To explore the correlation between MTHFR C677T gene polymorphism and hypertension, hyperhomocysteinemia(Hcy), and hyperlipidemia in the Tibetan population of Tibet.

Objective: To characterize perioperative dynamic changes in immune-cell phenotypes and inflammatory cytokines in patients undergoing CPB (cardiopulmonary bypass) cardiac surgery, and to explore their associations with postoperative outcomes. Methods: In this prospective cohort study, 120 adult patients who underwent elective cardiac surgery under CPB at West China Hospital from May 2022 to March 2023 were enrolled. Perioperative immune-cell phenotypes and concentrations of 40 inflammation-related cytokines were measured. The primary outcomes were the sequential organ failure assessment (SOFA) score at 24 h after surgery and ΔSOFA (the peak SOFA score within 48 h after surgery minus the preoperative SOFA score). Secondary outcomes included major adverse cardiovascular events (MACE), acute kidney injury (AKI), respiratory failure, severe liver injury, and infection. Results: The mean age of enrolled patients was 57±10 years. Of these, 52% (62/120) were male and 90% (108/120) underwent valve surgery. During the rewarming to the end of CPB, neutrophil counts rapidly increased (7.39×10 /L vs preoperative 3.07×10 /L, P<0.001), with significant upregulation of CD11b (7.30×10 /L vs preoperative 3.05×10 /L, P<0.001) and CD54 (7.15×10 /L vs preoperative 2.99×10 /L, P<0.001). Lymphocyte counts increased at the end of CPB (1.75×10 /L vs preoperative 1.12×10 /L, P<0.001) but decreased significantly at 24 h after surgery (0.59×10 /L vs preoperative 1.12×10 /L, P<0.001). Plasma analysis showed that multiple pro-inflammatory cytokines increased during CPB and remained elevated up to 24 h after surgery; five chemokines and the anti-inflammatory cytokine IL-10 peaked at the end of CPB. The SOFA score increased from 1 (1, 2) preoperatively to 7 (5, 10) at 24 h after surgery, with a ΔSOFA of 6 (4, 8). Within 30 days after surgery, 48 patients (40.0%) developed AKI, 17 (14.2%) developed infection, 4 (3.3%) developed severe liver injury, 3 (2.5%) developed respiratory failure, and 3 (2.5%) experienced MACE. During the 2-year follow-up, 8 patients (6.7%) experienced MACE and 5 (4.2%) died. Conclusion: Multi-organ dysfunction is common after cardiac surgery under CPB (median ΔSOFA, 6), accompanied by perioperative activation of multiple immune-cell subsets and upregulation of pro-inflammatory, anti-inflammatory, and chemotactic mediators. This study provides data-driven evidence and research clues for further investigation of the associations between CPB-related immune perturbations and postoperative organ dysfunction and clinical outcomes.

Objective To analyze the epidemiological characteristics of statutory infectious diseases in Yichang City from 2015 to 2023 and evaluate the effectiveness of non-pharmaceutical interventions (NPIs) in infectious disease prevention and control, and to provide a basis for formulating prevention and control strategies. Methods Descriptive epidemiological methods were used to analyze annual incidence rates. SARIMA and SARIMA intervention models were constructed to predict the incidence rates of infectious diseases. Interrupted time series analysis (ITS) was applied to assess the control effectiveness. Results The average annual incidence rate from 2015 to 2023 was 787.47/100 000, with the top five diseases being influenza, hand-foot-and-mouth disease, hepatitis B, tuberculosis, and diarrheal diseases. The average incidence rate from 2015 to 2019 (654.31/100 000) was significantly higher than that from 2020 to 2022 (489.01/100 000) (χ²= 3 499.6, P < 0.05). The total incidence rate in 2023 (2 396.51/100 000) was significantly higher than the average annual incidence rates from 2015-2019 (χ²= 108 186.1, P < 0.05) and 2020-2022 (χ²= 112 869.4, P < 0.05). SARIMA model results indicated that the actual incidence rate from 2020 to 2022 decreased by 73.49% compared to the predicted rate without intervention, with the highest decline observed in respiratory infectious diseases (79.57%). The SARIMA-intervention model showed a 55.48% relative decrease in the total incidence rate for 2023, with the largest reduction in respiratory infectious diseases (63.28%) and a slight increase in intestinal infectious diseases (5.48%). Conclusion NPIs effectively reduce the incidence of statutory infectious diseases in the short term, especially for acute respiratory and intestinal infectious diseases. However, long-term effectiveness faces challenges, necessitating the development of differentiated prevention and control strategies.

ObjectiveTo investigate the uric acid-lowering effects and mechanisms of acacetin on hyperuricemia （HUA） in mice. MethodsOteracil potassium and adenine were used to establish the mouse model of HUA. Male Kunming mice （n=48） were randomized into six groups： control， model， low-dose （12.5 mg·kg^-1） acacetin， medium-dose （25 mg·kg^-1） acacetin， high-dose （50 mg·kg^-1） acacetin， and allopurinol （10 mg·kg^-1）. Each group received continuous gavage administration for 21 days. An automatic biochemical analyzer was used to measure the levels of uric acid （UA）， creatinine （Cr）， urea nitrogen （BUN）， alanine aminotransferase （ALT） and aspartate aminotransferase （AST）. Additionally， the activity of xanthine oxidase （XOD） in the liver and the levels of tumor necrosis factor （TNF）-α， interleukin （IL）-1β， and IL-18 in the serum were measured by enzyme-linked immunosorbent assay （ELISA）. Pathological changes in the renal tissue were observed by hematoxylin-eosin （HE） staining. Western blot was employed to determine the levels of glucose transporter 9 （GLUT9）， urate transporter 1 （URAT1）， phospho-NF-κB p65 （p-NF-κB p65）， and nucleotide-binding oligomerization domain-like receptor pyrin domain-containing 3 （NLRP3） in the renal tissue. ResultsCompared with the control group， the model group showed elevated levels of UA， Cr， BUN， ALT， and AST， increased activity of XOD in the liver（P<0.01）， raised levels of TNF-α， IL-1β and IL-18 in the serum（P<0.01）， and significantly up-regulated expression of GLUT9， URAT1， p-NF-κB p65， and NLRP3 in the renal tissue（P<0.01）. Compared with the model group， acacetin reduced the UA level in a dose-dependent manner， significantly improved liver and kidney functions， decreased the XOD activity in the liver， ameliorated the pathological changes in the renal tissue， down-regulated the expression of GLUT9， URAT1， p-NF-κB p65 and NLRP3 in the renal tissue（P<0.01）， and lowered the levels of TNF-α， IL-1β， and IL-18 in the serum（P<0.01）. ConclusionAcacetin can ameliorate HUA by decreasing uric acid production， increasing uric acid excretion， and inhibiting the NF-κB/NLRP3 signaling pathway. Therefore， acacetin may be a potential drug for the treatment of HUA.

ObjectiveTo observe the effects of Yangjing Zhongyutang （YJZYT） on mitochondrial biogenesis and oxidative stress damage mediated by the silent information regulator 1 （SIRT1）/peroxisome proliferator-activated receptor gamma coactivator-1alpha （PGC-1α） signaling pathway in cyclophosphamide （CTX）-induced rats with diminished ovarian reserve （DOR）， and to explore its mechanism in improving ovarian reserve function and follicular development. MethodsForty-two 8-week-old female SD rats with normal estrous cycles were randomly divided into a blank control group （n=7） and a model group （n=35）. Rats in the model group received a single intraperitoneal injection of CTX （90 mg·kg^-1） to establish the DOR model. After modeling， estrous cycles were monitored for 7 consecutive days， and model success was confirmed based on criteria for estrous cycle disruption. After successful modeling， rats were divided into groups for intervention： estradiol valerate group （0.09 mg·kg^-1）， and YJZYT high-， medium-， and low-dose groups （19.98， 9.99， 5.00 g·kg^-1）. The blank control group and model group were given an equal volume of distilled water by gavage. All groups received daily gavage once for 4 consecutive weeks. The general state， body weight， and ovarian wet weight of rats were observed and recorded， and the ovarian organ index was calculated. Enzyme-linked immunosorbent assay （ELISA） was used to measure serum levels of follicle-stimulating hormone （FSH）， luteinizing hormone （LH）， estradiol （E₂）， anti-Müllerian hormone （AMH）， superoxide dismutase （SOD）， and glutathione peroxidase （GSH-Px）. Hematoxylin-eosin （HE） staining was performed to observe ovarian histomorphological changes and follicular development status. Immunofluorescence was used to detect reactive oxygen species （ROS） expression levels. Colorimetric assays were employed to measure adenosine triphosphate （ATP） and malondialdehyde （MDA） content in ovarian tissues. Quantitative Real-time polymerase chain reaction （Real-time PCR） was used to detect mitochondrial DNA （mtDNA） copy number and the mRNA expression levels of key genes including SIRT1， PGC-1α， nuclear respiratory factor 1 （NRF1）， and mitochondrial transcription factor A （TFAM）. Western blot was performed to detect the protein expression levels of SIRT1， PGC-1α， NRF1， and TFAM. ResultsCompared with the blank group， rats in the model group exhibited disrupted estrous cycles， obviously reduced body weight， and decreased ovarian index （P<0.05）. Ovarian histopathology revealed cortical thinning， loose structure， and a significant reduction in both primordial and growing follicles （P<0.01）. Serum FSH and LH levels were significantly elevated （P<0.01）， while E₂ and AMH levels were obviously reduced （P<0.05， P<0.01）. ATP content and mtDNA copy number decreased in ovarian tissue （P<0.01）， ROS expression increased， MDA levels rose， while SOD and GSH-Px activities obviously decreased （P<0.05， P<0.01）， mRNA and protein expression levels of SIRT1， PGC-1α， NRF1， and TFAM were obviously downregulated （P<0.05， P<0.01）. After treatment， compared with the model group， body weight and ovarian index obviously recovered in rats administered various doses of YJZYT （P<0.05）， serum E₂ and AMH levels increased， while FSH and LH levels obviously decreased （P<0.05， P<0.01）， ovarian tissue ATP content and mtDNA copy number were up-regulated， ROS and MDA levels decreased， and antioxidant enzymes SOD and GSH-Px activity obviously increased （P<0.05， P<0.01）， Gene and protein expression levels related to the SIRT1/PGC-1α /NRF1/TFAM signaling pathway were obviously up-regulated compared to the model group （P<0.05， P<0.01）， HE staining revealed that ovarian structure gradually recovered to integrity in all treatment groups， with a obviously increase in the number of primordial and growing follicles （P<0.05， P<0.01）. Granulosa cells were neatly arranged， indicating marked improvement in ovarian function. ConclusionYJZYT may improve ovarian function and follicular development in rats with diminished ovarian reserve by activating the SIRT1/PGC-1α signaling pathway， promoting mitochondrial biogenesis， enhancing mitochondrial function， and alleviating oxidative stress damage.

Objective: To explore the treatment plan for severe papillary defects in the aesthetic zone caused by severe periodontitis, providing a reference for clinical practice. Methods : A patient with severe periodontitis leading to severe papillary defects in the upper anterior teeth from 12 to 23 was treated using interdental tunnel technique combined with personalized connective tissue grafting for periodontal plastic surgery, and stable soft tissue augmentation was achieved. Resin restoration was conducted to modify the crown shape of the aesthetic zone teeth, reconstruct white aesthetics, guide the shaping of the gingival papillae, reduce “black triangles,” and enhance the patient’s confidence in smiling. Results : The patient’s periodontal condition and the regeneration of soft tissues in the aesthetic zone were good, and the smile aesthetics were restored. After a 3-year follow-up, the gingival morphology, color, and texture were good, and the effect was stable. The literature review indicates that for papillary defects in the aesthetic zone, analysis should be conducted based on the following aspects: whether a defect is present in periodontal hard and soft tissues, crown shape, and the distance from the most apical part of the crown contact area to the top of the alveolar crest. Based on the analysis of aesthetic defects and surgical indications, a personalized treatment plan should be designed. Conclusion For patients with obvious papillary defects in the aesthetic zone due to the reduction of periodontal support tissues caused by severe periodontitis, factors such as periodontal hard and soft tissue defects, crown shape, and the distance from the most apical part of the crown contact area to the top of the alveolar crest should be fully considered, and a personalized treatment plan should be formulated after multidisciplinary joint consultation.

Aromatic Chinese medicinal essential oils are volatile oils extracted from aromatic Chinese herbs， which can prevent and treat respiratory infectious diseases through multiple synergistic mechanisms including pathogen inhibition， immune regulation， and inflammatory response regulation. Essential oils are primarily used externally on the body to prevent infections and alleviate symptoms through methods like inhalation， smearing， topical application， bathing， gargling or as a suppository. They can also be utilized in the environment for disinfection and air purification， through methods like diffusion， vaporization， or spraying. The external application of essential oils extracted from Chinese aromatic herbs has the advantages of convenience， quick absorption， and simultaneous influence on both the body and mind. However， there are still challenges and deficiencies in aspects such as the positioning of functions， indications， safety， and the research on the mechanism of action. It has been proposed to combine the theory of aromatic Chinese medicinals with the characteristics of essential oils， and formulate prescriptions of Chinese medicinal essential oils under the principles of traditional Chinese medicine syndrome differentiation， and prevent and treat respiratory infectious diseases efficiently， accurately， and safely， thereby expanding the clinical application of aromatic Chinese medicinals and the preventive theory of traditional Chinese medicine.

Antibody drug conjugates (ADC) have emerged as a cutting-edge technology in anti-tumor treatment, making significant strides in recent years. ADC couple a highly active small molecule toxin payload to highly specific antibodies through a linker, enabling precise targeting of tumor cells while reducing systemic toxicity, thereby expanding the therapeutic window. However, due to the complexity of ADC molecule design, its efficacy and safety are influenced by various factors. Model-informed drug development (MIDD) is a powerful tool that utilizes various mathematical models for modeling and simulation to conduct quantitative analysis, guiding drug development and decision-making. By integrating multi-faceted data and information using mathematical models, it is possible to gain insights into the complex mechanisms, pharmacokinetics, and pharmacodynamics of ADC, providing unique perspectives for optimizing ADC development processes and clinical translation decisions. This review will introduce the basic concepts of MIDD and ADC and discuss application cases of MIDD in different stages of ADC development, aiming to provide beneficial references for the advancement of ADC.

Objective: To explore the possibility of performing allogeneic platelet-rich plasma (PRP) treatment for patients who were not suitable for autologous PRP collection through case reports of two patients with refractory wounds treated with allogeneic PRP. Methods: The ABO-compatible allogeneic whole blood was centrifuged 3 times to obtain allogeneic PRP within 6 hours of blood collection. Then the qualified allogeneic PRP was applied to 2 cases of refractory wound on the same day. Results: The platelet concentration in allogeneic PRP was higher than 1 000×10 /L, and the test results of infectious diseases, as well as the mixing of red blood cells and white blood cells, met the standard of quality control. Both patients achieved satisfactory wound healing outcomes (3 d). Conclusions: For patients who were not suitable for autologous PRP treatment, allogeneic PRP might be a new option.

OBJECTIVE To investigate the analgesic effect and potential mechanism of punicalagin on neuropathic pain （NP） rats based on the hypoxia-inducible factor-1α （HIF-1α）/nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3 （NLRP3） signaling pathway. METHODS Male SD rats were randomly divided into sham operation group （18 rats） and modeling group （72 rats）. NP rat model was established by chronic constriction injury （CCI） of sciatic nerve. The successfully modeled rats were divided into NP group， 2-methoxyestradiol group （HIF-1α antagonist 10 mg/kg）， punicalagin group （300 mg/kg）， and punicalagin+dimethyloxaloglycine group （punicalagin 300 mg/kg+HIF-1α agonist 175 mg/kg）， with 18 rats in each group. Rats in each group were injected intraperitoneally and/or intragastrically with the corresponding solution or 1% dimethyl sulfoxide/normal saline， once a day， for 14 consecutive days. After the last administration， the mechanical withdrawal threshold （MWT）， thermal withdrawal latency （TWL）， the levels of tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β） and IL-6 in spinal cord tissue were detected； the morphological changes in the spinal dorsal horn were observed. Apoptosis rate of spinal dorsal horn neurons， the co-localization of NLRP3/ionized calcium binding adapter molecule 1 （Iba-1） （calculated by the number of NLRP3+/Iba-1+ cells） and the protein expressions of HIF-1α， NLRP3， apoptosis-associated speck-like protein containing a CARD （ASC） and caspase-1 in spinal cord tissue were detected. RESULTS Compared with the sham operation group， neurofibril in spinal dorsal horn of rats in NP group was thickened and wound into knots， and vacuolar degeneration containing silver granules was observed； the MWT and TWL were reduced or shortened； the levels of TNF-α， IL-1β and IL-6 in spinal cord tissue， the apoptosis rate of spinal dorsal horn neurons， the number of NLRP3+/Iba-1+ cells， and protein expressions of HIF-1α， NLRP3， ASC and caspase-1 were significantly increased or up-regulated （P＜0.05）. Compared with the NP group， the above indexes were significantly improved in the 2-methoxyestradiol group and punicalagin group （P＜0.05）， while dimethyloxaloglycine could significantly reverse the improvement effect of punicalagin on the above indexes （P＜0.05）. CONCLUSIONS Punicalagin can relieve pain in NP rats， and its analgesic effect may be achieved by inhibiting HIF-1α/NLRP3 signaling pathway and blocking the activation of ma0o4e@163.com NLRP3 inflammasome in spinal dorsal horn microglia.