Aim To explore the influence of demethy-lase fat mass and obesity-related genes(FTO)on the abnormal contractile function of diabetic coronary smooth muscle.Methods Smooth muscle specific FTO knockout mice(FTOSMKO)were prepared by Cre-loxP recombinant technology.They were divided into four groups:control(WT)group,diabetes model group(DM),FTO knockout group(FTOSMKO),and FTOSMKO diabetic group(FTOSMKO-DM),with 15 mice in each group.Diabetic mice were prepared by intraperitoneal injection of streptozotocin(STZ);the remaining mice were injected with an equal amount of citric acid-sodi-um citrate buffer.The effects of 5-HTon the contractile response of coronary artery smooth muscle in the four groups of mice were observed by the technique of small-vessel ring tensiometry.Western blot and Dot blot were used to detect the changes of FTO protein and N6-methyladenine(m6A)methylation modification levels in mouse vascular tissues.Results Compared with the WT group,the DM group had significantly higher blood glucose(P＜0.01)and lower body weight(P＜0.05);the level of FTO protein in aorta of DM group increased(P＜0.01),and the level of m6A methylation modification decreased(P＜0.01).The 5-HT-induced contractile response significantly de-creased in the DM group compared with the WT group(P＜0.01),whereas the contractile response signifi-cantly increased in the FTOSMKO-DM group compared with the DM group(P＜0.01);the non-L-type calci-um channel-mediated vascular smooth muscle contrac-tile response was enhanced in the FTOSMKO-DM group,among which,the contractions induced by 1,4,5-triphosphate inositol receptor(IP3R)and caffeine-ac-tivated ranine receptor(RyR)mediated by sarcoplas-mic reticulum calcium release both significantly in-creased(P＜0.05).Conclusions Specific knock-down of smooth muscle FTO improves coronary artery responsiveness to the vasoconstrictor 5-HT in diabetic mice,which may be related to abnormalities in the FTO-mediated 5-HT receptor signaling pathway.

Aim To explore the influence of demethy-lase fat mass and obesity-related genes(FTO)on the abnormal contractile function of diabetic coronary smooth muscle.Methods Smooth muscle specific FTO knockout mice(FTOSMKO)were prepared by Cre-loxP recombinant technology.They were divided into four groups:control(WT)group,diabetes model group(DM),FTO knockout group(FTOSMKO),and FTOSMKO diabetic group(FTOSMKO-DM),with 15 mice in each group.Diabetic mice were prepared by intraperitoneal injection of streptozotocin(STZ);the remaining mice were injected with an equal amount of citric acid-sodi-um citrate buffer.The effects of 5-HTon the contractile response of coronary artery smooth muscle in the four groups of mice were observed by the technique of small-vessel ring tensiometry.Western blot and Dot blot were used to detect the changes of FTO protein and N6-methyladenine(m6A)methylation modification levels in mouse vascular tissues.Results Compared with the WT group,the DM group had significantly higher blood glucose(P＜0.01)and lower body weight(P＜0.05);the level of FTO protein in aorta of DM group increased(P＜0.01),and the level of m6A methylation modification decreased(P＜0.01).The 5-HT-induced contractile response significantly de-creased in the DM group compared with the WT group(P＜0.01),whereas the contractile response signifi-cantly increased in the FTOSMKO-DM group compared with the DM group(P＜0.01);the non-L-type calci-um channel-mediated vascular smooth muscle contrac-tile response was enhanced in the FTOSMKO-DM group,among which,the contractions induced by 1,4,5-triphosphate inositol receptor(IP3R)and caffeine-ac-tivated ranine receptor(RyR)mediated by sarcoplas-mic reticulum calcium release both significantly in-creased(P＜0.05).Conclusions Specific knock-down of smooth muscle FTO improves coronary artery responsiveness to the vasoconstrictor 5-HT in diabetic mice,which may be related to abnormalities in the FTO-mediated 5-HT receptor signaling pathway.

Objective To investigate the environmental contamination related to first patient with carbapenem-re-sistant Acinetobacter baumannii(CRAB)infection and the infection status of relevant patients in a newly established intensive care unit(ICU)of a hospital in Tibetan area,and analyze the transmission risk.Methods From the ad-mission in ICU of a patients who was first detected CRAB on November 15,2021 to the 60th day of hospitalization,all patients who stayed in ICU for＞48 hours were performed active screening on CRAB.On the 30th day and 60th day of the admission to the ICU of the first CRAB-infected patient,environment specimens were taken respectively 2 hours after high-frequency diagnostic and therapeutic activities but before disinfection,and after disinfection but before medical activities.CRAB was cultured with chromogenic culture medium.Results Among the 13 patients who were actively screened,1 case was CRAB positive,he was transferred from the ICU of a tertiary hospital to the ICU of this hospital on November 19th.On the 40th day of admission to the ICU,he had fever,increased frequency for sputum suction,and CRAB was detected.The drug sensitivity spectrum was similar to that of the first case,and he also stayed in the adjacent bed of the first case.64 environmental specimens were taken,and 9 were positive for CRAB,with a positive rate of 14.06％,8 sampling points such as the washbasin,door handle and bed rail were positive for CRAB after high-frequency diagnostic and therapeutic activities.After routine disinfection,CRAB was detected from the sink of the washbasin.Conclusion For the prevention and control of CRAB in the basic-level ICU in ethnic areas,it is feasible to conduct risk assessment on admitted patients and adopt bundled prevention and con-trol measures for high-risk patients upon admission.Attention should be paid to the contaminated areas(such as washbasin,door handle,and bed rail)as well as the effectiveness of disinfection of sink of washbasin.

Malnutrition is a significant risk factor for the progression of chronic kidney disease(CKD),and monitoring the nutritional status of CKD patients is crucial for delaying disease progression and improving patient prognosis.Currently,there is a scarcity of studies on malnutrition in CKD,and a unified standard for nutritional assessment in CKD is still lacking.Clinical evaluation must be conducted according to the condition of patients,combined with multiple indicators.Nutritional screening and assessment scales are the common nutritional assessment methods;however,due to limitations in the applicable populations,the applicability of some scales for the CKD population requires further verification.Additionally,anthropometric indicators,body composition analysis,and clinical laboratory indicators can also reflect human nutritional status,each with its respective advantages and limitations.This review summarizes the research status and clinical application characteristics of various nutritional assessment methods in CKD patients,aiming to provide references for the clinical assessment of malnutrition in CKD.

Aim To investigate the effects of baicalin on the inflammatory response and Toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD 88)/nuclear factor kappa B (N F-K B) signaling pathway in Alzheimer' s disease (AD) rat model induced by lateral ventricular injection of streptozotocin (STZ). Methods The AD animal model was constructed by lateral ventricular injection of STZ in SD rats, and divided into sham operation group, model group, low-dose (60 mg

This study investigated the mechanism of Danggui Shaoyao Powder(DSP) against mitophagy in rat model of Alzheimer's disease(AD) induced by streptozotocin(STZ) based on PTEN induced putative kinase 1(PINK1)-Parkin signaling pathway. The AD rat model was established by injecting STZ into the lateral ventricle, and the rats were divided into normal group, model group, DSP low-dose group(12 g·kg~(-1)·d~(-1)), DSP medium-dose group(24 g·kg~(-1)·d~(-1)), and DSP high-dose group(36 g·kg~(-1)·d~(-1)). Morris water maze test was used to detect the learning and memory function of the rats, and transmission electron microscopy and immunofluorescence were employed to detect mitophagy. The protein expression levels of PINK1, Parkin, LC3BⅠ/LC3BⅡ, and p62 were assayed by Western blot. Compared with the normal group, the model group showed a significant decrease in the learning and memory function(P<0.01), reduced protein expression of PINK1 and Parkin(P<0.05), increased protein expression of LC3BⅠ/LC3BⅡ and p62(P<0.05), and decreased occurrence of mitophagy(P<0.01). Compared with the model group, the DSP medium-and high-dose groups notably improved the learning and memory ability of AD rats, which mainly manifested as shortened escape latency, leng-thened time in target quadrants and elevated number of crossing the platform(P<0.05 or P<0.01), remarkably activated mitophagy(P<0.05), up-regulated the protein expression of PINK1 and Parkin, and down-regulated the protein expression of LC3BⅠ/LC3BⅡ and p62(P<0.05 or P<0.01). These results demonstrated that DSP might promote mitophagy mediated by PINK1-Parkin pathway to remove damaged mitochondria and improve mitochondrial function, thereby exerting a neuroprotective effect.
Rats ; Animals ; Mitophagy ; Alzheimer Disease/genetics* ; Powders ; Protein Kinases/metabolism* ; Ubiquitin-Protein Ligases/metabolism*

The successful development and application of mRNA COVID-19 vaccine fully illustrated the great potential and application prospect of mRNA technology in the field of biomedicine. Currently, many companies worldwide are developing drugs and vaccines based on mRNA technology for the prevention and treatment of various diseases. It can be foreseen that with the continuous launch of mRNA drugs, commercial GMP production capacity matching them is also urgent. The optimization of production processes, intelligent manufacturing and other risk control strategies, as well as the control of industrialization costs, will help improve the core competitiveness of mRNA innovative drug development. In view of this, this article will provide an overview of the global production process of mRNA drugs and the progress of related GMP production dynamics, sort out the key chain points of the mRNA industry chain, explore the construction of the mRNA pharmaceutical enterprise value chain and the formation of core competitiveness, and provide reference and reference for the research and development of innovative mRNA drugs and high-quality development in China.

Aim To investigate the mechanism of RhoA/ROCK signaling pathway in abnormal aortic contractility in type 2 diabetes (T2DM) mice. Methods The experiment was divided into two groups, the control group (db/m mice) and the model group (db/db mice). Changes of the response to different methods were measured in aorta rings using a Multi Myograph System. At the same time, the protein expression changes of aortic smooth muscle contraction signaling pathway in mice were determined by Western method. Results Compared with the control group, the blood glucose and body weight levels of the mice in the T2DM group significantly increased, and the cardiac function was abnormal (P <0. 01). The contractile response of the aorta of the diabetic mice induced by the contractile agents Phe, 5-HT and CaCl

With the postponement of marriage and childbirth age and the opening of the "three child" policy， the reproductive demand of advanced ages is increasing， and reproductive aging has become an important public health issue facing social development. Previous studies have shown that 40~55 years old may be the "watershed" of male fertility during aging. However， compared with female reproductive aging， male reproductive aging lacks distinctive characteristics， and its impact on the elderly men is multifaceted. In this review， we elaborated our understanding of the male reproductive aging from multiple perspectives of aging-related changes in male reproductive endocrine， gonads， and accessory sex glands.

Repairing glans dehiscence after failed hypospadias repair is challenging for pediatric surgeons. Here, we introduced and evaluated a newly modified Mathieu technique, Mathieu combined tunnel (MCT), which involves multiple custom-designed flaps for the shortage of flap source material after repeated operations; we also constructed a tunnel to avoid the glans incision that may carry new risks of dehiscence. This retrospective study included 26 patients who were consecutively admitted to the First Affiliated Hospital of Sun Yat-Sen University (Guangzhou, China) for glans dehiscence repair after failed hypospadias repair from October 2014 to October 2020; sixteen patients underwent surgery using the MCT (MCT group) and ten patients underwent surgery using the tubularized incised plate (TIP) technique (TIP group). The operative time, blood loss, postoperative complications, normal urethral meatus rate, success rate, and Hypospadias Objective Penile Evaluation (HOPE) score were compared between the two groups. The MCT group achieved an overall satisfactory penile appearance and voiding function, with a higher rate of normal urethral meatus (15/16, 93.8%) and a lower rate of glans dehiscence (1/16, 6.2%), compared with the TIP group (70.0% and 30.0%, respectively). However, these differences were not statistically significant, possibly because of the limited number of patients (all P > 0.05). Mean postoperative HOPE scores were similar in the MCT group (mean ± standard deviation: 8.83 ± 0. 89) and TIP group (8.94 ± 0.57) (P > 0.05). No significant differences were found between the two groups in terms of blood loss and success rate, nor in the rates of various complications (e.g., fistula, urethral stricture, and glans dehiscence). In conclusion, the MCT technique appears to be feasible and reliable for repairing glans dehiscence after failed hypospadias repair.
Child ; Female ; Humans ; Hypospadias/surgery* ; Infant ; Male ; Retrospective Studies ; Treatment Outcome ; Urethra/surgery* ; Urologic Surgical Procedures, Male/methods*