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.

The theoretical basis of premature aging originates from The Yellow Emperor's Inner Classic. The etiology of premature aging is complex， and the disease mechanism is based on deficiency. The treatment for premature aging is based on tonicity. The essence-Qi-spirit theory of Qiluo doctrine summarizes that "essence is the origin of life， Qi is the driving force of life， and spirit is the embodiment of life"， which is the law of life. The theory puts forward the core disease mechanism of aging， which states that "deficiency of kidney essence is the root of aging， deficiency of primordial Qi is the key to aging， impairment of soma and spirit is the manifestation of aging". The theory also proposes the treatment of "tonifying kidney and supplementing essence， harmonizing Yin and Yang， warming and supporting primordial Qi， and nourishing soma and spirit" and the representative anti-aging drugs. The article unfolds from the perspective of the concepts of natural life span， premature senility before fifty， decline， and aging and also explains the origins and connotations of premature aging. The article explains the disease mechanism of premature aging under the guidance of the essence-Qi-spirit theory of Qiluo doctrine， which is "early deprivation of kidney essence， deficiency of primordial Qi， accumulation of deficiencies into impairment， and decline and impairment of soma and spirit"， summarizes the progress of modern medical research on the treatment of premature aging and representative drugs， and finds that Bazi Bushen capsules have a precise therapeutic effect on the overall premature aging， systematic functional decline， and related diseases. The study provides theoretical basis and new ideas to solve the problems of premature aging and geriatric diseases.

OBJECTIVE To explore the effect and potential mechanism of the compatibility of Astragali Radix-Puerariae Lobatae Radix on ferroptosis of liver cells in type 2 diabetes mellitus （T2DM） insulin resistance （IR） rats. METHODS Sixty male SD rats were randomly divided into control group （12 rats） and modeling group （48 rats）. The modeling group was fed with a high- fat diet for 4 consecutive weeks and then given a one-time tail vein injection of 1% streptozotocin to establish T2DM IR model. The model rats were randomly divided into model group， the compatibility of Astragali Radix-Puerariae Lobatae Radix group [QG group， 4.05 g/（kg·d）， intragastric administration]， ferroptosis inhibitor ferrostatin-1 group [Fer-1 group， 5 mg/kg by intraperitoneal injection， once every other day]， the compatibility of Astragali Radix-Puerariae Lobatae Radix+ferroptosis inducer erastin group [QG+erastin group， 4.05 g/（kg·d） by intragastric administration+erastin 10 mg/（kg·d）， intraperitoneal injection]. After 4 weeks of intervention， serum fasting blood glucose （FBG） and fasting insulin （FINS） were measured in each group of rats， and homeostasis model assessment of insulin resistance （HOMA-IR） and the natural logarithm of insulin action index（IAI） were calculated； the serum levels of total cholesterol （TC）， triglyceride （TG）， low-density lipoprotein cholesterol （LDL-C）， high-density lipoprotein cholesterol （HDL-C）， aspartate transaminase （AST） and alanine transaminase （ALT）， Fe2+ and Fe content， glutathione （GSH）， malondialdehyde （MDA） and superoxide dismutase （SOD） levels， NADP+/NADPH ratio and reactive oxygen species （ROS） were determined. The pathological morphology of its liver tissue was observed； the protein expressions of glutathione peroxidase 4 （GPX4）， ferritin heavy chain 1 （FTH1）， long-chain acyl-CoA synthetase 3 （ACSL3）， ACSL4， ferritin mitochondrial （FTMT）， and cystine/glutamate anti-porter （xCT） in the liver tissue of rats were detected. RESULTS Compared with control group， the liver cells in the model group of rats showed disordered arrangement， swelling， deepened nuclear staining， and more infiltration of inflammatory cells， as well as a large number of hepatocyte vacuoles and steatosis； FBG （after medication）， the levels of TC， TG， LDL-C， AST， ALT， FINS， MDA and ROS， HOMA-IR， Fe2+ and Fe content， NADP+/NADPH ratio and protein expression of ACSL4 were significantly increased or up-regulated， while the levels of HDL-C， GSH and SOD， IAI， protein expressions of GPX4， FTH1， ACSL3， FTMT and xCT were significantly reduced or down-regulated （P＜0.01）. Compared with the model group， both QG group and Fer-1 group showed varying degrees of improvement in pathological damage of liver tissue and the levels of the above indicators， the differences in the changes of most indicators were statistically significant （P＜0.01 or P＜0.05）. Compared with QG group， the improvement of the above indexes of QG+erastin group had been reversed significantly （P＜0.01）. CONCLUSIONS The compatibility decoction of Astragali Radix-Puerariae Lobatae Radix can reduce the level of FBG in T2DM IR rats， and alleviate IR degree， ion overload and pathological damage of liver tissue. The above effects are related to the inhibition of ferroptosis.

OBJECTIVE To explore the effect and mechanism of Prunus mume against hepatic fibrosis （HF）. METHODS Male SD rats were randomly divided into normal control group （n＝10） and modeling group （n＝50）. The modeling group established HF model using carbon tetrachloride. The modeled rats were randomly divided into model group （normal saline）， positive control group [colchicine， 0.09 mg/（kg·d）]， and P. mume low-dose， medium-dose and high-dose groups [1.35， 2.70， 5.40 g/（kg·d）]， with 9 rats in each group. They were given the corresponding drug/normal saline intragastrically， once a day， for 8 consecutive weeks. After the last medication， the liver index was calculated， while liver function indexes， liver fiber indexes， oxidative stress indicators and inflammatory factors of rats were measured. HE staining was used to observe the pathological changes in liver tissue of rats； Masson staining was used to observe the degree of HF in liver tissue of rats； transmission electron microscopy was used to observe the ultrastructure of liver tissue in rats； TUNEL staining was used to detect liver cell apoptosis in each group of rats. Western blot method was used to detect the protein expressions of transforming growth factor-β1 （TGF-β1） and platelet-derived growth factor （PDGF） in liver tissue of rats. RESULTS Compared with normal control group， the levels of alanine transaminase， alkaline phosphatase， aspartate transaminase， total bilirubin， malondialdehyde， procollagen type Ⅲ protein， Ⅳ-type pre collagenase， laminin， hyaluronic acid， interleukin-6， tumor necrosis factor-α， as well as the protein expressions of TGF-β1 and PDGF in model group were increased significantly， while the levels of superoxide dismutase and glutathione peroxidase were significantly reduced （P＜0.01）； the HE， Masson staining and transmission electron microscopy observation results showed obvious HF characteristics in rats of model group. Compared with model group， varying degrees of improvement in above indexes were observed in P. mume groups， and the above 2021BSZR011） indicators of rats in P. mume medium-dose and high-dose groups were reversed significantly （P＜0.05 or P＜0.01）. CONCLUSIONS P. mume has an anti-HF effect， which may be achieved through mechanisms such as antioxidation， anti-inflammation， reduction of collagen production， inhibition of PDGF protein expression， and regulation of TGF- β1 signaling pathway.

OBJECTIVE To explore the effect and mechanism of Prunus mume against hepatic fibrosis （HF）. METHODS Male SD rats were randomly divided into normal control group （n＝10） and modeling group （n＝50）. The modeling group established HF model using carbon tetrachloride. The modeled rats were randomly divided into model group （normal saline）， positive control group [colchicine， 0.09 mg/（kg·d）]， and P. mume low-dose， medium-dose and high-dose groups [1.35， 2.70， 5.40 g/（kg·d）]， with 9 rats in each group. They were given the corresponding drug/normal saline intragastrically， once a day， for 8 consecutive weeks. After the last medication， the liver index was calculated， while liver function indexes， liver fiber indexes， oxidative stress indicators and inflammatory factors of rats were measured. HE staining was used to observe the pathological changes in liver tissue of rats； Masson staining was used to observe the degree of HF in liver tissue of rats； transmission electron microscopy was used to observe the ultrastructure of liver tissue in rats； TUNEL staining was used to detect liver cell apoptosis in each group of rats. Western blot method was used to detect the protein expressions of transforming growth factor-β1 （TGF-β1） and platelet-derived growth factor （PDGF） in liver tissue of rats. RESULTS Compared with normal control group， the levels of alanine transaminase， alkaline phosphatase， aspartate transaminase， total bilirubin， malondialdehyde， procollagen type Ⅲ protein， Ⅳ-type pre collagenase， laminin， hyaluronic acid， interleukin-6， tumor necrosis factor-α， as well as the protein expressions of TGF-β1 and PDGF in model group were increased significantly， while the levels of superoxide dismutase and glutathione peroxidase were significantly reduced （P＜0.01）； the HE， Masson staining and transmission electron microscopy observation results showed obvious HF characteristics in rats of model group. Compared with model group， varying degrees of improvement in above indexes were observed in P. mume groups， and the above 2021BSZR011） indicators of rats in P. mume medium-dose and high-dose groups were reversed significantly （P＜0.05 or P＜0.01）. CONCLUSIONS P. mume has an anti-HF effect， which may be achieved through mechanisms such as antioxidation， anti-inflammation， reduction of collagen production， inhibition of PDGF protein expression， and regulation of TGF- β1 signaling pathway.

In recent years, gastrointestinal stromal tumors (GIST) have increased incidence and mortality, and most GIST is caused by the activation mutation of the c-KIT gene. Therefore, c-KIT has become a promising therapeutic target of GIST. At present, the drugs approved for the treatment of GIST including imatinib, sunitinib, regorafenib and ripretinib, are mostly prone to developing resistance and accompanied by various degrees of adverse reactions. Therefore, there is an urgent need to develop new c-KIT inhibitors to solve the problem of resistance. In this study, we investigated the anti-tumor effect of a novel c-KIT inhibitor PN17-1 on gastrointestinal stromal tumor GIST-882 cells in vitro. We found that PN17-1 significantly inhibited the proliferation, colony formation and migration ability of GIST-882 cells, and significantly downregulated the protein expression levels of p-c-KIT and its downstream signals p-AKT, p-STAT5 and p-ERK in GIST-882 cells. In addition, PN17-1 induced apoptosis in GIST-882 cells, and the apoptosis may be mainly related to the mitochondrial-dependent endogenous pathway. In conclusion, the novel c-KIT inhibitor PN17-1 is a promising anti-GIST drug, and this study provides new ideas for further development of c-KIT inhibitors in the future.

With the rapid development of mobile internet technology, mobile health application (mHealth APP) are increasingly widely used in the field of health management and have been proven to play an important role in the management of chronic diseases. Solid organ transplant recipients face complex health management needs after surgery, including postoperative follow-up, medication management, prevention and treatment of complications and comorbidities, and lifestyle adjustment. mHealth APP can provide solid organ transplant recipients with convenient self-management tools. Although some progress has been made in this field, there are still many challenges, such as insufficient user experience, technological dependence, and data security risks. Therefore, this article discusses the development process, main functions and current application status of mHealth APP, and analyzes its advantages in improving the self-management ability of solid organ transplant recipients, promoting doctor-patient communication and reducing the incidence of complications. At the same time, based on the practical experience of author’s team in developing the “TransMate” mHealth APP, we propose the directions that mHealth APPs should focus on in the future, in order to provide more effective support and services for the health management of solid organ transplant recipients.

Background: Maturity-onset diabetes of the young (MODY) due to variants of hepatocyte nuclear factor 1-beta (HNF1β) (MODY5) has not been well studied in the Chinese population. This study aimed to estimate its prevalence and evaluate the application of a clinical screening method (Faguer score) in Chinese early-onset diabetes (EOD) patients. Methods: Among 679 EOD patients clinically diagnosed with type 2 diabetes mellitus (age at diagnosis ≤40 years), the exons of HNF1β were sequenced. Functional impact of rare variants was evaluated using a dual-luciferase reporter system. Faguer scores ≥8 prompted multiplex ligation-dependent probe amplification (MLPA) for large deletions. Pathogenicity of HNF1β variants was assessed following the American College of Medical Genetics and Genomics (ACMG) guidelines. Results: Two rare HNF1β missense mutations (E105K and G454R) were identified by sequencing in five patients, showing functional impact in vitro. Another patient was found to have a whole-gene deletion by MLPA in 22 patients with the Faguer score above 8. Following ACMG guidelines, six patients carrying pathogenic or likely pathogenic variant were diagnosed with MODY5. The estimated prevalence of MODY5 in Chinese EOD patients was approximately 0.9% or higher. Conclusion MODY5 is not uncommon in China. The Faguer score is helpful in deciding whether to perform MLPA analysis on patients with negative sequencing results.

Background: Maturity-onset diabetes of the young (MODY) due to variants of hepatocyte nuclear factor 1-beta (HNF1β) (MODY5) has not been well studied in the Chinese population. This study aimed to estimate its prevalence and evaluate the application of a clinical screening method (Faguer score) in Chinese early-onset diabetes (EOD) patients. Methods: Among 679 EOD patients clinically diagnosed with type 2 diabetes mellitus (age at diagnosis ≤40 years), the exons of HNF1β were sequenced. Functional impact of rare variants was evaluated using a dual-luciferase reporter system. Faguer scores ≥8 prompted multiplex ligation-dependent probe amplification (MLPA) for large deletions. Pathogenicity of HNF1β variants was assessed following the American College of Medical Genetics and Genomics (ACMG) guidelines. Results: Two rare HNF1β missense mutations (E105K and G454R) were identified by sequencing in five patients, showing functional impact in vitro. Another patient was found to have a whole-gene deletion by MLPA in 22 patients with the Faguer score above 8. Following ACMG guidelines, six patients carrying pathogenic or likely pathogenic variant were diagnosed with MODY5. The estimated prevalence of MODY5 in Chinese EOD patients was approximately 0.9% or higher. Conclusion MODY5 is not uncommon in China. The Faguer score is helpful in deciding whether to perform MLPA analysis on patients with negative sequencing results.

Background: Maturity-onset diabetes of the young (MODY) due to variants of hepatocyte nuclear factor 1-beta (HNF1β) (MODY5) has not been well studied in the Chinese population. This study aimed to estimate its prevalence and evaluate the application of a clinical screening method (Faguer score) in Chinese early-onset diabetes (EOD) patients. Methods: Among 679 EOD patients clinically diagnosed with type 2 diabetes mellitus (age at diagnosis ≤40 years), the exons of HNF1β were sequenced. Functional impact of rare variants was evaluated using a dual-luciferase reporter system. Faguer scores ≥8 prompted multiplex ligation-dependent probe amplification (MLPA) for large deletions. Pathogenicity of HNF1β variants was assessed following the American College of Medical Genetics and Genomics (ACMG) guidelines. Results: Two rare HNF1β missense mutations (E105K and G454R) were identified by sequencing in five patients, showing functional impact in vitro. Another patient was found to have a whole-gene deletion by MLPA in 22 patients with the Faguer score above 8. Following ACMG guidelines, six patients carrying pathogenic or likely pathogenic variant were diagnosed with MODY5. The estimated prevalence of MODY5 in Chinese EOD patients was approximately 0.9% or higher. Conclusion MODY5 is not uncommon in China. The Faguer score is helpful in deciding whether to perform MLPA analysis on patients with negative sequencing results.