Oral squamous cell carcinoma (OSCC) is a common head and neck malignancy. Approximately 50% to 60% of patients with OSCC are diagnosed at a locally advanced stage (clinical staging III-IVa). Even with comprehensive and sequential treatment primarily based on surgery, the 5-year overall survival rate remains below 50%, and patients often suffer from postoperative functional impairments such as difficulties with speaking and swallowing. Programmed death receptor-1 (PD-1) inhibitors are increasingly used in the neoadjuvant treatment of locally advanced OSCC and have shown encouraging efficacy. However, clinical practice still faces key challenges, including the definition of indications, optimization of combination regimens, and standards for efficacy evaluation. Based on the latest research advances worldwide and the clinical experience of the expert group, this expert consensus systematically evaluates the application of PD-1 inhibitors in the neoadjuvant treatment of locally advanced OSCC, covering combination strategies, treatment cycles and surgical timing, efficacy assessment, use of biomarkers, management of special populations and immune related adverse events, principles for immunotherapy rechallenge, and function preservation strategies. After multiple rounds of panel discussion and through anonymous voting using the Delphi method, the following consensus statements have been formulated: 1) Neoadjuvant therapy with PD-1 inhibitors can be used preoperatively in patients with locally advanced OSCC. The preferred regimen is a PD-1 inhibitor combined with platinum based chemotherapy, administered for 2-3 cycles. 2) During the efficacy evaluation of neoadjuvant therapy, radiographic assessment should follow the dual criteria of Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and immune RECIST (iRECIST). After surgery, systematic pathological evaluation of both the primary lesion and regional lymph nodes is required. For combination chemotherapy regimens, PD-L1 expression and combined positive score need not be used as mandatory inclusion or exclusion criteria. 3) For special populations such as the elderly (≥ 70 years), individuals with stable HIV viral load, and carriers of chronic HBV/HCV, PD-1 inhibitors may be used cautiously under the guidance of a multidisciplinary team (MDT), with close monitoring for adverse events. 4) For patients with a poor response to neoadjuvant therapy, continuation of the original treatment regimen is not recommended; the subsequent treatment plan should be adjusted promptly after MDT assessment. Organ transplant recipients and patients with active autoimmune diseases are not recommended to receive neoadjuvant PD-1 inhibitor therapy due to the high risk of immune related activation. Rechallenge is generally not advised for patients who have experienced high risk immune related adverse events such as immune mediated myocarditis, neurotoxicity, or pneumonitis. 5) For patients with a good pathological response, individualized de escalation surgery and function preservation strategies can be explored. This consensus aims to promote the standardized, safe, and precise application of neoadjuvant PD-1 inhibitor strategies in the management of locally advanced OSCC patients.

In this paper， by consulting the ancient and modern literature， the name， origin， quality evaluation， harvesting and processing， and others of the original animal and medicinal materials of Moschus were systematically sorted out and verified， in order to provide the basis for the development and utilization of the famous classical formulas containing Moschus. According to the textual research， musk deer was first recorded in Shanhaijing. Shennong Bencaojing was recorded as Moschus and all generations were used as the correct name， but there were also aliases such as Shefu， Xiangzhang and Xiangqizi. In ancient times， Moschus berezovskii， M. sifanicus and M. moschiferus were the main sources of Moschus， and the quality of Moschus produced in northwest China was better than that produced in the Yangtze River basin. In modern times， Moschus of M. moschiferus produced in northeast China， M. sifanicus produced in Gansu， Sichuan and other places， and M. berezovskii produced in Ningxia， Shaanxi and other places are regarded as genuine. In ancient times， gunshots， lassoes， arrow shots and other methods were generally used to hunt live musk deer， and the sachets were immediately cut off. Those with high quality were called Xiangshanhuo， and dried in the shade after harvesting， which was known as Maoke Shexiang. Cut open the sachet， remove the shell and dry preservation， commonly known as Moschus kernel. In modern times， the method of taking Moschus from the living body of cultured musk deer is adopted， that is， Moschus kernel is directly taken from its sachet， dried in the shade or dried in a closed dryer. This method realizes the sustainable utilization of Chinese herbal medicine resources， but attention should be paid to the frequency and quality of Moschus. The harvesting time is mostly after the autumnal equinox every year， and before the next summer， it is better to gather sachet in winter. In recent times， it is believed that the shell Moschus is dry， full， thin， elastic， loose inside， many particles， strong and persistent aroma for the best， while the Moschus kernel is particle purple-black， powder yellow-brown， soft and oily texture， strong and persistent aroma for the best. The ancient processing method of Moschus was extracting kernels from the shell. After removing impurities， it is ground and used as medicine. Because its composition is not suitable for heating， the processing method is most common in preparations such as grinding into powder and putting into pills or powders， which has the effect of opening up the orifices and refreshing the mind， and it has continued to this day. Based on the research conclusions， it is suggested that the development of famous classical formulas containing Moschus， M. sifanicus， M. moschiferus and M. berezovskii should be used as the origins. According to the processing requirements specified in the original formula， it should be processed and used as medicine， while those without processing requirements should be used as raw products.

Mechanical pain is one of the most common causes of clinical pain, but there remains a lack of effective treatment for debilitating mechanical and chronic forms of neuropathic pain. Recently, neurotoxin GsMTx4, a selective mechanosensitive (MS) channel inhibitor, has been found to be effective, while the underlying mechanism remains elusive. Here, with multiple rodent pain models, we demonstrated that a GsMTx4-based 17-residue peptide, which we call P10581, was able to reduce mechanical hyperalgesia and neuropathic pain. The analgesic effects of P10581 can be as strong as morphine but is not toxic in animal models. The anti-hyperalgesic effect of the peptide was resistant to naloxone (an μ-opioid receptor antagonist) and showed no side effects of morphine, including tolerance, motor impairment, and conditioned place preference. Pharmacological inhibition of TRPV4 by P10581 in a heterogeneous expression system, combined with the use of Trpv4 knockout mice indicates that TRPV4 channels may act as the potential target for the analgesic effect of P10581. Our study identified a potential drug for curing mechanical pain and exposed its mechanism.

Periodontal bone defects, primarily caused by periodontitis, are highly prevalent in clinical settings and manifest as bone fenestration, dehiscence, or attachment loss, presenting a significant challenge to oral health. In regenerative medicine, harnessing developmental principles for tissue repair offers promising therapeutic potential. Of particular interest is the condensation of progenitor cells, an essential event in organogenesis that has inspired clinically effective cell aggregation approaches in dental regeneration. However, the precise cellular coordination mechanisms during condensation and regeneration remain elusive. Here, taking the tooth as a model organ, we employed single-cell RNA sequencing to dissect the cellular composition and heterogeneity of human dental follicle and dental papilla, revealing a distinct Platelet-derived growth factor receptor alpha (PDGFRA) mesenchymal stem/stromal cell (MSC) population with remarkable odontogenic potential. Interestingly, a reciprocal paracrine interaction between PDGFRA⁺ dental follicle stem cells (DFSCs) and CD31⁺ Endomucin⁺ endothelial cells (ECs) was mediated by Vascular endothelial growth factor A (VEGFA) and Platelet-derived growth factor subunit BB (PDGFBB). This crosstalk not only maintains the functionality of PDGFRA⁺ DFSCs but also drives specialized angiogenesis. In vivo periodontal bone regeneration experiments further reveal that communication between PDGFRA⁺ DFSC aggregates and recipient ECs is essential for effective angiogenic-osteogenic coupling and rapid tissue repair. Collectively, our results unravel the importance of MSC-EC crosstalk mediated by the VEGFA and PDGFBB-PDGFRA reciprocal signaling in orchestrating angiogenesis and osteogenesis. These findings not only establish a framework for deciphering and promoting periodontal bone regeneration in potential clinical applications but also offer insights for future therapeutic strategies in dental or broader regenerative medicine.
Receptor, Platelet-Derived Growth Factor alpha/metabolism* ; Humans ; Neovascularization, Physiologic/physiology* ; Dental Sac/cytology* ; Single-Cell Analysis ; Transcriptome ; Mesenchymal Stem Cells/metabolism* ; Bone Regeneration ; Animals ; Dental Papilla/cytology* ; Periodontium/physiology* ; Stem Cells/metabolism* ; Regeneration ; Angiogenesis

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*

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

Objective:In this study,we aimed to explore the clinical features and factors affecting prognosis by collecting data from patients with ocular adnexal mucosa-associated lymphoid tissue lymphoma(OAML).Methods:Clinical data of 54 patients diagnosed with ocular ad-nexal lymphoma(OAL)at The Second Affiliated Hospital of Soochow University between September 2010 and October 2024 were retro-spectively analyzed.Of these,39(72.2%)had mucosa-asso-ciated lymphoid tissue(MALT)lymphoma,which constituted the focus of this study.The Kaplan-Meier method was used to estimate the progression-free survival(PFS)and overall survival(OS)rates.The Log-rank test was applied to compare survival differences across pathological types and treatment groups.Correlation analysis and univariate Cox regres-sion were conducted to assess the impact of various factors on PFS.Variables with P<0.050 were subsequently included in multivariate Cox regression analysis to identify independent risk factors.Results:Among the 39 patients,the median age at onset was 64 years.Thirty-two and seven patients had unilateral orbital involvement and bilateral orbital involvement,respectively.All the patients underwent surgery.After surgery,the 5-year PFS and the 5-year OS of patients with MALT lymphoma were 54.21%and 100%,respectively.Univariate Cox re-gression analysis indicated that lesion location(P=0.011,hazard ratio[HR]=0.07),remission status after the first treatment(P<0.001,HR=0.082),and EBV infection(P=0.011,HR=0.207)significantly affected PFS.Multivariate regression analysis showed that remission status after the first treatment(P=0.034,HR=0.193)was an independent risk factor for prognosis.Patients who had not achieved complete re-sponse(CR)had a worse prognosis.Conclusions:Remission status after the first treatment is an important prognostic indicator in patients with MALT lymphoma.Close follow-up should be performed for patients who have not achieved complete remission after the first treat-ment.

Objective:To analyze whether there are differences in reproductive outcomes between preimplantation genetic testing for aneuploidies (PGT-A) and conventional in vitro fertilization/intracytoplasmic sperm injection and embryo transfer (IVF/ICSI-ET) in patients with recurrent spontaneous abortion (RSA). Methods:A retrospective cohort study was conducted at the Reproductive Center of Sun Yat-sen Memorial Hospital, Sun Yat-sen University, including RSA patients who underwent assisted reproductive technology (ART) between January 2018 and June 2023. Patients were categorized into two groups based on the type of ART, the PGT-A group (78 patients, 100 embryo transfer cycles) and the IVF/ICSI group (95 patients, 105 embryo transfer cycles). Multivariate logistic regression analysis was performed to compare the impact of these two techniques on reproductive outcomes. Further analysis was conducted to evaluate the effects of maternal age, number of miscarriages, and previous chromosomal abnormalities in miscarried embryos on pregnancy outcomes. The primary outcome measure was the live birth rate, while secondary outcomes included the pregnancy rate and the miscarriage rate.Results:The live birth rate in the PGT-A group [50.0% (50/100)] was higher than that in the IVF/ICSI group [37.1% (39/105)], while the miscarriage rate [20.6% (13/63)] was lower than that in the IVF/ICSI group [39.1% (25/64)], with both differences being statistically significant ( P=0.043, P=0.023). Among RSA patients aged 37-45 years with ≥3 miscarriages, the miscarriage rate in the PGT-A group (0%) was significantly lower than that in the IVF/ICSI group [46.2%(6/13), P=0.017], whereas the differences in live birth rate and pregnancy rate between the two groups were not statistically significant (all P>0.05). For RSA patients with previous chromosomal abnormalities in miscarried embryos, the miscarriage rate in the PGT-A group [21.1% (12/57)] was significantly lower than that in the IVF/ICSI group [71.4% (5/7), P=0.012]. Additionally, the pregnancy rate [66.3% (57/86)] and the live birth rate [52.3% (45/86)] in the PGT-A group were significantly higher than those in the IVF/ICSI group [33.3% (7/21), P=0.006; 9.5% (2/21), P<0.001]. Among 37-45 years patients, the miscarriage rate in the PGT-A group [5.9% (1/17)] was significantly lower than that in the IVF/ICSI group [38.7% (12/31), P=0.035], and the live birth rate [57.1% (16/28)] was significantly higher than that in the IVF/ICSI group [31.7% (19/60), P=0.023]. These differences were statistically significant. Conclusion:Compared with conventional IVF/ICSI-assisted reproduction, the use of PGT-A in RSA patients younger than 37 years, with or without a history of chromosomally normal miscarried embryos, did not significantly improve reproductive outcomes, regardless of whether they had experienced more than three miscarriages. However, for RSA patients with chromosomal abnormalities in miscarried embryos, PGT-A significantly reduced the miscarriage rate across the age range of 26-45 years. In RSA patients aged 37-45 years, PGT-A significantly improved reproductive outcomes. However, for patients with two miscarriages and a history of chromosomally normal miscarried embryos, the therapeutic benefit of PGT-A was limited.

Objective:To analyze whether there are differences in reproductive outcomes between preimplantation genetic testing for aneuploidies (PGT-A) and conventional in vitro fertilization/intracytoplasmic sperm injection and embryo transfer (IVF/ICSI-ET) in patients with recurrent spontaneous abortion (RSA). Methods:A retrospective cohort study was conducted at the Reproductive Center of Sun Yat-sen Memorial Hospital, Sun Yat-sen University, including RSA patients who underwent assisted reproductive technology (ART) between January 2018 and June 2023. Patients were categorized into two groups based on the type of ART, the PGT-A group (78 patients, 100 embryo transfer cycles) and the IVF/ICSI group (95 patients, 105 embryo transfer cycles). Multivariate logistic regression analysis was performed to compare the impact of these two techniques on reproductive outcomes. Further analysis was conducted to evaluate the effects of maternal age, number of miscarriages, and previous chromosomal abnormalities in miscarried embryos on pregnancy outcomes. The primary outcome measure was the live birth rate, while secondary outcomes included the pregnancy rate and the miscarriage rate.Results:The live birth rate in the PGT-A group [50.0% (50/100)] was higher than that in the IVF/ICSI group [37.1% (39/105)], while the miscarriage rate [20.6% (13/63)] was lower than that in the IVF/ICSI group [39.1% (25/64)], with both differences being statistically significant ( P=0.043, P=0.023). Among RSA patients aged 37-45 years with ≥3 miscarriages, the miscarriage rate in the PGT-A group (0%) was significantly lower than that in the IVF/ICSI group [46.2%(6/13), P=0.017], whereas the differences in live birth rate and pregnancy rate between the two groups were not statistically significant (all P>0.05). For RSA patients with previous chromosomal abnormalities in miscarried embryos, the miscarriage rate in the PGT-A group [21.1% (12/57)] was significantly lower than that in the IVF/ICSI group [71.4% (5/7), P=0.012]. Additionally, the pregnancy rate [66.3% (57/86)] and the live birth rate [52.3% (45/86)] in the PGT-A group were significantly higher than those in the IVF/ICSI group [33.3% (7/21), P=0.006; 9.5% (2/21), P<0.001]. Among 37-45 years patients, the miscarriage rate in the PGT-A group [5.9% (1/17)] was significantly lower than that in the IVF/ICSI group [38.7% (12/31), P=0.035], and the live birth rate [57.1% (16/28)] was significantly higher than that in the IVF/ICSI group [31.7% (19/60), P=0.023]. These differences were statistically significant. Conclusion:Compared with conventional IVF/ICSI-assisted reproduction, the use of PGT-A in RSA patients younger than 37 years, with or without a history of chromosomally normal miscarried embryos, did not significantly improve reproductive outcomes, regardless of whether they had experienced more than three miscarriages. However, for RSA patients with chromosomal abnormalities in miscarried embryos, PGT-A significantly reduced the miscarriage rate across the age range of 26-45 years. In RSA patients aged 37-45 years, PGT-A significantly improved reproductive outcomes. However, for patients with two miscarriages and a history of chromosomally normal miscarried embryos, the therapeutic benefit of PGT-A was limited.

Objective:In this study,we aimed to explore the clinical features and factors affecting prognosis by collecting data from patients with ocular adnexal mucosa-associated lymphoid tissue lymphoma(OAML).Methods:Clinical data of 54 patients diagnosed with ocular ad-nexal lymphoma(OAL)at The Second Affiliated Hospital of Soochow University between September 2010 and October 2024 were retro-spectively analyzed.Of these,39(72.2%)had mucosa-asso-ciated lymphoid tissue(MALT)lymphoma,which constituted the focus of this study.The Kaplan-Meier method was used to estimate the progression-free survival(PFS)and overall survival(OS)rates.The Log-rank test was applied to compare survival differences across pathological types and treatment groups.Correlation analysis and univariate Cox regres-sion were conducted to assess the impact of various factors on PFS.Variables with P<0.050 were subsequently included in multivariate Cox regression analysis to identify independent risk factors.Results:Among the 39 patients,the median age at onset was 64 years.Thirty-two and seven patients had unilateral orbital involvement and bilateral orbital involvement,respectively.All the patients underwent surgery.After surgery,the 5-year PFS and the 5-year OS of patients with MALT lymphoma were 54.21%and 100%,respectively.Univariate Cox re-gression analysis indicated that lesion location(P=0.011,hazard ratio[HR]=0.07),remission status after the first treatment(P<0.001,HR=0.082),and EBV infection(P=0.011,HR=0.207)significantly affected PFS.Multivariate regression analysis showed that remission status after the first treatment(P=0.034,HR=0.193)was an independent risk factor for prognosis.Patients who had not achieved complete re-sponse(CR)had a worse prognosis.Conclusions:Remission status after the first treatment is an important prognostic indicator in patients with MALT lymphoma.Close follow-up should be performed for patients who have not achieved complete remission after the first treat-ment.