Objective:The possible enhancing effect of anlotinib on programmed death receptor ligand(PD-L1)antibody and the efficacy-predicting power of PD-L1 in micro-conduit endothelium,including lymphatic endothelial cells(LEC...Objective:The possible enhancing effect of anlotinib on programmed death receptor ligand(PD-L1)antibody and the efficacy-predicting power of PD-L1 in micro-conduit endothelium,including lymphatic endothelial cells(LECs)and blood endothelial cells(BECs),were determined to identify patients who would benefit from this treatment.Methods:PD-L1 positivity in LECs,BECs,and tumor cells(TCs)was assessed using paraffin sections with multicolor immunofluorescence in an investigator’s brochure clinical trial of TQB2450(PD-L1 antibody)alone or in combination with anlotinib in patients with non-small cell lung cancer.Progression-free survival(PFS)with different levels of PD-L1 expression was compared between the two groups.Results:Among 75 patients,the median PFS(mPFS)was longer in patients who received TQB2450 with anlotinib[10 and 12 mg(161 and 194 days,respectively)]than patients receiving TQB2450 alone(61 days)[hazard ratio(HR)_(10 mg)=0.390(95%confidence interval{CI},0.201–0.756),P=0.005;HR_(12 mg)=0.397(0.208–0.756),P=0.005].The results were similar among 58 patients with high PD-L1 expression in LECs and TCs[159 and 209 vs.82 days,HR_(10 mg)=0.445(0.210–0.939),P=0.034;HR_(12 mg)=0.369(0.174–0.784),P=0.009],and 53 patients with high PD-L1 expression in BECs and TCs[161 and 209 vs.41 days,HR_(10 mg)=0.340(0.156–0.742),P=0.007;HR_(12 mg)=0.340(0.159–0.727),P=0.005].No differences were detected in the mPFS between the TQB2450 and combination therapy groups in 13 low/no LEC-expressing and 18 low/no BEC-expressing PD-L1 cases.Conclusions:Mono-immunotherapy is not effective in patients with high PD-L1 expression in LECs and/or BECs.Anlotinib may increase efficacy by downregulating PD-L1 expression in LECs and/or BECs,which is presumed to be a feasible marker for screening the optimal immune patient population undergoing anti-angiogenic therapy.展开更多
Sepsis is a life-threatening multiple organ dysfunction syndrome caused by the imbalance of the immune response to infection,featuring complex and variable conditions,and is one of the leading causes of mortality in I...Sepsis is a life-threatening multiple organ dysfunction syndrome caused by the imbalance of the immune response to infection,featuring complex and variable conditions,and is one of the leading causes of mortality in ICU patients.Lung injury is a common organ damage observed in sepsis patients.Macrophages and Th17 cells,as crucial components of innate and adaptive immunity,play pivotal roles in the development of sepsis-induced acute lung injury(ALI).This review summarizes the alterations and mechanisms of macrophages and Th17 cells in sepsis-induced ALI.By focusing on the“cross-talk”between macrophages and Th17 cells,this review aims to provide a solid theoretical foundation for further exploring the therapeutic targets of traditional Chinese medicine formulas in the treatment of sepsis complicated with ALI,thereby offering insights and guidance for the clinical application of traditional Chinese medicine in managing sepsis-associated ALI.展开更多
Elevated fibroblast growth factor 23(FGF23)in X-linked hypophosphatemia(XLH)results in rickets and phosphate wasting,manifesting by severe bone and dental abnormalities.Burosumab,a FGF23-neutralizing antibody,an alter...Elevated fibroblast growth factor 23(FGF23)in X-linked hypophosphatemia(XLH)results in rickets and phosphate wasting,manifesting by severe bone and dental abnormalities.Burosumab,a FGF23-neutralizing antibody,an alternative to conventional treatment(phosphorus and active vitamin D analogs),showed significant improvement in the long bone phenotype.Here,we examined whether FGF23 antibody(FGF23-mAb)also improved the dentoalveolar features associated with XLH.Four-week-old male Hyp mice were injected weekly with 4 or 16 mg·kg−1 of FGF23-mAb for 2 months and compared to wild-type(WT)and vehicle(PBS)treated Hyp mice(n=3–7 mice).Micro-CT analyses showed that both doses of FGF23-mAb restored dentin/cementum volume and corrected the enlarged pulp volume in Hyp mice,the higher concentration resulting in a rescue similar to WT levels.FGF23-mAb treatment also improved alveolar bone volume fraction and mineral density compared to vehicle-treated ones.Histology revealed improved mineralization of the dentoalveolar tissues,with a decreased amount of osteoid,predentin and cementoid.Better periodontal ligament attachment was also observed,evidenced by restoration of the acellular cementum.These preclinical data were consistent with the retrospective analysis of two patients with XLH showing that burosumab treatment improved oral features.Taken together,our data show that the dentoalveolar tissues are greatly improved by FGF23-mAb treatment,heralding its benefit in clinics for dental abnormalities.展开更多
Hyperglycemia is associated with an increased risk of cardiovascular disease,and the consequences ofintensive therapy may depend on the mechanism of the anti-diabetic agent(s)used to achieve a tight control.In animal ...Hyperglycemia is associated with an increased risk of cardiovascular disease,and the consequences ofintensive therapy may depend on the mechanism of the anti-diabetic agent(s)used to achieve a tight control.In animal models,stable analogues of glucagon-like peptide-1(GLP-1)were able to reduce body weight and blood pressure and also had favorable effects on ischemia following coronary reperfusion.In a similar way,dipeptidyl peptidase IV(DPPIV)showed to have favorable effects in animal models of ischemia/reperfusion.This could be due to the fact that DPPIV inhibitors were able to prevent the breakdown of GLP-1 and glucose-dependent insulinotropic polypeptide,but they also decreased the degradation of several vasoactive peptides.Preclinical data for GLP-1,its derivatives and inhibitors of the DPPIV enzyme degradation suggests that these agents may be able to,besides controlling glycaemia,induce cardio-protective and vasodilator effects.Notwithstanding the many favorable cardiovascular effects of GLP-1/incretins reported in different studies,many questions remain unanswered due the limited number of studies in human beings that aim to examine the effects of GLP-1 on cardiovascular endpoints.For this reason,long-term trials searching for positive cardiovascular effects are now in process,such as the CAROLINA and CARMELINA trials,which are supported by small pilot studies performed in humans(and many more animal studies)with incretin-based therapies.On the other hand,selective renal sodium-glucose co-transporter 2 inhibitors were also evaluated in the prevention of cardiovascular outcomes in type 2 diabetes.However,it is quite early to draw conclusions,since data on cardiovascular outcomes and cardiovascular death are limited and long-term studies are still ongoing.In this review,we will analyze the mechanisms underlying the cardiovascular effects of incretins and,at the same time,we will present a critical position about the real value of these compounds in the cardiovascular system and its protection.展开更多
BACKGROUND Increased homocysteine levels are associated with the risk of cardiovascular disease(CVD)and death.However,their prevention has not been effective in decreasing CVD risk.This study investigated the individu...BACKGROUND Increased homocysteine levels are associated with the risk of cardiovascular disease(CVD)and death.However,their prevention has not been effective in decreasing CVD risk.This study investigated the individual and combined associations of hyperhomocysteinemia and hypertension with incident CVD events and all-cause death in the Chinese elderly population without a history of CVD.METHODS This prospective study was conducted among 1,257 elderly participants(mean age:69 years).A questionnaire survey,physical examinations,and laboratory tests were conducted to collect baseline data.Hyperhomocysteinemia was defined as homocysteine level≥15μmol/L.H-type hypertension was defined as concomitant hypertension and hyperhomocysteinemia.Multivariate Cox regression analysis was used to evaluate individual and combined associations of hyperhomocysteinemia and hypertension with the risks of incident CVD events and all-cause death.RESULTS Over a median of 4.84-year follow-up,hyperhomocysteinemia was independently associated with incident CVD events and all-cause death.The hazard ratios(HRs)were 1.45(95%CI:1.01−2.08)for incident CVD events and 1.55(95%CI:1.04−2.30)for all-cause death.After adjustment for confounding factors,H-type hypertension had the highest HRs for incident CVD events and all-cause death.The fully adjusted HRs were 2.44 for incident CVD events(95%CI:1.28−4.65),2.07 for stroke events(95%CI:1.01−4.29),8.33 for coronary events(95%CI:1.10−63.11),and 2.31 for all-cause death(95%CI:1.15−4.62).CONCLUSIONS Hyperhomocysteinemia was an independent risk factor,and when accompanied by hypertension,it contrib-uted to incident CVD events and all-cause death in the Chinese elderly population without a history of CVD.展开更多
Background : The objective of this study was to validate an animal model for dry eye during and after the administration of 1% ophthalmic atropine sulfate(OAS) in New Zealand white(NZW) rabbits.Methods : OAS(1%) was a...Background : The objective of this study was to validate an animal model for dry eye during and after the administration of 1% ophthalmic atropine sulfate(OAS) in New Zealand white(NZW) rabbits.Methods : OAS(1%) was applied three times per day to 30 eyes of 15 healthy NZW rabbits. Sacrifice, enucleation, and lacrimal gland removal took place on days 15, 21,and 30(OAS group). A second group(n = 5) was used as control. Clinical evaluations took place on days 3, 10, 15, 18, 21, 24 and 30. The primary endpoints were:Schirmer I test, tear break-up time(TBUT), and corneal fluorescein staining. As secondary endpoints, clinical changes including intraocular pressure, and histopathology were evaluated.Results : While OAS was administered, the Schirmer I test showed a statistically significant reduction for OAS group versus control( p < 0.001), and versus basal production( p < 0.001). TBUT showed statistically significant differences between groups(days 3 and 10;p = 0.001) and versus basal values(day 3;p < 0.001). Fluorescein staining showed a statistically significant difference(day 3;p = 0.001). The most frequent clinical finding was conjunctival hyperemia(76.9% OAS vs. 20% control). For histopathology, all OAS subjects presented some degree of inflammation(86.7% minimal;13.3% mild) whereas the control presented only 30% minimal inflammation. Goblet cell density showed no difference.Conclusions : The effectiveness of the OAS dry eye model in NZW rabbits as reported in previous studies was confirmed, provided that the application of the drug is maintained throughout the intervention;it is not a viable model after OAS administration is suspended.展开更多
The Systolic Heart failure treatment with the I( inhibitor ivabradine Trial (SHIFT, n = 6505) evaluated patients with symptomatic chronic heart failure (CHF), in sinus rhythm with resting heart rate ≥70 beats/min and...The Systolic Heart failure treatment with the I( inhibitor ivabradine Trial (SHIFT, n = 6505) evaluated patients with symptomatic chronic heart failure (CHF), in sinus rhythm with resting heart rate ≥70 beats/min and left ventricular ejection fraction (LVEF)≤ 35%, average age 60 ± 11 years[1].展开更多
Objective This study aimed to evaluate the effects of in-utero exposure to HIV and ART on pregnancy outcome and early growth of children.Methods This cohort study enrolled 802 HIV-infected pregnant women between Octob...Objective This study aimed to evaluate the effects of in-utero exposure to HIV and ART on pregnancy outcome and early growth of children.Methods This cohort study enrolled 802 HIV-infected pregnant women between October 2009 and May 2018 in Guangzhou, China. The women were assigned to receive combination ART(c ART) or mono/dual ART or no treatment. The primary outcomes were the combined endpoints of any adverse pregnancy outcome [including ectopic pregnancy, spontaneous abortion, stillbirth, preterm birth, small for gestational age(SGA)] and adverse early growth outcome(including infant death, HIV infection of mother-to-child transmission, and underweight, wasting and stunting of infants at 4 weeks of age).Results Adverse pregnancy outcomes occurred in 202(35.1%) of all enrolled HIV-infected women, and121(31.3%) of all infants exhibited adverse effects on early growth at 4 weeks of age. The rates of adverse pregnancy outcomes, spontaneous abortion, ectopic pregnancy, stillbirth, infant death and perinatal HIV infection were higher among women not receiving ART, compared to those treated with c ART or mono/dual ART(P < 0.05). However, women treated with c ART had a higher rate of SGA,compared to untreated women(P < 0.05). No differences in early infant growth were observed among the different treatment regimens.Conclusion Our findings underscore the essentiality of prioritizing HIV-positive pregnant women for ART, as even mono/dual ART available in resource-limited countries could improve pregnancy outcomes and infant survival.展开更多
BACKGROUND Diabetes mellitus is a worldwide public health problem associated with significant complications. There is lack of data on the quality of care of patients with diabetes, specifically among the non-Western c...BACKGROUND Diabetes mellitus is a worldwide public health problem associated with significant complications. There is lack of data on the quality of care of patients with diabetes, specifically among the non-Western countries. Efforts have been made in Lebanon to better study the characteristics of patients with diabetes mellitus in order to improve glycemic control and prevent late-term complications.AIM To investigate control and therapeutic management of patients with diabetes mellitus in the current medical practice in Lebanon.METHODS Wave 6 of the International Diabetes Management Practice Study in Lebanon is an international and multicenter study involving selected countries.RESULTS Only 1 patient with type 1 diabetes and 595 patients with type 2 diabetes were included in Wave 6. Average age was around 60 years, with a mean body mass index of 30. The mean fasting serum glucose was 159.42 mg/dL, and the mean glycosylated hemoglobin(HbA1 c) level was 7.98 with around 30% achieving an HbA1 c target of < 7%. More patients were on oral anti-diabetic medications.Screening of diabetic complications has improved over the years. A large percentage is diagnosed with hypertension and dyslipidemia, the majority ofwhom were treated but only a small percentage were controlled.CONCLUSION Diabetes, with its associated dyslipidemia and hypertension, is still not very well controlled. Screening for diabetes complications has improved over the years.Patients need to have more proper care, and physicians need to follow diabetes guidelines, and to have a larger number of patients who have appropriate treatment of diabetes, hypertension and lipids.展开更多
<strong>Objectives</strong>:<span> This retrospective study evaluated 1) benefits of single nucleotide polymorphism (SNP)-based chromosomal microarrays (CMAs) in the diagnosis of complete hydatidifor...<strong>Objectives</strong>:<span> This retrospective study evaluated 1) benefits of single nucleotide polymorphism (SNP)-based chromosomal microarrays (CMAs) in the diagnosis of complete hydatidiform mole (CHM) and partial HM (PHM) in products of conception (POC) and amniotic fluid (AF) specimens, and 2) frequency of whole-genome uniparental disomy (wgUPD) and triploidy in POC and AF specimens received at a US national reference laboratory.</span><span "=""> </span><b><span>Methods:</span></b><span> We reviewed consecutive 2138 POC and 3230 AF specimens and identified the cases with wgUPD and triploidy which are associated with molar pregnancy.</span><span "=""> </span><b><span>Results:</span></b><span "=""><span> Of 2138 consecutive POC specimens tested, SNP-based CMA detected wgUPD in 10 (0.47%) and triploidy in 84 (3.93%). Of the 10 wgUPD cases, 9 (90%) were confirmed as CHM. Of 3230 consecutive AF specimens, the array detected wgUPD in 1 case (0.03%) and triploidy in 11 (0.34%). </span><b><span>Conclusions:</span></b><span> SNP-based microarray allows detection of wgUPD in POC and AF specimens at a US national reference laboratory. Correctly diagnosing HM and differentiating CHM from PHM </span></span><span>are</span><span> important for clinical management. The effective SNP-based CMA detection of wgUPD in CHM may enable physicians to monitor patients at risk for gestational trophoblastic disease and neoplasm.</span><span "=""> </span><span "=""><span>Conventional chromosome analysis of POC has a high </span><span>failure rate, cannot be performed on formalin-fixed paraffin embedded samples, and cannot detect wgUPD. Further</span></span><span "=""> </span><span>multi-institutional collaborative assessmen</span><span> on accuracy, cost-effectiveness, and adequate access to SNP-based CMA, may lead this testing platform to be considered as the first-tier analysis tool for POC specimens, including those showing PHM or CHM.展开更多
Daily 20-mg and once-weekly 56.5-mg teriparatide(parathyroid hormone 1–34) treatment regimens increase bone mineral density(BMD) and prevent fractures, but changes in bone turnover markers differ between the two ...Daily 20-mg and once-weekly 56.5-mg teriparatide(parathyroid hormone 1–34) treatment regimens increase bone mineral density(BMD) and prevent fractures, but changes in bone turnover markers differ between the two regimens. The aim of the present study was to explain changes in bone turnover markers using once-weekly teriparatide with a simulation model. Temporary increases in bone formation markers and subsequent decreases were observed during once-weekly teriparatide treatment for 72 weeks. These observations support the hypothesis that repeated weekly teriparatide administration stimulates bone remodeling, replacing old bone with new bone and leading to a reduction in the active remodeling surface. A simulation model was developed based on the iterative remodeling cycle that occurs on residual old bone. An increase in bone formation and a subsequent decrease were observed in the preliminary simulation. For each fitted time point, the predicted value was compared to the absolute values of the bone formation and resorption markers and lumbar BMD. The simulation model strongly matched actual changes in bone turnover markers and BMD. This simulation model indicates increased bone formation marker levels in the early stage and a subsequent decrease. It is therefore concluded that remodeling-based bone formation persisted during the entire treatment period with once-weekly teriparatide.展开更多
Objective:Omicron,a severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)variant,is responsible for numerous infections in China.This study investigates the association between the use of Seven-Flavor Herb Tea(S...Objective:Omicron,a severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)variant,is responsible for numerous infections in China.This study investigates the association between the use of Seven-Flavor Herb Tea(SFHT)and the risk of SARS-CoV-2 infection to develop precise and differentiated strategies for control of the coronavirus disease 2019(COVID-19).Methods:This case-control study was conducted at shelter hospitals and quarantine hotels in China.A total of 5348 laboratory-confirmed COVID-19 patients were enrolled between April 1 and May 31,2022,while 2190 uninfected individuals served as healthy controls.Structured questionnaires were used to collect data on demographics,underlying diseases,vaccination status,and use of SFHT.Patients were propensity-score-matched using 1:1 nearest-neighbor matching of the logit of the propensity score.Subsequently,a conditional logistic regression model was used for data analysis.Results:Overall,7538 eligible subjects were recruited,with an average age of[45.54±16.94]years.The age of COVID-19 patients was significantly higher than that of uninfected individuals([48.25±17.48]years vs[38.92±13.41]years;t=22.437,P<0.001).A total of 2190 COVID-19 cases were matched with uninfected individuals at a 1:1 ratio.The use of SFHT(odds ratio=0.753,95%confidence interval:0.692,0.820)was associated with a lower risk of SARS-CoV-2 infection compared to untreated individuals.Conclusion:Our findings suggest that taking SFHT reduces the risk of SARS-CoV-2 infection.This is a useful study in the larger picture of COVID-19 management,but data from large-sample multi-center,randomized clinical trial are warranted to confirm the finding.展开更多
Ethnicity might be associated with treatment outcomes in advanced prostate cancer.This study aimed to evaluate the efficacy and safety of androgen deprivation therapy(ADT)combined with apalutamide in East Asians with ...Ethnicity might be associated with treatment outcomes in advanced prostate cancer.This study aimed to evaluate the efficacy and safety of androgen deprivation therapy(ADT)combined with apalutamide in East Asians with metastatic castration-sensitive prostate cancer(mCSPC).The original phase 3 Targeted Investigational Treatment Analysis of Novel Anti-androgen(TITAN)trial was conducted at 260 sites in 23 countries.This subgroup analysis included patients enrolled in 62 participating centers in China,Japan,and Korea.Radiographic progression-free survival(PFS),time to prostate-specific antigen(PSA)progression,and PSA changes from baseline were compared between groups in the East Asian population.The intent-to-treat East Asian population included 111 and 110 participants in the apalutamide and placebo groups,respectively.The 24-month radiographic PFS rates were 76.1%and 52.3%in the apalutamide and placebo groups,respectively(apalutamide vs placebo:hazard ratio[HR]=0.506;95%confidence interval[CI],0.302–0.849;P=0.009).Median time to PSA progression was more favorable with apalutamide than placebo(HR=0.210;95%CI,0.124–0.357;P<0.001).Median maximum percentages of PSA decline from baseline were 99.0%and 73.9%in the apalutamide and placebo groups,respectively.The most common adverse event(AE)was rash in the apalutamide group,with a higher rate than that in the placebo group(37.3%vs 9.1%).The most common grade 3 or 4 AEs were rash(12[10.9%])and hypertension(12[10.9%])for apalutamide.The efficacy and safety of apalutamide in the East Asian subgroup of the TITAN trial are consistent with the global results.展开更多
Introduction To improve compliance with voiding diaries in children with primary monosymptomatic nocturnal enuresis(PMNE),a new modified 3-day weekend frequency-volume chart(FVC)was designed,and the compliance and val...Introduction To improve compliance with voiding diaries in children with primary monosymptomatic nocturnal enuresis(PMNE),a new modified 3-day weekend frequency-volume chart(FVC)was designed,and the compliance and validity of this modified FVC was evaluated by comparing with the International Children's Continence Society(ICCS)recommended voiding diary.Methods A total of 1200 patients with PMNE were enrolled in the study from 13 centers in China and were randomly assigned to record this modified FVC or the ICCS-recommended voiding diary.The primary outcome measure was the compliance,assessed by comparing the completing index and the quality score of diaries between two groups.The secondary outcome measure was the validity,evaluated by comparing the constituent of subtypes,micturition parameters and response rate to desmopressin.Results Among the 1200 participants enrolled in the study,447 patients completed the ICCS-recommended voiding diary and 469 completed the modified diary.The diurnal completing index and the quality score of the modified FVC group were better than those of the ICCS group.In addition,there was no significant difference between these two groups in the subtype classification,or in the response rate to desmopressin.Conclusions The modified FVC could be applied to obtain the voiding characteristics of children with PMNE as the ICCS-recommended voiding diary does and offers a reasonable and better choice for children with PMNE from the unselected population in the future.展开更多
文摘Objective:The possible enhancing effect of anlotinib on programmed death receptor ligand(PD-L1)antibody and the efficacy-predicting power of PD-L1 in micro-conduit endothelium,including lymphatic endothelial cells(LECs)and blood endothelial cells(BECs),were determined to identify patients who would benefit from this treatment.Methods:PD-L1 positivity in LECs,BECs,and tumor cells(TCs)was assessed using paraffin sections with multicolor immunofluorescence in an investigator’s brochure clinical trial of TQB2450(PD-L1 antibody)alone or in combination with anlotinib in patients with non-small cell lung cancer.Progression-free survival(PFS)with different levels of PD-L1 expression was compared between the two groups.Results:Among 75 patients,the median PFS(mPFS)was longer in patients who received TQB2450 with anlotinib[10 and 12 mg(161 and 194 days,respectively)]than patients receiving TQB2450 alone(61 days)[hazard ratio(HR)_(10 mg)=0.390(95%confidence interval{CI},0.201–0.756),P=0.005;HR_(12 mg)=0.397(0.208–0.756),P=0.005].The results were similar among 58 patients with high PD-L1 expression in LECs and TCs[159 and 209 vs.82 days,HR_(10 mg)=0.445(0.210–0.939),P=0.034;HR_(12 mg)=0.369(0.174–0.784),P=0.009],and 53 patients with high PD-L1 expression in BECs and TCs[161 and 209 vs.41 days,HR_(10 mg)=0.340(0.156–0.742),P=0.007;HR_(12 mg)=0.340(0.159–0.727),P=0.005].No differences were detected in the mPFS between the TQB2450 and combination therapy groups in 13 low/no LEC-expressing and 18 low/no BEC-expressing PD-L1 cases.Conclusions:Mono-immunotherapy is not effective in patients with high PD-L1 expression in LECs and/or BECs.Anlotinib may increase efficacy by downregulating PD-L1 expression in LECs and/or BECs,which is presumed to be a feasible marker for screening the optimal immune patient population undergoing anti-angiogenic therapy.
基金supported by the National Natural Science Foundation of China(No.82104581,No.82060864).
文摘Sepsis is a life-threatening multiple organ dysfunction syndrome caused by the imbalance of the immune response to infection,featuring complex and variable conditions,and is one of the leading causes of mortality in ICU patients.Lung injury is a common organ damage observed in sepsis patients.Macrophages and Th17 cells,as crucial components of innate and adaptive immunity,play pivotal roles in the development of sepsis-induced acute lung injury(ALI).This review summarizes the alterations and mechanisms of macrophages and Th17 cells in sepsis-induced ALI.By focusing on the“cross-talk”between macrophages and Th17 cells,this review aims to provide a solid theoretical foundation for further exploring the therapeutic targets of traditional Chinese medicine formulas in the treatment of sepsis complicated with ALI,thereby offering insights and guidance for the clinical application of traditional Chinese medicine in managing sepsis-associated ALI.
基金supported by the Agence Nationale de la Recherche grant Hyposkel 18-CE14-0018-01 to C Bardetsupported by the Fondation pour la Recherche Médicale (SPF202209015771)+2 种基金supported by France Life Imaging (grant ANR-11-INBS-0006)Infrastructures Biologie-SanteDIM Therapie Génique
文摘Elevated fibroblast growth factor 23(FGF23)in X-linked hypophosphatemia(XLH)results in rickets and phosphate wasting,manifesting by severe bone and dental abnormalities.Burosumab,a FGF23-neutralizing antibody,an alternative to conventional treatment(phosphorus and active vitamin D analogs),showed significant improvement in the long bone phenotype.Here,we examined whether FGF23 antibody(FGF23-mAb)also improved the dentoalveolar features associated with XLH.Four-week-old male Hyp mice were injected weekly with 4 or 16 mg·kg−1 of FGF23-mAb for 2 months and compared to wild-type(WT)and vehicle(PBS)treated Hyp mice(n=3–7 mice).Micro-CT analyses showed that both doses of FGF23-mAb restored dentin/cementum volume and corrected the enlarged pulp volume in Hyp mice,the higher concentration resulting in a rescue similar to WT levels.FGF23-mAb treatment also improved alveolar bone volume fraction and mineral density compared to vehicle-treated ones.Histology revealed improved mineralization of the dentoalveolar tissues,with a decreased amount of osteoid,predentin and cementoid.Better periodontal ligament attachment was also observed,evidenced by restoration of the acellular cementum.These preclinical data were consistent with the retrospective analysis of two patients with XLH showing that burosumab treatment improved oral features.Taken together,our data show that the dentoalveolar tissues are greatly improved by FGF23-mAb treatment,heralding its benefit in clinics for dental abnormalities.
文摘Hyperglycemia is associated with an increased risk of cardiovascular disease,and the consequences ofintensive therapy may depend on the mechanism of the anti-diabetic agent(s)used to achieve a tight control.In animal models,stable analogues of glucagon-like peptide-1(GLP-1)were able to reduce body weight and blood pressure and also had favorable effects on ischemia following coronary reperfusion.In a similar way,dipeptidyl peptidase IV(DPPIV)showed to have favorable effects in animal models of ischemia/reperfusion.This could be due to the fact that DPPIV inhibitors were able to prevent the breakdown of GLP-1 and glucose-dependent insulinotropic polypeptide,but they also decreased the degradation of several vasoactive peptides.Preclinical data for GLP-1,its derivatives and inhibitors of the DPPIV enzyme degradation suggests that these agents may be able to,besides controlling glycaemia,induce cardio-protective and vasodilator effects.Notwithstanding the many favorable cardiovascular effects of GLP-1/incretins reported in different studies,many questions remain unanswered due the limited number of studies in human beings that aim to examine the effects of GLP-1 on cardiovascular endpoints.For this reason,long-term trials searching for positive cardiovascular effects are now in process,such as the CAROLINA and CARMELINA trials,which are supported by small pilot studies performed in humans(and many more animal studies)with incretin-based therapies.On the other hand,selective renal sodium-glucose co-transporter 2 inhibitors were also evaluated in the prevention of cardiovascular outcomes in type 2 diabetes.However,it is quite early to draw conclusions,since data on cardiovascular outcomes and cardiovascular death are limited and long-term studies are still ongoing.In this review,we will analyze the mechanisms underlying the cardiovascular effects of incretins and,at the same time,we will present a critical position about the real value of these compounds in the cardiovascular system and its protection.
基金This study was supported by the Commission of Science and Technology of Beijing(D121100004912002)the Beijing Natural Science Foundation(No.7152068)the Project for Collaboration between Basis and Clinic of Capital Medical University(No.17JL69).
文摘BACKGROUND Increased homocysteine levels are associated with the risk of cardiovascular disease(CVD)and death.However,their prevention has not been effective in decreasing CVD risk.This study investigated the individual and combined associations of hyperhomocysteinemia and hypertension with incident CVD events and all-cause death in the Chinese elderly population without a history of CVD.METHODS This prospective study was conducted among 1,257 elderly participants(mean age:69 years).A questionnaire survey,physical examinations,and laboratory tests were conducted to collect baseline data.Hyperhomocysteinemia was defined as homocysteine level≥15μmol/L.H-type hypertension was defined as concomitant hypertension and hyperhomocysteinemia.Multivariate Cox regression analysis was used to evaluate individual and combined associations of hyperhomocysteinemia and hypertension with the risks of incident CVD events and all-cause death.RESULTS Over a median of 4.84-year follow-up,hyperhomocysteinemia was independently associated with incident CVD events and all-cause death.The hazard ratios(HRs)were 1.45(95%CI:1.01−2.08)for incident CVD events and 1.55(95%CI:1.04−2.30)for all-cause death.After adjustment for confounding factors,H-type hypertension had the highest HRs for incident CVD events and all-cause death.The fully adjusted HRs were 2.44 for incident CVD events(95%CI:1.28−4.65),2.07 for stroke events(95%CI:1.01−4.29),8.33 for coronary events(95%CI:1.10−63.11),and 2.31 for all-cause death(95%CI:1.15−4.62).CONCLUSIONS Hyperhomocysteinemia was an independent risk factor,and when accompanied by hypertension,it contrib-uted to incident CVD events and all-cause death in the Chinese elderly population without a history of CVD.
基金sponsored by Laboratorios Sophia,SA de CV(Zapopan,Jalisco,Mexico)。
文摘Background : The objective of this study was to validate an animal model for dry eye during and after the administration of 1% ophthalmic atropine sulfate(OAS) in New Zealand white(NZW) rabbits.Methods : OAS(1%) was applied three times per day to 30 eyes of 15 healthy NZW rabbits. Sacrifice, enucleation, and lacrimal gland removal took place on days 15, 21,and 30(OAS group). A second group(n = 5) was used as control. Clinical evaluations took place on days 3, 10, 15, 18, 21, 24 and 30. The primary endpoints were:Schirmer I test, tear break-up time(TBUT), and corneal fluorescein staining. As secondary endpoints, clinical changes including intraocular pressure, and histopathology were evaluated.Results : While OAS was administered, the Schirmer I test showed a statistically significant reduction for OAS group versus control( p < 0.001), and versus basal production( p < 0.001). TBUT showed statistically significant differences between groups(days 3 and 10;p = 0.001) and versus basal values(day 3;p < 0.001). Fluorescein staining showed a statistically significant difference(day 3;p = 0.001). The most frequent clinical finding was conjunctival hyperemia(76.9% OAS vs. 20% control). For histopathology, all OAS subjects presented some degree of inflammation(86.7% minimal;13.3% mild) whereas the control presented only 30% minimal inflammation. Goblet cell density showed no difference.Conclusions : The effectiveness of the OAS dry eye model in NZW rabbits as reported in previous studies was confirmed, provided that the application of the drug is maintained throughout the intervention;it is not a viable model after OAS administration is suspended.
文摘The Systolic Heart failure treatment with the I( inhibitor ivabradine Trial (SHIFT, n = 6505) evaluated patients with symptomatic chronic heart failure (CHF), in sinus rhythm with resting heart rate ≥70 beats/min and left ventricular ejection fraction (LVEF)≤ 35%, average age 60 ± 11 years[1].
基金Transmission of HIV·Chinese Association of STD and AIDS Prevention and Control [PMTCT2018-001]National Center for Women and Children’s Health,China,CDC(He Sheng Yuan Maternal and Infant’s Nutrition and Health Program)[2018FYH008]the National Natural Science Foundation of China [81673245,81673232]
文摘Objective This study aimed to evaluate the effects of in-utero exposure to HIV and ART on pregnancy outcome and early growth of children.Methods This cohort study enrolled 802 HIV-infected pregnant women between October 2009 and May 2018 in Guangzhou, China. The women were assigned to receive combination ART(c ART) or mono/dual ART or no treatment. The primary outcomes were the combined endpoints of any adverse pregnancy outcome [including ectopic pregnancy, spontaneous abortion, stillbirth, preterm birth, small for gestational age(SGA)] and adverse early growth outcome(including infant death, HIV infection of mother-to-child transmission, and underweight, wasting and stunting of infants at 4 weeks of age).Results Adverse pregnancy outcomes occurred in 202(35.1%) of all enrolled HIV-infected women, and121(31.3%) of all infants exhibited adverse effects on early growth at 4 weeks of age. The rates of adverse pregnancy outcomes, spontaneous abortion, ectopic pregnancy, stillbirth, infant death and perinatal HIV infection were higher among women not receiving ART, compared to those treated with c ART or mono/dual ART(P < 0.05). However, women treated with c ART had a higher rate of SGA,compared to untreated women(P < 0.05). No differences in early infant growth were observed among the different treatment regimens.Conclusion Our findings underscore the essentiality of prioritizing HIV-positive pregnant women for ART, as even mono/dual ART available in resource-limited countries could improve pregnancy outcomes and infant survival.
文摘BACKGROUND Diabetes mellitus is a worldwide public health problem associated with significant complications. There is lack of data on the quality of care of patients with diabetes, specifically among the non-Western countries. Efforts have been made in Lebanon to better study the characteristics of patients with diabetes mellitus in order to improve glycemic control and prevent late-term complications.AIM To investigate control and therapeutic management of patients with diabetes mellitus in the current medical practice in Lebanon.METHODS Wave 6 of the International Diabetes Management Practice Study in Lebanon is an international and multicenter study involving selected countries.RESULTS Only 1 patient with type 1 diabetes and 595 patients with type 2 diabetes were included in Wave 6. Average age was around 60 years, with a mean body mass index of 30. The mean fasting serum glucose was 159.42 mg/dL, and the mean glycosylated hemoglobin(HbA1 c) level was 7.98 with around 30% achieving an HbA1 c target of < 7%. More patients were on oral anti-diabetic medications.Screening of diabetic complications has improved over the years. A large percentage is diagnosed with hypertension and dyslipidemia, the majority ofwhom were treated but only a small percentage were controlled.CONCLUSION Diabetes, with its associated dyslipidemia and hypertension, is still not very well controlled. Screening for diabetes complications has improved over the years.Patients need to have more proper care, and physicians need to follow diabetes guidelines, and to have a larger number of patients who have appropriate treatment of diabetes, hypertension and lipids.
文摘<strong>Objectives</strong>:<span> This retrospective study evaluated 1) benefits of single nucleotide polymorphism (SNP)-based chromosomal microarrays (CMAs) in the diagnosis of complete hydatidiform mole (CHM) and partial HM (PHM) in products of conception (POC) and amniotic fluid (AF) specimens, and 2) frequency of whole-genome uniparental disomy (wgUPD) and triploidy in POC and AF specimens received at a US national reference laboratory.</span><span "=""> </span><b><span>Methods:</span></b><span> We reviewed consecutive 2138 POC and 3230 AF specimens and identified the cases with wgUPD and triploidy which are associated with molar pregnancy.</span><span "=""> </span><b><span>Results:</span></b><span "=""><span> Of 2138 consecutive POC specimens tested, SNP-based CMA detected wgUPD in 10 (0.47%) and triploidy in 84 (3.93%). Of the 10 wgUPD cases, 9 (90%) were confirmed as CHM. Of 3230 consecutive AF specimens, the array detected wgUPD in 1 case (0.03%) and triploidy in 11 (0.34%). </span><b><span>Conclusions:</span></b><span> SNP-based microarray allows detection of wgUPD in POC and AF specimens at a US national reference laboratory. Correctly diagnosing HM and differentiating CHM from PHM </span></span><span>are</span><span> important for clinical management. The effective SNP-based CMA detection of wgUPD in CHM may enable physicians to monitor patients at risk for gestational trophoblastic disease and neoplasm.</span><span "=""> </span><span "=""><span>Conventional chromosome analysis of POC has a high </span><span>failure rate, cannot be performed on formalin-fixed paraffin embedded samples, and cannot detect wgUPD. Further</span></span><span "=""> </span><span>multi-institutional collaborative assessmen</span><span> on accuracy, cost-effectiveness, and adequate access to SNP-based CMA, may lead this testing platform to be considered as the first-tier analysis tool for POC specimens, including those showing PHM or CHM.
文摘Daily 20-mg and once-weekly 56.5-mg teriparatide(parathyroid hormone 1–34) treatment regimens increase bone mineral density(BMD) and prevent fractures, but changes in bone turnover markers differ between the two regimens. The aim of the present study was to explain changes in bone turnover markers using once-weekly teriparatide with a simulation model. Temporary increases in bone formation markers and subsequent decreases were observed during once-weekly teriparatide treatment for 72 weeks. These observations support the hypothesis that repeated weekly teriparatide administration stimulates bone remodeling, replacing old bone with new bone and leading to a reduction in the active remodeling surface. A simulation model was developed based on the iterative remodeling cycle that occurs on residual old bone. An increase in bone formation and a subsequent decrease were observed in the preliminary simulation. For each fitted time point, the predicted value was compared to the absolute values of the bone formation and resorption markers and lumbar BMD. The simulation model strongly matched actual changes in bone turnover markers and BMD. This simulation model indicates increased bone formation marker levels in the early stage and a subsequent decrease. It is therefore concluded that remodeling-based bone formation persisted during the entire treatment period with once-weekly teriparatide.
基金supported by the fund of COVID-19 Prevention and Treatment from Administration of Traditional Chinese Medicine (No. XGYJKY2022-09 and No. 2022ZYLCYJ05-10)the Threeyear Action Plan for Promoting Clinical Skills and Innovation Ability of Municipal Hospitals (No. SHDC2022CRS039)+2 种基金the Shanghai Natural Science Foundation (No.23ZR1464000 and No.23ZR1463900)Medical Innovation Research Special Project of the Shanghai ‘‘Science and Technology Innovation Action Plan”(No.21Y11922500 and No.21Y11922400)the Talent Fund of Longhua Hospital (No. LH001.007)
文摘Objective:Omicron,a severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)variant,is responsible for numerous infections in China.This study investigates the association between the use of Seven-Flavor Herb Tea(SFHT)and the risk of SARS-CoV-2 infection to develop precise and differentiated strategies for control of the coronavirus disease 2019(COVID-19).Methods:This case-control study was conducted at shelter hospitals and quarantine hotels in China.A total of 5348 laboratory-confirmed COVID-19 patients were enrolled between April 1 and May 31,2022,while 2190 uninfected individuals served as healthy controls.Structured questionnaires were used to collect data on demographics,underlying diseases,vaccination status,and use of SFHT.Patients were propensity-score-matched using 1:1 nearest-neighbor matching of the logit of the propensity score.Subsequently,a conditional logistic regression model was used for data analysis.Results:Overall,7538 eligible subjects were recruited,with an average age of[45.54±16.94]years.The age of COVID-19 patients was significantly higher than that of uninfected individuals([48.25±17.48]years vs[38.92±13.41]years;t=22.437,P<0.001).A total of 2190 COVID-19 cases were matched with uninfected individuals at a 1:1 ratio.The use of SFHT(odds ratio=0.753,95%confidence interval:0.692,0.820)was associated with a lower risk of SARS-CoV-2 infection compared to untreated individuals.Conclusion:Our findings suggest that taking SFHT reduces the risk of SARS-CoV-2 infection.This is a useful study in the larger picture of COVID-19 management,but data from large-sample multi-center,randomized clinical trial are warranted to confirm the finding.
基金This study was funded by Janssen Pharmaceutical Ltd.,which designed the study.
文摘Ethnicity might be associated with treatment outcomes in advanced prostate cancer.This study aimed to evaluate the efficacy and safety of androgen deprivation therapy(ADT)combined with apalutamide in East Asians with metastatic castration-sensitive prostate cancer(mCSPC).The original phase 3 Targeted Investigational Treatment Analysis of Novel Anti-androgen(TITAN)trial was conducted at 260 sites in 23 countries.This subgroup analysis included patients enrolled in 62 participating centers in China,Japan,and Korea.Radiographic progression-free survival(PFS),time to prostate-specific antigen(PSA)progression,and PSA changes from baseline were compared between groups in the East Asian population.The intent-to-treat East Asian population included 111 and 110 participants in the apalutamide and placebo groups,respectively.The 24-month radiographic PFS rates were 76.1%and 52.3%in the apalutamide and placebo groups,respectively(apalutamide vs placebo:hazard ratio[HR]=0.506;95%confidence interval[CI],0.302–0.849;P=0.009).Median time to PSA progression was more favorable with apalutamide than placebo(HR=0.210;95%CI,0.124–0.357;P<0.001).Median maximum percentages of PSA decline from baseline were 99.0%and 73.9%in the apalutamide and placebo groups,respectively.The most common adverse event(AE)was rash in the apalutamide group,with a higher rate than that in the placebo group(37.3%vs 9.1%).The most common grade 3 or 4 AEs were rash(12[10.9%])and hypertension(12[10.9%])for apalutamide.The efficacy and safety of apalutamide in the East Asian subgroup of the TITAN trial are consistent with the global results.
基金funding from the National Natural Foundation of China(81770710)Key Research and Development Plan of Zhejiang Province(2019C03028)+1 种基金the Major projects jointly constructed by the Zhejiang province and National Health Commission(WKJ-ZJ-1908)the Natural Science Foundation of Zhejiang Province(LQ18H050001).
文摘Introduction To improve compliance with voiding diaries in children with primary monosymptomatic nocturnal enuresis(PMNE),a new modified 3-day weekend frequency-volume chart(FVC)was designed,and the compliance and validity of this modified FVC was evaluated by comparing with the International Children's Continence Society(ICCS)recommended voiding diary.Methods A total of 1200 patients with PMNE were enrolled in the study from 13 centers in China and were randomly assigned to record this modified FVC or the ICCS-recommended voiding diary.The primary outcome measure was the compliance,assessed by comparing the completing index and the quality score of diaries between two groups.The secondary outcome measure was the validity,evaluated by comparing the constituent of subtypes,micturition parameters and response rate to desmopressin.Results Among the 1200 participants enrolled in the study,447 patients completed the ICCS-recommended voiding diary and 469 completed the modified diary.The diurnal completing index and the quality score of the modified FVC group were better than those of the ICCS group.In addition,there was no significant difference between these two groups in the subtype classification,or in the response rate to desmopressin.Conclusions The modified FVC could be applied to obtain the voiding characteristics of children with PMNE as the ICCS-recommended voiding diary does and offers a reasonable and better choice for children with PMNE from the unselected population in the future.