage， western Coptidis Rhizoma like chicken feet was highly praised. In the early stage， western Coptidis Rhizoma probably originated from C. chinensis and its genus， while Coptidis Rhizoma like chicken feet was cultivated， and no wild species has been found so far. As Coptidis Rhizoma has mixed use of multiple origins in ancient books of past dynasties， based on the current shortage of market resources in C. teeta and C. deltoidea， there are also endangered and protected plants of C. chinensis var. brevisepala and C. omeiensis， combined with the mainstream medicines and resources of past generations， it is recommended to choose C. chinensis as the base of the formulas. In ancient times， there were many processing methods for Coptidis Rhizoma， such as frying and wine-， ginger-， honey-processed. In the process of developing famous classical formulas， the appropriate processing specifications of Coptidis Rhizoma should be selected based on the original source records and the requirements of the medicinal material.

Effect of miltirone on proliferation and apoptosis of leukemia THP-1 cells / 中国中药杂志

To investigate the toxicity and related mechanism of miltirone to human acute myeloid leukemia THP-1 cells. To be specific, the active components and targets of miltirone were retrieved from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP), and the target proteins were converted into standard gene names with UniProt. Acute leukemia-rela-ted target genes were screened from GeneCards and DisGeNET. Venn diagram was constructed with Venny 2.1 to yield the common targets of the disease and the drug. The protein-protein interaction(PPI) network was constructed by STRING and Cytoscape 3.8.2. THP-1 cells in the logarithmic growth phase were treated with dimethyl sulfoxide(DMSO), and 2.5, 5, 10, 15, and 20 μmol·L~(-1) miltirone for 24 h, respectively. The proliferation rate of cells was analyzed by carboxyfluorescein diacetate succinimidyl ester(CFSE), apoptosis rate by flow cytometry with Annexin V-PE/7 AAD staining, and cell morphology by acridine orange staining. Real-time quantitative PCR(qPCR) was employed to detect the mRNA levels of nuclear receptor coactivator 2(NCOA2), poly(ADP-ribose) polymerase-1(PARP1), B-cell lymphoma-2(Bcl-2)-associated X protein(Bax), Bcl-2, and cysteine aspartyl protease-3(caspase-3). The effect of miltirone on apoptosis was detected in presence of caspase inhibitor Z-VAD-FMK. A total of 26 targets of miltirone, 1 046 genes related to acute leukemia, and 6 common targets of the two were screened out. Flow cytometry result showed miltirone at 10 μmol·L~(-1) can inhibit proliferation and promote apoptosis of THP-1 cells. The typical manifestations of apoptosis, such as cell shrinkage, nuclear rupture, and chromatin agglomerate were displayed by acridine orange staining. The decreased mRNA levels of NCOA2 and PARP1 and increased Bax/Bcl-2 ratio and the activity of pro-apoptotic protein caspase-3 were observed. Z-VAD-FMK can attenuate the apoptosis-inducing effect of miltirone. This study indicates that miltirone can inhibit the proliferation and promote the apoptosis of THP-1 cells, by down-regulating NCOA2 and PARP1, raising Bax/Bcl-2 ratio, and activating caspase-3.

Salidroside inhibits phenotypic transformation of rat pulmonary artery smooth muscle cells induced by hypoxia / 中国中药杂志

This study investigated the effect of salidroside on phenotypic transformation of rat pulmonary artery smooth muscle cells(PASMCs) induced by hypoxia. Rat pulmonary arteries were isolated by tissue digestion and PASMCs were cultured. The OD values of cells treated with salidroside at different concentrations for 48 hours were measured by cell counting kit-8(CCK-8) to determine the appropriate concentration range of salidroside. The cells were divided into a normal(normoxia) group, a model(hypoxia) group, and three hypoxia + salidroside groups(40, 60, and 80 μg·mL~(-1)). Quantitative real-time PCR(qRT-PCR) was used to detect the mRNA expression of cell contractile markers in each group, such as α-smooth muscle actin(α-SMA), smooth muscle 22(SM22), and calcium-binding protein(calponin), and synthetic marker vimentin. The expression levels of cell phenotypic markers and proliferating cell nuclear antigen(PCNA) were detected by Western blot. The proliferation of cells in each group was detected by the 5-ethynyl-2'-deoxyuridine(EdU) assay. Cell migration was measured by Transwell assay. As revealed by results, compared with the normal group, the model group showed decreased mRNA and protein expression of contractile phenotypic markers of PASMCs and increased mRNA and protein expression of synthetic markers. Compared with the conditions in the model group, salidroside could down-regulate the mRNA and protein expression of synthetic markers in PASMCs and up-regulated the mRNA and protein expression of contractile phenotypic markers. Compared with the normal group, the model group showed potentiated proliferation and migration. Compared with the model group, the hypoxia + salidroside groups showed blunted proliferation and migration of cells after phenotypic transformation. The results suggest that salidroside can inhibit the expression of synthetic markers in PASMCs and promote the expression of contractile markers to inhibit the hypoxia-induced phenotypic transformation of PASMCs. The mechanism of salidroside in inhibiting the proliferation and migration of PASMCs is related to the inhibition of the phenotypic transformation of PASMCs.

Risk factors of spinal cord injury after total aortic arch replacement and frozen elephant trunk / 中华胸心血管外科杂志

Objective:To investigate the risk factors of spinal cord injury after FET for ATAAD.Methods:We analyzed perioperative data of 111 patients with ATAAD who underwent FET in the First Affiliated Hospital of Nanjing Medical University from January 2020 to October 2021.Results:Eleven(9.9%)of 111 patients had postoperative spinal cord injury, which showed varying degrees of paralysis or paraplegia. There was no significant difference in age, sex, medical history, cardiopulmonary bypass time, aortic cross-clamping time, circulatory arrest time and FET length between spinal cord injury group and non-spinal cord injury group( P>0.05). Univariate analysis showed that aortic true lumen away from the spinal side( P<0.001) and the number of segmental arteries originating from the true lumen<3 in T9-L3( P<0.001), left subclavian artery involvement( P<0.05) and stent coverage at T8 or beyond( P<0.05) was associated with postoperative spinal cord injury. Multivariate Logistic analysis showed that aortic true lumen away from the spinal side( P<0.001) and the number of segmental arteries originating from the true lumen<3( P<0.001) in T9-L3 and left subclavian artery involvement( P<0.05) were independent risk factors for postoperative spinal cord injury. Conclusion:The pathogenesis of spinal cord injury is complicated. This study suggests that the occurrence of spinal cord injury is significantly related to aortic true lumen away from the spinal side and the number of segmental arteries originating from the true lumen<3 in T9-L3 and left subclavian artery involvement. It is of great clinical significance to identify the high risk factors of postoperative spinal cord injury as early as possible.

Real-world clinical data analysis of PARPi as first-line maintenance therapy in newly diagnosed epithelial ovarian cancer patients / 中华妇产科杂志

Objective:The real-world clinical data of patients with newly diagnosed ovarian cancer (including fallopian tube cancer and primary peritoneal cancer) who received first-line maintenance therapy with poly adenosine diphosphate ribose polymerase inhibitor (PARPi) were retrospectively analyzed, and the prognostic factors were preliminarily explored.Methods:(1) The clinicopathological data and follow-up data of ovarian cancer patients treated with PARPi first-line maintenance therapy from August 2018 (PARPi was launched in China) to December 31, 2021 in Sichuan Cancer Hospital were collected (real-world clinical data). (2) According to the different types of PARPi, real-world clinical data were divided into olaparib group and niraparib group, which were respectively compared with the inclusion and exclusion criteria of representative domestic and foreign phase Ⅲ randomized controlled trials (RCT), including olaparib as first-line maintenance therapy for advanced ovarian cancer patients with BRCA1/2 gene mutation (SOLO-1 study), niraparib as first-line maintenance therapy (PRIMA study), and niraparib as first-line maintenance therapy for Chinese advanced ovarian cancer patients (PRIME study). (3) The prognosis of the two groups and the prognostic factors were analyzed.Results:(1) A total of 83 patients were included in this study, with a median age of 51 years (47-57 years), including 75 cases of ovarian cancer, 5 cases of fallopian tube cancer, and 3 cases of primary peritoneal cancer; 5 cases of stage Ⅰ, 9 cases of stage Ⅱ, 55 cases of stage Ⅲ, 12 cases of stage Ⅳ, and 2 cases of unknown stage; neoadjuvant chemotherapy (NACT) was performed in 40 cases and non-NACT in 43 cases; 62 cases had no visible residual lesion after surgery (R0), 9 cases had residual disease lesions <1 cm (R1), 8 cases had residual disease lesions ≥1 cm (R2), and 4 cases with unknown postoperative residual disease. Thirty-two cases had PARPi treatment interruption, 40 cases had PARPi reduction, and 1 case terminated treatment due to acute leukemia. Of the 83 patients, 35 were in the olaparib group and 48 were in the niraparib group. The proportion of patients with high-grade serous carcinoma (100% and 75%, respectively) and the proportion of BRCA mutant patients (91% and 10%, respectively) in the olaparib group were higher than those in the niraparib group (all P<0.01). (2) Compared with the inclusion and exclusion criteria of the SOLO-1 study, the olaparib group had only 60% (21/35) coincidence rate; compared with the inclusion and exclusion criteria of PRIMA and PRIME studies, the coincidence rates of niraparib group were only 31% (15/48) and 69% (33/48). The most common reasons for non-compliance were number of chemotherapy courses, histopathological type, and surgical pathological stage. (3) Of the 83 cases received first-line maintenance therapy with PARPi, the median follow-up was 15.9 months (11.3-22.9 months), the median progression-free survival (PFS) was 29.7 months (95% CI: 25.9-33.6 months), and the median overall survival was 49.8 months (95% CI: 47.4-52.2 months). Univariate analysis showed that unilateral or bilateral ovarian cancer, efficacy after platinum-containing chemotherapy, presence or absence of measurable lesions at the end of chemotherapy, and total number of chemotherapy courses were significantly associated with PFS (all P<0.05). Multivariate analysis showed that unilateral or bilateral ovarian cancer, total number of chemotherapy courses, and efficacy after platinum-containing chemotherapy were independent factors affecting PFS in stage Ⅱ-Ⅳ patients with PARPi first-line maintenance therapy (all P<0.05). Conclusions:Unilateral ovarian cancer, the total number of chemotherapy courses no more than 9, and achieving complete response after platinum-containing chemotherapy before maintenance therapy are independent influencing factors of PFS benefit in patients with PARPi first-line maintenance therapy. Due to the large differences between the patients in real clinical practice and the research subjects of phase Ⅲ RCT, the results of representative retrospective studies still have important clinical reference significance.

Identification of triterpenoid saponins from Anemone rivularis var. flore-minore and study on their antitumor activities / 中国药房

OBJECTIVE To study the triterpenoid saponins from Anemone rivularis var. flore-minore and their antitumor activities. METHODS The n-butanol extract of 70％ ethanol extract from rhizome of the plant was separated. The triterpenoid saponins were separated and purified by normal silica gel column chromatography ，reversed phase ODS column chromatography ， Sephadex LH- 20 gel column chromatography and semi-preparation high performance liquid chromatography. The structures of these saponins were identified by spectral analysis （NMR and MS ）and physical and chemical properties. MTT assay was used to test the proliferation inhibitory activity of the compounds against five kinds of human tumor cells （HL-60 cells，A549 cells，HepG2 cells，HeLa cells and U 87MG cells ）. The apoptosis inducing effect of compound 7 on U 87MG cells was evaluated by flow cytometric Annexin V-FITC/PI staining test. RESULTS：Sixteen triterpenoid saponins were obtained and identified as 3 β-O-β-D-xylopyranosyl-（1→2）-α-L-arabinopyranosyl-oleanolic acid-28-O-α-L-rhamnopyranosyl- （1→4） -β-D-glucopyranosyl-（1→6）-β-D-glucopyranoside（1），3β-O-L-arabinopyranosyl oleanolic acid- 28-O-β-D-glucopyranoside（2），saponin B （3）， 163.com oleanolic acid- 3β-O-β-D-glucopyranosyl-（1→2）-α-L-arabino- pyranoside（4），HN-saponin F （5），clematoside S （6），prosapogenin CP 4（7），cussonside B （8），pulsatilla saponin C （9）， clemastanoside D （10），3 β-O-β-D-glucopyranosyl-（1→2）-β-L-arabinopyranosyl-hederagenin-28-O-β-D-glucopyranoside（11）， ciwujianoside C 3（12），ciwujianoside A 1（13），huzhangoside D （14），kalopanaxsaponin B （15）and hederacolchiside E （16）. Compounds 3，4，6-9 displayed inhibitory activities on the proliferation of tumor cells to different extent ，and compound 7 had the strongest activity ；compound 7 induced the apoptosis of U 87MG cell so as to inhibit the proliferation of cancer cells in a time-dependent manner. CONCLUSIONS The obtained 16 saponins are all identified as oleanolane-type ，among which compound 1 is a new compound. The monodesmosidic saponins ，the sugar chain of which attached at C- 3 and a free carboxyl at C- 28， possess stronger antitumor activity than others.

Comparative analysis of bone mineral content measured by bioelectrical impedance analysis and dual energy X ray absorption among children and adolescents / 中国学校卫生

Objective@#To compare bioelectrical impedance analysis (BIA) and dual energy X ray absorptiometry (DXA) for measuring body mineral content (BMC) of children and adolescents, and to provide a basis for BIA to accurately measure BMC in children and adolescents.@*Methods@#By using the convenience sampling method, among 1 469 children and adolescents aged 7-17 were recruited in Guangzhou from April to May 2019, the BMC was measured by DXA and BIA. The intraclass correlation coefficient ( ICC ) and Bland Altman analysis were used to evaluate the agreement between BIA and DXA. Bland Altman analysis was performed on log transformed data. The BMC was categorized into age and specific tertiles, and the agreement between methods was evaluated based on the kappa coefficients. Treating the BMC with DXA as the dependent variable, a prediction model was constructed for correcting the BIA measure.@*Results@#The ICC s were 0.93 and 0.94 for boys and girls, respectively. In Bland Altman analysis, the limits of agreements for the BIA to DXA ratio were wide in boys and girls, ranging from 0.27-0.76 and 0.17-0.72, respectively. The kappa coefficients for categorized BMC levels were 0.57 and 0.45 for boys and girls, respectively, showing a fair to good degree of agreement. When sub grouped by BMI, the kappa coefficients for all BMI groups of boys and overweight girls were all >0.75 , with an excellent agreement. The prediction models for boys and girls were as follows: BMC DXA =-0.51+0.44× BMC BIA + 0.06× Age +0.02× BMI ; and BMC DXA =-0.55+0.43× BMC BIA +0.06× Age +0.02× BMI , respectively. The R 2 for models of boys and girls were 0.87 and 0.87, respectively.@*Conclusion@#The agreement between BIA and DXA was poor for measuring BMC, but acceptable when evaluating the categorized BMC levels, suggesting the BIA may be applied in assessment of the BMC levels when compared to the age and gender specific population. Additionally, the prediction model for correcting BMC by BIA fis well to the measurement by DXA.

Study on HPLC fingerprint and chemical pattern recognition of Mongolian medicine Sanzisan / 中国药房

OBJECTIVE To establish the HPLC fingerprint of Mongolian medicine Sanzisan ，and to evaluate its internal quality by chemical pattern recognition technique comprehensively. METHODS HPLC method was used. Using geniposide as reference，HPLC fingerprints of 15 batches of Sanzisan were drawn with Similarity Evaluation System of TCM Chromatogram Fingerprint（2012 edition）. Similarity evaluation and common peaks identification were conducted. Combined with cluster analysis （CA），principal component analysis （PCA），and orthogonal partial least squares-discriminant analysis （OPLS-DA），the quality of 15 batches of Sanzisan was evaluated ，and the differential markers that affected its quality were screened. RESULTS There were 29 common peaks in 15 batches of Sanzisan ，and the similarity was no less than 0.952，indicating that the chemical composition of the 15 batches of Sanzisan had good consistency. A total of 13 common peaks were identified ，which were chebulic acid ，gallic acid，punicalin，punicalagin A ，punicalagin B ，jasminoside B ，caffeic acid ，corilagin，geniposide，chebulagic acid ，1，2，3，4，6- O-galloylglucose，chebulinic acid ，ellagic acid. Both CA and PCA could divide 15 batches of Sanzisan into four categories ，and the classification results were consistent ，indicating that the quality of 15 batches of Sanzisan had certain differences. Fourteen differential markers （chebulic acid ，gallic acid ，ellagic acid ，etc）that lead to the quality difference between batches were screened out by OPLS-DA. CONCLUSIONS Established HPLC fingerprint analysis method is simple and stable. Combined with chemical pattern recognition analysis ，it can be used for the quality control of Sanzisan.

Content determination of 11 components in Terminalia chebula from different origins and comprehensive evaluation of their chemometrics / 中国药房

OBJECTIVE To establi sh the method for the con tent determination of 11 components in Terminalia chebula from different origins ，and to provide reference for their quality evaluation and superior provenance screening. METHODS Taking 16 batches of T. chebula from different origins as test samples ，high performance liquid chromatography tandem triple quadrupole mass spectrometry was established to determine the contents of 11 components，such as vitexin ，gallic acid ，methyl gallate ，ethyl gallate，ellagic acid ，corilagin，shikimic acid ，ferulic acid ，luteolin，quercetin and rutin. The determination was performed on Shim-pack GIST-HP C 18 column with mobile phase consisted of 0.1％ formic acid solution-methanol at the flow rate of 0.25 mL/ min（gradient elution ）. The sample size was 3 μL，and the column temperature was 35 ℃. Electrospray ionization source was used in positive and negative ion mode ，with multiple reaction monitoring. The atomized gas flow rate was 3 L/min，the heating gas flow rate was 10 L/min，the interface temperature was 300 ℃，the desolvent temperature was 526 ℃，and the heating block temperature was 400 ℃ . Grey correlation analysis （GRA）and technique for order preference by similarity to ideal solution （TOPSIS）methods were used to compare ，analyze and comprehensively evaluate T. chebula from different origins. RESULTS The results of content determination methodology met the relevant requirements. The contents of 11 components in 16 batches of T. chebula were 7.27-106.38，5 370.24-31 010.43，21.42-1 097.50，4.26-111.09，17 940.42-38 490.18，6 247.26-40 182.18，12 125.94- 209 519.96，2.71-9.04，0.24-44.12，1.49-9.17 and 25.35-126.51 μg/g，respectively. The results of GRA and TOPSIS analysis showed that the comprehensive qualities of sample H 12（from Yunnan ），H11（from Guangxi ），H5（from Hunan ），H14（from Guangdong），H13（from Sichuan ），H8（from Guangdong ），H1（from Yunnan ）were better. CONCLUSIONS The established method is fast ，sensitive and reliable ，and can be suitable for comprehensive evaluation of the internal quality and superior provenance screening of T. chebula .

Application and research progress of different chronic disease management models in rheumatoid arthritis in China / 中国实用护理杂志

The chronic disease management of rheumatoid arthritis has been popularized and applied in China. This article will review the application and research progress of different chronic disease management models, including chronic care mode, chronic disease self-management, transitional care mode, community-based chronic disease management, and "internet + chronic disease management" in rheumatoid arthritis patients in China, and compare the advantages and disadvantages of different intervention models, in order to provide a theoretical basis for exploring the chronic management of rheumatoid arthritis under different regional medical resources.

Osteoporosis and risk factors in perimenopausal women / 上海预防医学

ObjectiveTo screen the risk factors of osteoporosis in perimenopausal women， and to provide direction for timely prevention and treatment. MethodsUsing multilevel stratified random sampling method， the perimenopausal women were investigated by questionnaire survey， and the determination of bone mineral density （BMD） and the levels of several important hormones. ResultsA total of 720 valid questionnaires were received. Among 720 perimenopausal women， 173 had osteoporosis and 547 had no osteoporosis. Univariate analysis of the influencing factors of osteoporosis showed that the levels of parathyroid hormone （PTH）， Estradiol （E2）， body mass index （BMI）， age， time of last period and age of menopause were significantly different among perimenopausal women in the prevalence of osteoporosis（χ2=4.23， 4.86， 16.06， 21.04， 10.52， 13.02； P<0.05）.Logistic regression analysis showed that the increase of PTH （OR=2.70， P<0.05）and menopause （OR=1.76， P<0.05） were the risk factors of osteoporosis . Higher BMI（OR=0.65， P<0.05）， higher personal monthly income（OR=0.72， P<0.05）， longer sunshine time（OR=0.69， P<0.05）， were the protective factors against osteoporosis. ConclusionThe increase of PTH levels and menopause are the risk factors for osteoporosis in women. Perimenopausal women should be monitored for bone mineral density and appropriate intervention. Necessary treatment measures should be taken for the patients with osteopenia and osteoporosis.

Analysis of dietary intake in the residents aged 15 years and above in Shanghai / 上海预防医学

ObjectiveTo provide basic data of daily dietary intake from various food categories as well as in different regions， seasons， genders， and age groups in Shanghai residents aged 15 and over. MethodsMultistage stratified proportional probability sampling （PPS） was used to extract the samples， and food frequency questionnaire （FFQ） was used to investigate the dietary intake of the subjects in four seasons from 2012 to 2013. The weighted statistical analysis of the samples comprehensively considered the sampling design weights， the stratified adjustment weights， and the non-response adjustment weights. ResultsThe total daily dietary intake （excluding drinking water） of residents aged 15 years and above was 1 174.71 g， and the highest three daily dietary intake categories were cereals （252.31 g）， vegetables （205.36 g） and fruits （141.00 g）. The total daily dietary intake of the residents in the urban area， the suburban area and the rural area was 1 209.15 g，1 172.27 g and 948.50 g， respectively， and the total daily dietary intake in the outer suburb area was significantly lower than that in other areas （F=74.12，P<0.001）. The total daily dietary intake in different seasons was 1 232.47 g in spring， 1 166.80 g in summer， 1 241.15 g in autumn and 1 088.83 g in winter， respectively. The total daily dietary intake in winter was lower than that in other seasons （F=15.96，P<0.001）. Fruits and beverages intake showed apparent seasonality. The total daily dietary intake in male and female residents was 1 234.03 g and 1 112.32 g， respectively， and the total daily dietary intake of male was higher than that of female （F=78.59，P<0.001）. The total daily dietary intake of residents in different age groups was 1 218.64 g for 15‒44 years old， 1 141.27 g for 45‒59 years old， and 1 064.54 g for 60 years old and above （F=20.28，P<0.001）. ConclusionThe daily intake of cereals， livestock and poultry meat， aquatic products， eggs and edible oil is relatively balanced， but the daily intake of vegetables， fruits and milk is relatively insufficient for the residents aged 15 years and above in Shanghai. The daily intake of different food types shows distinguishable characteristics in urban and rural areas， seasons， age groups and genders.

Epidemiological features of foodborne disease outbreaks in Shanghai 2010 to 2020 / 上海预防医学

ObjectiveTo analyze the epidemiological features of foodborne disease outbreaks in Shanghai and to find the risk factors. MethodsWe collected the data of foodborne disease outbreaks occurred in Shanghai between 2010 and 2020， analyzed the characteristics of outbreaks， including time and geographic distribution， pathogenic factors and possible reasons caused outbreaks. ResultsBetween 2010 and 2020， there were 108 foodborne disease outbreaks with 1 736 cases， 45 inpatient cases and 1 death. May to September was the epidemic period， with about 64.81% of the outbreak occurrence. 39.81% outbreaks occurred in Pudong， Songjiang and Chongming Districts. Most outbreaks occurred in small restaurants （25%） and most foodborne cases were in staff canteen outbreaks （27.53%）. The main possible reasons caused outbreaks were improper food storage （19.44%）， cross-contamination （14.81%） and improper cooking （12.04%）. The major pathogenic factor was biological， caused 75.92% outbreaks and 77.59% cases. Methanol poisoning caused 1 death. The main contaminated food caused outbreaks was meat （17.59%）， multiple food （12.04%） and aquatic products （11.11%）. ConclusionThe foodborne disease outbreaks in Shanghai caused inpatient cases and death. We should pay more attention to foodborne disease outbreaks and we can control the risk factors by strengthening supervision and carrying out health education to reduce foodborne disease outbreaks.

Dose-enhanced immunochemotherapy followed by first-line autologous peripheral blood stem cell transplantation for young patients with high-risk aggressive B-cell lymphoma: an efficacy and prognostic factor analysis / 中华血液学杂志

Objective: This study aimed to determine the efficacy of dose-enhanced immunochemotherapy followed by autologous peripheral blood stem cell transplantation (ASCT) in young patients with newly diagnosed high-risk aggressive B-cell lymphoma. Methods: A retrospective study was conducted to examine the clinical and survival data of young patients with high-risk aggressive B-cell lymphoma who received dose-enhanced immunochemotherapy and ASCT as first-line treatment between January 2011 and December 2018 in Blood Diseases Hospital. Results: A total of 63 patients were included in the study. The median age range was 40 (14-63) years old. In terms of the induction therapy regimen, 52 cases received R-DA-EP (D) OCH, and the remaining 11 received R-HyperCVAD/R-MA. Sixteen (25.4% ) patients achieved partial response in the mid-term efficacy assessment, and ten of them were evaluated as complete response after transplantation. The median follow-up was 50 (8-112) months, and the 3-year progression-free survival (PFS) rate and overall survival (OS) rate were (83.9±4.7) % and (90.4±3.7) % , respectively. Univariate analysis demonstrated that age-adjusted international prognostic index ≥2 scores was a negative prognostic factor for OS (P=0.039) , and bone marrow involvement (BMI) was an adverse prognostic factor for OS (P<0.001) and PFS (P=0.001) . However, multivariate analysis confirmed that BMI was the only independent negative predictor of OS (P=0.016) and PFS (P=0.001) . Conclusions: The use of dose-enhanced immunochemotherapy in combination with ASCT as first-line therapy in the treatment of young, high-risk aggressive B-cell lymphoma results in good long-term outcomes, and BMI remains an adverse prognostic factor.

Short-term efficacy of venetoclax combined with azacitidine in acute myeloid leukemia: a single-institution experience / 中华血液学杂志

Objective: To explore the safety and short-term efficacy of venetoclax combined with azacitidine (Ven+AZA) in previously untreated patients unfit for standard chemotherapy and patients with relapsed/refractory (R/R) acute myeloid leukemia (AML) in China. Methods: A retrospective study was conducted in 60 previously untreated patients unfit for standard chemotherapy and patients with R/R AML who received Ven+ AZA (venetoclax, 100 mg D1, 200 mg D2, 400 mg D3-28; azacitidine, 75 mg/m(2) D1- 7) at the Peking University Institute of Hematology from June 1, 2019 to May 31, 2021. The incidence of adverse events, complete remission (CR) /CR with incomplete hematological recovery (CRi) rate, objective remission rate (ORR) , and minimal residual disease (MRD) status in patients with different risk stratification and gene subtypes were analyzed. Results: The median age of the patients was 54 (18-77) years, 33 (55.0%) were males, and the median follow-up time was 4.8 (1.4-26.3) months. Among the 60 patients, 24 (40.0%) were previously untreated patients unfit for standard chemotherapy, and 36 (60.0%) were R/R patients. The median mumber cycles of Ven+AZA in the two groups were both 1 (1-5) . According to the prognostic risk stratification of the National Comprehensive Cancer Network, it was divided into 8 cases of favorable-risk, 2 cases of intermediate risk, and 14 cases of poor-risk. In previously untreated patients unfit for standard chemotherapy, after the first cycle of Ven+AZA, 17/24 (70.8%) cases achieved CR/CRi, 3/24 (12.5%) achieved partial remission (PR) , and the ORR was 83.3%. Among them, nine patients received a second cycle chemotherapy and two received a third cycle. Among CR/CRi patients, 8/17 (47.1%) achieved MRD negativity after two cycles of therapy. In the R/R group, after the first cycle of Ven+AZA, 21/36 (58.3%) cases achieved CR/CRi (7/21 achieved MRD negativity) , 3 achieved PR, and the ORR was 66.7%. Among R/R patients, 12 were treated for more than two cycles. There were no new CR/CRi patients after the second treatment cycle, and 14 cases (66.7%) achieved MRD negativity. According to the time from CR to hematological recurrence, the R/R group was divided into 12 cases in the favorable-risk group (CR to hematological recurrence ≥18 months) and 24 in the poor-risk group (CR to hematological recurrence<18 months, no remission after one cycle of therapy, and no remission after two or more cycles of therapy) . Eleven of 24 (45.8%) cases achieved CR/CRi after one cycle of Ven+AZA in the poor-risk R/R group, and 10 of 12 (83.3%) achieved CR/CRi in the favorable-risk R/R group, which was significantly superior to the poor-risk group (P=0.031) . After one cycle of treatment, 13 patients with IDH1/2 mutations and 4 that were TP53-positive all achieved CR/CRi. The CR/CRi rate of 18 patients with NPM1 mutations was 77.8%. Five patients with RUNX1-RUNX1T1 combined with KIT D816 mutation (two initial diagnoses and three recurrences) had no remission. Ven+ AZA was tolerable for AML patients. Conclusion: Ven+AZA has acceptable safety in previously untreated patients unfit for standard chemotherapy, patients with R/R AML can achieve a high response rate, and some patients can achieve MRD negativity. It is also effective in NPM1-, IDH1/IDH2-, and TP53-positive patients. The long-term efficacy remains to be observed.

Research Progress on Enzyme-free Blood Glucose Sensor / 中国医疗器械杂志

Blood glucose monitoring is of great significance to diabetic patients, and the development of rapid, accurate and real-time glucose detection technology has become a research hotspot nowadays. This study introduces the concept and classification of the enzyme-free glucose sensor, expounds enzymefree glucose sensor electrode characterization methods and the application progress of different materials in enzyme-free blood glucose sensors. Meanwhile, some problems of enzyme-free glucose sensor existing in the current research and its future application prospects also will be discussed.

Effects of the ITGA2B Nonsense Mutation (c.2659C > T, p.Q887X) on Platelet Function in a Mouse Model of Glanzmann's Thrombasthenia Generated with CRISPR/Cas9 Technology / 中国实验血液学杂志

OBJECTIVE@#To construct a mouse model of Glanzmann's thrombasthenia (GT) with ITGA2B c.2659 C>T (p.Q887X) nonsense mutation by CRISPR/Cas9 technology, and then further explore the expression and function of glycoprotein αIIbβ3 on the surface of platelet membrane.@*METHODS@#The donor oligonucleotide and gRNA vector were designed and synthesized according to the ITGA2B gene sequence. The gRNA and Cas9 mRNA were injected into fertilized eggs with donor oligonucleotide and then sent back to the oviduct of surrogate mouse. Positive F0 mice were confirmed by PCR genotyping and sequence analysis after birth. The F1 generation of heterozygous GT mice were obtained by PCR and sequencing from F0 bred with WT mice, and then homozygous GT mice and WT mice were obtained by mating with each other. The phenotype of the model was then further verified by detecting tail hemorrhage time, saphenous vein bleeding time, platelet aggregation, expression and function of αIIbβ3 on the surface of platelet.@*RESULTS@#The bleeding time of GT mice was significantly longer than that of WT mice (P<0.01). Induced by collagen, thrombin, and adenosine diphosphate (ADP), platelet aggregation in GT mice was significantly inhibited (P<0.01, P<0.01, P<0.05). Flow cytometry analysis showed that the expression of αIIbβ3 on the platelet surface of GT mice decreased significantly compared with WT mice (P<0.01), and binding amounts of activated platelets to fibrinogen were significantly reduced after thrombin stimulation (P<0.01). The spreading area of platelet on fibrinogen in GT mice was significantly smaller than that in WT mice (P<0.05).@*CONCLUSION@#A GT mouse model with ITGA2B c.2659 C>T (p.Q887X) nonsense mutation has been established successfully by CRISPR/Cas9 technology. The aggregation function of platelet in this model is defective, which is consistent with GT performance.

Kinetics of MDSC in Patients Treated Steroids-Ruxolitinib as the First Line Therapy for aGVHD / 中国实验血液学杂志

OBJECTIVE@#To analyze the kinetic characteristics of lymphocyte subsets and myeloid-derived suppressor cell (MDSC) in patients who newly diagnosed intermediate- to high-risk aGVHD and treated with steroids-ruxolitinib as the first line therapy from a single-arm, open clinical trial (NCT04061876).@*METHODS@#We prospectively observed the efficacy of 23 patients having intermediate- to high-risk aGVHD and treated with steroids-ruxolitinib as the first line therapy. The kinetic characteristics of lymphocyte subsets and MDSC were monitored, and then we compared them in steroids-ruxolitinib group (n=23), free-aGVHD group (n=20) and steroids group (n=23).@*RESULTS@#Of the 23 patients, the CR rate was 78.26% (18/23) on day 28 after first-line treatment with steroids-ruxolitinib. On day 28 after treatment, patients had lower level of CD4+CD29+ T cells (P=0.08) than that of pre-treatment, whereas levels of other lymphocyte subsets in this study were higher than that of pre-treatment; CD4+CD29+ T cells in CR patients decreased, compared with refractory aGVHD patients. On day 28 of treatment, CD8+CD28- T cells (P=0.03) significantly increased in patients with aGVHD than that in patients without aGVHD, so did CD8+CD28- T / CD8+CD28+ T cell ratio (P=0.03). Compared with patients without aGVHD, patients with aGVHD had lower level of G-MDSC, especially on day 14 after allo-HSCT (P=0.04). Compared with pre-treatment, M-MDSC was higher in CR patients on day 3 and 7 post-treatment (P3=0.01, P7=0.03), e-MDSC was higher on day 28 post-treatment (P=0.01). Moreover, compared with CR patients, M-MDSC was lower in refractory aGVHD patients on day 3 post-treatment (P=0.01) and e-MDSC was lower on day 28 post-treatment (P=0.01). Compared with steroids group, MDSC in steroids-ruxolitinib group was higher, with the most significant difference in M-MDSC (P3=0.0351; P7=0.0142; P14=0.0369).@*CONCLUSION@#We found that patients newly diagnosed intermediate- to high-risk aGVHD receiving first-line therapy with steroids-ruxolitinib achieved high response rate. Moreover, the novel first-line therapy has a small impact on the immune reconstitution of patients after allo-HSCT. Elevated MDSC might predict a better response in aGVHD patients receiving this novel first-line therapy. M-MDSC responded earlier to steroids-ruxolitinib than e-MDSC, G-MDSC.