The comorbidity rate of gastroesophageal reflux disease （GERD） and sleep disorders is high， and the two form a vicious circle through the “brain-gut axis”， which seriously impacts the patients’ quality of life. Traditional Chinese medicine （TCM）， guided by the core principles of “holistic concept” and “syndrome differentiation and treatment”， features multi-targeted therapeutic effects with minimal side effects， offering diverse intervention options for clinical practice. From the perspective of the “brain-gut axis”， this article reviews the relationship between the comorbidity of GERD and sleep disorders and systematically examines relevant research findings on how TCM regulates the “brain-gut axis” to intervene in this comorbid condition. The study reveals that the “brain-gut axis” may participate in the pathological progress of GERD accompanied by sleep disorders through pathways such as abnormalities in the secretion of brain-gut peptides （including gastrointestinal secretin）， as well as intestinal dysbiosis. By closely focusing on core pathogenic mechanisms such as “disharmony between the liver and stomach” and “insomnia due to stomach disharmony”， various approaches can be employed， including TCM formulas （e.g.， modified Sini powder combined with Zuojin pills）， external TCM therapies （e.g.， back-shu point digital acupressure）， and integrated traditional Chinese and Western medicine treatments （e.g.， modified Chaihu guizhi ganjiang decoction combined with proton pump inhibitors）. These methods can regulate the levels of neurotransmitters， gastrointestinal hormones， inflammatory factors， and the composition of intestinal microbiota associated with the “brain-gut axis”， thereby achieving simultaneous improvement in both GERD and sleep disorders.

Objective:To investigate the correlation between the timing of minimally invasive puncture drainage and the outcome of patients with hypertensive intracerebral hemorrhage (HICH) in the basal ganglia region.Methods:Patients with HICH in the basal ganglia region underwent minimally invasive puncture and drainage at Hanchuan People's Hospital from January 2019 to September 2023 were selected. According to the timing of surgery, the patients were divided into onset to surgery time ≤12-hour group and >12-hour group. According to the modified Rankin Scale score at 90 days after onset, they were divided into a good outcome group (0-2) and a poor outcome group (>2). Multivariate logistic regression analysis was used to evaluate the independent influencing factors of functional outcome. Results:A total of 150 patients were included, with 78 males (52.00%), aged 53.15±4.35 years (range, 40-75 years). Eighty-six patients (57.33%) underwent surgery within 12 hours after onset, while 64 (42.67%) underwent surgery after 12 hours; 97 patients (64.67%) had good outcome, while 53 (35.33%) had poor outcome. Univariate analysis showed that compared with the onset to surgery time ≤12-hour group, the onset to surgery time >12-hour group had a longer time from onset to admission, a larger postoperative hematoma volume, longer hospitalization time, lower postoperative hematoma clearance rate, and a higher proportion of patients with poor outcome and deaths within 90 days (all P<0.05). Compared with the good outcome group, the poor outcome group had a longer time from onset to admission, higher baseline National Institutes of Health Stroke Scale (NIHSS) scores, larger baseline and postoperative hematoma volumes, and a higher proportion of patients with onset to surgery time >12 hours. However, the postoperative hematoma clearance rate, baseline Glasgow Coma Scale (GCS) score, and the proportion of patients with baseline GCS score >8 was lower in the poor outcome group (all P<0.05). Multivariate logistic regression analysis showed that the higher baseline NIHSS score (odds ratio [ OR] 1.847, 95% confidence interval [ CI] 1.362-2.503; P=0.001) and the time from onset to surgery >12 hours (compared with ≤12 hours: OR 1.347, 95% CI 1.058-1.715; P=0.016) were the independent risk factors for poor outcome, while higher baseline GCS scores ( OR 0.723, 95% CI 0.558-0.937; P=0.006) and higher postoperative hematoma clearance rates ( OR 0.615, 95% CI 0.462-0.819; P=0.004) were the independent protective factors for good outcome. Conclusion:In patients with HICH in basal ganglia, it is ideal to perform minimally invasive puncture and drainage within 12 h after onset, and the postoperative recovery is relatively better.

Objective To investigate the pathological and molecular characteristics of subcutaneous implanted thyroid lesions after endoscopic thyroid surgery.Methods A retrospective analysis was conducted on three postoperative implantation cases diagnosed in the Department of Pathology of our hospital from 2017 to 2024.Morphological evaluation,immunohistochemical staining,and next generation sequencing(NGS)targeting 66 cancer-related genes and 177 fusion loci were performed to compare features between primary and implanted lesions.Results All three implanted lesions exhibited morphological similarity to their primary counterparts,but displayed enriched mutational profiles.Case 1:a 13-year-old female.The primary lesion was an atypical follicular adenoma progressing to follicular carcinoma,while the implanted lesion was follicular carcinoma.Both lesions harbored MEN1 mutations,with an additional PTPRT mutation detected in the implanted lesion.Case 2:a 45-year-old male.The primary lesion was bilateral nodular goiter,and the implanted lesion showed follicular epithelial hyperplasia with a 0.3 cm papillary carcinoma focus.No mutations were identified in the primary lesion,whereas the implanted lesion exhibited MEN1,GLIS3,EZH1,and KMT2C mutations.Case 3:a 42-year-old female.The primary lesion included a left thyroid adenoma with cystic degeneration and right nodular goiter.A nodular goiter-like implanted lesion was detected in the right breast 5 years postoperatively.The primary lesion harbored TERT,GLIS3,and SPOP mutations,while the implanted lesion showed TERT,GLIS3,EIF1AX,and KMT2C mutations.Conclusions Endoscopic thyroid surgery is widely applied in clinical practice,however,implantation dissemination of thyroid lesions along surgical pathways may occur,encompassing both benign and malignant entities.Implanted lesions exhibit pathological similarities to their primary counterparts,but demonstrate mutational enrichment.

Objective:To explore the clinical effects and value for application of the tibial flap of the second toe with the vascular pedicle including a plantar vein on the reconstruction of fingertip soft tissue defects.Methods:From October 2020 to August 2022, retrospective analysis of 12 patients (12 digits) were treated at the Department of Hand Surgery, Suzhou Ruihua Orthopaedic Hospital for small soft tissue defects of fingertip. The patients were 9 males and 3 females and aged 29-54 years, at 38 years in average. The fingertip defects were measured at approximately 1.2 cm × 0.8 cm to 1.2 cm × 1.2 cm. In the surgery, a tibial flap of second toe was designed to reconstruct the defect in fingertip. The flap were designed on the tibial of second toe without an extended incision in dorsal foot. The pedicle of the flap carried with the lateral proper digital artery, a nerve and the plantar vein of the second toe. At the recipient site, the artery, nerve and vein carried by the pedicle of the flap were end-to-end anastomosed with the digital artery, digital nerve and subcutaneous vein of the finger. The flaps were measured at 1.5 cm×1.0 cm - 1.5 cm×1.5 cm in size. All donor sites were reconstructed with skin grafts from the ipsilateral calf. Scheduled postoperative follow-ups were conducted at the outpatient clinic. The Michigan Hand Function Questionnaire (MHQ) evaluation criteria was employed to assess the recovery of hand function, and Total Active Movement (TAM) was used to evaluate the recovery of range of motion of the interphalangeal joints of the affected fingers.Results:All 12 flaps in the fingertips survived. Postoperative follow-ups lasted from 6 months to 2 years, with an average of 11 months. One flap was slightly bloated and a flap aesthetic surgery was followed at 3 months after the primary reconstructive surgery, and the rest of flaps were all in good appearance. TPD was found at 12 -14 mm for all flaps at 9 months after surgery. All donor sites in the feet and calfs had primary healing, without a contracture or rupture of skin graft or an obvious dysfunction at the donor sites. According to the evaluation criteria of the MHQ, 8 patients were very satisfied with the overall appearance of the hand, and 4 were satisfied. Finger movement was evaluated according to TAM criteria, all 12 fingers were rated excellent.Conclusion:Reconstruction of a fingertip defect with a tibial flap of the second toe with the vascular pedicle including a plantar vein of the second toe has a good clinical efficacy. It has advantages in flap harvest, avoids an extended incision on dorsal foot, and makes a minimal damage to the donor site.

Bio-mineralization has emerged as a promising strategy to enhance vaccine immunogenicity. This study optimized the calcium phosphate (CaP) mineralization process of foot-and-mouth disease virus-like particles (FMD VLPs) to achieve high mineralization efficiency and scalability. Key parameters, including concentrations of Ca²⁺, HPO₄^2-, NaCl, and VLPs, as well as stirring speed, were systematically optimized. Stability of the scaled-up reaction system and immunogenicity of the mineralized vaccine were evaluated. Optimal conditions [25.50 mmol/L Ca(NO₃)₂, 15 mmol/L Na₂HPO₄, 300 mmol/L NaCl, 0.75 mg/mL VLPs, and 1 500 r/min] yielded CaP-mineralized VLPs (VLPs-CaP) with high mineralization efficiency, uniform morphology, and a favorable particle size. Scaling up the reaction by 25 folds maintained consistent mineralization efficiency and particle characteristics. Immunization in mice demonstrated that VLPs-CaP induced higher titers of specific antibodies and neutralizing antibodies than unmineralized VLPs (P < 0.05). Higher IgG2a/IgG1 ratio and enhanced IFN-γ secretion (P < 0.05) further indicated robust cellular immune responses. We establish a stable and scalable protocol for VLPs-CaP, providing a theoretical and technical foundation for developing high-efficacy VLPs-CaP vaccines.
Vaccines, Virus-Like Particle/immunology* ; Immunogenicity, Vaccine ; Calcium Phosphates/chemistry* ; Foot-and-Mouth Disease Virus ; Biomineralization ; Particle Size ; Animals ; Mice ; Antibodies, Neutralizing/blood* ; Antibodies, Viral/blood* ; Immunity, Cellular

Vaccination is a crucial strategy for the prevention and control of infectious diseases. Virus-like particles (VLPs), composed of structural proteins, have garnered significant attention as a novel type of vaccine due to their excellent safety and immunogenicity. However, similar to most vaccine antigens, VLPs exhibit insufficient thermal stability, which not only restricts the widespread application of vaccines but also increases the risk of vaccine inactivation. This study aims to enhance the stability and shelf life of VLPs derived from type A foot-and-mouth disease virus (FMDV) by employing vacuum freeze-drying technology. The optimal lyoprotectant formulation was determined through single-factor and combinatorial screening. Subsequently, the correlation between the immunogenicity of the freeze-dried vaccine and the content of FMDV VLPs was evaluated via a mouse model. The stability of FMDV VLPs before and after freeze-drying was further assessed by storing them at 4, 25, and 37 ℃ for varying time periods. Results indicated that the lyoprotectant formulation No.1, composed of 7.5% trehalose, 0.1% Tween 80, 50 mmol/L glycine, 1% sodium glutamate, and 3% polyvinylpyrrolidone (PVP), effectively preserved the content of FMDV VLPs during the vacuum freeze-drying process. The immunization trial in mice revealed that the levels of specific antibodies, immunoglobulin G1 (IgG1), interleukin-4 (IL-4), and neutralizing antibodies induced by freeze-dried FMDV VLPs were comparable to those induced by non-freeze-dried FMDV VLPs. The heat treatment results showed that the storage periods of freeze-dried FMDV VLPs at 4, 25, and 37 ℃ were significantly longer than those of non-freeze-dried FMDV VLPs. In conclusion, the selected lyoprotectant formulation effectively improved the stability of FMDV VLPs vaccines. This study provides valuable insights for enhancing the stability of novel subunit vaccines.
Freeze Drying/methods* ; Animals ; Foot-and-Mouth Disease Virus/immunology* ; Mice ; Vaccines, Virus-Like Particle/chemistry* ; Foot-and-Mouth Disease/immunology* ; Vacuum ; Drug Stability ; Mice, Inbred BALB C ; Viral Vaccines/immunology*

Objective To investigate the pathological and molecular characteristics of subcutaneous implanted thyroid lesions after endoscopic thyroid surgery. Methods A retrospective analysis was conducted on three postoperative implantation cases diagnosed in the Department of Pathology of our hospital from 2017 to 2024. Morphological evaluation, immunohistochemical staining, and next generation sequencing (NGS) targeting 66 cancer-related genes and 177 fusion loci were performed to compare features between primary and implanted lesions. Results All three implanted lesions exhibited morphological similarity to their primary counterparts, but displayed enriched mutational profiles. Case 1: a 13-year-old female. The primary lesion was an atypical follicular adenoma progressing to follicular carcinoma, while the implanted lesion was follicular carcinoma. Both lesions harbored MEN1 mutations, with an additional PTPRT mutation detected in the implanted lesion. Case 2: a 45-year-old male. The primary lesion was bilateral nodular goiter, and the implanted lesion showed follicular epithelial hyperplasia with a 0.3 cm papillary carcinoma focus. No mutations were identified in the primary lesion, whereas the implanted lesion exhibited MEN1, GLIS3, EZH1, and KMT2C mutations. Case 3: a 42-year-old female. The primary lesion included a left thyroid adenoma with cystic degeneration and right nodular goiter. A nodular goiter-like implanted lesion was detected in the right breast 5 years postoperatively. The primary lesion harbored TERT, GLIS3, and SPOP mutations, while the implanted lesion showed TERT, GLIS3, EIF1AX, and KMT2C mutations. Conclusions Endoscopic thyroid surgery is widely applied in clinical practice, however, implantation dissemination of thyroid lesions along surgical pathways may occur, encompassing both benign and malignant entities. Implanted lesions exhibit pathological similarities to their primary counterparts, but demonstrate mutational enrichment.

Nanotechnologies seek to overcome inherent deficiencies of conventional diagnosis and treatment, which attracted sustained attention and a limited number of nanomedicines approved by the FDA. However, the critical gaps in clinical translation remain, and nanomedicines that were initially heralded as magic bullets have yet to reach their realistic potential. The major obstacles of fabrication technologies may be overlooked in the nanoparticles' journey. Suboptimal manufacturing strategies partly hampered the inefficient transformation. In this review, we discuss the nanoparticle manufacturing strategies of "Top-Down" and "Bottom-Up" on precise nanoscale fabrication, including artificial intelligence introduced to guided nanomedicine fabrication for accelerating the transformation. Re-engineering existing nanomedicine fabrication, individual manufacturing, and modular technology might highlight the dilemmas of nanomedicines to meet their initial expectations.

Adolescent depression is increasingly recognized as a serious mental health disorder with distinct clinical and molecular features. Using single-nucleus RNA sequencing, we identified cell-specific transcriptomic changes in the nucleus accumbens (NAc), particularly in astrocytes, of adolescent macaques exhibiting depressive-like behaviors. The level of diacylglycerol kinase beta was significantly reduced in neurons and glial cells of depressed macaques, while FKBP5 levels increased in glial cells. Disruption of GABAergic synapses and disruption of D-glutamine and D-glutamate metabolism were linked to depressive phenotypes in medium spiny neurons (MSNs) and subtypes of astrocytes. Communication pathways between astrocytes and D1/D2-MSNs were also disrupted, involving factors like bone morphogenetic protein-6 and Erb-B2 receptor tyrosine kinase-4. Bulk transcriptomic and proteomic analyses corroborated these findings, and FKBP5 upregulation was confirmed by qRT-PCR, western blotting, and immunofluorescence in the NAc of rats and macaques with chronic unpredictable mild stress. Our results highlight the specific roles of different cell types in adolescent depression in the NAc, offering potential targets for new antidepressant therapies.
Animals ; Nucleus Accumbens/metabolism* ; Male ; Transcriptome ; Depression/genetics* ; Astrocytes/metabolism* ; Neurons/metabolism* ; Rats

Objective Through in vitro experiments,biomechanical data of the transtibial pullout suture(TPS),tendon reconstruction(TR),and tendon reconstruction with suture augmentation(TRS)were collected,so as to evaluate the biomechanical effectiveness of tendon reconstruction for repairing medial meniscus posterior root tear(MMPRT).Methods Eighteen porcine knee joint models were divided into TPS,TR,and TRS groups.Sutures were used to fix the meniscal root in TPS group.Tendons were passed through an incision at the meniscal root in TR group.Tendons were passed through an incision at the meniscal root and secured at tendon-meniscus contact area with additional sutures in TRS group.The sutures and tendons were pulled out through tibial tunnels and fixed at the anteromedial tibia.All groups underwent failure load tests,and ultimate failure load,displacement at failure load,load at clinical failure,stiffness,and failure modes of the samples were recorded.Results The maximum failure load in TPS group was significantly higher than that in TR group(P＜0.05),but there was no significant difference between TPS group and TRS group(P＞0.05).The maximum failure load in TRS group was significantly higher than that in TR group(P＜0.05).The displacement under failure load in TR group and TRS group was significantly lower than that in TPS group(P＜0.05),but there was no significant difference between TR group and TRS group(P＞0.05).There were no significant differences in the load under clinical failure among the 3 groups(P＞0.05).The stiffness of TRS group was significantly greater than that of TPS group(P＜0.05),but no significant difference was observed between TR group and TPS group,as well as between TR group and TRS group(P＞0.05).All failures were caused by suture or tendon cutting through the meniscus.Conclusions The tendon reconstruction techniques is superior to the TPS in terms of failure displacement and stiffness,while the TRS further enhances the stability of the repair.