Hepatic fibrosis is a reversible pathological process in various chronic liver diseases and is closely associated with the development and progression of severe liver diseases such as liver cirrhosis and hepatocellular carcinoma， and it has emerged as a significant global health challenge. In recent years， studies have shown that histone lactylation， a newly discovered epigenetic modification， actively participates in regulating the progression of hepatic fibrosis. This article systematically reviews the core regulatory effect of histone lactylation modification in the interaction between inflammatory microenvironment and hepatic fibrosis， in order to clarify the cascade regulatory mechanism of “inflammation-hepatic fibrosis” and provide new insights for early diagnosis， targeted intervention， and prevention of malignant transformation in hepatic fibrosis.

Chronic heart failure （CHF） is a complex clinical syndrome caused by ventricular dysfunction， with mitochondrial energy metabolism disorder being a critical factor in disease progression. Heart-Yang deficiency syndrome， as the core pathogenesis of CHF， persists throughout the disease course. Insufficiency of heart-Yang leads to weakened warming and propelling functions， resulting in the accumulation of phlegm-fluid， blood stasis， and dampness. This eventually causes Qi stagnation with phlegm obstruction and blood stasis with water retention， forming a vicious cycle that exacerbates disease progression. According to the theory of reinforcing Yang， the clinical experience of the traditional Chinese medicine （TCM） master Tang Zuxuan in treating CHF with heart-Yang deficiency syndrome， and achievements from molecular biological studies， this study innovatively proposes an integrated research framework of "TCM syndrome differentiation and staging-mitochondrial metabolism mechanisms-intervention with Yang-reinforcing prescriptions" which is characterized by the integration of traditional Chinese and Western medicine. Heart-Yang deficiency syndrome is classified into mild （Stage Ⅰ-Ⅱ）， severe （Stage Ⅲ）， and critical （Stage Ⅳ） stages. The study elucidates the precise correlations between the pathogenesis of each stage and mitochondrial metabolism disorders from theoretical， pathophysiological， and therapeutic perspectives. The mild stage is characterized by impaired biogenesis and substrate-utilization imbalance， corresponding to heart-Yang deficiency and phlegm-fluid aggregation. Linggui Zhugantang and similar prescriptions can significantly improve the expression of peroxisome proliferator-activated receptor gamma co-activator-1α（PGC-1α）/silent information regulator 2 homolog 1 （SIRT1） and ATPase activity. The severe stage centers on oxidative stress and structural damage， reflecting Yang deficiency with water overflow and phlegm-blood stasis intermingling. At this stage， Zhenwu Tang and Qiangxin Tang can effectively mitigate oxidative stress damage， increase adenosine triphosphate （ATP） content， and repair mitochondrial structure. The critical stage arises from calcium overload and mitochondrial disintegration， leading to the collapse of Yin-Yang equilibrium. At this stage， Yang-restoring and crisis-resolving prescriptions such as Fuling Sini Tang and Qili Qiangxin capsules can inhibit abnormal opening of the mitochondrial permeability transition pore （MPTP）， reduce cardiomyocyte apoptosis rate， and protect mitochondrial function. By summarizing the characteristics of mitochondrial energy metabolism disorders at different stages of CHF， this study explores the application of the theory of reinforcing Yang in treating heart-Yang deficiency syndrome and provides new insights for the clinical diagnosis and treatment of CHF.

ObjectiveTo explore the mechanism of ventricular remodeling mediated by the p38 mitogen-activated protein kinase （MAPK）/nuclear factor kappa B （NF-κB） signaling pathway in the rat model of chronic heart failure （CHF） with heart-blood stasis syndrome， as well as the intervention effect of Danhong injection. MethodsIn vivo experiment： SPF-grade male SD rats were assigned via the random number table method into 4 groups： Sham operation， model， captopril （8.8 mg·kg^-1）， and Danhong injection （6.0 mL·kg^-1）. The model of CHF with heart-blood stasis syndrome was established by abdominal aortic constriction， and the sham operation group only underwent laparotomy without constriction. All the groups were treated continuously for 15 days. The tongue color of rats was observed. Echocardiography， hemorheology， heart mass index （HMI）， and left ventricular mass index （LVMI） were measured. Hematoxylin-eosin （HE） staining and Masson staining were performed to observe the pathological and fibrotic changes of the myocardial tissue. Enzyme-linked immunosorbent assay （ELISA） was employed to quantify the levels of N-terminal pro-B-type natriuretic peptide （NT-proBNP）， interleukin-6 （IL-6）， angiotensin Ⅱ （AngⅡ）， tumor necrosis factor-α （TNF-α）， and Creactive protein （CRP） in the serum， as well as the levels of matrix metalloproteinase-2 （MMP-2） and matrix metalloproteinase-9 （MMP-9） in the myocardial tissue. Western blot was used to quantify the protein levels of p-p38 MAPK/p38 MAPK and p-NF-κB p65/NF-κB p65 in the myocardial tissue. In vitro experiment： H9C2 cardiomyocytes were treated with 1×10^-6 mol·L^-1 AngⅡ to establish a model of myocardial hypertrophy. H9C2 cardiomyocytes were allocated into normal， model， inhibitor + Danhong injection， Danhong injection （20 mL·L^-1）， and inhibitor （SB203580， 5 μmol·L^-1） groups. CCK-8 assay was used to detect the viability of H9C2 cardiomyocytes. Rhodamine-labeled phalloidin staining was used to reveal the area of cardiomyocytes. Real-time PCR was performed to determine the mRNA levels of atrial natriuretic peptide （ANP） and brain natriuretic peptide （BNP）. Western blot was used to assess the protein levels of p-p38 MAPK/p38 MAPK and p-NF-κB p65/NF-κB p65. ResultsIn vivo experiment： Compared with the sham operation group， the model group showed purplish-dark tongue with decreased R， G， B values of the tongue surface （P<0.01）， increased whole blood viscosity （at low， medium， and high shear rates） （P<0.01）， decreased left ventricular ejection fraction （LVEF） and left ventricular fractional shortening （LVFS） （P<0.01）， increased left ventricular end-diastolic diameter （LVIDd）， left ventricular end-systolic diameter （LVIDs）， and left ventricular posterior wall thickness at end-diastole （LVPWd） （P<0.01）， raised LVMI and HMI （P<0.01）， and elevated levels of NT-proBNP， TNF-α， IL-6， and CRP in the serum and MMP-2 and MMP-9 in the myocardial tissue （P<0.01）. The HE and Masson staining of the myocardial tissue showed compensatory myocardial hypertrophy， fibrosis， and massive inflammatory cell infiltration in the model group. Additionally， the model group presented up-regulated protein levels of p-p38 MAPK/p38 MAPK and p-NF-κB p65/NF-κB p65 in the myocardial tissue （P<0.01）. Compared with the model group， each administration group showed increased R， G， B values of the tongue surface （P<0.05， P<0.01）， decreased whole blood viscosity （at low， medium， and high shear rates） （P<0.05， P<0.01）， increased LVEF and LVFS （P<0.01）， decreased LVIDd， LVIDs， and LVPWd （P<0.05， P<0.01）， declined LVMI and HMI （P<0.05， P<0.01）， and lowered levels of NT-proBNP， TNF-α， IL-6， and CRP in the serum and MMP-2 and MMP-9 in the myocardial tissue （P<0.01）. HE and Masson staining showed alleviated compensatory myocardial hypertrophy， reduced fibrosis， and decreased expression of p-p38 MAPK/p38 MAPK and p-NF-κB p65/NF-κB p65 in the myocardial tissue （P<0.01）. In vitro experiment： When the concentration of Danhong injection reached 20 mL·L^-1， the survival rate of H9C2 cardiomyocytes was the highest （P<0.01）. Compared with the normal group， the model group showed up-regulated mRNA levels of ANP and BNP （P<0.01）， increased relative cell surface area （P<0.01）， and raised protein levels of p-p38 MAPK/p38 MAPK and p-NF-κB p65/NF-κB p65 （P<0.01）. Compared with the model group， each administration group showed down-regulated mRNA levels of ANP and BNP （P<0.01）， reduced relative cell surface area （P<0.05， P<0.01）， and down-regulated protein levels of p-p38 MAPK/p38 MAPK and p-NF-κB p65/NF-κB p65 （P<0.05， P<0.01）. ConclusionDanhong injection can regulate ventricular remodeling through the p38 MAPK/NF-κB pathway， thereby exerting a protective effect on the rat model of CHF with heart-blood stasis syndrome.

Based on the theory of toxin in The Inner Canon of Yellow Emperor （《黄帝内经》）， this paper explores the concept and connotation of toxin from several aspects， including medicinal toxicity， pathogenic toxicity， pathoge-nesis and treatment of toxin pathogen. It explores the mechanism and significance of using toxin substances in curing and inducing diseases， sorts out the etiological and pathological evolution of toxic pathogens， clarifies the derivation and differentiation process from external toxins to internal toxins， and elucidates the interactions between toxin and other pathogenic factors such as phlegm， stasis， dampness， and fire. It further distinguishes the logical hierarchy of toxin caused by metabolic disorders such as sugar， fat， and drowning， clarifies that the essence of the etiology of "hidden toxin"， and determines the corresponding treatment principles and methods for toxic pathogens. It establishes a theoretical framework of traditional Chinese medicine toxic pathogen theory， providing theoretical basis for the clinical treatment of many diseases.

Testicular histology based on testicular biopsy is an important factor for determining appropriate testicular sperm extraction surgery and predicting sperm retrieval outcomes in patients with azoospermia. Therefore, we developed a deep learning (DL) model to establish the associations between testicular grayscale ultrasound images and testicular histology. We retrospectively included two-dimensional testicular grayscale ultrasound from patients with azoospermia (353 men with 4357 images between July 2017 and December 2021 in The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China) to develop a DL model. We obtained testicular histology during conventional testicular sperm extraction. Our DL model was trained based on ultrasound images or fusion data (ultrasound images fused with the corresponding testicular volume) to distinguish spermatozoa presence in pathology (SPP) and spermatozoa absence in pathology (SAP) and to classify maturation arrest (MA) and Sertoli cell-only syndrome (SCOS) in patients with SAP. Areas under the receiver operating characteristic curve (AUCs), accuracy, sensitivity, and specificity were used to analyze model performance. DL based on images achieved an AUC of 0.922 (95% confidence interval [CI]: 0.908-0.935), a sensitivity of 80.9%, a specificity of 84.6%, and an accuracy of 83.5% in predicting SPP (including normal spermatogenesis and hypospermatogenesis) and SAP (including MA and SCOS). In the identification of SCOS and MA, DL on fusion data yielded better diagnostic performance with an AUC of 0.979 (95% CI: 0.969-0.989), a sensitivity of 89.7%, a specificity of 97.1%, and an accuracy of 92.1%. Our study provides a noninvasive method to predict testicular histology for patients with azoospermia, which would avoid unnecessary testicular biopsy.
Humans ; Male ; Azoospermia/diagnostic imaging* ; Deep Learning ; Testis/pathology* ; Retrospective Studies ; Adult ; Ultrasonography/methods* ; Sperm Retrieval ; Sertoli Cell-Only Syndrome/diagnostic imaging*

OBJECTIVES: To investigate the genomic characteristics and prognostic factors of juvenile myelomonocytic leukemia (JMML) with RAS mutations. METHODS: A retrospective analysis was conducted on the clinical data of JMML children with RAS mutations treated at the Hematology Hospital of Chinese Academy of Medical Sciences, from January 2008 to November 2022. RESULTS: A total of 34 children were included, with 17 cases (50%) having isolated NRAS mutations, 9 cases (27%) having isolated KRAS mutations, and 8 cases (24%) having compound mutations. Compared to children with isolated NRAS mutations, those with NRAS compound mutations showed statistically significant differences in age at onset, platelet count, and fetal hemoglobin proportion (P<0.05). Cox proportional hazards regression model analysis revealed that hematopoietic stem cell transplantation (HSCT) and hepatomegaly (≥2 cm below the costal margin) were factors affecting the survival rate of JMML children with RAS mutations (P<0.05); hepatomegaly was a factor affecting survival in the non-HSCT group (P<0.05). CONCLUSIONS Children with NRAS compound mutations have a later onset age compared to those with isolated NRAS mutations. At initial diagnosis, children with NRAS compound mutations have poorer peripheral platelet and fetal hemoglobin levels than those with isolated NRAS mutations. Liver size at initial diagnosis is related to the prognosis of JMML children with RAS mutations. HSCT can improve the prognosis of JMML children with RAS mutations.
Humans ; Leukemia, Myelomonocytic, Juvenile/therapy* ; Mutation ; Male ; Female ; Child, Preschool ; Retrospective Studies ; Child ; Infant ; GTP Phosphohydrolases/genetics* ; Membrane Proteins/genetics* ; Adolescent ; Hematopoietic Stem Cell Transplantation ; Proportional Hazards Models ; Proto-Oncogene Proteins p21(ras)/genetics* ; Prognosis

OBJECTIVES: To evaluate the strategies and outcomes of assisted reproductive technology (ART) for fertility preservation and promotion in women with malignant tumors, and to analyze ART outcomes across different tumor types. METHODS: We conducted a retrospective analysis of female patients who underwent ART for fertility preservation or treatment at the Reproductive Center of the Women's Hospital, Zhejiang University School of Medicine, between January 1, 2018, and December 31, 2023. A total of 163 ART-aided pregnancy patients with malignant tumors were included in the case group, among which 6 patients underwent embryo cryopreservation for fertility preservation before radiotherapy or chemotherapy. Additionally, 11 unmarried women underwent oocyte cryopreservation due to borderline ovarian tumors, ovarian cancer, breast cancer, or hematological malignancies. The control group was selected from women without a history of malignant tumors who received ART treatment during the same period, using propensity score matching at a ratio of 1∶2, resulting in 326 cases. Data were collected through the reproductive medical record system and telephone follow-up (as of October 31, 2024). Baseline characteristics, controlled ovarian hyperstimulation parameters, laboratory indicators, and pregnancy outcomes were compared between case and control groups and among patients with different tumor types, and the tumor recurrence of the patients was followed up. RESULTS: Patients in the case group had significantly lower ovarian reserve (AMH, AFC) and a higher proportion of diminished ovarian reserve compared to the control group (all P<0.01). Regarding the ovulation induction protocol, the proportion of patients using the minimal stimulation protocol in the case group was significantly higher than that in the control group (29.45% vs. 12.88%, P<0.01), and the total dosage of gonadotropins used was lower (P<0.01). In terms of assisted reproductive outcomes, there were no statistically significant differences between the two groups in the number of retrieved oocytes, number of high-quality embryos, fertilization rate, cumulative pregnancy rate, cumulative live birth rate, or miscarriage rate (all P>0.05). However, the number of oocyte retrieval cycles and embryo transfer cycles required to achieve a live birth outcome in the case group were significantly higher than those in the control group (both P<0.05). Subgroup analysis showed that there were no significant differences in cumulative pregnancy rate and live birth rate among patients with different tumor types (thyroid cancer, reproductive system tumors, breast cancer, lung cancer). Nevertheless, lung cancer patients had the lowest ovarian reserve and required the most oocyte retrieval cycles due to their older age; breast cancer patients had a relatively lower fertilization rate partially because some of them were complicated with male factors. A follow-up of 154 tumor patients (with a follow-up rate of 88.5%) revealed that 6 patients (4.20%) had tumor recurrence, and 1 breast cancer patient died due to tumor recurrence. None of the 11 unmarried patients who had undergone oocyte cryopreservation had used the cryopreserved oocytes for assisted pregnancy yet, and 1 patient who had undergone fertility preservation died due to tumor recurrence. CONCLUSIONS Women of reproductive age with malignant tumors are at risk of diminished fertility. ART can effectively preserve and promote fertility, enabling favorable pregnancy and live birth outcomes. It is recommended to initiate a multidisciplinary assessment promptly prior to radiotherapy/chemotherapy and formulate an individualized ART regimen for fertility preservation or promotion, so as to achieve reproductive goals or safeguard future fertility potential.

Objective Exploring the clinical efficacy of using autologous rib cartilage grafting to reconstruct finger hemiarticular defects.Methods From August 2022 to February 2024,for 6 patients with hemiarticular surface defects in the metacarpophalangeal joints and interphalangeal joints of 8 fingers,costal cartilage was used for joint remodeling and transplantation to reconstruct the hemiarticular surface defects of the fingers.All 8 joint transplants in 6 patients were two-stage surgeries.In the first stage,antibiotic bone cement was used to fill the space-occupying lesions,and in the second stage,costal cartilage joint remodeling was performed to reconstruct the finger joint defects.Postoperative follow-up and assessment of fracture healing according to Paley fracture healing scoring criteria.Outpatient and WeChat follow-up,upper limb function is evaluated according to the upper limb functional assessment standards of the Chinese Medical Association Hand Surgery Society.Record VAS pain score.Results In this group,there were a total of 6 patients with 8 cases of hemiarticular defects.Among them,2 patients had two joint surgical sites,while the remaining 4 patients had a single joint surgical site.There were 2 cases of metacarpophalangeal joint head defects,2 cases of proximal articular surface defects,3 cases of proximal articular head defects,and 1 case of thumb proximal articular head defect.After surgery,8 out of 6 patients'hand wounds healed successfully.All patients were followed up for 6-12 months postoperatively,with an average of 9 months.The VAS pain score(affected finger)for the last follow-up was 0-2 points,with an average of 0.6 points.According to Paley's scoring criteria,all 6 patients had excellent fracture healing.According to the evaluation criteria for upper limb functional assessment of the Chinese Medical Association Hand Surgery Society,3 cases were rated as excellent,3 cases were rated as good,and 2 cases were rated as fair.Conclusion For patients with half joint defects on one side of the finger,rib rib cartilage was used for joint reconstruction,which significantly improved the joint shape and function at the defect site,and reduced joint pain scores.

Objective:To explore the effects of remimazolam versus dexmedetomidine combined with spinal-epidural anesthesia in elderly patients undergoing hip replacement.Methods:A total of 100 elderly patients who needed total hip replacement in the Nanjing Lishui People′s Hospital from March 2021 to March 2023 were selected and divided into two groups by dynamic randomization, with 50 cases in each group. Both groups underwent surgery under combined spinal-epidural anesthesia. The control group was given dexmedetomidine for anesthesia, and the observation group was given remimazolam for anesthesia. The depth of sedation [eye-opening time, post anesthesia care unit (PACU) stay time, awakening time], cognitive function at different time periods [Mini-Mental State Examination (MMSE) score], inflammatory factor indexes [interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α)], and hemodynamic indexes [heart rate (HR), mean arterial pressure (MAP)] were compared between the two groups.Results:The eye-opening time and PACU stay time in the observation group were shorter than those in the control group (all P<0.05), and there was no significant difference in awakening time between the two groups ( P>0.05). The MAP of both groups at post-skin incision (T 1) and completion of internal fixation (T 2) was higher than that after anesthesia induction (T 0), and decreased at the end of surgery (T 3); the HR of both groups at T 1 was lower than that at T 0, but increased at T 2, and then decreased at T 3. There were no significant differences in MAP and HR between the two groups at each time point (all P>0.05). The MMSE scores of the observation group at 1, 4, and 7 days after surgery were significantly higher than those of the control group (all P<0.05). The serum levels of IL-1β, IL-6, and TNF-α in both groups at post-anesthesia (t 1), end of surgery (t 2), and post-surgery (t 3) were significantly higher than those at 1 day before surgery (t 0), and the serum levels of IL-1β, IL-6, and TNF-α in the observation group at t 1, t 2, and t 3 were lower than those in the control group (all P<0.05). Conclusions:Both remimazolam and dexmedetomidine can effectively maintain hemodynamic stability in elderly patients undergoing hip replacement surgery, while remimazolam can more effectively shorten the time to reach the required depth of sedation, reduce the occurrence of cognitive dysfunction, and decrease the secretion of inflammatory factors.

Currently,the first-generation of proton pump inhibitors(PPIs)commonly utilized in clinical practice for the treatment of peptic ulcer include omeprazole,lansoprazole,and pantoprazole,and the second generation include rabeprazole and esomeprazole.The predominant mode of PPI administration is oral,which poses numerous challenges in clinical settings owing to their poor solubility,susceptibility to gastric acid degradation,short half-life,and limited stability.This article presents a comprehensive review of studies exploring the novel states of these five PPIs,include polymorphism,co-crystal drugs,and nanodrugs.Furthermore,it summarizes the advancements in research aimed at modifying the physicochemical properties of these drugs through innovative solid states,thereby enhancing their bioavailability and stability.This work offers a new perspective for researchers endeavoring to develop new states of pharmaceutical substances that incorporate PPIs.