Background Lead is a typical persistent environmental pollutant that can accumulate in bones for decades. During pregnancy, alterations in calcium metabolism promote the mobilization of bone lead, resulting in secondary exposure; however, the mechanisms by which pregnancy-associated bone lead mobilization affects maternal renal function remain unclear. Objective To investigate the role of mitochondrial dysfunction in pregnancy-related bone lead mobilization-induced renal injury. Methods Newly weaned female Wistar rats were randomly assigned to a control or a lead-exposed group administered either 0.05% sodium acetate or 0.05% lead acetate in drinking water. Following a 4-week lead exposure and a 4-week washout period, the females were co-housed with healthy age-matched males for mating. Rats were sacrificed at early (gestational day 3) and late (gestational day 17) pregnancystages, respectively. Renal histopathology was assessed using hematoxylin and eosin staining staining. Mitochondria-related indicators, including oxidative stress, inflammatory responses, and energy metabolism, were measured. Differential metabolites were identified using serum metabolomics. Results Renal injury in the lead-exposed pregnant rats progressed in a time-dependent manner, characterized by degeneration of proximal tubular epithelial cells, glomerular hyaline changes, and interstitial inflammatory cell infiltration. Repeated measures ANOVA indicated a significant interaction between the treatment factor (lead exposure) and the temporal factor (gestational stage) on renal injury (P<0.001). Further analysis of mitochondrial function-related indicators in late-pregnancy renal tissue revealed that the lead exposure group exhibited significantly increased levels of malondialdehyde (MDA) and reactive oxygen species (ROS) (P<0.05), accompanied by a reduction in superoxide dismutase (SOD) and reduced glutathione (GSH) activities (P<0.05); regarding inflammatory markers, levels of interleukin-18 (IL-18) and interleukin-1β (IL-1β) were elevated (P<0.01), whereas interleukin-33 (IL-33) was decreased in the lead-exposed group (P<0.05); energy metabolism-related indicators, including adenosine triphosphate (ATP) level, Na⁺-K⁺-ATPase and Ca²⁺-Mg²⁺-ATPase activities, and mitochondrial respiratory chain complexes I, III, and V activities, were significantly reduced (P<0.05) in the lead-exposed gorup. The typical differential metabolite N-methylisoleucine, identified through serum metabolomics analysis, was negatively correlated with blood lead levels, kidney injury scores, and IL-1β, while positively correlated with catalase (CAT) activity and Ca²⁺-Mg²⁺-ATPase. Conclusions Mitochondrial dysfunction may play a critical role in renal injury induced by bone lead mobilization during late gestation.

ObjectiveTo investigate the efficacy of sequential tenofovir alafenamide fumarate （TAF） therapy versus the regimen of entecavir （ETV） combined with TAF in chronic hepatitis B （CHB） patients experiencing low-level viremia （LLV） after ETV therapy， as well as their impact on virologic response， liver and renal function， and blood lipid levels. MethodsA total of 217 CHB patients with LLV after ETV treatment who were admitted to Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine from May 2020 to December 2023 were enrolled， and according to the treatment regimen， they were divided into TAF group （180 patients receiving sequential TAF therapy） and combined group （37 patients receiving ETV+TAF therapy）. The propensity score matching （PSM） method was used to match the patients at a ratio of 1∶1， and finally 37 patients were included in each group to balance the baseline confounding factors. The two groups were compared in terms of hepatitis B virus DNA （HBV DNA） clearance rate， hepatitis B envelope antigen （HBeAg） clearance rate， liver and renal function parameters （liver stiffness measurement ［LSM］， platelet count ［PLT］， aspartate aminotransferase ［AST］， alanine aminotransferase ［ALT］， and creatinine ［Cr］）， blood lipid levels （total cholesterol ［TC］， triglyceride ［TG］， high-density lipoprotein cholesterol ［HDL-C］， and low-density lipoprotein cholesterol ［LDL-C］）， and the incidence rate of adverse reactions. The independent samples t-test was used for comparison of normally distributed continuous data between two groups， and the paired t-test was used for comparison within each group； the chi-square test was used for comparison of categorical data between groups. ResultsAfter 48 weeks of treatment， compared with the TAF group， the combined group had significantly higher HBV DNA clearance rate （86.49% vs 59.46%， χ²=6.852， P=0.009） and HBeAg clearance rate （59.46% vs 35.14%， χ²=4.391， P=0.036）. After treatment， compared with the TAF group， the combined group had significantly lower levels of LSM （7.01±1.50 kPa vs 7.90±1.68 kPa， t=2.404， P=0.019）， AST （18.02±2.28 U/L vs 21.12±2.85 U/L， t=5.166， P<0.001）， and ALT （19.85±3.86 U/L vs 22.00±3.90 U/L， t=2.383， P=0.020） and significantly higher levels of PLT ［（218.35±42.60）×10⁹/L vs （192.82±44.13）×10⁹/L， t=2.532， P=0.014］ and Cr （70.92±6.54 μmoL/L vs 67.60±6.13 μmoL/L， t=2.253， P=0.027）. After treatment， there was a slight increase in the level of TC in both the TAF group （5.60±0.89 mmol/L vs 5.18±0.85 mmol/L， t=2.076， P=0.041） and the combined group （5.45±0.80 mmol/L vs 5.02±0.83 mmol/L， t=2.269， P=0.026）. There was no significant difference in the incidence rate of adverse reactions between the TAF group and the combined group （21.62% vs 18.92%， χ²=0.084， P=0.772）. ConclusionFor ETV-treated CHB patients experiencing LLV， compared with sequential TAF therapy， the ETV+TAF combined therapy can effectively increase virologic response rate， alleviate liver fibrosis， and improve liver function， whereas sequential TAF therapy has less impact on renal function. Sequential or combined therapy with TAF may induce a slight increase in the level of TC， which should be taken seriously in clinical practice.

Objective: To evaluate the clinical efficacy and safety of injectable platelet-rich fibrin (i-PRF) in the treatment of mild to moderate female pattern hair loss (FPHL), and to analyze the related clinical factors affecting the therapeutic efficacy of i-PRF. Methods: This was a secondary analysis of a prospective, randomized controlled trial. A total of 29 FPHL patients with Sinclair grade Ⅱ-Ⅲ, who attended the outpatient clinics of Beijing Friendship Hospital, Capital Medical University and Peking University Third Hospital from March 2024 to April 2025, were enrolled. All patients received i-PRF treatment once every 4 weeks for a total of 4 sessions, with follow-up up to 24 weeks. Standardized clinical photographs were taken at baseline, week 12 and week 24. Trichoscopic examination was performed to measure the non-vellus target area hair count (TAHC) and hair diameter (HD) in the target area, and all adverse events were recorded. The Mann-Whitney U test was used to compare the intergroup differences in efficacy for categorical influencing factors; Spearman rank correlation analysis was employed to assess the correlation between continuous influencing factors and efficacy; and multiple linear regression (enter method) was performed to identify independent influencing factors of efficacy. Results: A total of 27 patients completed the trial. At week 12, TAHC significantly increased from 112 (105, 120) hairs/cm at baseline to 128 (110, 150) hairs/cm , with a median increase of 12 (5, 28) hairs/cm and a median growth rate of 10.5 (4.2, 24.5)% (P=0.045); hair diameter significantly increased from 42.5 (39.8, 45.2) μm to 52.0 (47.0, 58.0) μm, with a median increase of 7.5 (3.0, 12.5) μm and a median growth rate of 18.0 (7.5, 29.0)% (P<0.001). At week 24, TAHC further significantly increased to 141 (125, 158) hairs/cm (P<0.001), with a median growth rate of 24.8 (18.5, 32.0)%; hair diameter continued to improve to 55.0 (50.0, 61.0) μm (P=0.008), with a median growth rate of 21.5 (16.0, 27.0)%. The overall incidence of adverse events was 10.34% (3/29), mainly presenting as mild scalp pruritus and transient headache, without severe adverse effects. Multiple linear regression analysis revealed that baseline TAHC was an independent influencing factor for i-PRF efficacy (P<0.05), while age, BMI, disease duration, Sinclair grade, family history of AGA, and baseline HD showed no significant independent effect on efficacy in this model (P>0.05). Conclusion: This preliminary study indicates that i-PRF can improve hair density and hair shaft diameter in patients with FPHL with a favorable safety profile. Patients with FPHL and lower baseline TAHC may achieve greater clinical improvement.

Objective To systematically evaluate the similarities between six-gene-modified pig red blood cells and human red blood cells in multiple dimensions, including cell morphology, hematological parameters, microbial safety and serological compatibility, and to verify the feasibility of using six-gene-modified pig red blood cells as an alternative for blood transfusion in cases of traumatic hemorrhage. Methods Blood samples from O-type human donor, six-gene-modified O-type pig and wild-type O-type pig were collected. The pig gene-modified phenotype was identified by flow cytometry. The morphology was observed using field emission scanning electron microscopy and the diameter was measured. Hematological tests, including blood routine, osmotic fragility test, adenosine triphosphate (ATP) and 2,3-diphosphoglycerate (2,3-DPG) content and partial pressure of oxygen at 50% hemoglobin saturation (P50), were conducted to assess the deformability of red blood cells. Real-time fluorescent quantitative polymerase chain reaction was used to screen for zoonotic viruses, and cross-matching was performed using column gel method, condensation amine method and saline tube method. Results The six-gene-modified pig red blood cells successfully knocked out the α-Gal, Neu5Gc and Sda antigens and expressed hCD55. Wild-type pig red blood cells expressed these three antigens but did not express human complement regulatory proteins. All three types of red blood cells presented a biconcave discoid morphology. The diameter of O-type human red blood cells was larger than that of the six-gene-modified porcine red blood cells and wild-type pig red blood cells (all P < 0.05). The average red blood cell volume and average red blood cell hemoglobin of O-type humans were higher than those of the six-gene-modified pig red blood cells, and the distribution width-variable coefficient of O-type human red blood cells was lower than that of the six-gene-modified pig red blood cells (all P < 0.05). There were no statistically significant differences in the permeability fragility, ATP content, 2,3-DPG content, P50 and red blood cell deformability indicators of the three types of red blood cells (all P > 0.05). The screening for zoonotic viruses in human and animal cells of the six-gene-modified pigs and wild-type pigs was negative. The cross-matching results showed that in the column gel method and condensation amine method, the primary and secondary sides of the six-gene-modified pig red blood cells did not agglutinate with human red blood cells, while the wild-type pig red blood cells agglutinated with human red blood cells in all cross-matching methods. Conclusions The six-gene-modified pig red blood cells are highly similar to human red blood cells in terms of morphology, key hematological parameters, energy metabolism, oxygen-carrying capacity, mechanical properties, microbial safety and serological compatibility, providing an experimental basis for the clinical transformation of xenotransfusion.

In recent years, remarkable advances have been made in lung transplantation regarding donor evaluation, perioperative support, and immune regulation, laying a foundation for improving the long-term survival of recipients. The rational application of extended criteria donor lungs and the popularization of ex vivo lung perfusion technology have enhanced the utilization efficiency and safety of marginal donor lungs. Refined assessment of risk factors such as donors’ smoking history and infectious status has reduced the incidence of primary graft dysfunction and postoperative infection. In terms of recipient management, individualized assessment systems have been gradually optimized. The standardized application of intraoperative extracorporeal membrane oxygenation and the development of minimally invasive surgical techniques have effectively alleviated perioperative injuries. The optimization of postoperative immunosuppressive regimens and advances in rejection monitoring technologies have further improved the long-term survival of grafts. Nevertheless, chronic graft dysfunction and recurrent or refractory infections remain the major bottlenecks restricting long-term prognosis. Future research should focus on expanding donor sources, improving the repair quality of marginal donor lungs, promoting precise immunosuppression and anti-infection strategies, and comprehensively enhancing the long-term survival rate and quality of life of lung transplant recipients.

OBJECTIVE To investigate the ameliorative effects of Coptidis Rhizoma-Ophiopogonis Radix herb pair （HLMD） in rats with type 2 diabetes mellitus （T2DM） and its potential mechanisms.METHODS Male Wistar rats were randomly divided into a control group （6 rats） and a model induction group （30 rats）. The T2DM rat model was established by feeding a high-sugar and high-fat diet combined with intraperitoneal injection of streptozotocin. The successfully modeled rats were subsequently divided into the model group， the metformin group （200 mg/kg）， and the low-， medium-， and high-dose HLMD groups （100， 200 and 400 mg/kg， respectively）， with six rats in each group. Rats in each group were administered the corresponding drug solution or normal saline by oral gavage once daily for six consecutive weeks. Body weight， fasting blood glucose （FBG）， the area under the curve （AUC） of the oral glucose tolerance test， serum lipid profiles [total cholesterol （TC）， triglyceride （TG）， low-density lipoprotein cholesterol （LDL-C）， and high-density lipoprotein cholesterol （HDL-C）]， and inflammatory cytokine [interleukin-6 （IL-6）， IL-1β， tumor necrosis factor-α （TNF-α）， and IL-10] levels were measured. Histopathological changes in liver and pancreatic tissues， as well as hepatic lipid accumulation， were evaluated. Changes in gut microbiota composition were analyzed in the control， model， and high-dose HLMD groups. Network pharmacology and molecular docking analyses were performed to identify potential therapeutic targets of HLMD against T2DM， followed by experimental validation.RESULTS Compared with the model group， the body weight generally recovered in rats in all HLMD dose groups， while FBG levels consistently decreased. Histopathological abnormalities， including disrupted pancreatic islet architecture， disorganized hepatocyte arrangement， hepatic cord necrosis， and lipid accumulation， were alleviated to varying degrees. AUC （except for the low-dose group）， levels of TC， TG， LDL-C， IL-6（except for the low-dose group）， IL-1β and TNF-α， Simpson and Shannon indices， as well as the relative abundances of Firmicutes， Proteobacteria， and Clostridium were significantly reduced； meanwhile， the levels of HDL-C（except for the low-dose group） and IL-10 （except for the low-dose group）， as well as the relative abundances of Bacteroidota and Ligilactobacillus were significantly increased （ P ＜0.05）. Network pharmacology and molecular docking analyses suggested that the active constituents of HLMD， including quercetin， adenosine， oleanolic acid， stigmasterol， and ophiopogonin D′， may exert antidiabetic effects by targeting key proteins such as protein kinase B1（Akt1）， TNF， IL-6， P53 and IL-1β. Experimental validation further demonstrated that HLMD significantly downregulated the protein expressions of P53 （except for the low-dose group）， IL-6 （except for the low-dose group）， IL-1β and TNF-α in the liver tissues of T2DM rats （ P ＜0.05）.CONCLUSIONS HLMD alleviates glucose and lipid metabolism disorders， attenuates inflammatory responses， and ameliorates hepatic and pancreatic tissue damage in T2DM rats. These beneficial effects may be associated with the modulation of gut microbiota composition and the downregulation of inflammation-related targets， including P53， IL-6， IL-1β and TNF-α.

Depression is a common psychiatric disorder characterized by persistent low mood or mental disorders. Current treatments primarily focus on regulating neurotransmitter levels， but their effectiveness is limited. The mechanisms underlying its onset are complex， and there is no unified consensus. Abnormal signaling pathway transmission plays a crucial role in the development of depression， involving multiple pathways， including Toll-like receptor 4/nucleotide-binding oligomerization domain-like receptor protein 3 （TLR4/NLRP3）， nuclear factor-κB （NF-κB）， Janus kinase/signal transducer and activator of transcription （JAK/STAT）， mitogen-activated protein kinase/extracellular signal-regulated kinase （MAPK/ERK）， brain-derived neurotrophic factor/tyrosine kinase receptor B （BDNF/TrkB）， cyclic AMP/protein kinase A/cAMP response element-binding protein （cAMP/PKA/CREB）， and others. Traditional Chinese medicine（TCM） is based on a holistic approach and the principle of treatment based on the differentiation of syndromes， regulating the balance of multiple systems and organ functions from a macroscopic perspective. This approach has shown unique advantages in the treatment of depression. TCM attributes the onset of depression to dysfunction of the organ systems， involving liver Qi stagnation， heart spirit deficiency， kidney essence depletion， and spleen dysfunction. TCM compound treatments focus on soothing the liver， strengthening the spleen， calming the heart， and replenishing essence， with formulas such as Xiaoyaosan， Zishui Qinggan Yin， and Chahu Jia Guizhi Longgu Muli Tang. The active components of Chinese herbs mainly aim to tonify and regulate Qi， such as salidroside， ginsenoside Rb₁， astragaloside， and muscone. External TCM treatments， primarily acupuncture， aim to open the orifices and invigorate the spirit. Acupoints such as Baihui， Shenting， and Yintang are commonly used. Additionally， massage and moxibustion therapy can intervene in depression by regulating signaling pathways. This article reviews the core role of signaling pathways in the development of depression and the mechanism of TCM regulation of signaling pathways to intervene in depression， aiming to discover new therapeutic approaches that can improve the symptoms of depressed patients.

In recent years,a growing body of research has demonstrated that acupuncture can be used to effectively treat a diverse range of diseases,including functional gastrointestinal disorders,cardiovascular diseases,as well as anxiety and depression,through the modulation of the paraventricular hypothalamic nucleus(PVN).Acupuncture may exert its therapeutic effect either by modulating specific neurons within the PVN,such as corticotropin releasing hormone(CRH)neurons,or by regulating the release of hormones,such as oxytocin(OXT)and vasopressin(VP),and the activity of neural circuits associated with the PVN.This review summarizes the mechanisms by which PVN is involved in acupuncture treatment,including its regulatory mechanisms in gastrointestinal diseases,cardiovascular diseases,and negative emotions and pain.Future research should be conducted to further explore the precise mechanisms by which acupuncture regulates PVN to treat diseases,focusing on clarifying the specific processes of signaling pathway transduction,and exploring the specific effects of acupunture of different acupoint combinations and stimulation frequencies and intensity on PVN.

Objective To investigate the diagnostic value of 4 novel inflammatory markers related to routine blood tests,namely neutrophil-to-lymphocyte ratio(NLR),red blood cell distribution width(RDW),hemoglobin-to-RDW ratio(HRR)and systemic immune-inflammation index(SII),in elderly patients with chronic cardiovascular disease(CVD)complicated with frailty.Methods Retrospectively analyze 110 patients with chronic stable CVD who were hospitalized in the cadre ward of cardiovascular medicine at the Air Force Characteristic Medical Center from January 2022 to June 2023.According to the assessment results of the Fried scale,they were divided into three groups:non-frailty group(Fried score=0,n=30),the pre-frailty group(Fried score 1 or 2,n=40)and frailty group(Fried score≥3,n=40).The differences in general information,the impairment rate of daily living activities,miniature nutritional assessment-short form(MNA-SF)scores,mini-mental state examination(MMSE)scores,and the indicators such as NLR,RDW,HRR,and SII among the three groups were compared.Spearman rank correlation was used to analyze the correlation between NLR,RDW,HRR,SII and frailty scores as well as each frailty indicator.Multivariate logistic regression analysis was performed to identify the independent risk factors for frailty in elderly patients with chronic CVD,and the receiver operating characteristic(ROC)curve was used to assess the clinical diagnostic value of NLR and HRR in elderly patients with chronic CVD complicated with frailty.Results Compared with non-frailty group and pre-frailty group,patients in frailty group were older,with higher impaired rates of daily living activities,NLR,RDW,and SII,and lower MNA-SF scores,MMSE scores,and HRR,and differences were statistically significant(P<0.05).Spearman rank correlation analysis showed that the frailty score was positively correlated with NLR(rs=0.354,P<0.001),and RDW(rs=0.448,P<0.001),negatively correlated with HRR(rs=-0.232,P=0.024),and had no significant correlation with SII(rs=0.144,P=0.167).Further analysis of the correlation between the above novel inflammatory markers and the 5 components of frailty showed that NLR was positively correlated with fatigue(rs=0.228,P=0.017),slowed walking speed(rs=0.299,P<0.001),and low physical function(rs=0.319,P<0.001);RDW was positively correlated with decreased grip strength(rs=0.321,P<0.001),slowed walking speed(rs=0.422,P<0.001),and low physical function(rs=0.246,P=0.001);and HRR was negatively correlated with slowed walking speed(rs=-0.230,P=0.025),and low physical function(rs=-0.299,P=0.003).Multivariate logistic regression analysis showed that MNA-SF score(OR=0.577,95%CI 0.342-0.973)was an independent protective factor for pre-frailty in elderly patients with chronic CVD(P<0.05);NLR(OR=7.866,95%CI 1.101-56.185)was an independent risk factor for frailty,while HRR(OR=0.344,95%CI 0.120-0.983)and MNA-SF score(OR=0.292,95%CI 0.146-0.580)were independent protective factors for frailty in elderly CVD patients(P<0.05).The area under the ROC curve of NLR and HRR for diagnosing frailty in elderly patients with chronic CVD were 0.778 and 0.749,respectively.Conclusion NLR and HRR have high clinical diagnostic value for frailty in elderly patients with chronic CVD,and are expected to become effective inflammatory markers for screening elderly patients with chronic CVD complicated with frailty.

Objective To develop a melanoma diagnosis framework based on large-scale vision-language models,and to explore the feasibility and accuracy of the framework for melanoma diagnosis.Methods The publicly available Derm7pt dataset,which was divided into a training set(346 cases),a validation set(161 cases),and a test set(320 cases)was utilized.A melanoma diagnosis framework based on large-scale vision-language models was proposed,comprising two text branches and one visual branch.In the text branches,one branch processed fixed clinical prompts,while the other handled learnable prompts.This design aimed to optimize the effectiveness of learnable prompts through guidance from fixed clinical prompts.The visual branch processed dermoscopic images and enhanced melanoma feature recognition through fine-tuning the image encoder.Results On the Derm7pt dataset,our method outperformd other existing method.It achieved an area under the receiver operating characteristic curve(AUC)of 87.35％,an accuracy of 84.17％,and an F1-score of 84.01％.Conclusion The study demonstrates that with appropriate fine-tuning strategies,methods based on large-scale vision-language pre-trained models can effectively adapt to melanoma diagnosis tasks.This approach can serve as a powerful auxiliary tool for doctors,helping them make more accurate diagnostic decisions.