Expression of serum circFTO and miR-141-3p in patients with diabetes retinopathy and their relationship with pathological stage / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To explore the relationship between the changes of serum circFTO and microRNA-141-3p(miR-141-3p)levels and the different disease stages of diabetes retinopathy.METHODS: A total of 198 patients with type 2 diabetes admitted to our hospital from October 2019 to November 2022 were collected as the study subjects, the patients were grouped into non diabetes retinopathy(NDR)group(70 cases), non proliferative diabetes retinopathy(NPDR)group(66 cases)and proliferative diabetes retinopathy(PDR)group(62 cases)according to different stages; meantime, 67 volunteers with normal physical examination results were collected as the control group. The levels of serum circFTO and miR-141-3p were detected by real-time fluorescent quantitative PCR(qRT-PCR); Pearson correlation analysis was used to examine the correlation between the serum circFTO, miR-141-3p and various indicators in patients with diabetes retinopathy; multivariate Logistic regression analysis was applied to explore the influencing factors of diabetes retinopathy.RESULTS: CircFTO, systolic blood pressure(SBP), and diastolic blood pressure(DBP)in PDR group were higher than those in control group, NDR group and NPDR group, while miR-141-3p and high-density lipoprotein cholesterol(HDL-C)were lower than those in control group, NDR group and NPDR group(P<0.05). Fasting blood glucose(FPG)and glycosylated hemoglobin(HbA1c)in NDR group, NPDR group and PDR group were higher than those in the control group(all P<0.05). The course of disease in PDR group was longer than that in NDR group and NPDR group(P<0.05). Serum circFTO in patients with diabetes retinopathy was positively correlated with SBP, DBP, FPG, HbA1c, and miR-141-3p was negatively correlated with SBP, DBP, FPG, HbA1c(all P<0.05). CircFTO was a risk factor for diabetes retinopathy, and miR-141-3p was a protective factor for diabetes retinopathy(P<0.05).CONCLUSION: Serum circFTO is obviously increased and miR-141-3p is obviously decreased in patients with diabetes retinopathy, both of them are closely related to disease stage, and are expected to become important indicators for evaluating disease progress.

Lignans from stems and leaves of Cephalotaxus fortunei (Ⅱ) / 中国中药杂志

The present study aimed to explore the chemical constituents from the stems and leaves of Cephalotaxus fortunei. Seven lignans were isolated from the 75% ethanol extract of C. fortunei by various chromatographic methods, including silica gel, ODS column chromatography, and HPLC. The structures of the isolated compounds were elucidated according to physicochemical properties and spectral data. Compound 1 is a new lignan named cephalignan A. The known compounds were identified as 8-hydroxy-conidendrine(2), isolariciresinol(3), leptolepisol D(4), diarctigenin(5), dihydrodehydrodiconiferyl alcohol 9'-O-β-D-glucopyranoside(6), and dihydrodehydrodiconiferyl alcohol 4-O-β-D-glucopyranoside(7). Compounds 2 and 5 were isolated from the Cephalotaxus plant for the first time.

Efficacy of different anti-vascular endothelial growth factor drugs in the treatment of diabetic macular edema and their relationship with optical coherence tomography classification / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To explore the clinical efficacy of different anti-vascular endothelial growth factor(VEGF)drugs in the treatment of diabetic macular edema(DME), and analyze their relationship with optical coherence tomography(OCT)classification.METHODS: A total of 45 DME patients treated with ranibizumab(admitted to our hospital from February 2020 to February 2022)were selected as the ranibizumab group, and 45 DME patients treated with conbercept during the same period were selected as the conbercept group. The ranibizumab group was treated with retinal photocoagulation combined with ranibizumab, and the conbercept group was treated with retinal photocoagulation combined with conbercept. The improvement of symptoms(improvement time of macular edema, time of retinal thickness returning to normal, disappearance time of neovascularization and absorption time of fundus hemorrhage), levels of serum interleukin-6(IL-6)and VEGF, central macular thickness(CMT), best corrected visual acuity(BCVA), and complications were compared between the two groups, and the relationship between their clinical efficacy and different OCT types were analyzed.RESULTS: There was no significant difference in the improvement time of macular edema, time of retinal thickness returning to normal, disappearance time of neovascularization and absorption time of fundus hemorrhage between the two groups(P>0.05); After treatment, the values of IL-6, VEGF and BCVA in the two groups were significantly lower than those before treatment(P<0.01), but there was no significant difference between the two groups(P>0.05); compared with before treatment, CMT was significantly decreased in both groups after treatment(P<0.05), and compared with ranibizumab group, the CMT was significantly decreased in the conbercept group(P<0.01); there was no significant difference in the incidence of complications between two groups(P>0.05); there were significant differences in the total effective rate among patients with serous retinal detachment(SRD), cystoid macular edema(CME)and diffuse retinal thickening(DRT; P<0.05), among which DRT had the highest total effective rate and SRD had the lowest total effective rate.CONCLUSION: Both conbercept and ranibizumab in the treatment of DME can effectively improve the clinical symptoms of patients and reduce the inflammatory response, but conbercept can better reduce the level of CMT, and has better treatment effect on DRT-type DME patients.

Interpretation of the 2022 American Academy of Pediatrics guidelines for the management of hyperbilirubinemia in newborn infants / 中国当代儿科杂志

The American Academy of Pediatrics updated the guidelines for the management of hyperbilirubinemia in the newborn infants with a gestational age of ≥35 weeks in September 2022. Based on the evidence over the past 18 years, the guidelines are updated from the aspects of the prevention, risk assessment, intervention, and follow-up of hyperbilirubinemia in the newborn infants with a gestational age of ≥35 weeks. This article gives an interpretation of the key points in the guidelines, so as to safely reduce the risk of bilirubin encephalopathy and unnecessary intervention.

Structure and Function of Glycosyltransferase from Common Pathogenic Bacteria / 中国生物化学与分子生物学报

Glycosyltransferases (GTs) catalyze the transfer of sugar moieties from activated donormolecules to acceptors such as sugars, lipids, proteins, and nucleic acids. Protein glycosylation is one ofthe most important post-translational modifications (PTMs). In recent years, increasing studies haveshown that glycosyltransferases are closely related to the virulence of pathogenic bacteria, and play a keyrole in adhesion, immune evasion, and host colonization. According to the features of three-dimensionalstructure, glycosyltransferases are classified into three groups (GT-A, GT-B and GT-C), among whichGT-A and GT-B folds are more common. Glycosyltransferases, which play a role in bacterial adhesion, adopt the GT-B or GT-C fold and glycosylate the surface proteins of pathogenic bacteria (adhesionproteins, autotransporters, etc.). It plays an important role in the adhesion of pathogenic bacteria, theformation of biofilm, and the virulence mechanisms. Glycosyltransferases take part in bacterial adhesionprocess of infection, and glycosyltransferases belonging to GT-A directly glycosylate host proteins andaffect host signal transduction, protein translation, and immune response. This review discusses thestructure of common pathogenic bacteria glycosyltransferases and the pathogenic mechanisms underlyingthese diseases of glycosylation. One kind of glycosyltransferases mainly modify their surface proteins, suchas the glycosyltransferase for specifically glycosylating high-molecular-weight(HMW) adhesion proteins, glycosyltransferases for glycosylation modification of serine-rich repeat proteins (SRRPs), bacterialautotransporter heptosyltransferase (BAHT) family, and N-linked protein system. The other kinds ofglycosyltransferases modulate host responses by directly modifying host proteins, such as Clostridium largecytotoxin, Legionella glycosyltransferase, and the NleB effector from enterobacteria. This review providesa reference for systematically revealing the pathogenic mechanism of glycosyltransferase in pathogenicbacteria, and contributes scientific knowledge in the development of pathogenic bacteria diagnosis, drugdesign, and vaccine development.

Efficacy and safety of autologous hematopoietic stem cell transplantation in elderly multiple myeloma patients: a single center retrospective study / 中华血液学杂志

Objective: To evaluate the efficacy and safety of autologous hematopoietic stem cell transplantation (auto-HSCT) in elderly patients (≥65 years old) with multiple myeloma (MM) . Methods: From June 1, 2006 to July 31, 2020, 22 MM patients (≥65 years old) who were diagnosed in the First Affiliated Hospital, Sun Yat-sen University and received novel drug induction followed by auto-HSCT were analyzed retrospectively. These patients were evaluated for important organ functions before transplantation, and the International Myeloma Working Group frail score was used in 2016 to screen out transplant-eligible patients. Results: The median (interquartile range, IQR) age at the time of transplantation of the 22 patients was 66.75 (IQR 4.50) years. A total of 20 patients received stem cell mobilization. The median number of mononuclear cells collected was 4.53×10(8)/kg, that of CD34(+) cells was 3.37×10(6)/kg, and the median number of apheresis procedures performed was 2. After stem cell transfusion, the median time of neutrophil implantation was 11 days, that of platelet implantation was 13 days, and the treatment-related mortality was 0 at 100 days after transplantation. The median follow-up was 48.7 months. The median time to progression time was not reached, and the median overall survival time was 111.8 months. Conclusion: Auto-HSCT is a safe and effective treatment for selected elderly patients of 65 years or older with MM.

In Vitro Fatigue Test of Lung Volume Reduction Loop / 中国医疗器械杂志

Lung volume reduction loop uses bronchoscopic lung volume reduction(BLVR) technology to compress and collapse the necrotic emphysema tissue and exhaust the internal gas to achieve the purpose of lung volume reduction to treat emphysema. After the lung volume reduction loop is implanted into the human body, the compressed part of the lung tissue tends to expand with breathing, which makes the lung volume reduction loop expand into a linear trend periodically. Fatigue resistance is one of the most important performance indexes of the lung volume reduction loop. In the paper, Z-direction vibration fatigue machine was used to simulate the changes of human respiratory cycle movement to test the fatigue performance of lung volume reduction loop, which can provide some reference for the test method of in vitro fatigue performance of lung volume reduction related products in the future.

Correlation analysis of smell and taste loss with COVID-19 outbreak trend based on big data of internet / 中华耳鼻咽喉头颈外科杂志

Objective: To analyze the correlation between loss of smell/taste and the number of real confirmed cases of coronavirus disease 2019 (COVID-19) worldwide based on Google Trends data, and to explore the guiding role of smell/taste loss for the COVID-19 prevention and control. Methods: "Loss of smell" and "loss of taste" related keywords were searched in the Google Trends platform, the data were obtained from Jan. 1 2019 to Jul. 11 2021. The daily and newly confirmed COVID-19 case number were collected from World Health Organization (WHO) since Dec. 30 2019. All data were statistically analyzed by SPSS 23.0 software. The correlation was finally tested by Spearman correlation analysis. Results: A total of data from 80 weeks were collected. The retrospective analysis was performed on the new trend of COVID-19 confirmed cases in a total of 186 292 441 cases worldwide. Since the epidemic of COVID-19 was recorded on the WHO website, the relative searches related to loss of smell/taste in the Google Trends platform had been increasing globally. The global relative search volumes of "loss of smell" and "loss of taste" on Google Trends was 10.23±2.58 and 16.33±2.47 before the record of epidemic while 80.25±39.81 and 80.45±40.04 after (t value was 8.67, 14.43, respectively, both P<0.001). In the United States and India, the relative searches for "loss of smell" and "loss of taste" after the record of epidemic were also much higher than before (all P<0.001). The correlation coefficients between the trend of weekly new COVID-19 cases and the Google Trends of "loss of smell" in the global, United States, and India was 0.53, 0.76, and 0.82 respectively (all P<0.001), the correlation coefficients with Google Trends of "loss of taste" was 0.54, 0.78, and 0.82 respectively (all P<0.001). The lowest and highest point of loss of smell/taste search curves of Google Trends in different periods appeared 7 to 14 days earlier than that of the weekly newly COVID-19 confirmed cases curves, respectively. Conclusions: There is a significant positive correlation between the number of newly confirmed cases of COVID-19 worldwide and the amount of keywords, such as "loss of smell" and "loss of taste", retrieved in Google Trends. The trend of big data based on Google Trends might predict the outbreak trend of COVID-19 in advance.

The construction of comprehensive stroke prevention and control system requires attention to the precise policies of young stroke / 中华预防医学杂志

Youth is the core force of social and economic development, once the occurrence of youth stroke will place a heavy burden on society and family. However, the prevention and control of stroke in China is mainly aimed at middle-aged and elderly patients, the part of young stroke is relatively easy to be ignored. This article focuses on the characteristics, research progress, prevention and control status of young stroke, pointing out the importance of centering on the prevention and treatment of young stroke. At the same time, it hopes that the industry can concentrate on the prevention and treatment of young stroke, making precise policies in the future, and developing secondary prevention guidelines for the causes or risk factors of young stroke, so as to improve comprehensive stroke prevention and control system. On this basis, the health level of the whole population will be improved, and the life expectancy of residents will be extended, thus promoting the realization of the strategic goal of "Healthy China 2030".

Identification of critical influencing factors in dropping process of Xuesaitong Dropping Pills / 中国中药杂志

With the dropping process of Xuesaitong Dropping Pills(XDP) as the study object, critical factors affecting the quality indicators of pill pass rate, average weight of drop pills and roundness were screened out, so as to deepen the understanding of the dropping process. The critical process units, critical quality attributes and potential critical process influencing factors of XDP were determined by risk analysis and prior knowledge, and then the critical influencing factors were screened out by Plackett-Burman design. First, according to the risk assessment, the critical technique of XDP preparation process was dropping, and then the critical quality attributes of dropping process were pill pass rate, average weight of drop pills and roundness. Then, according to fishbone diagram and failure mode and effects analysis(FMEA), potential critical influencing factors were determined as flow rate, matrix ratio, solid-liquid ratio, feed-liquid temperature, top temperature of condensate, bottom temperature of condensate and dropping distance. Finally, among these seven potential factors, the critical influencing factors were determined as material liquid ratio, dropping distance, top temperature of condensate, bottom temperature of condensate. This study revealed the potential of Plackett-Burman design in screening and understanding the influence of selected factors on XDP dropping process, which could provide a reference for studying the dropping process.

Peripheral blood indicators in medical radiation workers in Yangpu District of Shanghai， 2017-2019 / 上海预防医学

Objective:To explore the impact of occupational ionizing radiation exposure on blood indicators including white blood cell（ WBC）， red blood cell （RBC）， hemoglobin （Hb）， platelet （PLT） were analyzed. Methods:A total of 237 medical radiation workers in Yangpu district， Shanghai were recruited and divided into observation group and control group， according to individual average dose of external exposure. The annual effective dose in observation group was 0.357 7-4.704 3 mSv， and the median dose was 0.536 8 mSv （0.441 2-0.893 8）. The annual effective dose in control group was 0.031 2-0.350 8 mSv， and the median dose was 0.199 2 mSv （0.143 8-0.252 8）. Routine blood tests were conducted twice in the occupational health examinations from 2017 to 2019 and the results were collected. Chi-square test， Mann-Whitney U test， and generalized estimating equations （GEE） model were used for statistical analysis. Results:Compared to the first examination， the risk of having abnormal Hb increased （OR=1.029， 95%CI： 1.006-1.053）. After adjusting the factors of age， gender， seniority and exposure time， the risk of Hb abnormality in the observation group was lower than that in the control group （OR=0.422， 95%CI：0.198-0.898）. There was no significant difference between the observation and control groups in the risk of abnormal WBC， RBC， and PLT. Conclusion:Exposure to occupational ionizing radiation may increase the risk of abnormal Hb， while there is no significant change in WBC， RBC and PLT. Radiation workers should have full protection at work and be under appropriate occupational health management.

Renormalization of Thalamic Sub-Regional Functional Connectivity Contributes to Improvement of Cognitive Function after Liver Transplantation in Cirrhotic Patients with Overt Hepatic Encephalopathy

Objective@#The role of preoperative overt hepatic encephalopathy (OHE) in the neurophysiological mechanism of cognitive improvement after liver transplantation (LT) remains elusive. This study aimed to explore changes in sub-regional thalamic functional connectivity (FC) after LT and their relationship with neuropsychological improvement using resting-state functional MRI (rs-fMRI) data in cirrhotic patients with and without a history of OHE. @*Materials and Methods@#A total of 51 cirrhotic patients, divided into the OHE group (n = 21) and no-OHE group (n = 30), and 30 healthy controls were enrolled in this prospective study. Each patient underwent rs-fMRI before and 1 month after LT. Using 16 bilateral thalamic subregions as seeds, we conducted a seed-to-voxel FC analysis to compare the thalamic FC alterations before and after LT between the OHE and no-OHE groups, as well as differences in FC between the two groups of cirrhotic patients and the control group. Correction for multiple comparisons was conducted using the false discovery rate (p < 0.05). @*Results@#We found abnormally increased FC between the thalamic sub-region and prefrontal cortex, as well as an abnormally decreased FC between the bilateral thalamus in both OHE and no-OHE cirrhotic patients before LT, which returned to normal levels after LT. Compared with the no-OHE group, the OHE group exhibited more extensive abnormalities prior to LT, and the increased FC between the right thalamic subregions and right inferior parietal lobe was markedly reduced to normal levels after LT. @*Conclusion@#The renormalization of FC in the cortico-thalamic loop might be a neuro-substrate for the recovery of cognitive function after LT in cirrhotic patients. In addition, hyperconnectivity between thalamic subregions and the inferior parietal lobe might be an important feature of OHE. Changes in FC in the thalamus might be used as potential biomarkers for recovery of cognitive function after LT in cirrhotic patients.

Quality control analysis of brain tissue samples from Shanghai Brain Bank / 解剖学报

Objective To evaluate the feasibility of using brain tissues from Shanghai Brain Bank for the applications on biological research through the analysis of pH value of cerebrospinal fluids, RNA integrity number (RIN), transcriptome, proteome and morphology of brain tissues. Methods The pH value of fresh cerebrospinal fluid was detected by pH test paper; the RNA integrity of cryopreserved brain tissues was examined by Agilent RNA 6000 Nano chip and Agilent 2100 bioanalyzer; the transcriptome sequencing of superior temporal gyrus or caudate was performed using BGIseq-500 sequencer; the proteome of cryopreserved brain tissues was analyzed by Q Exactive HF mass spectrometer; at last, the morphology of the superior temporal gyrus was observed by HE staining. Results The pH value of the cerebrospinal fluid on average was about 6.5. The RIN values of more than 65% of brain tissues were more than 6, indicating good RNA quality. The clean reads ratio after transcriptome sequencing filtering was basically above 80%, indicating that the quality of sequencing library was high. The mass spectrometry analysis of frozen brain samples yielded more than 4000 protein groups and 30 000 peptides, indicating high quality of proteomic data. The morphology of brain tissues was relatively normal, with clearly visible neurons. Conclusion The quality of RNA and protein of brain tissues from Shanghai Brain Bank meets the basic needs for molecular and biological research, and the fixed brain samples can be used for morphological observations.

Quality Control of Appliance Products of Medical Devices for Human Assisted Reproductive Technology / 中国医疗器械杂志

Infertility has become one of the global problems, with the continuous improvement and penetration of human assisted reproductive technology, appliance products of medical devices for assisted reproductive technology, such as aspiration needles, micromanipulator and embryo transfer catheter, have been widely used. In order to ensure the safety and effectiveness of such products, it is necessary to establish an appropriate quality control system. This paper mainly discusses the quality control points of human assisted reproductive medical devices from the aspects of raw materials, product design, production process, key performance, packaging, preservation and transportation, so as to provide technical reference for the research and development, production and supervision of such products.

Irreducible Indirect Inguinal Hernia Caused by Sigmoid Colon Cancer Entering Right Groin:A Case Report / 中国医学科学院学报

We reported a case of irreducible indirect inguinal hernia caused by sigmoid colon cancer entering the right groin.The patient complained about a right groin mass for more than 60 years with progressive enlargement for 3 years and pain for half a month.Abdominal CT examination at admission showed rectum and sigmoid colon hernia in the right inguinal area and thickening of sigmoid colon wall.Electronic colonoscopy and pathological diagnosis showed sigmoid colon cancer.Therefore,the result of preliminary diagnosis was irreducible indirect inguinal hernia caused by sigmoid colon cancer entering the right groin.We converted laparoscopic exploration to laparotomy followed by radical sigmoidectomy and employed end-to-end anastomosis of descending colon and rectum in combination with repair of right inguinal hernia.The patient recovered well after operation and was discharged.

The Embryo Toxicity Research of Manufacturing Water of Medical Device of in Vitro Fertilization Technology / 中国医疗器械杂志

Water is an important component in liquid medical device products for human assisted reproductive technology. Water traits, conductivity, microbial limits, total organic carbon, easy oxides, heavy metal content, bacterial endotoxin and other indicators have an important impact on sperm, egg and embryo development in vitro, so for such products, the quality of water control is extremely important. The production water for producing such products is generally prepared by MilliQ purification system. In this research, we used four different types of water to fabricate the IVF liquids. It included deionized reverse osmosis water, ultra purified water and ultra purified water without endotoxin or nucleic acid, and compared with tap water. The in vitro rat embryo test system was used to study the embryotoxicity of this four different culture liquid production waters. From the result, the group of the super purified water without endotoxin and nucleic acid has the best result of the embryo formation rate, the number of total cell number and the inner cell number. This study proved the importance of removing endotoxin and nucleic acid from the water used for the preparation of the liquid products for assisted reproduction, and provided the basis for the selection of water quality for the liquid products for assisted reproduction.

Lignans from stems and leaves of Cephalotaxus fortunei / 中草药

Objective: To study chemical constituents of Cephalotaxus fortunei. Methods: The chemical constituents were separated and purified by preparative thin-layer chromatography, silica gel, ODS, HP20 macroporous resin and Sephadex LH-20 gel column chromatography, and semi-preparative HPLC. Their structures were determined by NMR and ESI-MS spectroscopic techniques. Results: Seventeen lignans were isolated from the ethanol extracts of C. fortunei and their structures were identified as shonanin (1), arctigenin (2), α-conidendrin (3), matairesinol (4), nortrachelogenin (5), epinortrachelogenin (6), (7'S)- hydroxymatairesinol (7), (7'R)-hydroxymatairesanol (8), (7'S)-hydroxyarctigenin (9), secoisolariciresinol (10), 4,4'-di-O-methylcephafortin A (11), 5-(3″,4″-dimethoxyphenyl)-3-hydroxy-3-(4'-hydroxy-3'-methoxybenzyl)-4-hydroxymethyl-dihydrofuran-2-one (12), cephafortin B (13), dihydrodehydrodiconiferyl alcohol (14), 7R,8S-4,7,9,9'-tetrahydroxy-3,3'-dimethoxy-8-O-4'-neolignan (15), 7R,8R-4,7,9,9'- tetrahydroxy-3,3'-dimethoxy-8-O-4'-neolignan (16), and threo-1,2-bis-(4-hydroxy-3-methoxyphenyl)-1,3-propanediol (17). Conclusion: Compounds 3, 6, 10 and 17 were isolated from genus Cephalotaxus for the first time, and compounds 4, 5, 7-9, 12 and 14 were isolated from C. fortunei for the first time.

Treatment patterns of patients with multiple sclerosis in Guangzhou, China

@#Background & Objective: Disease-modifying treatments (DMTs) for multiple sclerosis (MS) are widely used in Western countries. In China, however, the current treatment patterns of MS patients are not well characterized. This is to explore the gap between the current treatments in Guangzhou, Southern China and those given in Western countries. Methods: We performed a survey of MS patients at department of neurology, a tertiary MS referral centre in Guangzhou, concerning treatments of MS in Southern China. The clinical data in patients were collected. The initial treatment, drug withdrawal or switching profile, and therapeutic effect of existing treatments in MS patients were analyzed. Results: The ratio of MS patients who receive DMTs in Guangzhou China is extremely low. Among the 178 patients studied, only 28.09% received initial treatment with DMTs. MS patients who receive initial treatment with first-line DMTs have higher drug withdrawal rates (32.6%) and drug switching rates (30.43%) than those of western populations. The main reasons for withdrawal of first-line DMTs were doctor’s advice (maintenance of remission) (40.00%), economic burden(20.00%), and no channels to buy drugs(13.33%). In MS patients initially treated with first-line DMTs who switched to other drugs, a gap between treatments was common (8/14;57.14%). There were 18 patients with highly active MS receiving treatment with rituximab. Annual relapse rate after treatment significantly decreased than that before treatment (0.74 vs. 1.50 , P < 0.001). Conclusions: DMTs for MS in Guangzhou, Southern China appear to lag behind those in Western countries. Much work is needed to improve drug accessibility and affordability of DMTs in China. Rituximab is an option for highly active MS in limited medical-resource countries.

High dose melphalan (HDM) is superior to cyclophosphamide plus etoposide and busulfan (CVB) as the conditioning regimen in autologous stem cell transplantation for multiple myeloma / 中华血液学杂志

Objective: To compare the efficacy, response and survival between high-dose melphalan (HDM) and cyclophosphamide+ etoposide+ busulfan (CVB) as the conditioning regimen in autologous stem cell transplantation (ASCT) for newly diagnosed multiple myeloma (NDMM) . Methods: Retrospectively enrolled 123 consecutive NDMM patients who had received PAD induction with subsequent ASCT from Jan 2011 to Aug 2017. The CVB group and HDM group had 82 and 41 patients respectively. Results: ①No differences existed between these 2 groups in non-hematological side effects. ②Patients of CVB group had faster neutrophil and platelet engraftment time, with the median neutrophil engraftment time of 10 (9-35) day vs 11 (9-12) day for patients of HDM group (z=-3.433, P=0.001) , and with median platelet engraftment time of 11 (7-55) day vs 13 (10-35) day for patients of HDM group (z=-3.506, P<0.001) . CVB group entered neutropenia and severe thrombocytopenia more earlier than the HDM group, resulting similar neutropenia duration and severe thrombocytopenia duration between the CVB group and HDM group. However, patients of CVB group had significantly longer fever persistent time and antibiotic administration time. ③The response rate was significantly lower in patients of CVB group vs. patients of HDM group (9/46 vs 14/28, P=0.021) . Further, the minimal residual disease (MRD) negative rate at 3(rd) month post-transplantation seemed to be lower in CVB group than that in HDM group (31.7%vs 48.8%, P=0.065) . ④Both the univariate and multivariate analysis showed that HDM and CVB groups had similar duration to progression (TTP) (P=0.619) and overall survival (OS) (P=0.295) . Conclusion: HDM conditioning regimen is superior to CVB regimen in hematological side effects, tumor burden reduction and administration convenience. However, these two regimen had similar TTP and OS in MM patients receiving ASCT.

Bortezomib-based induction chemotherapy followed by autologous hematopoietic stem cell transplantation and maintenance in 200 patients with multiple myeloma: long-term follow-up results from single center / 中华血液学杂志

Objective: To study the efficacy, safety and long-term outcomes of integrated strategy of bortezomib-based induction regimens followed by autologous hematopoietic stem cell (ASCT) and maintenance therapy in Chinese multiple myeloma (MM) patients. Methods: 200 MM patients receiving integrated strategy of bortezomib--based induction regimens followed by ASCT and maintenance therapy were retrospectively and prospectively analyzed from December 1. 2006 to April 30. 2018. Results: The complete remission rates (CR) and better than very good partial remission rates (VGPR) after induction therapy, transplantation and maintenance therapy were respectively 31% and 75.5%, 51.8% and 87.7%,73.6% and 93.4%. There was no difference between 4 cycles and more than 5 cycles induction chemotherapy. The negative rate of MRD detection by flow cytometry was 17.6% and 38.2% respectively after induction and 3 months after transplantation. The negative rate of MRD gradually increased during the maintenance therapy. The success rate of high dose CTX combined with G-CSF mobilization was 95.5% and transplantation related mortality (TRM) was zero. The median time to progress (TTP) was 75.3 months and the median overall survival (OS) was 99.5 months. TTP of patients obtaining CR and negative MRD after induction were longer that those of no CR and positive MRD. TTP and OS of patients receiving triple-drug induction and ASCT in early stage were longer than those of double-drug induction and ASCT in late stage. LDH≥240 U/L, high risk cytogenetics, ISS II+III stage and HBsAg positive were prognostic factors at diagnosis. However, only MRD and high risk cytogenetics were independent prognostic factors after transplantation and maintenance therapy. The clinical characteristics of patients of TTP ≥6 years were listed below: light-chain type M protein, ISS I stage, normal level of hemoglobin and platelet, normal LDH, HBsAg negative, chromosome 17p-negative, good response and sustained good response. Conclusions: Integrated strategy of bortezomib-based induction regimens followed by ASCT and maintenance therapy can significantly improve the short-term and long-term efficacy. The prognostic factors of TTP in different disease stages were different. Response to treatment, especially MRD, played a more important role in prognostic factors.