Calcineurin inhibitor（CNI） is potent immunosuppressive agents and serve as cornerstone therapies in the treatment of organ transplantation and autoimmune diseases， with cyclosporine A and tacrolimus being the representative drugs. Long-term use of CNI can lead to drug-induced hyperglycemia， severely affecting patients’ prognosis. The pathogenesis involves multilevel pathological alterations： at the pancreatic β-cell level， CNI directly damage β-cell by inducing calcium overload， oxidative stress， and mitochondrial dysfunction， suppressing the expression of key insulin synthesis factors and promoting apoptosis； in peripheral tissues， CNI interfere with insulin receptor substrate phosphorylation and inhibit the phosphatidylinositol 3 kinase/protein kinase B signaling pathway， resulting in decreased glucose uptake and insulin resistance； additionally， CNI can also induce β-cell injury by suppressing the secretion and receptor signal transduction of glucagon-like peptide-1， as well as by activating the nuclear factor kappa B pathway to promote inflammatory responses. Clinical studies demonstrate that the incidence of CNI-associated hyperglycemia is closely related to drug type， dosage， and individual patient factors. For high-risk patients， dose adjustment of CNI， switching to agents with lower metabolic toxicity when necessary， and selection of appropriate glucose-lowering regimens based on glycemic levels are recommended. Future research should further elucidate the molecular mechanisms of CNI metabolic toxicity and optimize individualized pharmacotherapy strategies to improve long-term patient outcomes.

ObjectiveTo investigate the effect of nicotinamide adenine dinucleotide on vascular endothelial injury in hypertension and its molecular mechanism. MethodsC57BL/6J mice were randomly divided into saline group （Saline） and hypertension group （Ang Ⅱ， which were infused with Ang Ⅱ via subcutaneously implanted osmotic pumps）， and supplemented daily with nicotinamide mononucleotide （300 mg/kg）， a precursor of NAD⁺. Blood pressure， endothelial relaxation function and pulse wave velocity were measured after 4 weeks. Wound healing assay and adhesion assay were used to evaluate the function of endothelial cells in vitro. mtROS levels were detected by immunofluorescence staining. RT-PCR was used to detect the mRNA expression of mtDNA， SIRT3 and isocitrate dehydrogenase 2 （IDH2）. 8-hydroxy-2'-deoxyguanosine levels were detected by enzyme-linked immunosorbent assay. The protein expression levels of p-eNOS， eNOS， SIRT3 and IDH2 were detected by Western blot. ResultsNMN supplementation reduced blood pressure （P<0.001） and improved endothelial function and arterial stiffness （P<0.001） in hypertensive mice. In vitro， NMN improved endothelial function in AngII-stimulated endothelial cells （P<0.05） and attenuated mitochondrial oxidative stress levels （P<0.001）. Mechanistically， NMN elevated SIRT3 activity （P<0.001）， which subsequently enhanced IDH activity （P<0.001） and reduced oxidative stress levels in endothelial cells. Conversely， knockdown of IDH2 would reverse the effect of SIRT3 in improving endothelial function （P<0.001）. ConclusionNAD⁺ lowers blood pressure and enhances vascular function in hypertension by reducing the level of oxidative stress in endothelial cells through activation of the SIRT3/IDH2 signal pathway.

BACKGROUND:As the end bearing joint of the human body,the ankle joint bears the top-down pressure of the body,which leads to the ankle joint is easy to be damaged in the movement,can induce functional ankle instability,which negatively affects daily life.The study of lower extremity biomechanics in patients with functional ankle instability during counter movement jump is of great significance for scientific training,prevention of ankle injury,and clinical rehabilitation after injury. OBJECTIVE:To investigate the kinetics and kinematics of lower limbs in the longitudinal jumping of functional ankle instability population. METHODS:From March to September 2023,15 male patients with functional ankle instability and 15 healthy people,aged 22-28 years old,were recruited in Soochow University.All subjects completed counter movement jump experiment.Vicon infrared high-speed motion capture system and Kistler three-dimensional force measuring table were used to simultaneously collect the lower limb kinematics and kinetics indexes of the two groups of subjects at the take-off stage of counter movement jump,the instant off the ground,the initial landing moment and the peak moment of vertical ground reaction force. RESULTS AND CONCLUSION:(1)At the instant off the ground,the affected side of the functional ankle instability group showed smaller knee internal rotation moment(P=0.020)and smaller ankle internal rotation moment(P=0.009)compared with the affected side of the healthy control group.(2)At the moment of landing,the affected side of the functional ankle instability group showed a smaller hip flexion angle than the affected side of the healthy control group(P=0.039).Compared with the healthy control group,functional ankle instability group showed smaller hip abduction angle(P=0.022),smaller knee varus angle(P=0.010),larger knee external rotation angle(P=0.021),smaller ankle varus angle(P=0.004),and smaller external ankle rotation angle(P=0.008).(3)At the peak of vertical ground reaction force,functional ankle instability group showed a smaller ankle varus angle than healthy control group(P=0.044).(4)The results showed that the lower limb biomechanical characteristics of the patients with functional ankle instability were abnormal compared with the healthy people during counter movement jump,which mainly showed the changes of the kinematics and kinetics indexes of the lower limb joints in the sagittal plane and the frontal plane at the moment of lift-off and landing.These changes reflect that people with functional ankle instability adopt rigid take-off and landing patterns when performing counter movement jump,tend to transfer the load of the affected ankle joint to other joints of the lower limb,and show compensatory phenomenon of the healthy lower limb.Therefore,detection and correction of abnormal biomechanical features should be a part of rehabilitation training for those with functional ankle instability.

Houshiheisan, a classic prescription for stroke treatment, originates from Chapter 5 on Pulse Syndrome Complex and Treatment of Apoplexy and Acute Arthritis of Synopsis of Golden Chamber, which discusses pulse syndrome complex and apoplexy and acute arthritis treatment. Renowned as a primary prescription for stroke, it exemplifies the therapeutic principle of tonifying deficiencies while reducing excesses. This study showed that Houshiheisan improves hemorheology, reduces oxidative damage, protects neurovascular units after cerebral ischemic injury, promotes neovascularization maturation, and maintains cerebrovascular endothelial barrier integrity. Based on the pathogenesis theory of stroke, which is the cause of internal deficiency and pathogenic factor invasion, studies on Houshiheisan disassembling were conducted. The herbs in the prescription were divided into wind-dispelling herbs such as Flos Chrysanthemi, Radix Saposhnikoviae, and Ramulus Cinnamomi and deficiency-tonifying herbs such as Radix Ginseng, Radix Angelicae Sinensis, and Rhizoma Atractylodis Macrocephalae. Wind-dispelling herbs primarily reduced cerebral ischemia injury by downregulating Caspase-3 expression, an apoptotic protein, and deficiency-tonifying herbs reduced cerebral ischemia by upregulating poly ADP-ribose polymerase expression, a DNA repair protein. Wind-dispelling herbs exhibited a rapid yet short-lived effect by significantly downregulating aquaporin-4 (AQP4) expression in the lateral ventricle six hours after cerebral ischemia. In contrast, deficiency-tonifying herbs showed a delayed but sustained regulatory impact on AQP4 expression. These complementary time-dependent effects reflect the dual function of the prescription of dispelling wind and tonifying deficiencies, aligning well with the early pathogenesis of cerebral small vessel disease, which is characterized by wind-phlegm and blood stasis obstructing the brain collaterals. Additionally, Houshiheisan reduces blood pressure and blood lipids, improves patients′ hemorheology, and alleviates vascular endothelial cell dysfunction. Therefore, Houshiheisan is a safe and effective classic prescription for preventing and treating early cerebral small vessel disease. Future research should focus on exploring its molecular mechanisms in treating cerebral small vessel diseases.

Objective　To explore the parainfluenza virus (PIV) infection in children hospitalized in Hainan between March 2012 and December 2022, and to analyze its epidemiological characteristics. Methods　The samples were obtained from 62 553 kids with respiratory infections who were hospitalized in the Department of Pediatrics of multiple hospitals in various regions of Hainan from March 2012 to December 2022. Indirect immunofluorescence was employed to detect IgM antibodies in serum for nine respiratory pathogens, including PIV, adenovirus, influenza A virus, Legionella pneumophila, respiratory syncytial virus, Mycoplasma pneumoniae, influenza B virus, Coxiella burnetii, and Chlamydia pneumoniae. Epidemiological and clinical data (time, gender, age, season, etc.) of PIV-IgM antibody-positive cases were analyzed in a descriptive study. Results　The total PIV-IgM antibody positive rate of 62 553 respiratory tract infected children was 3.29% (2 015/62 553), with the highest positive rate of 11.01% (385/3 496) in 2017, and the second highest positive rate of 8.37% (351/4 196) in 2016, which were significantly higher than the positive rate of the rest of the years (P<0.001). The PIV positive rate was 3.18% (1 248/39 225) in males and 3.29% (767/23 328) in females, with no statistically significant difference (P>0.05). PIV infection occurred in all age groups, with the highest positive rate in the 6 to <12 years group at 4.50% (357/7 941), followed by the 3 to <6 years group at 4.47% (656/14 689), significantly higher than other age groups (P<0.001). The highest positive rate for PIV was in summer at 4.30% (693/16 093), followed by 3.78% (598/15 804) in spring, and the lowest rate of 2.27% (342/15 065) in winter, with statistically significant differences (P<0.001). Single PIV infection accounted for 63.08% (1 271/2 015), while mixed infections accounted for 36.92% (744/2 015), and the most common co-infection being with Mycoplasma pneumoniae infection at 23.13% (466/2 015). Conclusions　PIV is an important pathogen for children's acute respiratory infections in Hainan Province, exhibiting year-round sporadic occurrence with alternating high and low periods characteristics. PIV infection is to the gender of the child, predominantly affects preschool and school-age children, peaks in spring and summer, and commonly co-infects with Mycoplasma pneumoniae infection.

Diabetic retinopathy(DR)is a prevalent microvascular complication of diabetes and a leading cause of vision loss globally.Although anti-vascular endothelial growth factor(anti-VEGF)therapies remain the clinical mainstay, a significant proportion of patients exhibit suboptimal responses, highlighting the urgent need for novel therapeutic targets. Calcitonin gene-related peptide(CGRP), a multifunctional neuropeptide, is gaining attention due to its roles in vascular regulation, neuroprotection, and immunomodulation. This review summarizes the biological characteristics of CGRP and its receptor-mediated signaling, and explores emerging evidence of CGRP's involvement in DR through its vasodilatory effects and regulatory effect on neurodegenerative disorders and release of inflammatory cytokines. Furthermore, the therapeutic potential of targeting the CGRP pathway in DR is evaluated, especially in cases unresponsive to VEGF inhibition. Despite currently the lack of CGRP-targeted drugs applied for DR, the peptide demonstrates efficacy and safety in other diseases, such as migraine, suggests promising translational opportunities. However, CGRP may play a dual role in different pathological stages of DR, thus its treatment strategy needs to be considered precisely. Future research elucidating the precise mechanisms of CGRP in DR may pave the way for innovative intervention strategies.

Homeostasis and energy and substance metabolism reprogramming shape various tumor microenvironment to sustain cancer stemness, self-plasticity and treatment resistance. Aiming at them, a lipid-based pharmaceutical loaded with CaO₂ and glucose oxidase (GOx) (LipoCaO₂/GOx, LCG) has been obtained to disrupt calcium homeostasis and interfere with glycometabolism. The loaded GOx can decompose glucose into H₂O₂ and gluconic acid, thus competing with anaerobic glycolysis to hamper lactic acid (LA) secretion. The obtained gluconic acid further deprives CaO₂ to produce H₂O₂ and release Ca²⁺, disrupting Ca²⁺ homeostasis, which synergizes with GOx-mediated glycometabolism interference to deplete glutathione (GSH) and yield reactive oxygen species (ROS). Systematical experiments reveal that these sequential multifaceted events unlocked by Ca²⁺ homeostasis disruption and glycometabolism interference, ROS production and LA inhibition, successfully enhance cancer immunogenic deaths of breast cancer cells, hamper regulatory T cells (Tregs) infiltration and promote CD8⁺ T recruitment, which receives a considerably-inhibited outcome against breast cancer progression. Collectively, this calcium homeostasis disruption glycometabolism interference strategy effectively combines ion interference therapy with starvation therapy to eventually evoke an effective anti-tumor immune environment, which represents in the field of biomedical research.

Objective To explore the regulatory effect of long non-coding RNA HOX transcript anti-sense RNA(lnRNA HOTAIR)targeting tuberous sclerosis complex 1(TSC1)on podocyte injury in diabetic nephropathy(DN).Methods Mice podocyte MPC5 were divided into 6 groups:the control group,the high glucose group(the HG group),the HG+si-NC group,the HG+si-HOTAIR group,the HG+si-HOTAIR+sh-NC group,and the HG+si-HOTAIR+sh-TSC1 group.qPCR was used to detect the levels of lnRNA HO-TAIR and TSC1 mRNA.Cell viability was detected by cell counting kit-8(CCK-8),and apoptosis was detec-ted by flow cytometry.ELISA was used to detect the levels of inflammatory factors[IL-6,tumor necrosis fac-tor-α(TNF-α)]and the levels of oxidative stress indicators[reactive oxygen species(ROS),malondialdehyde(MDA),superoxide dismutase(SOD)]were detected by corresponding reagent kit.Results Compared with the control group,the levels of lnRNA HOTAIR,apoptosis rate,IL-6,TNF-α,ROS and MDA in the HG group were significantly increased(P<0.05),while the levels of TSC1 mRNA,cell viability and SOD were significantly decreased(P<0.05).Compared with the HG+si-NC group,the levels of lnRNA HOTAIR,ap-optosis rate,IL-6,TNF-α,ROS and MDA in the HG+si-HOTAIR group significantly decreased(P<0.05),the levels of TSC1 mRNA,cell viability and SOD were significant increased(P<0.05).Compared with the HG+si-HOTAIR+sh-NC group,the levels of apoptosis rate,IL-6,TNF-α,ROS and MDA in the HG+si-HOTAIR+sh-TSC1 group were significantly increased(P<0.05),the levels of TSC1 mRNA,cell viability and SOD were significantly decreased(P<0.05).Conclusion Silencing lnRNA HOTAIR can target TSC1 to regulate the activity,apoptosis rate,inflammatory level and oxidative stress levels of podocyte injury in DN,thereby alleviating podocyte damage in DN.