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.

This paper aimed to investigate the therapeutic effect and mechanism of action of the Yiqi Fumai Formula(YQFM), a kind of traditional Chinese medicine(TCM), on mice with experimental heart failure based on the "heart-gut axis" theory. Based on the network pharmacology integrated with the group collaboration algorithm, the active ingredients were screened, a "component-target-disease" network was constructed, and the potential pathways regulated by the formula were predicted and analyzed. Next, the model of experimental heart failure was established by intraperitoneal injection of adriamycin at a single high dose(15 mg·kg~(-1)) in BALB/c mice. After intraperitoneal injection of YQFM(lyophilized) at 7.90, 15.80, and 31.55 mg·d~(-1) for 7 d, the protective effects of the formula on cardiac function were evaluated using indicators such as ultrasonic electrocardiography and myocardial injury markers. Combined with inflammatory factors in the cardiac and colorectal tissue, as well as targeted assays, the relevant indicators of potential pathways were verified. Meanwhile, 16S rDNA sequencing was performed on mouse fecal samples using the Illumina platform to detect changes in gut flora and analyze differential metabolic pathways. The results show that the administration of injectable YQFM(lyophilized) for 7 d significantly increased the left ventricular end-systolic internal diameter, fractional shortening, and ejection fraction of cardiac tissue of mice with experimental heart failure(P<0.05). Moreover, markers of myocardial injury were significantly decreased(P<0.05), indicating improved cardiac function, along with significantly suppressed inflammatory responses in cardiac and intestinal tissue(P<0.05). Additionally, the species of causative organisms was decreased, and the homeostasis of gut flora was improved, involving a modulatory effect on PI3K-Akt signaling pathway-related inflammation in cardiac and colorectal tissue. In conclusion, YQFM can affect the "heart-gut axis" immunity through the homeostasis of the gut flora, thereby exerting a therapeutic effect on heart failure. This finding provides a reference for the combination of TCM and western medicine to prevent and treat heart failure based on the "heart-gut axis" theory.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Heart Failure/microbiology* ; Mice ; Mice, Inbred BALB C ; Male ; Disease Models, Animal ; Gastrointestinal Microbiome/drug effects* ; Heart/physiopathology* ; Humans ; Signal Transduction/drug effects*

Objective： The aim of this study is to explore the predictive value of biparametric magnetic resonance imaging(bpMRI)for pelvic lymph node metastasis in prostate cancer patients with PSA≤20 μg/L and establish a nomogram. Methods： The imaging data and clinical data of 363 patients undergoing radical prostatectomy and pelvic lymph node dissection in the First Affiliated Hospital of Nanjing Medical University from July 2018 to December 2023 were retrospectively analyzed. Univariate analysis and multivariate logistic regression were used to screen independent risk factors for pelvic lymph node metastasis in prostate cancer, and a nomogram of the clinical prediction model was established. Calibration curves were drawn to evaluate the accuracy of the model. Results： Multivariate logistic regression analysis showed extrocapusular extension (OR=8.08,95%CI=2.62－24.97, P<0.01), enlargement of pelvic lymph nodes (OR=4.45,95%CI=1.16－17.11,P=0.030), and biopsy ISUP grade(OR=1.97,95%CI=1.12－3.46, P=0.018)were independent risk factors for pelvic lymph node metastasis. The C-index of the prediction model was 0.834, which indicated that the model had a good prediction ability. The actual value of the model calibration curve and the prediction probability of the model fitted well, indicating that the model had a good accuracy. Further analysis of DCA curve showed that the model had good clinical application value when the risk threshold ranged from 0.05 to 0.70.Conclusion： For prostate cancer patients with PSA≤20 μg/L, bpMRI has a good predictive value for the pelvic lymph node metastasis of prostate cancer with extrocapusular extension, enlargement of pelvic lymph nodes and ISUP grade≥4.
Humans ; Male ; Prostatic Neoplasms/diagnostic imaging* ; Lymphatic Metastasis ; Retrospective Studies ; Nomograms ; Prostate-Specific Antigen/blood* ; Lymph Nodes/pathology* ; Pelvis ; Predictive Value of Tests ; Prostatectomy ; Lymph Node Excision ; Risk Factors ; Magnetic Resonance Imaging ; Logistic Models ; Middle Aged ; Aged

Objective To explore the effect of rehmanniae radix extract(RRE)on chondrocyte apoptosis in the rabbit model of knee osteoarthritis(KOA)by regulating the miR-485-5p/heat shock protein 90 beta family member 1(Hsp90b1)axis.Methods New Zealand rabbits were randomly assigned into control,KOA,low-dose RRE,medium-dose RRE,high-dose RRE,celecoxib,high-dose RRE+antagonist control,and high-dose RRE+miR-485-5p antagonist groups,with 12 rabbits in each group.Rabbits in other groups except the control group were modeled for KOA with the improved Hulth method.After modeling for 8 weeks,the rabbits were administrated with corresponding agents for 4 weeks.The changes in the activity rating of rabbits were recorded.ELISA was employed to measure the levels of tumor necrosis factor-α(TNF-α)and interleukin(IL)-6 in the serum.Safranine O-fast green staining was conducted to reveal the pathological changes in the cartilage tissue and Mankin scoring was performed.TUNEL was employed to detect chondrocyte apoptosis.Real-time fluorescence quantitative PCR was performed to determine the expression of miR-485-5p in the cartilage tissue.Western blot was employed to determine the protein levels of Hsp90b1,cleaved cysteinyl aspartate-specific proteinase-3(Caspase-3),and Bcl2-associated-X(Bax)in the cartilage tissue.The dual-luciferase reporter assay was employed to examine the relationship between miR-485-5p and Hsp90b1.Results Compared with the control group,the KOA group showed down-regulated expression of miR-485-5p,elevated levels of TNF-α and IL-6 in the serum,cartilage erosion and losses,and increases in activity rating,Mankin score,chondrocyte apoptosis rate,and protein levels of Hsp90b1,cleaved Caspase-3,and Bax(all P<0.001).Compared with the KOA group,RRE at low,medium,and high doses,and celecoxib up-regulated the expression of miR-485-5p,lowered the levels of TNF-α and IL-6 in the serum,alleviated the pathological damage to the cartilage tissue,and decreased the activity rating,Mankin score,chondrocyte apoptosis rate,and protein levels of Hsp90b1,cleaved Caspase-3,and Bax(all P<0.05).Compared with the high-dose RRE group and the high-dose RRE+antagonist control group,high-dose RRE+miR-485-5p antagonist down-regulated the expression of miR-485-5p,elevated the levels of TNF-α and IL-6 in the serum,exacerbated the pathological damage to the cartilage tissue,and increased the activity rating,Mankin score,chondrocyte apoptosis rate,and protein levels of Hsp90b1,cleaved Caspase-3,and Bax(all P<0.05).The results indicated that there was a targeted regulatory relationship between miR-485-5p and Hsp90b1.Conclusion RRE may inhibit the expression of Hsp90b1 by up-regulating miR-485-5p,thereby inhibiting chondrocyte apoptosis in the rabbit model of KOA.
Animals ; Rabbits ; Apoptosis/drug effects* ; Chondrocytes/pathology* ; Osteoarthritis, Knee/drug therapy* ; MicroRNAs/metabolism* ; Rehmannia/chemistry* ; Disease Models, Animal ; Tumor Necrosis Factor-alpha/blood* ; Plant Extracts/pharmacology* ; Interleukin-6/blood* ; HSP90 Heat-Shock Proteins/metabolism* ; Male ; Drugs, Chinese Herbal/pharmacology*

Objective:To investigate which indicator is more advantageous when using arterial oxygen saturation(SaO2)and fingertip pulse oxygen saturation(SpO2)for blood oxygen detection in patients with hyperleukocytic acute leukemia(HAL).Methods:In this prospective research,the difference between SaO2 and SpO2 of 18 HAL patients(observation group)and 14 patients(control group),as well as the relationship between the difference and white blood cell(WBC)counts were analyzed.Results:SaO2 was lower than SpO2 in the observation group(P＜0.05),and SpO2-SaO2 difference was positively correlated with WBC counts(r=0.47).However,there was no statistical difference between SaO2 and SpO2 in the control group.SaO2 and PO2 showed a downward trend with the prolongation of detection time after arterial blood was collected in the observation group,but there was no statistical difference.There was no downward trend of SaO2 and PO2 in the control group.Conclusion:HAL patients have a phenomenon where SaO2 is lower than SpO2,that is pseudohypoxemia,and this phenomenon may be caused by excessive consumption of oxygen by the leukemia cells in vitro.SpO2 can be monitored bedside in real time and is non-invasive,it is a better way to detect the blood oxygen status of HAL patients.

Objective:To explore the clinical characteristics of pediatric kidney transplant recipients reinfected with SARS-CoV-2.Method:The relevant clinical data were retrospectively reviewed for 191 pediatric kidney transplant recipients at a single center. Based upon whether or not there was a reinfection of SARS-CoV-2, they were assigned into two groups of single infection (group A, 127 cases) and reinfection (group B, 64 cases). Baseline profiles, clinical symptoms, diagnostic and therapeutic strategies, markers of disease progression, immune status, respiratory support modalities, comorbidities and transplantation-related data were collected for comparing the inter-group differences during primary infection and between two infections in reinfected group.Result:As compared with group A, group B recipients had a higher proportion of age <12 years (71.9% vs 54.3%) ,unvaccinated (81.2% vs 66.1%) and such symptoms as high fever (34.4% vs 12.6% ), dry cough (43.8% vs 23.6% ) and chest tightness (14.1% vs 3.9 %) during primary infection (all P<0.05). During primary infection, the levels of IL-6 and CRP were higher in group B than in group A and inter-group difference was statistically significant (both P<0.01). The levels of IL-6 ( P<0.01), CRP ( P<0.01) and PCT ( P= 0.023) were lower in group B during reinfection than those during primary infection and the difference was statistically significant. During primary infection, the counts of CD3+, CD4+, CD8+, NK and B lymphocyte of group B were lower than those of group A. And inter-group differences were statistically significant (all P<0.01). During reinfection, the levels of CD3+, CD4+, CD8+, NK and B lymphocyte counts of group B spiked as compared with those of group A during primary infection and the differences were statistically significant (all P<0.01). The levels of SCr and UA in group B differed insignificantly before and after primary infection with SARS-CoV-2. However, the differences before and after reinfection were statistically significant (both P<0.01) . Conclusion:Symptomatic and immunocompromised pediatric KT recipients during primary infection with SARS-CoV-2 are more prone to reinfection during subsequent epidemics. Though mildly symptomatic, reinfection may exacerbate impairments of graft kidney function in pediatric KT recipients.

Objective:To explore the characteristic pathological manifestations of non-HLA antibodies after kidney transplantation (KT) and examine the differences of MFT values of non-HLA antibodies in different pathological manifestations.Methods:The study was conducted on KT recipients at the First Affiliated Hospital of Zhengzhou University from February 2021 to June 2023 with unexplained elevated serum creatinine. Patients undergoing pathological puncture and concurrent HLA antibody testing were included, focusing on those with DSA (MFI>4 000) and non-HLA antibody negativity. According to the detection results of non-HLA and HLA antibodies, they were assigned into two groups of non-HLA antibody positive (45 cases) and HLA-DSA positive (28 cases). Both non-HLA and HLA antibodies were detected by luminex single antigen microbeads, χ2, t or Mann-Whitney U nonparametric tests were utilized for examining the inter-group differences in pathological manifestations. The recipients with positive non-HLA antibodies were grouped according to the differential pathological features[microvascular inflammation group (22 cases) and non-microvascular inflammation group (23 cases), interstitial fibrosis group (39 cases) and non-interstitial fibrosis (9 cases) ]. MFI values of non-HLA antibodies were standardized and heat map was generated with R language ComplexHeatmap package. The differences of response values of non-HLA antibodies with different pathological manifestations were examined by rank-sum test. Results:The positive rates of microvascular inflammation were 48.9% (22/45) and 82.1% (23/28) in HLA-DSA positive and non-HLA antibody positive groups with statistical significance ( χ2=8.073, P=0.006). The positive rates of interstitial fibrosis in two groups were 80.8% (36/45) and 53.6% (15/28) and the difference was statistically significant ( χ2=5.726, P=0.021). The relative levels of anti-arachnotoxin receptor 1 (Latrophilin 1, LPHN1), keratin 8 (KRT8), keratin 18 (KRT18) and Sjogren's syndrome antigen B (SSB) were higher in microvascular inflammation group than those in non-microvascular inflammation group. The differences were statistically significant [559.50 (262.00, 801.25) vs 285.00 (183.00, 460.00), P=0.024; 504.50 (369.5, 725.25) vs 317.00 (231.50, 458.00), P=0.014; 672.50 (454.50, 969.50) vs 399.00 (246.50, 772.50), P=0.030; 967.50 (482.00, 2 066.50) vs 399.00 (246.50, 772.50), P=0.033]. The relative levels of anti-cyclic citrullinate peptide (CCP), colony-stimulating factor 2 (CSF2), intercellular adhesion molecule 1 (ICAM1) and collagen Ⅳ antibody were higher in interstitial fibrosis group than those in non-interstitial fibrosis group with statistical significance [100.00 (79.88, 167.50) vs 64.50 (37.00, 89.00), P=0.016; 146.25 (93.38, 244.75) vs 87.00 (66.00, 105.00), P=0.041; 132.50 (106.38, 229.50) vs 95.00 (55.00, 125.00), P=0.037; 432.50 (280.75, 653.75) vs 208.00 (192.00, 301.00), P=0.028]. Conclusions:As compared with HLA-DSA, the characteristic pathological manifestations of non-HLA antibodies post-KT include a lower incidence of microvascular inflammation and a higher incidence of interstitial fibrosis. For non-HLA antibody response values of characteristic pathological manifestations, the expressions of different non-HLA antibodies vary statistically.

Non-alcoholic fatty liver disease(NAFLD)is a kind of disease caused by a variety of reasons,which is characterized by steatosis and fat accumulation in liver parenchymal cells.In recent years,the morbidity of NAFLD has been relatively high in China.In the field of traditional Chinese medicine,NAFLD can be classified into the categories of"hepatic mass","abdominal mass"and"concretions and conglomerations".Spleen failing in transportation is the core pathogenesis of NAFLD,and the intervention of NAFLD with the method of activating spleen and resolving accumulation(shortened to Yunpi Huaji method)has achieved good results.In this paper,the clinical research of Yunpi Huaji method for the treatment of NAFLD and experimental research on its therapeutic mechanism in the past 10 years were reviewed.The results showed that the treatment of NAFLD by Yunpi Huaji method can be achieved by oral use of compound preparations and external treatment such as acupuncture,tuina and physiotherapy,and the therapeutic mechanism in the prevention and treatment of NAFLD was through multi-action,multi-target and multiple signaling pathways.The review will provide thoughts for the clinical diagnosis and treatment of NAFLD in traditional Chinese medicine,and will supply theoretical support for the medicine development and mechanism exploration of Yunpi Huaji method for the prevention and treatment of NAFLD.

Stress is a non-specific adaptive response of organisms to internal and external stimuli,which helps maintain the homeostasis of the body's internal environment.However,when the stress response exceeds the body's adaptation threshold,a variety of diseases will be induced.The morbidity and mortality of breast cancer rank the highest among female malignant tumors.Professor LIN Yi,the first master of traditional Chinese medicine(TCM)in the field of breast diseases who founded the theory of'treating breast diseases from the perspective of six stagnations',believes that six stagnations are the core pathogenesis of breast cancer,and six stagnations are closely related to the body's stress response system.TCM has unique advantages in adjusting the balance of stress homeostasis.By reviewing the classical TCM theory,the theory of'treating breast diseases from the perspective of six depressions'and the modern stress theory,this paper put forward the theory of'stress-based breast cancer prevention & treatment',and expounded the pathogenesis features,pathogenic characteristics and molecular mechanism of stress factors in mediating the development and progression of breast cancer.Moreover,the core idea and treatment principle based on the regulation of stress homeostasis were proposed,and the prescription and medication guided by the theory of'stress-based breast cancer prevention & treatment'were summarized.The establishment of the theory of'stress-based breast cancer prevention & treatment'enriches the theoretical system of breast cancer in TCM,and is expected to provide a new approach for improving the clinical prognosis of breast cancer patients.