Intravitreal aflibercept 8 mg in neovascular age-related macular degeneration (PULSAR): 48-week results from a randomised, double-masked, non-inferiority, phase 3 trial.

BACKGROUND: Intravitreal aflibercept 8 mg could improve treatment outcomes and provide sustained disease control in patients with neovascular age-related macular degeneration (nAMD), with extended dosing compared with aflibercept 2 mg. METHODS: PULSAR is a phase 3, randomised, three-group, double-masked, non-inferiority, 96-week trial conducted across 223 sites worldwide. Adults with nAMD were randomised 1:1:1 to aflibercept 8 mg every 12 weeks (8q12), aflibercept 8 mg every 16 weeks (8q16), or aflibercept 2 mg every 8 weeks (2q8), following three initial monthly doses in all groups. From week 16, patients in the aflibercept 8 mg groups had their dosing interval shortened if pre-specified dose regimen modification criteria denoting disease activity were met. The primary endpoint was change from baseline in best-corrected visual acuity (BCVA) at week 48. All patients with at least one dose of study treatment were included in the efficacy and safety analyses. This trial is registered with ClinicalTrials.gov (NCT04423718) and is ongoing. FINDINGS: Of 1011 patients randomised to aflibercept 8q12 (n=336), 8q16 (n=338), or 2q8 (n=337) between Aug 11, 2020, and July 30, 2021, 1009 patients received study treatment (aflibercept 8q12 n=335; aflibercept 8q16 n=338; and aflibercept 2q8 n=336). Aflibercept 8q12 and 8q16 showed non-inferior BCVA gains versus aflibercept 2q8 (mean BCVA change from baseline +6·7 [SD 12·6] and +6·2 [11·7] vs +7·6 [12·2] letters). The least squares mean differences between aflibercept 8q12 versus 2q8 and 8q16 versus 2q8, respectively, were -0·97 (95% CI -2·87 to 0·92) and -1·14 (-2·97 to 0·69) letters (non-inferiority margin at 4 letters). The incidence of ocular adverse events in the study eye was similar across groups (aflibercept 8q12 n=129 [39%]; aflibercept 8q16 n=127 [38%]; and aflibercept 2q8 n=130 [39%]). INTERPRETATION: Aflibercept 8 mg showed efficacy and safety with extended dosing intervals, which has the potential to improve the management of patients with nAMD. FUNDING: Bayer AG and Regeneron Pharmaceuticals.

Immunostimulatory gene therapy combined with checkpoint blockade reshapes tumor microenvironment and enhances ovarian cancer immunotherapy

Immune evasion has made ovarian cancer notorious for its refractory features, making the development of immunotherapy highly appealing to ovarian cancer treatment. The immune-stimulating cytokine IL-12 exhibits excellent antitumor activities. However, IL-12 can induce IFN-γ release and subsequently upregulate PDL-1 expression on tumor cells. Therefore, the tumor-targeting folate-modified delivery system F-DPC is constructed for concurrent delivery of IL-12 encoding gene and small molecular PDL-1 inhibitor (iPDL-1) to reduce immune escape and boost anti-tumor immunity. The physicochemical characteristics, gene transfection efficiency of the F-DPC nanoparticles in ovarian cancer cells are analyzed. The immune-modulation effects of combination therapy on different immune cells are also studied. Results show that compared with non-folate-modified vector, folate-modified F-DPC can improve the targeting of ovarian cancer and enhance the transfection efficiency of pIL-12. The underlying anti-tumor mechanisms include the regulation of T cells proliferation and activation, NK activation, macrophage polarization and DC maturation. The F-DPC/pIL-12/iPDL-1 complexes have shown outstanding antitumor effects and low toxicity in peritoneal model of ovarian cancer in mice. Taken together, our work provides new insights into ovarian cancer immunotherapy. Novel F-DPC/pIL-12/iPDL-1 complexes are revealed to exert prominent anti-tumor effect by modulating tumor immune microenvironment and preventing immune escape and might be a promising treatment option for ovarian cancer treatment.

Expert consensus on COVID-19 vaccination for children with special medical conditions / 上海预防医学

Children with certain comorbidities and immunocompromising conditions are highly vulnerable to SARS-CoV-2 infection. Vaccination against SARS-CoV-2 is an important strategy to reduce death， critical illness and overall disease burden. With the evolving and increasing transmission of SARS-CoV-2， universal vaccination is essential to achieve this goal. Children with special medical conditions are considered as the priorities for SARS-CoV-2 vaccination. However， vaccine hesitancy towards the implementation of SARS-CoV-2 vaccination currently remains an urgent challenge. In order to promote the sustainable vaccination for those children in Shanghai as well as China， Shanghai municipal center for disease control and prevention， together with the national children’s medical center， children’s hospital of Fudan university and the expert group on immunization planning of the Shanghai preventive medicine association， organized a consensus expert working group to formulate the evidence-based recommendations and implementation suggestions for children with common chronic diseases， allergy history， diseases involving adverse events related to vaccination， and immunocompromising conditions， based on the published evidence of SARS-CoV-2 vaccination for populations and children with special medical conditions.

Improvement effect and mechanism of Baicao fuyanqing suppository on bacterial vaginitis in rats / 中国药房

OBJECTIVE To explore the improvement effect and potential mechanism of Baicao fuyanqing suppository on bacterial vaginitis （BV） in rats. METHODS The female SD rats were randomly divided into normal group， model group， metronidazole group （positive control， 0.03 g/kg）， Baicao fuyanqing suppository low-dose， medium-dose and high-dose groups （0.18， 0.36， 0.72 g/kg）， with 8 rats in each group. Except for the normal group， the rats in other groups were injected subcutaneously with 0.2 g of Estradiol benzoate injection+20 μL of Escherichia coli suspension （2×108～3×108 cfu/mL） through the vaginal opening to establish the BV rat model. Administration groups were given relevant medicine vaginally， while the normal group and the model group were given normal saline， once a day， for 6 consecutive days. Twenty-four hours after the last administration， the vaginal appearance score and vaginal pH were measured for each group of rats. The levels of cytokines [interleukin-1β （IL-1β）， IL-2， IL-13， immunoglobulin A （IgA）] in vaginal lavage fluid were determined. The morphology of the uterus and accessories， and pathological changes in the vaginal tissue were observed. The expressions of Toll-like receptor 2 （TLR2）， TLR4 and nuclear factor-κB （NF-κB） in vaginal tissues were determined. RESULTS Compared with the normal group， the uterus edema， the irregular shape of uterus and accessories， the vaginal mucosa hyperplasia， and the massive desquamation of epithelial cells were observed in the model group， complicating with massive infiltration of inflammatory cells； vaginal opening redness and swelling score and secretion score， vaginal pH， the levels of proinflammatory cytokine IL-1β and IL-2， the protein expressions of TLR2， TLR4 and NF- κB were all increased or up-regulated， while the levels of IgA and anti-inflammatory cytokine IL-13 decreased significantly （P＜0.05 or P＜0.01）. Compared with the model group， varying cn degrees of improvement in uterine and accessories， and vaginal tissue lesions in rats were observed in administration groups， and most of the quantitative indicators mentioned above showed significant improvement （P＜0.05 or P＜0.01）. CONCLUSIONS Baicao fuyanqing suppository has a certain improvement effect on inflammatory symptoms in BV rats， and its mechanism may be related to the inhibition of the TLR/NF-κB signaling pathway.

Features of severe acute respiratory syndrome coronavirus 2 co-infected with other common respiratory pathogens in Shanghai City, 2020-2021 / 中华传染病杂志

Objective:To analyze the features of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) co-infected with other common respiratory pathogens among coronavirus disease 2019 (COVID-19) patients in Shanghai City, and to provide a reference for scientific prevention and control of COVID-19 and other respiratory infectious diseases.Methods:Descriptive epidemiological approaches were used to analyze the data of COVID-19 reported cases in Shanghai City from January 2020 to February 2021 in the information system of Chinese Disease Prevention and Control. Clinical data of the participants were collected, and their SARS-CoV-2 nucleic acid-positive respiratory specimens were collected at the time of illness onset or admission. Multiplex reverse transcription-polymerase chain reaction (RT-PCR) was performed to detect the 22 respiratory pathogens. Independent-samples t test was used for statistical analysis. Results:Of the 272 patients with COVID-19, 15(5.5%) had co-infection of SARS-CoV-2 with other respiratory pathogens, all of which were double infection. There were three cases infected with enterovirus/rhinovirus, two of each with adenovirus, human metapneumovirus and coronavirus NL63/HKU1, and one of each with coronavirus 229E, influenza A virus H1N1, parainfluenza virus 1 and respiratory syncytial virus B. Two cases infected with Mycoplasma pneumoniae. Among the 272 COVID-19 patients, 212(77.9%) had fever, 117(43.0%) had cough, 46(16.9%) had fatigue, and 35(12.9%) had sore throat. The white blood cell count of co-infection cases was higher than that of non-co-infection cases ((6.8±1.7)×10 9/L vs (5.3±1.6)×10 9/L), and the difference was statistically significant ( t=3.09, P=0.008). Conclusions:There is a certain proportion of co-infection of SARS-CoV-2 with other respiratory pathogens among the COVID-19 cases in Shanghai City, mainly viral pathogens, especially enterovirus/rhinovirus. A rational combination of drugs was recommended to improve the cure rate. Surveillance of acute respiratory infection should be further strengthened as well.

A chiral metal-organic framework {(HQA)(ZnCl2)(2.5H2O)}n for the enantioseparation of chiral amino acids and drugs / 药物分析学报

Chiral metal-organic frameworks(CMOFs)with enantiomeric subunits have been employed in chiral chemistry.In this study,a CMOF formed from 6-methoxyl-(8S,9R)-cinchonan-9-ol-3-carboxylic acid(HQA)and ZnCl2,{(HQA)(ZnCl2)(2.5H2O)｝n was constructed as a chiral stationary phase(CSP)via an in situ fabrication approach and used for chiral amino acid and drug analyses for the first time.The{(HQA)(ZnCl2)(2.5H2O)}n nanocrystal and the corresponding chiral stationary phase were systematically characterised using a series of analytical techniques including scanning electron microscopy,X-ray diffraction,Fourier transform infrared spectroscopy,circular dichroism,X-ray photoelectron spectros-copy,thermogravimetric analysis,and Brunauer-Emmett-Teller surface area measurements.In open-tubular capillary electrochromatography(CEC),the novel chiral column exhibited strong and broad enantioselectivity toward a variety of chiral analytes,including 19 racemic dansyl amino acids and several model chiral drugs(both acidic and basic).The chiral CEC conditions were optimised,and the enantioseparation mechanisms are discussed.This study not only introduces a new high-efficiency member of the MOF-type CSP family but also demonstrates the potential of improving the enantiose-lectivities of traditional chiral recognition reagents by fully using the inherent characteristics of porous organic frameworks.

Recent applications and chiral separation development based on stationary phases in open tubular capillary electrochromatography(2019-2022) / 药物分析学报

Capillary electrochromatography(CEC)plays a significant role in chiral separation via the double sepa-ration principle,partition coefficient difference between the two phases,and electroosmotic flow-driven separation.Given the distinct properties of the inner wall stationary phase(SP),the separation ability of each SP differs from one another.Particularly,it provides large room for promising applications of open tubular capillary electrochromatography(OT-CEC).We divided the OT-CEC SPs developed over the past four years into six types:ionic liquids,nanoparticle materials,microporous materials,biomaterials,non-nanopolymers,and others,to mainly introduce their characteristics in chiral drug separation.There also added a few classic SPs that occurred within ten years as supplements to enrich the features of each SP.Additionally,we discuss their applications in metabolomics,food,cosmetics,environment,and biology as analytes in addition to chiral drugs.OT-CEC plays an increasingly significant role in chiral separation and may promote the development of capillary electrophoresis(CE)combined with other instruments in recent years,such as CE with mass spectrometry(CE/MS)and CE with ultraviolet light detector(CE/UV).

Research progress of mitochondrial genetics in age-related macular degeneration / 中华实验眼科杂志

Mitochondria are the center of cellular energy metabolism, and their functions are tightly regulated by the nuclear and mitochondria genomes.Potential mechanisms responsible for age-related mitochondrial dysfunction include the accumulation of mitochondrial DNA (mtDNA) damage caused by replication errors or oxidative damage, and the epigenetic changes in mtDNA (mitoepigenetics). These mechanisms are essential for the development and progression of age-related macular degeneration (AMD). Age-related mtDNA damage disrupts energy metabolism and cellular function in the retinal pigment epithelium (RPE) and neuroretinal cells, which further mediates oxidative stress, lysosomal dysfunction and pyroptosis, resulting in RPE degeneration, drusen deposition and retinal inflammation.Mitochondrial genome protection, such as humanin administration, may be a promising preventive or therapeutic target in the early stages of AMD.This review focused on the research progress of the mitochondrial genetic mechanism in AMD pathogenesis and provided new ideas for exploring the prevention and treatment strategies of AMD.

Research progress on circular RNA in fundus oculi proliferative diseases / 中华实验眼科杂志

Fundus oculi proliferative diseases, such as choroidal neovascularization, diabetic retinopathy, and proliferative vitreoretinopathy, are characterized by cell proliferation and neovascularization.It can lead to damage to the ocular structure and visual acuity.Circular RNA (CircRNA) is a non-coding endogenous RNA, which has been confirmed to be involved in the pathophysiological process of many ophthalmic diseases by recent studies.Thus, circRNA may become a promising target of fundus oculi proliferative diseases.This review concluded the physiological function of circRNA and its role in the physiological and pathological process of diabetic retinopathy, proliferative vitreoretinopathy and glaucoma-related glia proliferation.

Impact of inclusion of varicella vaccine into the immunization program on the incidence of varicella / 上海预防医学

ObjectiveTo analyze the epidemiological characteristics of varicella in Minhang District， Shanghai from 2013 to 2022， and to evaluate the impact of adjusting the varicella vaccination program to a two-dose regimen and its inclusion in the Shanghai immunization program on the incidence of varicella. MethodsData on reported varicella cases from 2013 to 2022 in Minhang District were collected. Interrupted time series analysis and segmented regression models were used to analyze the changes in varicella incidence before and after the adjustment of varicella immunization strategies. ResultsFrom 2013 to 2022， the average annual incidence of varicella was 76.58/100 000， with the highest incidence in 2017 （119.21/100 000） and the lowest in 2022 （27.02/100 000）. The varicella incidence exhibited seasonal patterns with peaks occurring from March to June and October to January of the following year. Prior to the adjustment of varicella immunization strategies （2013‒2017）， the varicella incidence showed an upward trend （z=2.20， P=0.03）， while after the adjustment （2018‒2022）， a adownward trend was observed （2018‒2022） （z=-2.25， P=0.02）. Interrupted time series analysis showed that following the adjustment of varicella immunization strategies， an immediate change of -33.91/100 000 （t=-4.35， P<0.001） in varicella incidence was observed， and the incidence slope was -17.59/100 000 with a decline of 28.61/100 000 （t=-12.16， P<0.001） compared to before inclusion. ConclusionThe incidence of varicella in Minhang District， Shanghai from 2013 to 2022 exhibits distinct seasonal patterns. After adjusting the varicella vaccination program to a two-dose regimen and incorporating it into the immunization program， the second dose of varicella vaccine administration substantially increases. As a result， the rising trend of varicella incidence is effectively controlled， and the incidence level decreases significantly， showing a sustained downward trend.

Effects of X-ray volume imaging registration methods on position verification for radiotherapy in treatment of middle/lower-segment esophageal cancer / 中国辐射卫生

@#<b>Objective</b> To compare the set up errors derived from different registration methods of the X-ray volume imaging (XVI) system for radiotherapy in the treatment of middle/lower-segment esophageal cancer, and to provide a reference for radiation treatment of esophageal cancer. <b>Methods</b> We randomly selected 63 patients with middle/lower-segment esophageal cancer, and obtained their reconstructed XVI images at the first therapy to perform automatic registration with gray-value and bone registration methods. We acquired and compared the three translation errors (along <i>x</i> [left to right], <i>y</i> [head to feet], and <i>z</i> [front to back] axes) and three rotation errors (around the <i>x</i>, <i>y</i>, and <i>z</i> axes) derived from the two registration methods. <b>Results</b> Gray-value registration had significantly smaller translation errors along the <i>x</i> and <i>z</i> axes than bone registration (<i>x</i> azes <i>t</i> = −2.78, <i>z</i> azes <i>t</i> = −2.15, <i>P</i> < 0.05), but there was no significant difference along the <i>y</i> axes (<i>P</i> > 0.05). The rotation errors around the three axes were all smaller than 1°, and were smaller with gray-value registration than with bone registration, but without significant differences (<i>P</i> > 0.05). <b>Conclusion</b> We recommend gray-value registration for radiotherapy in the treatment of middle/lower-segment esophageal cancer. Manual verification or fine-tuning is recommended after automatic registration in clinical practice. Besides translation errors, rotation errors should also be paid attention to.

Pathogenesis of delayed gastric emptying after pancreaticoduodenectomy and related risk factors / 临床肝胆病杂志

Delayed gastric emptying (DGE) is a common complication after pancreaticoduodenectomy (PD). The etiology and pathogenesis of DGE have not been fully elucidated in China and globally, and the majority of patients can be cured after general symptomatic treatment. This article reviews the risk factors and pathophysiological mechanisms of DGE after PD, in order to provide a reference for the effective management of DGE after PD in clinical practice.

Associations of cholecystectomy with the risk of colorectal cancer: a Mendelian randomization study / 中华医学杂志(英文版)

BACKGROUND@#Cholecystectomy is a standard surgery for patients suffering from gallbladder diseases, while the causal effects of cholecystectomy on colorectal cancer (CRC) and other complications are still unknown.@*METHODS@#We obtained genetic variants associated with cholecystectomy at a genome-wide significant level ( P value <5 × 10 -8 ) as instrumental variables (IVs) and performed Mendelian randomization (MR) to identify the complications of cholecystectomy. Furthermore, the cholelithiasis was also treated as the exposure to compare its causal effects to those of cholecystectomy, and multivariable MR analysis was carried out to judge whether the effect of cholecystectomy was independent of cholelithiasis. The study was reported based on Strengthening the Reporting of Observational Studies in Epidemiology Using Mendelian Randomization guidelines.@*RESULTS@#The selected IVs explained 1.76% variance of cholecystectomy. Our MR analysis suggested that cholecystectomy cannot elevate the risk of CRC (odds ratio [OR] =1.543, 95% confidence interval [CI]: 0.607-3.924). Also, it was not significant in either colon or rectum cancer. Intriguingly, cholecystectomy might decrease the risk of Crohn's disease (OR = 0.078, 95% CI: 0.016-0.368) and coronary heart disease (OR = 0.352, 95% CI: 0.164-0.756). However, it might increase the risk of irritable bowel syndrome (IBS) (OR = 7.573, 95% CI: 1.096-52.318). Cholelithiasis could increase the risk of CRC in the largest population (OR = 1.041, 95% CI: 1.010-1.073). The multivariable MR analysis suggested that genetic liability to cholelithiasis could increase the risk of CRC in the largest population (OR = 1.061, 95% CI: 1.002-1.125) after adjustment of cholecystectomy.@*CONCLUSIONS@#The study indicated that cholecystectomy might not increase the risk of CRC, but such a conclusion needs further proving by clinical equivalence. Additionally, it might increase the risk of IBS, which should be paid attention to in clinical practice.

Effectiveness of inactivated and Ad5-nCoV COVID-19 vaccines against SARS-CoV-2 Omicron BA. 2 variant infection, severe illness, and death

BackgroundLimited data are available on effectiveness of inactivated and Ad5-nCoV COVID-19 vaccines in real-world use - especially against Omicron variants in SARS-CoV-2 infection-naive population. During an outbreak in Shanghais SARS-CoV-2 infection-naive population, we evaluated vaccine effectiveness (VE) against Omicron infection, severe or critical COVID-19, and COVID-19-related death. MethodsA matched case-control study was conducted among people aged [≥]3 years between 2 December 2021 through 13 May 2022. Cases were SARS-CoV-2 infected individuals, individuals with severe/critical COVID-19, or COVID-19-related deaths. Controls were selected from consecutively test negative individuals at the same time as cases were diagnosed and were exact-matched on year-of-age, gender, birthplace, illness onset date, and residency district in ratios of 1:1 with infected individuals and 4:1 with severe/critical COVID-19 and COVID-19-related deaths. ResultsOur study included 612597 documented SARS-CoV-2 infections, among which 1485 progressed to severe or critical illness and 568 died. Inactivated vaccine was 16.3% (95% CI: 15.4%-17.2%) effective against infection, 88.6% (95% CI: 85.8%-90.9%) effective against severe/critical COVIID-19 and 91.7% (95% CI: 86.9%-94.7%) against COVID-19 death. Ad5-vectored vaccine was 13.2% (95% CI: 10.9%-15.5%) effective against infection and 77.9% (95% CI: 15.6%-94.2%) effective against severe/critical COVIID-19. Booster vaccination with inactivated vaccines enhanced protection against severe COVID-19 (92.7%, 95% CI: 90.1%-94.6%) and COVID-19 death (95.9%, 95% CI: 91.4%-98.1%). Inactivated VE against infection began to wane 12 weeks after the last dose but two- and three-dose sustained high protection levels (>80%) against severe/critical illness and death. ConclusionsOur real-world study found high and durable two- and three-dose inactivated VE against Omicron-associated severe/critical illness and death across all age groups, but lower effectiveness against Omicron infection. High direct protection from severe/fatal Omicron COVID-19 provided by inactivated vaccines, and a consequent potential reduction in health-care utilization, reinforces the critical importance of full-series vaccination and timely booster dose administration for all eligible individuals.

Pay attention to the detection and treatment of ocular gene therapy viral vector-associated immunity / 中华眼底病杂志

The application of gene therapy in ocular diseases is gradually expanding from mono-gene inherited diseases to multigene, multifactorial, common and chronic diseases. This emerging therapeutic approach is still in the early exploratory stage of treating diseases, and the expected benefits and risks remain highly uncertain. In the delivery process of gene therapy drugs, viral vector is currently one of the most mature and widely used vectors. The occurrence of vector-associated immunity will affect the short-term and long-term effects of gene therapy, and even cause permanent and serious damage to visual function. Therefore, gene therapy vector-associated immunity is the focus and challenge for the safety and long-term efficacy of gene therapy. During the perioperative and follow-up of gene therapy, attention should be paid to the monitoring of vector-associated immune inflammation, and appropriate measures should be taken to deal with the corresponding immune response, so as to achieve the best visual benefits for patients.

Planned initiation of extracorporeal membrane oxygenation prior to liver transplantation: a report of 3 cases / 中华器官移植杂志

Objective:To explore the feasibility and advantages of planned initiation of extracorporeal membrane oxygenation(ECMO)prior to liver transplantation.Methods:From November 2017 to July 2021, clinical data were retrospectively reviewed for 3 liver transplantation recipients assisted by ECMO.There were such preoperative symptoms of right ventricular dysfunction as fatigue, chest tightness and palpitations.In the first case, right heart catheterization was not performed due to patient refusal; another two patients were screened by transthoracic Doppler echocardiography(TDE)and diagnosed through right heart catheterization as portopulmonary hypertension(POPH)and pulmonary hypertension.Results:Three recipients with pulmonary hypertension received catheterization in right femoral artery and vein.After freeing of diseased liver and before blocking inferior vena cava, V-A ECMO support was performed.The dose of heparin was adjusted according to activated clotting time(ACT)and perioperative vital signs remained stable.They were ventilated for 54, 12 and 62 hours and supported by ECMO for 27, 61 and 14 hours.All were smoothly discharged.During a mean follow-up period of 26(9-22)months, liver functions were normal.Conclusions:Patients with end-stage liver disease with pulmonary hypertension should undergo routine TDE examinations during waiting period before liver transplantation.Those with pulmonary hypertension should undergo further right heart catheterization to confirm the diagnosis and severity of the disease.Planned application of ECMO through multidisciplinary consultations can expand surgical indications for liver transplantation, maintain intraoperative hemodynamic stability and facilitate smooth liver transplantation and postoperative patient recovery.

Analysis of clinical characteristics of bullous pemphigoid developing after the treatment with dipeptidyl peptidase-Ⅳ inhibitors in 32 patients with diabetes mellitus / 中华皮肤科杂志

Objective:To investigate clinical characteristics of bullous pemphigoid (BP) developing after the treatment with dipeptidyl peptidase-Ⅳ inhibitors (DPP4i) in patients with diabetes mellitus.Methods:A total of 116 inpatients with BP complicated by diabetes mellitus were collected from the Seventh People′s Hospital of Shenyang between January 2014 and December 2020, and divided into 2 groups: DPP4i-BP group treated with DPP4i before the onset of BP, and general BP group receiving no treatment with DPP4i. General clinical data, skin lesion area, laboratory indicators, treatment regimens, and prognosis were analyzed and compared between the above 2 groups, the time interval from the administration of DPP4i to the diagnosis of BP was recorded in the DPP4i-BP group. One-way analysis of variance was used to compare measurement data among multiple groups, two-independent-sample t test was used for comparisons between two groups, and paired t-test for intra-group comparisons before and after treatment; chi-square test was used to compare enumeration data between groups. Results:There were 32 patients aged 77.17 ± 15.32 years in the DPP4i-BP group, with a male-to-female ratio being 15∶17; there were 84 patients aged 76.65 ± 19.32 years in the general BP group, with a male-to-female ratio being 43∶41. The time interval from the administration of DPP4i to the diagnosis of BP was 14.61 ± 3.93 months in the DPP4i-BP group. The time interval for vildagliptin was the shortest (5.42 ± 2.84 months) , and there was a significant difference in the time interval among vildagliptin, sitagliptin, linagliptin and saxagliptin ( F= 8.93, P < 0.001) . The proportion of patients with severe BP was significantly higher in the DPP4i-BP group (16 cases, 50%) than in the general BP group (25 cases, 29.76%; Z= 2.63, P= 0.008) . There was no significant difference in the positivity rate of anti-BP180 antibody between the two groups ( χ2= 0.03, P= 0.870) . However, the level of anti-BP180 antibody was significantly higher in the DPP4i-BP group than in the general BP group before and after treatment ( P= 0.015, < 0.001, respectively) , and the decrease in the level of anti-BP180 antibody was significantly less in the DPP4i-BP group than in the general BP group after treatment ( t= 5.11, P < 0.001) . There was no significant difference in the average effective dose of glucocorticoids required to control the disease between the two groups ( t= 1.00, P= 0.322) . However, the DPP4i-BP group showed a significant increase in the average time required to control the disease and in the proportion of patients requiring combined treatment with immunosuppressants or other drugs compared with the general BP group ( t= 6.72, 10.05, P < 0.001,= 0.002, respectively) . Within 6 months after the start of systemic treatment, the recurrence rate was significantly higher in the general BP group (17 cases, 27.86%) than in the DPP4i-BP group (2 cases, 7.69%; χ2= 4.35, P= 0.037) ; at 6 months, the average dose of glucocorticoids was also significantly higher in the general BP group than in the DPP4i-BP group ( t= 7.04, P < 0.001) . Conclusions:Among the DPP4i hypoglycemic drugs, vildagliptin was the most common drug administrated by patients before the onset of BP, with the shortest interval from the administration to the onset of BP. DPP4i-BP may be difficult to control at the early stage, but the prognosis is good.

Application of exosomes in the diagnosis and treatment of cardiovascular diseases / 国际儿科学杂志

The cardiovascular diseases, which have the increasing incidence and high mortality rate, have brought a great impact on people′s lives and health.Being lipid inclusions with 30~150 nm in diameter, exosomes can be secreted by most cells in the body, and proteins, lipids, nucleic acids and other substances derived from those cells are wrapped inside.Exosomes play a variety of biological roles in the communication between cells, such as mediating immune response, inflammatory response, cell migration and differentiation.Research on exosomes has made significant progress, and the roles of exosomes in cardiovascular diseases have consequently attracted more and more attention in recent years.The communication of exosomes between cardiomyocytes and between heart and peripheral tissues has provided new strategies for the diagnosis and treatment of cardiovascular diseases.Application of exosomes in the diagnosis and treatment of cardiovascular diseases such as heart failure, viral myocarditis, Kawasaki disease and dilated cardiomyopathy is summarized in this review.

Research advances in the treatment of primary biliary cirrhosis / 临床肝胆病杂志

Primary biliary cholangitis (PBC) is an autoimmune disease commonly observed in middle-aged women, and it may progress to liver cirrhosis and liver failure. Ursodeoxycholic acid and obeticholic acid are the only first - and second-line drugs approved by the FDA, but about 40% of patients are insensitive to UDCA. Studies are being conducted on a variety of second-line drugs such as fibrates and immunosuppressive drugs, and liver transplantation is the only treatment method for end-stage PBC. This article reviews the research advances in the treatment of PBC and related mechanisms, in order to provide a reference for clinical practice.

Analysis of influencing factors for anastomotic biliary stricture after liver transplantation / 中华消化外科杂志

Objective:To investigate the influencing factors for anastomotic biliary stric-ture after liver transplantation.Methods:The retrospective case-control study was conducted. The clinical data of 428 recipients who underwent allogeneic orthotopic liver transplantation in the First Hospital of Jilin University from September 2014 to August 2021 were collected. There were 324 males and 104 females, aged (52±10)years. Observation indicators: (1) surgical conditions of recipients; (2) occurrence of anastomotic biliary stricture after liver transplantation and its treat-ment; (3) analysis of influencing factors for anastomotic biliary stricture after liver transplantation. Follow-up was conducted using outpatient examination to detect occurrence of anastomotic biliary stricture and treatment up to August 30, 2021. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was analyzed using the t test. Measure-ment data with skewed distribution were represented as M( Q1, Q3) or M(range), and comparison between groups was analyzed using the Mann-Whitney U test. Count data were represented as absolute numbers, and the chi-square test was used for comparison between groups. Logistic regression model was used for multivariate analysis. Results:(1) Surgical conditions of recipients: the operation time of 428 recipients was 465(420,520)minutes, the cold ischemia time was 368(320,450)minutes, and the volume of intraoperative blood loss was 2 500(1 500,4 000)mL. Of the 428 recipients, 142 cases were performed continuous biliary posterior wall anastomosis + interrup-ted anterior wall anastomosis by polygluconate sutures, 286 cases were anastomosed with polypro-pylene sutures, including 169 cases undergoing continuous biliary posterior wall anastomosis combined with interrupted anterior wall anastomosis, 73 cases undergoing completely interrupted biliary anterior and posterior wall anastomosis, and 44 cases undergoing completely continuous biliary anterior and posterior wall anastomosis. None of the 428 recipients had indwelling T tubes. (2) Occurrence of anastomotic biliary stricture after liver transplantation and its treatment:all the 428 recipients were followed up for 3 to 72 months, with a median follow-up time of 28 months. During the follow-up, 50 patients developed anastomotic biliary stricture, of which 41 patients were treated with endoscopic retrograde cholangiopancreatography, 8 patients were treated with percutaneous transhepatic cholangial drainage, and 1 patient was treated with surgery, showing no recurrence. (3)Analysis of influencing factors for anastomotic biliary stricture after liver transplanta-tion: results of univariate analysis showed that anastomosis method and donor liver cold ischemia time were related factors for postoperative anastomotic biliary stricture of recipients undergoing allogeneic orthotopic liver transplantation ( χ2=15.74, Z=-2.04, P<0.05). Results of multivariate analysis showed that completely interrupted biliary anterior and posterior wall anastomosis and donor liver cold ischemia time were independent influencing factors for postoperative anastomotic biliary stricture of recipients undergoing allogeneic orthotopic liver transplantation ( odds ratio=0.25, 1.00, 95% confidence interval as 0.08-0.85, 1.00-1.01, P<0.05). Conclusions:Suture type is not an influencing factor for postoperative anastomotic biliary stricture of recipients undergoing allogeneic orthotopic liver transplantation. Completely interrupted biliary anterior and posterior wall anastomosis and donor liver cold ischemia time were independent influencing factors.