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OBJECTIVE: Recaticimab (SHR-1209) significantly reduces low-density lipoprotein cholesterol levels. However, its effect on glucose metabolism remains unclear. This study aimed to evaluate its effect on glycemic parameters in a Chinese population. METHODS: Recaticimab versus placebo was administered in a 5:1 ratio to 110 hyperlipidemia patients who were followed up for 24 weeks. Glycated hemoglobin (HbA1c) levels were measured at baseline every 12 weeks. Fasting plasma glucose (FPG) levels were measured at baseline at week 1, 3, 5, 8, 12, 16, 20, and 24. Repeated-measures mixed-effects models were used to determine the longitudinal association between reacticimab and FPG and HbA1c levels. RESULTS: Among the 81 participants with normal glucose metabolism, HbA1c levels significantly decreased ( F = 4.568, P = 0.036). In the 29 participants with abnormal glucose metabolism, a significant time effect was observed for FPG levels ( F = 2.492, P = 0.016). For participants with normal and abnormal glucose metabolism, no significant group × time interaction effects on FPG or HbA1c levels were identified. CONCLUSION Recaticimab showed no adverse glycemic effects in participants with normal or abnormal glucose metabolism, indicating its safety in patients with or without diabetes.
Humans ; Male ; Female ; Blood Glucose/drug effects* ; Middle Aged ; Double-Blind Method ; Hyperlipidemias/blood* ; Antibodies, Monoclonal, Humanized/therapeutic use* ; PCSK9 Inhibitors ; Glycated Hemoglobin ; Aged ; Adult ; Proprotein Convertase 9

Objective To explore the regulatory mechanism of non-structural maintenance of chromosome condensin Ⅰ complex submit G(NCAPG)on proliferation,migration,and invasion of ovarian cancer cells.Methods The bioinformatics database was used to analyze the differential expression of NCAPG in ovarian cancer tissues.Western blotting was used to detect the protein expression of NCAPG in normal ovarian epithelial cells IOSE80,ovarian cancer A2780 and SKOV3 cells.The silencing experiments of NCAPG siRNA were divided into blank,control,siNCAPG-1 and siNCAPG-2 groups.The overexpression experiments of NCAPG plasmid were divided into blank,control,NCAPG,NCAPG+MK2206 and MK2206 groups.MTT assay was used to detect cell proliferation activity.Cell scoring assay and transwell assay were used to analyze cell migration and invasion.The protein expressions of p-Akt,total(t)-Akt,proliferative cellular nucleus antigen(PCNA),matrix metallopeptidase 9(MMP-9),vimentin,N-cadherin,and E-cadherin were detected by Western blotting.Results NCAPG was highly expressed in ovarian cancer tissues and cells.Knockdown of NCAPG significantly inhibited the proliferation,invasion and migration of ovarian cancer SKOV3 cells.The protein expressions of p-Akt,PCNA,MMP-9,vimentin and N-cadherin decreased while E-cadherin expression increased.Overexpression of NCAPG significantly promoted the proliferation,invasion and migration of ovarian cancer A2780 cells.The protein expressions of p-Akt,PCNA,MMP-9,vimentin,and N-cadherin increased while E-cadherin expression decreased.Akt inhibitor MK2206 significantly attenuated the above effects of NCAPG.Conclusion NCAPG promotes the proliferation,invasion,and migration of ovarian cancer cells by activating the Akt signaling pathway and regulating the expression of PCNA,MMP-9,and epithelial-mesenchymal transition(EMT)-related proteins.

Objective To study chest computed tomography(CT)manifestations in neonates with chronic granulomatous disease(CGD)to provide clues for early diagnosis of this disease.Methods A retrospective analysis was conducted on the clinical data and chest CT scan results of neonates diagnosed with CGD from January 2015 to December 2022 at Anhui Provincial Children's Hospital.Results Nine neonates with CGD were included,with eight presenting respiratory symptoms as the initial sign.Chest CT findings included:consolidation in all 9 cases;nodules in all 9 cases,characterized by multiple,variably sized scattered nodules in both lungs;masses in 4 cases;cavities in 3 cases;abscesses in 6 cases;bronchial stenosis in 2 cases;pleural effusion,interstitial changes,and mediastinal lymphadenopathy each in 1 case.CT enhancement scans showed nodules and masses with uneven or ring-shaped enhancement;no signs of pulmonary emphysema,lung calcification,halo signs,crescent signs,bronchiectasis,or scar lesions were observed.There was no evidence of rib or vertebral bone destruction.Fungal infections were present in 8 of the 9 cases,including 6 with Aspergillus infections;three of these involved mixed infections with Aspergillus,with masses most commonly associated with mixed Aspergillus infections(3/4).Conclusions The primary manifestations of neonatal CGD on chest CT are consolidation,nodules,and/or masses,with Aspergillus as a common pathogen.These features can serve as early diagnostic clues for neonatal CGD.

A series of phthalimide-donepezil (PTA-DPZ) hybrids (5a-e, 6a-l) were designed, synthesized and evaluated as selective inhibitors of acetylcholinesterase (AChE). The results showed that some hybrids had strong AChE inhibitory activity with half maximal inhibitory concentration (IC₅₀) at nanomolar range, which was better than the control drugs galanthamine and tacrine, and equivalent to DPZ. Compound 6k exhibited the strongest inhibition to AChE with an IC₅₀ value of 0.13 μmol·L^-1. Kinetic and molecular modeling studies showed that 6k targeted both catalytic active site and peripheral anionic site of AChE. Moreover, some compounds could inhibit AChE-induced β-amyloid (Aβ) aggregation. In addition, absorption, distribution, metabolism and excretion prediction results showed 6k conforms to the Lipinski's rule of five and had high partition coefficient P value. These compounds, especially 6k, may be considered as a dual-functional lead compound for in-depth research.

Objective To observe the efficacy of Chinese medicine in the treatment of pregnancy complicated with thalassemia and to investigate its influence on pregnancy outcomes.Methods A retrospective cohort study was carried out in 175 pregnant women complicated with thalassemia who met the inclusion criteria.According to the treatment methods,the patients were divided into Chinese medicine group(105 cases),iron supplementation group(41 cases)and untreated group(29 cases).The changes of hematological indicators and pregnancy outcomes in the second and third trimesters of pregnancy were compared among the three groups.The Chinese medicine group was further divided into three subgroups:56 cases in the Chinese patent medicine group,20 cases in the single Chinese medicine group and 29 cases in the Chinese herbal compound group.The changes of hematological indexes in the second and third trimesters of pregnancy in the three subgroups were compared.Moreover,the normative management of pregnant women with thalassemia during pregnancy was explored.Results(1)The concentration of hemoglobin(Hb)in the third trimester of the Chinese medicine group was(2.28±7.27)g/L higher than that in the second trimester,and the curative effect of Chinese medicine group was superior to that in the iron supplementation group and the untreated group(P＜0.05).The Hb concentration in the Chinese medicine group before delivery was(12.17±10.81)g/L higher than that in the second trimester,and the increase in the Chinese medicine group was more significantly than that in the other two groups(P＜0.05).(2)The level of serum ferritin(FER)in the third trimester of the three groups was lower than that in the second trimester,and the decrease of FER level in the iron supplementation group was less significantly than that in the other two groups(P＜0.05).(3)The Hb concentration in the third trimester of the single Chinese medicine group and the Chinese herbal compound group increased by(4.50±4.66),(3.62±8.77)g/L respectively compared with that in the second trimester,and the increase in the above two groups was more significantly than that in the Chinese patent medicine group(P＜0.05).(4)There was no significant difference in pregnancy outcomes among the three groups of pregnant women with thalassemia(P＞0.05).(5)Only 52.0％(91/175)of pregnant women with thalassemia underwent three or more blood routine tests after 20-24 weeks of pregnancy,34.3％(60/175)of pregnant women failed in re-examining the FER levels,and 21.2％(37/175)of pregnant women had no standardized iron supplementation.Conclusion Chinese medicine therapy is effective on improving anemia in pregnant women with thalassemia.Chinese herbal compound and single Chinese medicinal are more effective than Chinese patent medicine,and have not increased the risk of adverse pregnancy outcomes.Oral administration of iron can increase the iron reserve of pregnant women with thalassemia,but its effect on improving anemia is not as good as that of Chinese medicine.Attention should be got to the monitoring of anemia and iron metabolism indicators as well as the standardized use of iron supplements and Chinese patent medicines in pregnant women with thalassemia.

  Objective  To analyze the current status of the development of adaptation guidelines in China, as well as their methodological quality and the reporting quality, in order to provide reference for the development of adaptation guidelines.  Methods  We searched and collected adaptation guidelines led by Chinese researchers or institutions from 2015 to 2023 from four electronic databases, China National Knowledge Infrastructure, WanFang Data Knowledge Service Platform, SinoMed and PubMed, extracted the basic information of the adapted guidelines, and assessed their methodological quality and reporting quality using the Appraisal of Guidelines for REsearch and Evaluation (AGREE) Ⅱ and RIGHT-Ad@pt tools.  Results  A total of 14 adaptation guidelines were included, mainly focusing on nursing (42.9%, 6/14), with the most frequently used adaptation method of ADAPTE (71.4%, 10/14), and with reference to pre-existing guidelines mainly from the United States, the United Kingdom, and international organizations. Assessment by the AGREE Ⅱ tool showed that the average methodological quality score of the adapted guidelines was 36.6%. The scores were relatively high in the domains of clarity of expression and rigor of formulation (44.4% and 54.9%), and lowest in the domain of applicability (15.3%). The results of the RIGHT-Ad@pt tool showed that the reporting quality of the adaptation guidelines was relatively good, with the highest reporting rate of 91.2% and the lowest of 35.3%, and the reporting rates of seven articles were higher than 70%.  Conclusions  Adaptation guidelines in China are still in their infancy, with a relatively small number and mainly focusing on the nursing field. The most commonly used adaptation method is the ADAPTE method. The methodological quality and reporting quality of adaptation guidelines need to be further improved, and more research should be conducted on the specific conditions and timing of adaptation guidelines development.

Objective To evaluate tolerability,safety and pharmacokinetics of JS026 and JS026-JS016 single dose intravenous infusion in healthy adults.Methods This phase 1,randomized,double-blind,placebo-controlled,dose-escalation study totally included 48 participants:32 healthy subjects were enrolled in JS026 single intravenous infusion groups and 16 healthy subjects were enrolled in JS026-JS016 groups.JS026 was sequentially administered from low dose to high dose(30-1 000 mg),with intravenous infusion of JS026 or placebo in JS026 single-dose groups,and intravenous infusion of JS026-JS016 or placebo in the combination drug groups.Blood was collected according to the time point designed for trial.Serum concentrations of JS026 and JS016 were determined by enzyme linked immunosorbnent assay(ELISA),and pharmacokinetics parameters were calculated by WinNonlin 8.2.The power model method was used to evaluate the linear analysis of dose and drug exposure.Results 47 subjects completed trial and 1 subject lost to follow-up.After a single intravenous injection of JS026 of 30 mg,100 mg,300 mg,600 mg,and 1 000 mg,mean Cmax were(9.47±1.53),(33.20±4.95),(96.10±13.70),(177.00±22.20)and(353.00±56.70)μg·mL-1,respectively;mean AUC0-∞ were(4 225.00±607.00),(1.78 × 104±3 268.00),(5.83 × 104±1 038.00),(1.07 × 105±152.00),(1.66 × 105±327.00)μg·h·mL-1,respectively;mean t1/2 of JS026 were 563-709 h.The Cmax and AUC0-∞ of JS026 were basically similar alone or in combination with JS016.The results of Power model showed that Cmax and AUC0-∞ increased approximately linearly with the increasing dose of JS026.Treatment emergent adverse event was not increasing when dose increased and most of adverse event associated with drugs were abnormal on laboratory tests and haematuria,thus JS026 and JS016 was well tolerated in all groups.Conclusion The single intravenous infusion of JS026 can almost be thought to be a linear relationship between the doses and drug serum exposure.JS016 had no significant effect on serum concentration of JS026 and JS026 was well tolerated and safe in healthy subjects within 30-1 000 mg.

Ankylosing spondylitis (AS) combined with lower cervical fracture is often categorized into unstable fracture, with a high incidence of neurological injury and a high rate of disability and morbidity. As factors such as shoulder occlusion may affect the accuracy of X-ray imaging diagnosis, it is often easily misdiagnosed at the primary diagnosis. Non-operative treatment has complications such as bone nonunion and the possibility of secondary neurological damage, while the timing, access and choice of surgical treatment are still controversial. Currently, there are no clinical practice guidelines for the treatment of AS combined with lower cervical fracture with or without dislocation. To this end, the Spinal Trauma Group of Orthopedics Branch of Chinese Medical Doctor Association organized experts to formulate Clinical guidelines for the treatment of ankylosing spondylitis combined with lower cervical fracture in adults ( version 2024) in accordance with the principles of evidence-based medicine, scientificity and practicality, in which 11 recommendations were put forward in terms of the diagnosis, imaging evaluation, typing and treatment, etc, to provide guidance for the diagnosis and treatment of AS combined with lower cervical fracture.