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.

OBJECTIVE: To observe the effects of acupoint catgut embedding (ACE) on gut microbiota and fecal short-chain fatty acids (SCFAs) levels in patients with Parkinson's disease (PD) with constipation. METHODS: A total of 80 PD patients with constipation were randomly divided into an observation group and a control group, 40 cases in each group. Additionally, 40 healthy individuals were recruited as a healthy control group. The control group received conventional Western medical treatment for PD combined with polyethylene glycol (PEG), once daily for eight weeks. The observation group received additional ACE treatment at bilateral Tianshu (ST25), Zusanli (ST36), and Shangjuxu (ST37), once every two weeks for eight weeks. The healthy control group received no intervention. The spontaneous bowel movements (SBMs) per week and patient assessment of constipation quality of life (PAC-QOL) scores were assessed at baseline and after treatment in the two groups. Fecal samples were collected at the end of treatment for the observation and the control groups and at baseline for the healthy control group. Gut microbiota composition and diversity were analyzed using 16S rRNA method, and SCFA levels were measured using high-performance liquid chromatography (HPLC). RESULTS: Compared before treatment, the observation group showed a significant increase in SBMs (P<0.01), and PAC-QOL scores including physical discomfort, psychosocial discomfort, worry and concern, and total score were significantly reduced (P<0.01) after treatment; the control group also showed a reduction in PAC-QOL total score after treatment (P<0.01). After treatment, the observation group had significantly more SBMs (P<0.01), and lower PAC-QOL physical discomfort, psychosocial discomfort, worry and concern scores, and total score (P<0.01), and higher PAC-QOL satisfaction score (P<0.01) than the control group. Compared with the healthy control group, the control group showed decreased Chao1 and Ace indices (P<0.01). Compared with the healthy control group, the relative abundance of Prevotella and Roseburia was increased (P<0.05), while that of Enterobacter and Ruminococcus torques (six species in total) was decreased (P<0.05) in the control group. Compared with the control group, the observation group had increased relative abundance of Dialister, Parabacteroides, and Ruminococcus torques (P<0.05), and decreased relative abundance of Prevotella and Eubacterium ruminantium (P<0.05). Compared with the healthy control group, the control group had increased fecal SCFA levels (P<0.05); compared with the control group, the observation group had reduced fecal SCFA levels (P<0.05). Compared with the healthy control group, acetic acid, propionic acid, and butyric acid levels were elevated in the control group (P<0.05); compared with the control group, acetic acid, propionic acid, and butyric acid levels were decreased in the observation group (P<0.05). CONCLUSION ACE could increase spontaneous bowel movements and improve the quality of life in PD patients with constipation, which may be related to the regulation of gut microbiota composition and SCFA levels.
Humans ; Constipation/metabolism* ; Male ; Gastrointestinal Microbiome ; Acupuncture Points ; Female ; Middle Aged ; Parkinson Disease/complications* ; Aged ; Fatty Acids, Volatile/metabolism* ; Catgut ; Feces/microbiology* ; Acupuncture Therapy ; Quality of Life ; Adult

BACKGROUND: While emotional distress, encompassing anxiety and depression, has been associated with negative clinical outcomes, its impact across various clinical departments and general hospitals has been less explored. Previous studies with limited sample sizes have examined the effectiveness of specific treatments (e.g., antidepressants) rather than a systemic management strategy for outcome improvement in non-psychiatric inpatients. To enhance the understanding of the importance of addressing mental health care needs among non-psychiatric patients in general hospitals, this study retrospectively investigated the impacts of emotional distress and the effects of early detection and management of depression and anxiety on hospital length of stay (LOS) and rate of long LOS (LLOS, i.e., LOS >30 days) in a large sample of non-psychiatric inpatients. METHODS: This retrospective cohort study included 487,871 inpatients from 20 non-psychiatric departments of a general hospital. They were divided, according to whether they underwent a novel strategy to manage emotional distress which deployed the Huaxi Emotional Distress Index (HEI) for brief screening with grading psychological services (BS-GPS), into BS-GPS ( n = 178,883) and non-BS-GPS ( n = 308,988) cohorts. The LOS and rate of LLOS between the BS-GPS and non-BS-GPS cohorts and between subcohorts with and without clinically significant anxiety and/or depression (CSAD, i.e., HEI score ≥11 on admission to the hospital) in the BS-GPS cohort were compared using univariable analyses, multilevel analyses, and/or propensity score-matched analyses, respectively. RESULTS: The detection rate of CSAD in the BS-GPS cohort varied from 2.64% (95% confidence interval [CI]: 2.49%-2.81%) to 20.50% (95% CI: 19.43%-21.62%) across the 20 departments, with a average rate of 5.36%. Significant differences were observed in both the LOS and LLOS rates between the subcohorts with CSAD (12.7 days, 535/9590) and without CSAD (9.5 days, 3800/169,293) and between the BS-GPS (9.6 days, 4335/178,883) and non-BS-GPS (10.8 days, 11,483/308,988) cohorts. These differences remained significant after controlling for confounders using propensity score-matched comparisons. A multilevel analysis indicated that BS-GPS was negatively associated with both LOS and LLOS after controlling for sociodemographics and the departments of patient discharge and remained negatively associated with LLOS after controlling additionally for the year of patient discharge. CONCLUSION Emotional distress significantly prolonged the LOS and increased the LLOS of non-psychiatric inpatients across most departments and general hospitals. These impacts were moderated by the implementation of BS-GPS. Thus, BS-GPS has the potential as an effective, resource-saving strategy for enhancing mental health care and optimizing medical resources in general hospitals.
Humans ; Retrospective Studies ; Male ; Length of Stay/statistics & numerical data* ; Female ; Middle Aged ; Adult ; Psychological Distress ; Inpatients/psychology* ; Aged ; Anxiety/diagnosis* ; Depression/diagnosis*

Objective : To analyze the relationship between tongue volume, tongue position, dental and skeletal parameters in adult patients with different skeletal malocclusions, providing references for the etiology, diagnosis, and treatment of skeletal malocclusions. Methods: This study has been reviewed and approved by the Ethics Committee, and informed consent has been obtained from patients. Cone-beam computed tomography (CBCT) and cephalometric radiographs were collected from 60 adult patients, divided into three groups based on ANB angle values: skeletal Class I (0° < ANB < 4°), II (ANB > 4°), and III (ANB < 0°), with 20 cases in each group. Dental and skeletal parameters were measured using Dolphin software. Mimics software was used for 3D reconstruction of the tongue, oral cavity, and upper airway to measure tongue position, tongue volume, oral cavity volume, and upper airway volume, followed by statistical analysis. Results: The skeletal Class III group had significantly larger tongue and oral cavity volumes than the skeletal Class I and Class II groups (P = 0.02). Tongue length in the skeletal Class III group was also greater than in the skeletal Class I and Class II groups (P = 0.016). There was no significant difference in the ratio of tongue volume/oral cavity capacity among the three skeletal malocclusion groups (P > 0.05). Tongue volume was positively correlated with U1-SN and negatively correlated with overbite and overjet (P < 0.05). Additionally, tongue volume showed a significant positive correlation with Go-Gn and Pg-Np (P < 0.01), as well as with maxillary and mandibular dental arch width and basal bone arch width (P < 0.01). Upper airway volume was positively correlated with TT-VRL and TP-VRL (P < 0.05). Conclusion Patients with skeletal Class III malocclusion have larger tongue volumes and longer tongues. Patients with larger tongue volumes may also have larger, more forward-positioned mandibles. Patients with more posterior tongue positions may have smaller upper airway volumes. When developing orthodontic or orthognathic treatment plans, it is crucial to consider the relationship between tongue position, tongue volume, the jaws, and the airway to ensure optimal outcomes for both dental and orofacial function.

OBJECTIVE: To evaluate the analgesic efficacy of ultrasound-guided high fascia iliaca compartment block (HFICB) in managing tourniquet-related pain following total knee arthroplasty (TKA). METHODS: A prospective randomized controlled trial was conducted involving 84 patients with severe knee osteoarthritis or rheumatoid arthritis who underwent unilateral TKA between March 2024 and December 2024. Patients were randomly assigned to two groups ( n=42) using a random number table. In the trial group, ultrasound-guided HFICB was performed preoperatively, with 0.2% ropivacaine injected into the fascia iliaca compartment. No intervention was administered in the control group. Baseline characteristics, including gender, age, surgical side, body mass index, and preoperative visual analogue scale (VAS) scores at rest and during movement, showed no significant difference between the two groups ( P>0.05). In both groups, a tourniquet was applied after osteotomy and before pulsed lavage, and removed after the closure of the first layer of the joint capsule. Postoperative assessments were conducted at 6, 12, 24, and 48 hours, including VAS scores at the tourniquet site (at rest and during movement), Bromage motor block scores, Ramsay sedation scores, and Bruggrmann comfort scale (BCS) scores to evaluate patient comfort. Additionally, the average tramadol consumption and incidence of nausea and vomiting within 48 hours postoperatively were recorded and compared. RESULTS: In the trial group and control group, VAS scores during movement at the tourniquet site significantly improved at all postoperative time points compared to preoperative levels ( P<0.05). VAS scores at rest increased transiently at 6 hours after operation in both groups, and then gradually decreased to the preoperative level. Except that there was no significant difference at 48 hours after operation in the trial group ( P>0.05), there were significant differences at other time points of two groups compared to preoperative score ( P<0.05). Except for VAS score at rest at 6 hours, VAS score during movement at 48 hours, and BCS comfort score at 48 hours ( P>0.05), the trial group showed significantly better outcomes than the control group in terms of VAS score at rest, VAS score during movement, Ramsay sedation scores, and BCS comfort scores at all other time points ( P<0.05). No significant difference was found in Bromage motor block scores between the groups ( P>0.05). Tramadol was used in 3 patients in the trial group and 7 patients in the control group within 48 hours after operation, the dosage was (133.30±14.19) mg and (172.40±22.29) mg, showing significant difference ( P<0.05). Nausea and vomiting occurred in 4 patients (9.5%) in the trial group and 3 patients (7.1%) in the control group, with no significant difference in incidence between groups ( P>0.05). CONCLUSION Ultrasound-guided HFICB provides effective analgesia for tourniquet-related pain following TKA, facilitates early postoperative functional recovery of the knee joint, and may serve as a valuable clinical option for postoperative pain management in TKA patients.
Humans ; Arthroplasty, Replacement, Knee/adverse effects* ; Nerve Block/methods* ; Male ; Female ; Pain, Postoperative/etiology* ; Tourniquets/adverse effects* ; Prospective Studies ; Middle Aged ; Ropivacaine/administration & dosage* ; Aged ; Ultrasonography, Interventional ; Anesthetics, Local/administration & dosage* ; Pain Measurement ; Fascia ; Osteoarthritis, Knee/surgery* ; Treatment Outcome ; Arthritis, Rheumatoid/surgery*

OBJECTIVE: To investigate the characteristics of central nervous system regulation in patients with refractory overactive bladder (rOAB) using resting-state functional magnetic resonance imaging (rs-fMRI), and to analyze the differences in brain function and connection between the patients and healthy population. METHODS: From May 1 to November 30, 2024, we performed rs-fMRI for 47 rOAB patients and another 47 matched healthy controls, documented relevant clinical data from all the participants and obtained their Overactive Bladder Symptom Scores (OABSS) and Overactive Bladder Questionnaire (OAB-Q) scores. Based on rs-fMRI, we compared the results of Independent Component Analysis (ICA), amplitude of low-frequency fluctuations (ALFF), fractional amplitude of low-frequency fluctuations (fALFF), regional homogeneity (ReHo) and degree centrality (DC) between the rOAB patients and healthy controls. RESULTS: The rOAB patients, in comparison with the healthy controls, showed dramatically higher daytime urination frequency (11.64 ± 3.85) vs (5.76 ± 0.91), nighttime urination frequency (3.72 ± 1.64) vs (0.31 ± 0.47), OABSS (8.22 ± 2.21) vs (0.64±0.78), OAB-Q1 score (20.85 ± 5.28) vs (6.78 ± 1.04), and OAB-Q2 score (45.04 ± 12.11) vs (14.51 ± 1.66) (all P<0.01). No statistically significant differences were observed in the results of ICA and ALFF between the right superior frontal and right middle frontal regions in the rOAB patients (P>0.05), but fALFF, ReHo and DC were significantly decreased in the patients compared with those in the healthy controls (P<0.01). CONCLUSION Compared with healthy population, the functions and connection of the frontal superior right and frontal middle right brain regions in rOAB patients are significantly down-regulated, which may serve as new therapeutic targets.
Humans ; Urinary Bladder, Overactive/physiopathology* ; Magnetic Resonance Imaging ; Brain/physiopathology* ; Female ; Male ; Adult ; Surveys and Questionnaires ; Case-Control Studies ; Middle Aged ; Rest ; Brain Mapping

[This corrects the article DOI: 10.11909/j.issn.1671-5411.2017.08.005.].

OBJECTIVE: To investigate the anti-tumor effects of cinobufacini (CINO) on hepatocellular carcinoma (HCC) induced by des-gamma-carboxy-prothrombin (DCP) and to uncover the underlying mechanisms. METHODS: The inhibitory effect of CINO on HCC cell proliferation was evaluated using the cell counting kit-8 method, and the apoptosis rate was quantified using flow cytometry. Immunofluorescence and Western blot analyses were used to investigate the differential expression of proteins associated with cell growth, apoptosis, migration, and invasion pathways after CINO treatment. The therapeutic potential of CINO for HCC was confirmed, and the possibility of combining cinobufacini with c-Met inhibitor for the treatment of primary HCC was further validated by in vivo experiments. RESULTS: Under the induction of DCP, CINO inhibited the activity of HCC cells, induced apoptosis, and inhibited migration and invasion. Upon the induction of DCP, CINO regulated c-Met activation and the activation of the phosphatidylinositol-3 kinase/protein kinase B (PI3K/AKT) and mitogen-activated protein kinase kinase/extracellular signal-regulated kinase (MEK/ERK) pathways. In a mouse model of HCC, CINO exhibited significant antitumor effects by inhibiting the phosphorylation of c-Met and the downstream PI3K/AKT and MEK/ERK pathways in tumor tissues. CONCLUSIONS CINO inhibited HCC cell growth, promoted apoptosis, and suppressed HCC cell invasion and migration by targeting c-Met and PI3K/AKT and MEK/ERK signaling pathways under DCP induction.
Carcinoma, Hepatocellular/drug therapy* ; Proto-Oncogene Proteins c-met/metabolism* ; Liver Neoplasms/drug therapy* ; Signal Transduction/drug effects* ; Animals ; Humans ; Cell Movement/drug effects* ; Apoptosis/drug effects* ; Cell Proliferation/drug effects* ; Amphibian Venoms/therapeutic use* ; Cell Line, Tumor ; Neoplasm Metastasis ; Cell Survival/drug effects* ; Proto-Oncogene Proteins c-akt/metabolism* ; Phosphatidylinositol 3-Kinases/metabolism* ; Neoplasm Invasiveness ; Mice, Inbred BALB C ; Mice, Nude ; Mice ; Male ; Bufanolides/therapeutic use* ; Protein Precursors ; Prothrombin ; Biomarkers

OBJECTIVE: To investigate the effect of zedoarondiol on neovascularization of atherosclerotic (AS) plaque by exosomes experiment. METHODS: ApoE^-/- mice were fed with high-fat diet to establish AS model and treated with high- and low-dose (10, 5 mg/kg daily) of zedoarondiol, respectively. After 14 weeks, the expressions of anti-angiogenic protein thrombospondin 1 (THBS-1) and its receptor CD36 in plaques, as well as platelet activation rate and exosome-derived miR-let-7a were detected. Then, zedoarondiol was used to intervene in platelets in vitro, and miR-let-7a was detected in platelet-derived exosomes (Pexo). Finally, human umbilical vein endothelial cells (HUVECs) were transfected with miR-let-7a mimics and treated with Pexo to observe the effect of miR-let-7a in Pexo on tube formation. RESULTS: Animal experiments showed that after treating with zedoarondiol, the neovascularization density in plaques of AS mice was significantly reduced, THBS-1 and CD36 increased, the platelet activation rate was markedly reduced, and the miR-let-7a level in Pexo was reduced (P<0.01). In vitro experiments, the platelet activation rate and miR-let-7a levels in Pexo were significantly reduced after zedoarondiol's intervention. Cell experiments showed that after Pexo's intervention, the tube length increased, and the transfection of miR-let-7a minics further increased the tube length of cells, while reducing the expressions of THBS-1 and CD36. CONCLUSION Zedoarondiol has the effect of inhibiting neovascularization within plaque in AS mice, and its mechanism may be potentially related to inhibiting platelet activation and reducing the Pexo-derived miRNA-let-7a level.
Animals ; MicroRNAs/genetics* ; Exosomes/drug effects* ; Plaque, Atherosclerotic/genetics* ; Neovascularization, Pathologic/genetics* ; Human Umbilical Vein Endothelial Cells/metabolism* ; Humans ; Blood Platelets/drug effects* ; Apolipoproteins E/deficiency* ; Thrombospondin 1/metabolism* ; CD36 Antigens/metabolism* ; Platelet Activation/drug effects* ; Male ; Mice ; Mice, Inbred C57BL

OBJECTIVE: To evaluate the dynamic changes of glucocorticoid (GC) dose and the feasibility of GC discontinuation in rheumatoid arthritis (RA) patients under the background of Chinese medicine (CM). METHODS: This multicenter retrospective cohort study included 1,196 RA patients enrolled in the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine (CERTAIN) from September 1, 2019 to December 4, 2023, who initiated GC therapy. Participants were divided into the Western medicine (WM) and integrative medicine (IM, combination of CM and WM) groups based on medication regimen. Follow-up was performed at least every 3 months to assess dynamic changes in GC dose. Changes in GC dose were analyzed by generalized estimator equation, the probability of GC discontinuation was assessed using Kaplan-Meier curve, and predictors of GC discontinuation were analyzed by Cox regression. Patients with <12 months of follow-up were excluded for the sensitivity analysis. RESULTS: Among 1,196 patients (85.4% female; median age 56.4 years), 880 (73.6%) received IM. Over a median 12-month follow-up, 34.3% (410 cases) discontinued GC, with significantly higher rates in the IM group (40.8% vs. 16.1% in WM; P<0.05). GC dose declined progressively, with IM patients demonstrating faster reductions (median 3.75 mg vs. 5.00 mg in WM at 12 months; P<0.05). Multivariate Cox analysis identified age <60 years [P<0.001, hazard ratios (HR)=2.142, 95% confidence interval (CI): 1.523-3.012], IM therapy (P=0.001, HR=2.175, 95% CI: 1.369-3.456), baseline GC dose ⩽7.5 mg (P=0.003, HR=1.637, 95% CI: 1.177-2.275), and absence of non-steroidal anti-inflammatory drugs use (P=0.001, HR=2.546, 95% CI: 1.432-4.527) as significant predictors of GC discontinuation. Sensitivity analysis (545 cases) confirmed these findings. CONCLUSIONS RA patients receiving CM face difficulties in following guideline-recommended GC discontinuation protocols. IM can promote GC discontinuation and is a promising strategy to reduce GC dependency in RA management. (Trial registration: ClinicalTrials.gov, No. NCT05219214).
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Arthritis, Rheumatoid/drug therapy* ; Glucocorticoids/therapeutic use* ; Medicine, Chinese Traditional ; Retrospective Studies