Research progress of Hp infection and blood system related diseases / 重庆医学

Helicobacter Pylori(Hp)is a spiral bacterium that colonized on the surface of gastric muco-sal epithelium.It is the main cause of gastrointestinal diseases because human is the only natural host and can survive in gastric acid.In recent years,relevant clinical studies have shown that Hp infection is closely related to hematological diseases such as allergic purpura(HSP),immune thrombocytopenic purpura(ITP),iron de-ficiency anemia(IDA),megaloblastic anemia(MA),lymphoma,leukemia and so on.Therefore,for Hp infec-tion,early diagnosis and treatment are of great significance for improving the efficacy of hematological diseases.

Study on the Synthesis,Structural Characterization and Activity of Fluorine-Containing Borneol Ester / 广州中医药大学学报

Objective Four fluorine-containing borneol ester were synthesized and analyzed for structure characterization and activity.Methods Four fluorine-containing borneol ester derivatives were synthesized by the reaction of fluorinated carboxylic acid and borneol by using p-toluenesulfonic acid as catalyst,and the structures of borneol esters were characterized by 1HNMR and 13CNMR.Molecular docking of the four fluorine-containing borneol ester with P-glycoprotein was carried out by Autodock Vina software.Results Four fluorine-containing borneol ester,bornyl 2-chloro-4-trifluoromethyl benzoate,bornyl 2-chloro-5-fluoro benzoate,bornyl 2-chloro-5-trifluoromethyl benzoate,bornyl 3-trifluoromethyl benzoate,were synthesized.The structures of the borneol ester were confirmed by 1HNMR and 13CNMR.4 fluorine-containing borneol ester had good binding ability with P-glycoprotein.Conclusion Four borneol ester compounds were synthesized,and the borneol ester enriched the types of borneol derivatives,which is of reference value for expanding the application range of borneol.

Changes in serum autophagy markers in infants with retinopathy of prematurity and the clinical value / 实用医学杂志

Objective To study the changes in serum autophagy markers in children with retinopathy of prematurity(ROP)and its clinical value.Methods Premature infants who were screened for ROP in our hospital from January 2020 to December 2022 were selected as the study subjects.Those screened out with ROP at 4-6 weeks of birth were assigned to the ROP group and those without ROP to the control group.The levels of serum autophagy markers LC3-Ⅱ,Beclin-1 and P62 were detected at the 3rd day,1st,2nd and 3rd weeks of birth.The two groups were compared in terms of serum autophagy markers.The diagnostic efficacy of serum autophagy markers on ROP was analyzed.Results There was no significant difference in serum LC3-Ⅱ,Beclin-1 and P62 levels between the ROP group and control group at the 3rd day of birth(P>0.05).At the first,second and third weeks of birth,how-ever,the ROP group showed significantly lower levels of serum LC3-Ⅱ and Beclin-1 but higher level of P62 com-pared to the control group(both P<0.05).The levels of serum LC3-Ⅱ,Beclin-1 and P62 at the first,second and third weeks of birth had diagnostic value for ROP.The children in the ROP group who did not receive mechanical ventilation and oxygen inhalation,and did not develop with sepsis and bronchopulmonary dysplasia showed lower serum LC3-Ⅱ and Beclin-1 levels and higher P62 levels at the first,second and third weeks of birth compared to those without the above-mentioned treatment as well as those complications(all P<0.05).In the ROP group,those with severe ROP showed lower serum LC3-Ⅱ and Beclin-1 levels and higher P62 levels at the 3rd day,and 1st,2nd and 3rd week of birth(all P<0.05).Conclusion The levels of serum autophagy markers in children with ROP show significant changes since the first week of birth,so they have diagnostic efficacy for the diseases.

Clinical analysis of 10 neonates with primary segmental volvulus / 中国新生儿科杂志

Objective:To summarize the clinical features of primary segmental volvulus (PSV) in neonates.Methods:A retrospective analysis was conducted on the clinical data of neonates with PSV who were admitted to the Department of Neonatal Surgery, Children's Hospital Affiliated to Capital Institute of Pediatrics from May 2014 to May 2023. The clinical manifestations, auxiliary examinations, treatment and prognosis of the neonates were summarized, and descriptive statistical analysis was performed on the collected data.Results:A total of 10 neonates with PSV were included, with a mean gestational age of (34.1±3.0) weeks and birth weight of (2 291±646) g. Eight cases had an onset age of 3 d or less, and 2 cases had an onset age of more than 3 d. Abdominal distension was observed as the main manifestation in all cases, while bilious vomiting occurred in seven cases and hematochezia in five cases. Imaging examinations mainly revealed low intestinal obstruction without specific manifestations. Laboratory tests showed metabolic acidosis and varing degrees of anaemia. Nine cases underwent diagnostic abdominal puncture, of which five had bloody ascites, two had clear ascites, one had bloody mixed with fecal-like ascites, and one had chylous ascites. All the cases underwent emergency exploratory laparotomy and segmental small bowel resections with either primary intestinal anastomosis or enterostomy. All cases were successfully cured and had been followed up to the age of 4 months to 9 years with good growth and development as normal children of the same age.Conclusions:Neonatal PSV is an independent abdominal emergency characterized by non-specific clinical manifestations and difficult preoperative diagnosis, but the overall prognosis is favorable after active surgical treatment.

Salvage radical surgery in early-stage colorectal cancer patients undergoing non-curative endoscopic resection / 中华普通外科杂志

Objective:To evaluate whether additional radical surgery is necessary following non-curative endoscopic resection of early colorectal cancer.Method:Clinicopathological data in 104 patients following non-curative endoscopic resection of early colorectal coucer at the Department of General Surgery, Peking University First Hospital between Jan 2011 and Dec 2021.Results:Lymph node metastasis and/or residual cancer was found in 23 patients (22%), including 12 cases of lymph node metastasis, 7 cases of residual cancer and 4 patients with both residual cancer and lymph node metastasis. Univariate analysis indicated that vascular infiltration, positive vertical margin, and female gender were risk factors for lymph node metastasis. Risk factors for residual cancer were tumors ≥2 cm in size, negative lift sign, infiltration depth of ≥1 000 μm, and positive horizontal and vertical margins. Multivariate Logistic regression analysis revealed that vascular invasion, positive vertical margins, and being female were independent risk factors for lymph node metastasis, while positive vertical margins was independent risk factor for residual cancer. Salvage surgery lasted for a median of 184 (156-233) minutes, with an estimated blood loss of 50 (20-100) ml and an average postoperative hospital stay of 9 (8-11) days. Seven cases of Clavein-Dindo Ⅱ or higher complications were observed, including pulmonary embolism in 1 case , anastomotic leakage in one, lymphatic fistula in one, bowel obstruction in 2 cases and urinary tract infection in 2 cases.Conclusion:Salvage surgery is mandatory for early endoscopic non-curative resection of colorectal cancer.

The Regulatory Function of ADAR1-mediated RNA Editing in Hematological Malignancies / 生物化学与生物物理进展

RNA editing, an essential post-transcriptional reaction occurring in double-stranded RNA (dsRNA), generates informational diversity in the transcriptome and proteome. In mammals, the main type of RNA editing is the conversion of adenosine to inosine (A-to-I), processed by adenosine deaminases acting on the RNAs (ADARs) family, and interpreted as guanosine during nucleotide base-pairing. It has been reported that millions of nucleotide sites in human transcriptome undergo A-to-I editing events, catalyzed by the primarily responsible enzyme, ADAR1. In hematological malignancies including myeloid/lymphocytic leukemia and multiple myeloma, dysregulation of ADAR1 directly impacts the A-to-I editing states occurring in coding regions, non-coding regions, and immature miRNA precursors. Subsequently, aberrant A-to-I editing states result in altered molecular events, such as protein-coding sequence changes, intron retention, alternative splicing, and miRNA biogenesis inhibition. As a vital factor of the generation and stemness maintenance in leukemia stem cells (LSCs), disordered RNA editing drives the chaos of molecular regulatory network and ultimately promotes the cell proliferation, apoptosis inhibition and drug resistance. At present, novel drugs designed to target RNA editing(e.g., rebecsinib) are under development and have achieved outstanding results in animal experiments. Compared with traditional antitumor drugs, epigenetic antitumor drugs are expected to overcome the shackle of drug resistance and recurrence in hematological malignancies, and provide new treatment options for patients. This review summarized the recent advances in the regulation mechanism of ADAR1-mediated RNA editing events in hematologic malignancies, and further discussed the medical potential and clinical application of ADAR1.

Research progress of selinexor in the treatment of recurrent and refractory multiple myeloma / 中国医师杂志

Multiple myeloma is an incurable hematological malignancy. Although the continuous development of therapeutic drugs such as proteasome inhibitors and immune modulators, as well as chimeric antigen receptor T-cell (CAR-T) therapy, has improved the prognosis in recent years, some patients are still drug-resistant, presenting as refractory and recurrent disease with limited treatment options. Selinexor, a first-in-class oral selective nuclear export protein inhibitor, binds to and inhibits nuclear export protein XPO-1 to function, leading to the accumulation of tumor suppressor proteins in the nucleus and selective apoptosis of cancer cells. It has shown controllable toxicity and good efficacy in the treatment of recurrent and refractory multiple myeloma. This article discusses the anti-tumor mechanism of selinexor, its clinical research progress, and adverse reactions.

Sterol transport proteins in yeast: a review / 生物工程学报

Sterols are a class of cyclopentano-perhydrophenanthrene derivatives widely present in living organisms. Sterols are important components of cell membranes. In addition, they also have important physiological and pharmacological activities. With the development of synthetic biology and metabolic engineering technology, yeast cells are increasingly used for the heterologous synthesis of sterols in recent years. Nevertheless, since sterols are hydrophobic macromolecules, they tend to accumulate in the membrane fraction of yeast cells and consequently trigger cytotoxicity, which hampers the further improvement of sterols yield. Therefore, revealing the mechanism of sterol transport in yeast, especially understanding the working principle of sterol transporters, is vital for designing strategies to relieve the toxicity of sterol accumulation and increasing sterol yield in yeast cell factories. In yeast, sterols are mainly transported through protein-mediated non-vesicular transport mechanisms. This review summarizes five types of sterol transport-related proteins that have been reported in yeast, namely OSBP/ORPs family proteins, LAM family proteins, ABC transport family proteins, CAP superfamily proteins, and NPC-like sterol transport proteins. These transporters play important roles in intracellular sterol gradient distribution and homeostasis maintenance. In addition, we also review the current status of practical applications of sterol transport proteins in yeast cell factories.

Chemical constituents from Nelumbinis Stamen / 中成药

AIM To study the chemical constituents from Nelumbinis Stamen.METHODS The methanol extract from Nelumbinis Stamen was isolated and purified by silica gel,C8 reversed phase column,Sephadex LH-20,preparative TLC and preparative HPLC,then the structures of obtained compounds were identified by physicochemical properties and spectral data.RESULTS Twenty-one compounds were isolated and identified as erythrodiol(1),erythordiol-3-acetate(2),2α-hydroxy-oleanolic acid(3),oleanolic acid(4),4-epi-hederagenin(5),4-epi-hederagenin methyl ester(6),28α-homo-β-amyrin acetate(7),betulinic acid(8),24-ketocholesterol(9),7β-hydroxy-sitosterol(10),7α-hydroxy-sitosterol(11),3β-hydroxy-stigmast-5-en-7-one(12),(3β,5α,6β,22E)-6-methoxyergosta-7,22-diene-3,5-diol(13),dankasterone A(14),demethylincisterol A3(15),β-sitostenone(16),β-sitosterol(17),quercetin(18),isorhamnetin(19),kaempferol(20),luteolin(21).CONCLUSION Compounds 2,4-15 are isolated from genus Nelumbo for the first time.Compound 16 is isolated from this plants for the first time.

Optimization of the extraction process for Xuelian yishen formula by the combination of entropy weight method-analytic hierarchy process with Box-Behnken response surface methodology / 中国药房

OBJECTIVE To optimize the extraction process of Xuelian yishen formula. METHODS The contents of total flavone， echinacoside and acteoside， and extraction yield in Xuelian yishen formula were chosen as indexes， entropy weight method-analytic hierarchy process was adopted to determine the weight coefficient. Box-Behnken response surface methodology was used to optimize the extraction process of Xuelian yishen formula with extraction time， solid-liquid ratio and extraction times as factors， using comprehensive score of above indexes as index. RESULTS The optimal extraction process of Xuelian yishen formula was extraction time of 2 h， solid-liquid ratio of 1∶12， extracting for 3 times. Average comprehensive score of 3 validation tests was 96.40 points （RSD＝0.28%）， the deviation of which with predictive value was 0.98%. CONCLUSIONS The optimized extraction process is stable， feasible and reproducible， which can provide reference for the extraction process of Xuelian yishen formula.

Clinicopathological features and prognostic analysis of primary duodenal adenocarcinoma / 中华普通外科杂志

Objective:By analyzing the clinical data of patients with primary duodenal adenocarcinoma (PDA), the risk factors affecting the postoperative prognosis of PDA patients were discussed.Methods:The clinical data of 191 patients diagnosed with PDA in Peking University First Hospital from Jan 2009 to Dec 2022 were collected. The survival rate was calculated and the survival curve was plotted by Kaplan-Meier method. Univariate analysis was performed by Log-Rank test, and multivariate analysis was performed by COX proportional hazards regression model to obtain independent risk factors.Results:The median age of onset in patients with PDA is 65 years old, and the most common symptoms are abdominal pain and abdominal distension. Prognostic analysis showed that the survival rates at 1, 3 and 5 years were 73.8%, 44.6%, and 23.0%. The analysis of Cox risk proportional regression model showed that preoperative CA19-9 level, depth of tumor invasion, degree of differentiation, TNM stage, and surgical mode were independent risk factors for the prognosis of PDA (all P<0.01). Conclusion:The overall incidence of PDA is low, but the prognosis is rather poor. Multvariable factors are associated with its prognosis and surgery is still the mainstay for hope of cure.

Research advance of mesenchymal stem cell-derived exosomes in graft-versus-host disease / 中华器官移植杂志

Mesenchymal stem cells (MSCs) are pluripotent stem cells with self-renewing differentiation, immunoactivity and anti-inflammatory potentials.Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is currently the most effective treatment for hematologic malignancies.However, the presence of graft-versus-host disease (GVHD) after transplantation has hindered the development of allo-HSCT.MSC-derived exosomes (MSC-exo) derived from mesenchymal stem cells have been confirmed to have broad therapeutic prospects in allo-HSCT and GVHD.This review focused upon immunomodulatory effects of MSC, biological activities of MSC-exo and research advances of MSC-exo on managing GVHD, aiming to provide new therapeutic rationales for GVHD in the future.

Bilateral hypertensive intracerebral hemorrhage in basal ganglia: a case report / 中华神经科杂志

Hypertensive intracerebral hemorrhage (ICH) is mostly single in basal ganglia, thalamus and pons. Simultaneous hemorrhage in other brain regions is relatively rare, accounting for only 5.6% of all hemorrhagic strokes, while bilateral symmetrical hemorrhage is extremely rare. A case of bilateral basal ganglia symmetrical hemorrhage is reported for clinical reference.

Early diagnostic value of mNGS for 15 cases with critical rickettsial disease in Hainan / 中华检验医学杂志

Objective:To explore the clinical utility of metagenomic next-generation sequencing (mNGS) for patients with critically ill atypical rickettsial infections in the early diagnosis and therapy.Methods:From Jan 2020 to Aug 2022, clinical features, blood biochemical results, imaging data and mNGS results in patients with unexplained critical illnesses were collected and analyzed retrospectively. Fisher's exact test was used to compare the positive rate of mNGS and weil felix reaction.Results:All 15 patients with rickettsial disease had fever, 12 cases had headache, but only 3 had a typical rash or scab of diagnostic significance, 6 had septic shock and all had multi-organ dysfunction; blood mNGS tests were positive in 15 cases, of which 10 had Orientia tsutsugamushi detected in their blood and the remaining five had Rickettsia moschata detected in their blood. The positive rate of mNGS was significantly higher than that of the weil felix reaction (15/15 vs 0, P<0.001). All patients were given doxycycline and other treatments after diagnosis, of which 14 improved and were discharged, and one died 1 week after discharge due to critical condition and abandonment of treatment. Conclusion:mNGS can improve the detection rate of atypical rickettsiae in patients with negative routine test results, which can provide valuable reference basis for early diagnosis and early anti-infection treatment of patients with critical rickettsial disease.

Analysis of typical experiences of public hospital salary system reform in Sichuan province / 中华医院管理杂志

Objective:To analyze the experiences and practice in the reform of public hospital salary system in Sichuan province, summarize the typical modes of such reform in the province, and provide references for further reform.Methods:As of October 29, 2021, the research group received 77 sets of typical experience materials submitted by the health commissions and public hospitals in Sichuan province on enforcing the reform of the public hospital salary system. The analysis framework was based on the five main elements proposed in the Guidance to Deepening the Reform of the Salary System of Public Hospitals for the purpose of furthering the reform. These five elements refer to " reasonably determining the level of salary in public hospitals" " fully implementing the autonomy of internal distribution in public hospitals " " establishing and improving the incentive and restraint mechanism for the remuneration of public hospital leaders" " improving the assessment and evaluation mechanism oriented to public welfare" and " funding sources ". A quantitative analysis was made on the typical experience materials using the social network analysis method, while a qualitative analysis was made on the typical experience materials using the content analysis method. Results:The results of social network analysis showed that the network density was 0.272; the highest point centrality was " fully implement the autonomy of internal distribution in public hospitals" (0.935), and the highest intermediary centrality was " improving the assessment and evaluation mechanism oriented to public welfare" (0.870), while the closeness to centrality of " establishing and improving the incentive and constraint mechanism for the salary of public hospital leaders" (0.434) and " funding sources" (0.421) were relatively low. The results of content analysis showed that the ones with higher frequency among all the typical experience materials were " fully implementing the autonomy of internal distribution of hospitals" (72 times) and " improving the assessment and evaluation mechanism oriented to public welfare" (67 times), while the ones with lower frequency were " establishing and improving the salary incentive and constraint mechanism for public hospital leaders" (17 times) and " funding sources" (14 times). In terms of unity and synergy, the typical models of public hospital salary system reform in the province could be categorized as the fine standard mode, the fair value mode, the autonomous synergy mode and the circular symbiosis mode.Conclusions:Deepening the reform of the salary system of public hospitals should unify the standards and improve the fair and refined assessment and evaluation mechanism; explore various forms of distribution and build an internal autonomous and synergistic incentive mechanism; pay attention to the weak remuneration incentive mechanism for hospital leaders and the problem of a relatively single source of funding.

Development of shared traditional Chinese medicine pharmacy from the perspective of primary medical care / 中国药房

In order to make the shared traditional Chinese medicine （TCM） pharmacy develop more efficiently and normatively at the grass-roots level， using the “shared TCM pharmacy” as the retrieval word， this paper uses the literature research method to retrieve the reports， documents and policies from CNKI， the websites of people’s governments at all levels， the official websites of the State Administration of Traditional Chinese Medicine， people.com， China News Network， Xinhua News and other platforms before May 20， 2022， sort out the development mode and history of two “Internet plus” TCM pharmacies， namely “shared TCM pharmacies” and “smart TCM pharmacies”， and compare them with each other. Combined with the actual work of community hospitals and community service centers （stations）， the necessity and advantages （such as reducing the costs of the intermediate links of drug circulation and standardizing the grass-roots drug use process） of the development of “shared TCM pharmacy” are obtained from the perspective of primary medical care. Combined with the current situation of the promotion and application of shared TCM pharmacy in county medical communities， it is concluded that the shared TCM pharmacy should be further constructed from four aspects： improving the work process of drug centralized procurement under the background of normalization， improving the compatibility and synchronization of the whole process dispensing information system module， unifying pharmaceutical services and personnel training， defining the authority of data query and clarifying the boundaries of patient privacy to further build a shared TCM pharmacy. Finally， it integrates information technology， summarizes the definition of shared TCM pharmacy and its future construction direction， and provides reference for the next development of shared TCM pharmacy at the grass-roots level.

The role of the high-level public health school in the development of the Center for Disease Control and Prevention / 中华流行病学杂志

The Ministry of Education and other four departments jointly issued the Notice on the Construction of high-level schools of public Health, proposing that "it will take ten years to build a number of high-level schools of public health, and form a high-quality education development system to adapt to the construction of modern public health system". At present, the construction of high-level public health schools in various universities in China is in full swing. The high-level School of Public Health and the CDC have played an important role in constructing the national public health system and the human health community. The high-level public health schools are of strategic significance and important value to the development of the CDC. The review presents reflections and insights on the role of high-level public health schools in the development of the CDC and the challenges they might face.

Establishment and behavioral evaluation of a mouse model of long-term free-choice alcohol drinking / 北京大学学报(医学版)

OBJECTIVE@#To establish a model of long-term free drinking mouse by feeding mice with alcohol to simulate the state of human voluntary long-term drinking, and on this basis, to further discuss the evaluation criteria of long-term free drinking mice model in sports, anxiety and cognitive behavior.@*METHODS@#Forty six-week-old SPF C57BL/6 male mouse were randomly divided into two groups: Long-term free drinking group (n=20) and normal control group (n=20). The two groups were given solid feed normally. The long-term free drinking group was free to take 10% alcohol and water every day, while the normal drinking group only took water every day. The mice were fed for 7 months, and were evaluated by a series of behavioral methods, including Rota-rod test, balance beam test, open filed test, the elevated plus maze, two-box social behavior, new object recognition, Y maze and water maze.@*RESULTS@#With the increase of drinking days, the mice showed significant alcohol addiction in the alcohol preference test. With the increase of alcohol intake, the mice in the long-term free choice drinking group had slightly shiny fur and reduced diet. Compared with the control group, the weight gain began to slow down from the third month, and the weight decreased significantly by the sixth and seventh months (P=0.006, P < 0.001). The mice showed reduced balance locomotion ability (P=0.003, P=0.001) in the rotary bar and balance beam test. In the open field and elevated cross test, the mice had obvious anxiety-like behavior (P < 0.001). The mice showed decreased social ability in the two boxes of social behavior (P < 0.016). In the experiment of new object recognition and Y maze, the exploration of new object decreased (P=0.018, P=0.040). In the water maze, cognitive functions, such as learning and spatial memory were reduced (P < 0.001).@*CONCLUSION@#The successful establishment of the long-term free drinking mouse model is more convenient for us to carry out further research on the neural mechanism of alcohol addiction, and lays an experimental foundation for exploring the neural mechanism of alcohol addiction and related new targets.

Genotype-environment interaction on arterial stiffness: A pedigree-based study / 北京大学学报(医学版)

OBJECTIVE@#To utilized the baseline data of the Beijing Fangshan Family Cohort Study, and to estimate whether the association between a healthy lifestyle and arterial stiffness might be modified by genetic effects.@*METHODS@#Probands and their relatives from 9 rural areas in Fangshan district, Beijing were included in this study. We developed a healthy lifestyle score based on five lifestyle behaviors: smoking, alcohol consumption, body mass index (BMI), dietary pattern, and physical activity. The measurements of arterial stiffness were brachial-ankle pulse wave velocity (baPWV) and ankle-brachial index (ABI). A variance component model was used to determine the heritability of arterial stiffness. Genotype-environment interaction effects were performed by the maximum likelihood methods. Subsequently, 45 candidate single nucleotide polymorphisms (SNPs) located in the glycolipid metabolism pathway were selected, and generalized estimated equations were used to assess the gene-environment interaction effects between particular genetic loci and healthy lifestyles.@*RESULTS@#A total of 6 302 study subjects across 3 225 pedigrees were enrolled in this study, with a mean age of 56.9 years and 45.1% male. Heritability of baPWV and ABI was 0.360 (95%CI: 0.302-0.418) and 0.243 (95%CI: 0.175-0.311), respectively. Significant genotype-healthy diet interaction on baPWV and genotype-BMI interaction on ABI were observed. Following the findings of genotype-environment interaction analysis, we further identified two SNPs located in ADAMTS9-AS2 and CDH13 might modify the association between healthy dietary pattern and arterial stiffness, indicating that adherence to a healthy dietary pattern might attenuate the genetic risk on arterial stiffness. Three SNPs in CDKAL1, ATP8B2 and SLC30A8 were shown to interact with BMI, implying that maintaining BMI within a healthy range might decrease the genetic risk of arterial stiffness.@*CONCLUSION@#The current study discovered that genotype-healthy dietary pattern and genotype-BMI interactions might affect the risk of arterial stiffness. Furthermore, we identified five genetic loci that might modify the relationship between healthy dietary pattern and BMI with arterial stiffness. Our findings suggested that a healthy lifestyle may reduce the genetic risk of arterial stiffness. This study has laid the groundwork for future research exploring mechanisms of arterial stiffness.

Metformin use and risk of ischemic stroke in patients with type 2 diabetes: A cohort study / 北京大学学报(医学版)

OBJECTIVE@#To explore the association between the use of metformin and the risk of ischemic stroke in patients with type 2 diabetes.@*METHODS@#A prospective cohort study was designed from the Fangshan family cohort in Beijing. According to metformin use at baseline, 2 625 patients with type 2 diabetes in Fangshan, Beijing were divided into metformin group or non-metformin group and the incidence of ischemic stroke between the different groups during follow-up was estimated and compared by Cox proportional hazard regression model. The participants with metformin were first compared with all the parti-cipants who did not use metformin, and then were further compared with those who did not use hypoglycemic agents and those who used other hypoglycemic agents.@*RESULTS@#The patients with type 2 diabetes were with an average age of (59.5±8.7) years, and 41.9% of them were male. The median follow-up time was 4.5 years. A total of 84 patients developed ischemic stroke during follow-up, with a crude incidence of 6.4 (95%CI: 5.0-7.7) per 1 000 person-years. Among all the participants, 1 149 (43.8%) took metformin, 1 476 (56.2%) were metformin non-users, including 593 (22.6%) used other hypoglycemic agents, and 883 (33.6%) did not use any hypoglycemic agents. Compared with metformin non-users, the Hazard ratio (HR) for ischemic stroke in metformin users was 0.58 (95%CI: 0.36-0.93; P = 0.024). Compared with other hypoglycemic agents, HR was 0.48 (95%CI: 0.28-0.84; P < 0.01); Compared with the group without hypoglycemic agents, HR was 0.65 (95%CI: 0.37-1.13; P=0.13). The association between metformin and ischemic stroke was statistically significant in the patients ≥ 60 years old compared with all the metformin non-users and those who used other hypoglycemic agents (HR: 0.48, 95%CI: 0.25-0.92; P < 0.05). Metformin use was associated with a lower incidence of ischemic stroke in the patients with good glycemic control (0.32, 95%CI: 0.13-0.77; P < 0.05). In the patients with poor glycemic control, and the association was not statistically significant (HR: 0.97, 95%CI: 0.53-1.79; P>0.05). There was an interaction between glycemic control and metformin use on incidence of ischemic stroke (Pinteraction < 0.05). The results of the sensitivity analysis were consistent with the results in the main analysis.@*CONCLUSION@#Among patients with type 2 diabetic in rural areas of northern China, metformin use was associated with lower incidence of ischemic stroke, especially in patients older than 60 years. There was an interaction between glycemic control and metformin use in the incidence of ischemic stroke.