Triple-negative breast cancer is therapeutically challenging due to the low expression of tumor markers and 'cold' tumor immunosuppressive microenvironment. Here, we present a dual-targeting peptide-drug conjugate (PDC) for tumor inhibition. Our PDC efficiently and selectively delivers cytotoxic Monomethyl Auristatin E (MMAE) into tumor cells via C-X-C chemokine receptor type 4 (CXCR4) and folate receptor 1 (FOLR1) for synergistic inhibition of growth and metastasis. Our results show that the dual-targeting PDC has potent antitumor activity in cultured human cells and several murine transplanted tumor models without apparent toxicity. The combination of dual-targeting PDC and radiotherapy modulates the tumor immunosuppressive microenvironment by increasing CD8⁺ T cell infiltration and attenuating the proportion of myeloid-derived suppressor and regulatory T cells. Therefore, our dual-targeting PDC represents a promising new strategy for cancer therapy that rebalances the immune system and promotes tumor regression.

Pristimerin, which is one of the compounds present in Celastraceae and Hippocrateaceae, has antitumor effects. However, its mechanism of action in esophageal squamous cell carcinoma (ESCC) remains unclear. This study aims to investigate the efficacy and mechanism of pristimerin on ESCC in vitro and in vivo. The inhibitory effect of pristimerin on cell growth was assessed using trypan blue exclusion and colony formation assays. Cell apoptosis was evaluated by flow cytometry. Gene and protein expressions were analyzed through quantitative reverse transcription-polymerase chain reaction (qRT-PCR), Western blotting, and immunohistochemistry. RNA sequencing (RNA-Seq) was employed to identify significantly differentially expressed genes (DEGs). Cell transfection and RNA interference assays were utilized to examine the role of key proteins in pristimerin?s effect. Xenograft models were established to evaluate the antitumor efficiency of pristimerin in vivo. Pristimerin inhibited cell growth and induced apoptosis in ESCC cells. Upregulation of Noxa was crucial for pristimerin-induced apoptosis. Pristimerin activated the Forkhead box O3a (FoxO3a) signaling pathway and triggered FoxO3a recruitment to the Noxa promoter, leading to Noxa transcription. Blocking FoxO3a reversed pristimerin-induced Noxa upregulation and cell apoptosis. Pristimerin treatment suppressed xenograft tumors in nude mice, but these effects were largely negated in Noxa-KO tumors. Furthermore, the chemosensitization effects of pristimerin in vitro and in vivo were mediated by Noxa. This study demonstrates that pristimerin exerts an antitumor effect on ESCC by inducing AKT/FoxO3a-mediated Noxa upregulation. These findings suggest that pristimerin may serve as a potent anticancer agent for ESCC treatment.
Forkhead Box Protein O3/genetics* ; Humans ; Apoptosis/drug effects* ; Esophageal Squamous Cell Carcinoma/physiopathology* ; Esophageal Neoplasms/physiopathology* ; Pentacyclic Triterpenes ; Animals ; Cell Line, Tumor ; Proto-Oncogene Proteins c-bcl-2/genetics* ; Mice ; Signal Transduction/drug effects* ; Mice, Nude ; Cell Proliferation/drug effects* ; Triterpenes/pharmacology* ; Xenograft Model Antitumor Assays ; Mice, Inbred BALB C ; Male ; Gene Expression Regulation, Neoplastic/drug effects*

ObjectiveTo understand the prevalence of tobacco use among residents aged 15 years old and above in Jiading District of Shanghai, and to provide a scientific basis for formulating effective regional tobacco control policies. MethodsThe Probability Proportional to Size (PPS) sampling method was employed to select one neighborhood committee (village) from each of Jiading District’s 11 subdistricts as survey monitoring sites. From the household registry of each selected neighborhood committee (village), 50 residential households were randomly sampled, resulting in a total of 550 households surveyed. Within each selected household, one permanent resident aged 15 years old or above was randomly chosen to complete the questionnaire. The content covered general information, exposure to secondhand smoke, awareness of tobacco related health hazards, etc. Statistical analyses were performed using SPSS 27.0 software. ResultsA total of 550 questionnaires were distributed, with 549 valid responses collected, and the effective response rate was 99.82%. The survey findings revealed that in 2023, the current smoking rate among individuals aged 15 years old and above in Jiading District of Shanghai was 18.76%, with males accounting for 38.93% and females accounting for 2.62%. Male gender was identified as a relative factor for smoking (OR=34.108, 95%CI: 14.440‒80.722), whereas higher education attainment emerged as a protective factor against smoking (OR=0.388, 95%CI: 0.184‒0.820). Among non-smokers aged 15 years old and above in Jiading District, the secondhand smoke exposure rate was 46.86%, with statistically significant differences observed across different age groups and occupations (P<0.001). Restaurants exhibited the highest secondhand smoke exposure rate of 42.14%, followed by households bearing (36.79%). The overall awareness rate among individuals aged 15 years old and above in Jiading District regarding four smoking-related diseases, namely stroke, heart disease, lung cancer, and impotence, was 48.45%, while the awareness rate for three secondhand smoke-induced diseases, namely adult heart disease, pediatric pulmonary disease, and adult lung cancer, was 64.29%. ConclusionThere is still room for reduction in the prevalence of tobacco use among individuals aged 15 yeas old and above in Jiading District. The exposure to secondhand smoke is severe, and residents have low awareness of the harm of tobacco. Tobacco control law enforcement should be strengthened, smoke-free-home health education should be included in tobacco control efforts, and targeted health education should be carried out.

This article aimed to summarise the clinical experience of Professor XIONG Jibai in treating henoch-schonlein purpura （HSP） from the perspective of "simultaneous treatment of wind and blood". HSP was devided into acute phase and transitional phase in clinic. It was considered that the wind pathogen exists throughout the disease course， and the treatment is guided by the "four methods of treating blood" in TANG Rongchuan's Treatise on Blood Syndromes - Blood Vomiting （《血证论·吐血》）， which are stanching bleeding， expelling stasis， tranquilising blood， and tonifying blood. In the acute phase， wind-heat damaging collateral symdrome and blood-heat frenetic flow syndrome are common， which could be treated by the method of cooling blood to dispel wind， and eliminating stasis to stop bleeding， with self-prescribed modified Ziping Xiaofeng Powder （紫萍消风散）； in the transitional phase， syndrome of effulgent fire due to yin deficiency and syndrome of qi deficiency failing to control are common， which could be treated by the method of tranquilising blood and tonifying deficiency， with modified Zhibai Dihuang Decoction （知柏地黄汤） and Guipi Decoction （归脾汤）. At the same time， it is believed that wind-related medicinal has the function of eliminating stasis， stanching bleeding， and cooling blood， and the wind-related medicinal should be used throughout the treatment.

Recent clinical studies have shown that mutation of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) gene in cancer cells may be associated with immunosuppressive tumor microenvironment (TME) and poor response to immune checkpoint blockade (ICB) therapy. Therefore, efficiently restoring PTEN gene expression in cancer cells is critical to improving the responding rate to ICB therapy. Here, we screened an adeno-associated virus (AAV) capsid for efficient PTEN gene delivery into B16F10 tumor cells. We demonstrated that intratumorally injected AAV6-PTEN successfully restored the tumor cell PTEN gene expression and effectively inhibited tumor progression by inducing tumor cell immunogenic cell death (ICD) and increasing immune cell infiltration. Moreover, we developed an anti-PD-1 loaded phospholipid-based phase separation gel (PPSG), which formed an in situ depot and sustainably release anti-PD-1 drugs within 42 days in vivo. In order to effectively inhibit the recurrence of melanoma, we further applied a triple therapy based on AAV6-PTEN, PPSG^@anti-PD-1 and CpG, and showed that this triple therapy strategy enhanced the synergistic antitumor immune effect and also induced robust immune memory, which completely rejected tumor recurrence. We anticipate that this triple therapy could be used as a new tumor combination therapy with stronger immune activation capacity and tumor inhibition efficacy.

In order to promote the development of hair transplantation, particularly the establishment of standards, the Hair Transplantation Expert Group of Plastic and Aesthetic National Medical Quality Control Center invited experts in the field of hair transplantation across China and formed a draft of the Expert Consensus on Standard Terminology for Hair Transplantation based on the collation of relevant literature and monographs. By combining Delphi methodology and consensus meetings, the expert group conducted several rounds of consultations on issues such as follicular unit anatomy, harvesting, dissection, and implantation, ultimately presenting 54 terminologies. This consensus considers the original Chinese and English meanings as well as the professional characteristics of terms used in hair transplantation, highlights the unique features and advantages of hair transplantation, and preserves its essence while promoting innovation, with the hope of providing valuable reference for clinical researchers engaged in hair transplantation both domestically and internationally, and better facilitating the standardization and advancement of the field.

There are many kinds of zirconia repair materials that have been introduced at home and abroad.Mechanical and aesthetic properties are the important factors for selecting zirconia materials.The process of diagnosis and treatment by dentists and the production by the workers in laboratory affect the final repair effects.To achieve accurate and efficient simulation of dental repair and treatment,effective cooperation between dentists and technicians is required.In this paper,the factors affecting mechanical and aes-thetic properties in the process of material selection,tooth wearing,restoration design and fabrication,concerning zirconia veneer,sin-gle-crown,fixed bridge and edentulous jaw implant fixed repair were discussed and summarized.The common failure reasons were ana-lyzed in order to improve the communication efficiency between dentists and technicians in the process of zirconia repair system and to a-chieve better repair effects.

Objective:In chronic hepatitis B (CHB) patients with previous 96-week treatment with tenofovir amibufenamide (TMF) or tenofovir disoproxil fumarate (TDF), we investigated the efficacy of sequential TMF treatment from 96 to 144 weeks.Methods:Enrolled subjects who were previously assigned (2:1) to receive either 25 mg TMF or 300 mg TDF with matching placebo for 96 weeks received extended or switched TMF treatment for 48 weeks. Efficacy was evaluated based on virological, serological, biological parameters, and fibrosis staging. Statistical analysis was performed using the McNemar test, t-test, or Log-Rank test according to the data. Results:593 subjects from the initial TMF group and 287 subjects from the TDF group were included at week 144, with the proportions of HBV DNA<20 IU/ml at week 144 being 86.2% and 83.3%, respectively, and 78.1% and 73.8% in patients with baseline HBV DNA levels ≥8 log10 IU/ml. Resistance to tenofovir was not detected in both groups. For HBeAg loss and seroconversion rates, both groups showed a further increase from week 96 to 144 and the 3-year cumulative rates of HBeAg loss were about 35% in each group. However, HBsAg levels were less affected during 96 to 144 weeks. For patients switched from TDF to TMF, a substantial further increase in the alanine aminotransferase (ALT) normalization rate was observed (11.4%), along with improved FIB-4 scores.Conclusion:After 144 weeks of TMF treatment, CHB patients achieved high rates of virological, serological, and biochemical responses, as well as improved liver fibrosis outcomes. Also, switching to TMF resulted in significant benefits in ALT normalization rates (NCT03903796).

Objective:In chronic hepatitis B (CHB) patients with previous 96-week treatment with tenofovir amibufenamide (TMF) or tenofovir disoproxil fumarate (TDF), we investigated the safety profile of sequential TMF treatment from 96 to 144 weeks.Methods:Enrolled subjects that previously assigned (2:1) to receive either 25 mg TMF or 300 mg TDF with matching placebo for 96 weeks received extending or switching TMF treatment for 48 weeks. Safety profiles of kidney, bone, metabolism, body weight, and others were evaluated.Results:666 subjects from the initial TMF group and 336 subjects from TDF group with at least one dose of assigned treatment were included at week 144. The overall safety profile was favorable in each group and generally similar between extended or switched TMF treatments from week 96 to 144. In subjects switching from TDF to TMF, the non-indexed estimated glomerular filtration rate (by non-indexed CKD-EPI formula) and creatinine clearance (by Cockcroft-Gault formula) were both increased, which were (2.31±8.33) ml/min and (4.24±13.94) ml/min, respectively. These changes were also higher than those in subjects with extending TMF treatment [(0.91±8.06) ml/min and (1.30±13.94) ml/min]. Meanwhile, switching to TMF also led to an increase of the bone mineral density (BMD) by 0.75% in hip and 1.41% in spine. On the other side, a slight change in TC/HDL ratio by 0.16 (IQR: 0.00, 0.43) and an increase in body mass index (BMI) by (0.54±0.98) kg/m 2 were oberved with patients switched to TMF, which were significantly higher than that in TMF group. Conclusion:CHB patients receiving 144 weeks of TMF treatment showed favorable safety profile. After switching to TMF, the bone and renal safety was significantly improved in TDF group, though experienceing change in metabolic parameters and weight gain (NCT03903796).

Objective To investigate the effects of insulin therapy on the mechanical behavior of solids,characteristics of fluid flow,and bone marrow stromal cells(BMSCs)differentiation in the distal femoral cancellous bone of type 2 diabetic rats under normal activity and vigorous exercise conditions.Methods The finite element models of cancellous bones and fluids in the distal femurs of rats in the control,diabetes,treatment,and placebo groups in 4-week and 8-week insulin treatment experiments under normal activity and vigorous exercise conditions were established based on micro-CT scanning images.The mechanical and cell differentiation parameters of the models in each group were analyzed using the fluid-solid interaction numerical simulation method.Correlations between mechanical,cell differentiation,and microstructural morphology parameters were also analyzed.Results Insulin therapy under normal activity and vigorous exercise conditions improved the solid and fluid mechanical parameters and BMSC differentiation parameters in type 2 diabetic rats.In the 4-week experiment,insulin treatment under normal activity and vigorous exercise conditions increased the differentiation areas of bone in type 2 diabetic rats from 64.024%to 69.372%and from 73.225%to 75.336%,respectively;in the 8-week experiment,insulin treatment under normal activity and vigorous exercise conditions increased the differentiation areas of bone in type 2 diabetic rats from 67.239%to 72.910%and from 76.147%to 78.291%,respectively.Morphological parameters BV/TV,Tb.N,Tb.Th,Tb.Sp,and structure model index were significantly correlated with the differentiation areas of the bone and cartilage(P<0.05).Conclusions Under vigorous exercise conditions,BMSCs on the surface of cancellous bone in the 8-week insulin treatment group were more likely to differentiate into bone tissue.This study is of great significance for further understanding the effects of insulin on the bone under normal activity and vigorous exercise conditions,and provides theoretical guidance for the selection of the insulin therapy cycle and exercise mode in the clinical treatment of type 2 diabetes.