ObjectiveTo observe the effect of Huayu Mingmu prescription on retinal angiogenesis and phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin （PI3K/Akt/mTOR）-hypoxia inducible factor-1α/vascular endothelial growth factor A （HIF-1α/VEGFA） signaling pathway in diabetic retinopathy （DR） rats. MethodsSixty-four SPF-grade male SD rats were used in the study. Eleven rats were randomly selected as the normal group， while the remaining 53 rats were fed a high-sugar， high-fat diet combined with low-dose streptozotocin （STZ） intraperitoneal injection to establish a type 2 diabetes mellitus （T2DM） rat model. DR model evaluation was performed after 12 weeks of diabetes. The rats were then divided into model， low-dose， medium-dose， and high-dose groups of Huayu Mingmu prescription （9.29， 18.57， 37.14 g·kg^-1）， and a calcium dobesilate group （0.16 g·kg^-1）， with 10 rats in each group. The rats were orally administered the corresponding doses of Huayu Mingmu prescription and calcium dobesilate. The normal and model groups received equal volumes of physiological saline via gavage for 8 consecutive weeks. Retinal vascular changes were observed through fundus photography， and pathological changes in retinal tissue were evaluated using hematoxylin-eosin （HE） staining. Retinal microvascular pathological changes were examined through retinal vascular network preparation and periodic acid-Schiff （PAS） staining. Immunofluorescence （IF） was used to detect the expression of VEGFA and angiopoietin-2 （Ang-2） in retinal tissue. Western blot was employed to detect the protein expression of PI3K， Akt， mTOR， HIF-1α， VEGFA， and VEGFR2 in retinal tissue. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to assess the mRNA expression of PI3K， Akt， mTOR， HIF-1α， VEGFA， and VEGFR2 in retinal tissue. ResultsCompared with the normal group， the model group exhibited significant pathological changes in retinal tissue， including the appearance of acellular capillaries， as well as significant endothelial cell （E） proliferation and pericyte （P） loss （P<0.01）. The E/P was significantly elevated （P<0.01）. Protein and mRNA expression levels of PI3K， Akt， mTOR， HIF-1α， VEGFA， and VEGFR2 in retinal tissue were significantly increased （P<0.01）， and the expression of Ang-2 protein was significantly elevated （P<0.01）. In contrast， retinal tissue in the treatment groups showed alleviated pathological changes， with reduced endothelial cell proliferation and pericyte loss （P<0.05， P<0.01）. Among the treatment groups， the high-dose Huayu Mingmu prescription and the calcium dobesilate group exhibited a decreased E/P （P<0.01）. Protein and mRNA expression levels of PI3K， Akt， mTOR， HIF-1α， VEGFA， and VEGFR2 in retinal tissue were significantly reduced （P<0.05， P<0.01）， and the expression of Ang-2 protein was significantly decreased （P<0.01）. ConclusionHuayu Mingmu prescription can intervene in retinal neovascularization in DR rats， delay the progression of DR， and its mechanism may be related to antagonizing the PI3K/Akt/mTOR-HIF-1α/VEGFA signaling pathway.

Objective To investigate whether activation of mitochondrial acetal dehydrogenase 2(ALDH2)alleviates hypoxic pulmonary hypertension by regulating the SIRT1/PGC-1α signaling pathway.Methods Thirty 8-week-old C57 BL/6 mice were randomized into control,hypoxia,and hypoxia+Alda-1(an ALDH2 activator)group(n=10),and the mice in the latter two groups,along with 10 ALDH2 knockout(ALDH2-/-)mice,were exposed to hypoxia(10%O2,90%N2)with or without daily intraperitoneal injection of Alda-1 for 4 weeks.The changes in right ventricular function and pressure(RVSP)of the mice were evaluated by echocardiography and right ventricular catheter test,and pulmonary artery pressure was estimated based on RVSP.Pulmonary vascular remodeling,right ventricular injury,myocardial α-SMA expression,distal pulmonary arteriole muscle normalization,right ventricular cross-sectional area,myocardial cell hypertrophy,and right cardiac hypertrophy index were assessed with HE staining,immunofluorescence staining and WGA staining,and the expressions of ALDH2,SIRT1,PGC-1α,P16INK4A and P21CIP1 were detected.In pulmonary artery smooth muscle cells with hypoxic exposure,the effect of Alda-1 and EX527 on cell senescence and protein expressions was evaluated using β-galactose staining and Western blotting.Results The wild-type mice with hypoxic exposure showed significantly increased RVSP,right ventricular free wall thickness and myocardial expressions of P16INK4A and P21CIP1,which were effectively lowered by treatment with Alda-1 but further increased in ALDH2-/-mice.In cultured pulmonary artery smooth muscle cells,hypoxic exposure significantly increased senescent cell percentage and cellular expressions of P16INK4A and P21CIP1,which were all lowered by treatment with Alda-1,but its effect was obviously attenuated by EX527 treatment.Conclusion ALDH2 alleviates hypoxia-induced senescence of pulmonary artery smooth muscle cells by upregulating the SIRT1/PGC-1α signaling pathway to alleviate pulmonary hypertension in mice.

Background::Atopic dermatitis (AD) affects approximately 10% of adults worldwide. CM310 is a humanized monoclonal antibody targeting interleukin-4 receptor alpha that blocks interleukin-4 and interleukin-13 signaling. This trial aimed to evaluate the efficacy and safety of CM310 in Chinese adults with moderate-to-severe AD.Methods::This multicenter, randomized, double-blind, placebo-controlled, phase 2b trial was conducted in 21 medical institutions in China from February to November 2021. Totally 120 eligible patients were enrolled and randomized (1:1:1) to receive subcutaneous injections of 300 mg CM310, 150 mg CM310, or placebo every 2 weeks for 16 weeks, followed by an 8-week follow-up period. The primary endpoint was the proportion of patients achieving ≥75% improvement in the Eczema Area and Severity Index (EASI-75) score from baseline at week 16. Safety and pharmacodynamics were also studied.Results::At week 16, the proportion of EASI-75 responders from baseline was significantly higher in the CM310 groups (70% [28/40] for high-dose and 65% [26/40] for low-dose) than that in the placebo group (20%[8/40]). The differences in EASI-75 response rate were 50% (high vs. placebo, 95% CI 31%–69%) and 45% (low vs. placebo, 95% CI 26%–64%), with both P values <0.0001. CM310 at both doses also significantly improved the EASI score, Investigator’s Global Assessment score, daily peak pruritus Numerical Rating Scale, AD-affected body surface area, and Dermatology Life Quality Index compared with placebo. CM310 treatment reduced levels of thymus and activation-regulated chemokine, total immunoglobulin E, lactate dehydrogenase, and blood eosinophils. The incidence of treatment-emergent adverse events (TEAEs) was similar among all three groups, with the most common TEAEs reported being upper respiratory tract infection, atopic dermatitis, hyperlipidemia, and hyperuricemia. No severe adverse events were deemed to be attributed to CM310. Conclusion::CM310 at 150 mg and 300 mg every 2 weeks demonstrated significant efficacy and was well-tolerated in adults with moderate-to-severe AD.Trial Registration::ClinicalTrials.gov, NCT04805411.

Developing and implementing biosafety standards for pathogenic microbiology laboratories is essential to achieving scientific, efficient, and standardized management and operation. This article analyzes the current standardization construction in biosafety in pathogenic microbiology laboratories domestically and internationally. It proposes a framework for the biosafety standard system of pathogenic microbiology laboratories, which mainly includes four parts: basic standards, management standards, technical standards, and industry applications. It provides a reference for the standardization work of pathogenic microbiology laboratories and helps to standardize the biosafety industry in China.

Contrast-induced acute kidney injury(CI-AKI)is an iatrogenic acute kidney injury(AKI)observed after diagnostic or therapeutic angiographic interventions with the intravascular application of contrast media(CM).CM leads to impaired renal function through tubular toxicity,intrarenal vasocon-striction,and excessive reactive oxygen species(ROS)production.Dexmedetomidine(DEX)is a selective α2 adrenergic receptor agonist that has been shown to have good antioxidant and anti-inflammatory effects,and its organ protective effect in the perioperative period is increasingly prominent.Several studies have found that DEX has an excellent protective effect on postoperative renal function.This article aims to explore the protective effect,possible mechanism,and clinical application of DEX in CI-AKI.

Objective·To investigate the expression of metastasis-associated protein 1(MTA1)in placental tissues of preeclampsia(PE)patients and its impact on trophoblast cell function.Methods·Placental specimens were collected from pregnant women with PE(PE group,20 cases)patients and healthy pregnant women as controls(control group,35 cases).Western blotting and immunofluorescent double staining were performed to analyze the expression changes of MTA1.The human first-trimester placental trophoblast cell line HTR8/SVneo was cultured,and the cell migration ability was assessed through wound healing assay.The cell invasion ability was detected using Transwell invasion assay.Under hypoxic conditions simulating the invasion of extravillous trophoblasts into the uterus,quantitative real-time polymerase chain reaction(qRT-PCR)was performed to analyze the mRNA expression of hypoxia-induced matrix metalloproteinases(MMP-2 and MMP-9),thus assessing their secretion levels.An extravillous trophoblast explant model was constructed to assess the overall villus outgrowth capacity of the explants.Immunohistochemistry(IHC)was performed to confirm the presence of the endothelial marker CD31 for placental angiogenesis analysis in mice.Fifteen Mta1-/-female mice and fifteen wild-type C57 female mice were mated with wild-type male C57 mice for fertility testing.Results·Western blotting revealed significantly decreased expression of MTA1 protein in placental tissues of the PE group compared to the control group.Immunofluorescent double staining showed that MTA1 was mainly localized in the nuclei of trophoblast cells.The wound healing assay demonstrated that HTR8/SVneo with stable MTA1 knockdown exhibited weaker cell migration ability compared to the control group(P=0.002).The Transwell invasion assay demonstrated a marked decrease in invasiveness in MTA1-knockdown cells,significantly lower than the control group(P=0.015).Hypoxia-induced expression levels of matrix metalloproteinases MMP-2 and MMP-9 were significantly reduced(P=0.020,P=0.003).After MTA1 knockdown,the overall villus outgrowth capacity of the explants was decreased compared to the control group(P=0.003).IHC results showed that CD31 expression in the placenta of Mta1-/-female mice was significantly lower than that of wild-type female mice(P=0.004).The litter size of Mta1-/-female mice was significantly reduced(P=0.000).Conclusion·The expression level of MTA1 is closely related to PE.Endogenous MTA1 may be involved in trophoblast invasion into the endometrium and villous capillary remodeling.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objective:To present a method of modeling 3D-printed guide templates (3DPGTs) strictly based on pre-plans for the interstitial implantation brachytherapy of cervical cancer, and elucidate the advantages of 3DPGTs in the interstitial implantation brachytherapy of cervical cancer.Methods:This study retrospectively selected six cases of locally advanced cervical cancer treated with interstitial implantation brachytherapy using 3DPGTs. Based on the CT images of 3DPGTs and pre-plans, the mechanical precision of 3DPGTs was verified through image registration. The dosimetric differences were compared between the 3DPGT treatment plan and the pre-plan/the freehand implantation plan. The dosimetric parameters included the volume and D90 for the high-risk clinical target volume (HR-CTV), and the D2 cm 3, D1 cm 3, and D0.1 cm 3 for the bladder, rectum, intestine, and sigmoid. Results:The 3DPGTs modeled using the method strictly based on pre-plans exhibited relatively high mechanical precision, with deviations all below 1 mm. Regarding the D90 of the HR-CTV, the 3DPGT treatment plan resulted in a dose of (713.37±143.26) cGy, reduced by 6.95% ( z= -1.98, P<0.05) compared to the (766.62±145.97) cGy in the pre-plan, and increased by 107.6% ( z= -1.89, P<0.05) compared to the (343.56±188.72) cGy in the freehand implantation plan. For dosimetric parameters of organs at risk (OARs), no statistical differences were observed ( P>0.05) between the 3DPGT treatment plan and the pre-plan/the freehand implantation plan. Conclusions:The method of modeling 3DPGTs for cervical cancer proposed in this study demonstrates high accuracy. Hence, the dose for the HR-CTV can be substantially increased under the condition that the OARs are protected from over-irradiation.

Objective:To compare the clinical efficacy of arthroscopic partial and complete repair for massive rotator cuff tears.Methods:A total of 32 patients who underwent arthroscopic partial repair of massive rotator cuff tears in the Department of Sports Medicine, Peking University Third Hospital from March 2016 to December 2019 were retrospectively analyzed, including 15 males and 17 females, aged 62±6.8 years (range, 51-77 years), with 5 cases on the left side and 27 cases on the right side. Cause of injury: 4 cases were injured by car accident, 8 were injured by fall, and 20 had no obvious cause. 32 patients who underwent arthroscopic complete repair of massive rotator cuff tears during the same period were included according to a sample size of 1∶1 matched based on age, sex, tear size and fat infiltration index. Clinical outcomes were evaluated using the visual analogue scale (VAS) for pain, American Shoulder and Elbow Surgeons (ASES) score, University of California Los Angeles (UCLA) shoulder score, Simple Shoulder Test (SST) score, and range of motion. Fatty infiltration and cuff healing were assessed using the Goutallier and Sugaya classifications on MRI, respectively.Results:All patients successfully completed the surgery and were followed up for 46.1±11.3 months (range, 36-72 months). Preoperative and final follow-up VAS scores were 6.6±1.8 and 1.6±1.1 in the complete repair group, and 6.4±1.9 and 1.4±1.3 in the partial repair group. Both groups showed significant postoperative improvement ( P<0.05), with no significant difference between groups at the final follow-up ( t=-0.729, P=0.468). The ASES score, UCLA shoulder score, and SST at the final follow-up were 81.7±6.5, 28.6±2.9, and 9.8±2.5, respectively, in the complete repair group, and 82.4±7.3, 28.1±2.6, and 9.1±1.9 in the partial repair group, and the difference between the groups was not statistically significant ( P>0.05). In the complete repair group, one case underwent reverse shoulder replacement for rotator cuff re-tear two years after surgery, and one case developed pseudoparalysis for rotator cuff re-tear 8 months after surgery but had no significant pain and did not receive further treatment; in the partial repair group, two cases underwent tendon transposition surgery for shoulder pain. Conclusion:Arthroscopic partial repair improves shoulder function and reduces pain in patients with massive rotator cuff tears, with similar efficacy to complete repair and has high surgical safety.

Objective To investigate whether activation of mitochondrial acetal dehydrogenase 2(ALDH2)alleviates hypoxic pulmonary hypertension by regulating the SIRT1/PGC-1α signaling pathway.Methods Thirty 8-week-old C57 BL/6 mice were randomized into control,hypoxia,and hypoxia+Alda-1(an ALDH2 activator)group(n=10),and the mice in the latter two groups,along with 10 ALDH2 knockout(ALDH2-/-)mice,were exposed to hypoxia(10%O2,90%N2)with or without daily intraperitoneal injection of Alda-1 for 4 weeks.The changes in right ventricular function and pressure(RVSP)of the mice were evaluated by echocardiography and right ventricular catheter test,and pulmonary artery pressure was estimated based on RVSP.Pulmonary vascular remodeling,right ventricular injury,myocardial α-SMA expression,distal pulmonary arteriole muscle normalization,right ventricular cross-sectional area,myocardial cell hypertrophy,and right cardiac hypertrophy index were assessed with HE staining,immunofluorescence staining and WGA staining,and the expressions of ALDH2,SIRT1,PGC-1α,P16INK4A and P21CIP1 were detected.In pulmonary artery smooth muscle cells with hypoxic exposure,the effect of Alda-1 and EX527 on cell senescence and protein expressions was evaluated using β-galactose staining and Western blotting.Results The wild-type mice with hypoxic exposure showed significantly increased RVSP,right ventricular free wall thickness and myocardial expressions of P16INK4A and P21CIP1,which were effectively lowered by treatment with Alda-1 but further increased in ALDH2-/-mice.In cultured pulmonary artery smooth muscle cells,hypoxic exposure significantly increased senescent cell percentage and cellular expressions of P16INK4A and P21CIP1,which were all lowered by treatment with Alda-1,but its effect was obviously attenuated by EX527 treatment.Conclusion ALDH2 alleviates hypoxia-induced senescence of pulmonary artery smooth muscle cells by upregulating the SIRT1/PGC-1α signaling pathway to alleviate pulmonary hypertension in mice.