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 investigate the mechanism through which Danggui buxue decoction regulates neutrophil extracellular traps （NETs） to improve osteoporosis （OP） in rats with premature ovarian failure （POF）. METHODS Female SD rats were randomly divided into normal group， model group， calcitriol group， and Danggui buxue decoction low-dose， medium-dose and high-dose groups， with 9 rats in each group. Except for the normal group， all other groups were administered cisplatin via intraperitoneal injection on days 1 and 8 to establish a POF complicated with OP model. Each group received the corresponding drugs or normal saline intragastrically starting from day 5， once a day， for 4 consecutive weeks. After the last medication， serum levels of estradiol （E2）， NETs， 25-hydroxyvitamin D3 [25（OH）D3]， receptor activator of nuclear factor-κB ligand （RANKL）， and osteocalcin （BGP） were measured. The histopathological changes in bone tissue were observed. The expressions of vitamin D receptor （VDR）， myeloperoxidase （MPO）， neutrophil elastase （NE） and citrullinated histone H3 （CitH3） in bone tissue were detected； the protein expressions of 25-hydroxyvitamin D-1α-hydroxylase （CYP27B1） and 1α，25-dihydroxyvitamin D3-24-hydroxylase （CYP24A1） were also determined. RESULTS Compared with the normal group， the bone tissue of rats in the model group showed a significant reduction in the number of trabeculae， which was thinner broken and poorly connected， with significant destruction of the reticular structure， and an enlarged marrow cavity. Serum levels of NETs and RANKL， the protein expressions of MPO， NE， CitH3 and CYP24A1 in bone tissue were significantly increased or upregulated， while serum levels of E2， 25（OH）D3 and BGP as well as protein expressions of VDR and CYP27B1 were significantly decreased or downregulated （P＜0.05）. Compared with the model group， the histopathological changes in the bone tissue of rats in each administration group showed some degree of recovery， with significant improvements observed in most quantitative indicators （P＜0.05）. CONCLUSIONS Danggui buxue decoction can restore the E2 level in POF complicated with OP rats， and improve OP. The mechanism may be related to its ability to upregulate VD level and inhibit the formation of NETs.

This study aimed to explore the molecular mechanism of rubioncolin C(RuC) in inhibiting gastric cancer(GC). AGS and MGC803 cell lines were selected as cellular models. After treating the cells with RuC at different concentrations, the effects of RuC on the proliferation ability of GC cells were assessed using the CCK-8 method, real-time cellular analysis(RTCA), and colony formation assays. Transmission electron microscopy was used to observe subcellular structural changes. Immunofluorescence was applied to detect LC3 fluorescent foci. Acridine orange staining was used to evaluate the state of intracellular lysosomes. Western blot was employed to detect the expression of autophagy-related proteins LC3Ⅱ, P62, and lysosomal cathepsin D(CTSD). The SuperPred online tool was used to predict the target proteins that bound to RuC, and molecular docking analysis was conducted to identify the interaction sites between RuC and CTSD. The drug affinity responsive target stability(DARTS) assay was performed to detect the direct binding interaction between RuC and CTSD. The results showed that RuC significantly inhibited the proliferation and colony formation of GC cells at low concentrations, with 24-hour half-maximal inhibitory concentrations(IC_(50)) of 3.422 and 2.697 μmol·L~(-1) for AGS and MGC803 cells, respectively. After 24 hours of treatment with RuC at concentrations of 1, 2, and 3 μmol·L~(-1), the colony formation rates for AGS cells were 61.0%±1.5%, 28.0%±0.5%, and 18.2%±0.5%, respectively, while the rates for MGC803 cells were 56.0%±0.5%, 23.3%±1.0%, and 11.8%±1.0%, all of which were significantly reduced. Transmission electron microscopy revealed that RuC promoted an increase in autophagosome formation in GC cells. Immunofluorescence detection showed that LC3 fluorescent foci of GC cells increased with the increase in RuC dose. RuC up-regulated the expression of autophagy-related proteins LC3Ⅱ and P62 in GC cells. Acridine orange staining indicated that RuC altered the acidic environment of lysosomes. SuperPred online prediction identified CTSD as a potential target protein of RuC. Western blot analysis revealed that RuC induced the up-regulation of the inactive precursor of CTSD in GC cells. CTSD activity assays indicated that RuC reduced the activity of CTSD. Molecular docking simulations found that RuC bound to the substrate-binding region of CTSD, forming hydrogen bonds with the Tyr205 and Asp231 residues. Microscale thermophoresis and DARTS assays further confirmed that RuC directly bound to CTSD. In summary, RuC inhibits lysosomal activity by targeting and down-regulating the expression of CTSD, thereby inducing autophagosome accumulation in GC cells.
Humans ; Stomach Neoplasms/enzymology* ; Cathepsin D/chemistry* ; Cell Line, Tumor ; Molecular Docking Simulation ; Cell Proliferation/drug effects* ; Autophagosomes/metabolism* ; Autophagy/drug effects*

This study aims to explore the effects and action mechanisms of the active ingredients in Buyang Huanwu Decoction(BYHWD), namely tetramethylpyrazine(TMP) and hydroxy-safflor yellow A(HSYA), on oxygen-glucose deprivation/reglucose-reoxygenation(OGD/R)-induced inflammation and oxidative stress of microglia(MG). Network pharmacology was used to screen the effective monomer ingredients of BYHWD and determine the safe concentration range for each component. Inflammation and oxidative stress models were established to further screen the best ingredient combination and optimal concentration ratio with the most effective anti-inflammatory and antioxidant effects. OGD/R BV2 cell models were constructed, and BV2 cells in the logarithmic growth phase were divided into a normal group, a model group, an HSYA group, a TMP group, and an HSYA + TMP group. Enzyme-linked immunosorbent assay(ELISA) was used to detect the levels of inflammatory cytokines such as interleukin-1β(IL-1β), tumor necrosis factor-α(TNF-α), and interleukin-6(IL-6). Oxidative stress markers, including superoxide dismutase(SOD), nitric oxide(NO), and malondialdehyde(MDA), were also measured. Western blot was used to analyze the protein expression of both inflammation-related pathway [Toll-like receptor 4(TLR4)/nuclear factor-kappa B(NF-κB)] and oxidative stress-related pathway [nuclear factor erythroid 2-related factor 2(Nrf2)/heme oxygenase-1(HO-1)]. Immunofluorescence was used to assess the expression of proteins such as inducible nitric oxide synthase(iNOS) and arginase-1(Arg-1). The most effective ingredients for anti-inflammatory and antioxidant effects in BYHWD were TMP and HSYA. Compared to the normal group, the model group showed significantly increased levels of IL-1β, TNF-α, IL-6, NO, and MDA, along with significantly higher protein expression of NF-κB, TLR4, Nrf2, and HO-1 and significantly lower SOD levels. The differences between the two groups were statistically significant. Compared to the model group, both the HSYA group and the TMP group showed significantly reduced levels of IL-1β, TNF-α, IL-6, NO, and MDA, lower expression of NF-κB and TLR4 proteins, higher levels of SOD, and significantly increased protein expression of Nrf2 and HO-1. Additionally, the expression of the M1-type MG marker iNOS was significantly reduced, while the expression of the M2-type MG marker Arg-1 was significantly increased. The results of the HSYA group and the TMP group had statistically significant differences from those of the model group. Compared to the HSYA group and the TMP group, the HSYA + TMP group showed further significant reductions in IL-1β, TNF-α, IL-6, NO, and MDA levels, along with significant reductions in NF-κB and TLR4 protein expression, an increase in SOD levels, and elevated Nrf2 and HO-1 protein expression. Additionally, the expression of the M1-type MG marker iNOS was reduced, while the M2-type MG marker Arg-1 expression increased significantly in the HSYA + TMP group compared to the TMP or HSYA group. The differences in the results were statistically significant between the HSYA + TMP group and the TMP or HSYA group. The findings indicated that the combined use of HSYA and TMP, the active ingredients of BYHWD, can effectively inhibit OGD/R-induced inflammation and oxidative stress of MG, showing superior effects compared to the individual use of either component.
Oxidative Stress/drug effects* ; Drugs, Chinese Herbal/pharmacology* ; Animals ; Mice ; Glucose/metabolism* ; Cell Line ; Inflammation/genetics* ; Oxygen/metabolism* ; Pyrazines/pharmacology* ; Microglia/metabolism* ; NF-E2-Related Factor 2/immunology* ; NF-kappa B/immunology* ; Toll-Like Receptor 4/immunology* ; Anti-Inflammatory Agents/pharmacology* ; Humans

OBJECTIVE: Meta-analysis of the clinical efficacy of plate and external fixator fixation in the treatment of AO-C type distal radius fractures. METHODS: PubMed, Embase, Cochrane Medical Library, Web of Science, CNKI, Wanfang, VIP and SinoMed databases were searched for all literature on randomized controlled clinical trials of AO-C distal radius fractures. The search time limits were from each database. The database will be established until June 30, 2023. The included studies were extracted according to the Cochrane Handbook (Version 6.3, 2022) for information extraction and literature quality evaluation. RevMan 5.4 was used to evaluate the risk of Publication bias, test heterogeneity and Perform Meta-analysis. The outcome indicators were:imaging anatomy indicators (volar inclination angle, ulnar deviation angle, radial height), wrist joint mobility (flexion, extension, rotation, ulnar deviation), complication rate, and comparison of surgical treatments (operative blood loss, operation time, hospitalization time, fracture healing time) and wrist joint function scores and related scales. RESULTS: (1) A total of 28 studies were included, with a total of 2 192 patients, including 1 096 cases in the plate internal fixation group and 1 096 cases in the external fixation group.(2) Meta analysis results showed:the surgical treatment situation of the external fixation group:surgical blood loss MD=-37.93, 95%CI(-48.54, -27.31), P<0.000 01;operation time MD=-31.58, 95%CI(-48.96, -14.20), P<0.000 4;hospitalization time MD=-4.58, 95%CI(-5.44, -3.71), P<0.000 01;the fracture healing time MD=-0.88, 95%CI(-1.35, -0.41), P<0.000 2, which were significantly better than that of the plate internal fixation group(P<0.05).(3) The two groups:palmar inclination angle MD=-0.17, 95%CI(-0.95, 0.61), P=0.68;ulnar declination MD=0.22, 95%CI(-0.73, 1.17), P=0.65, radial height MD=-0.24, 95%CI(-1.15, 0.67), P=0.60;flexion and extension MD=-5.63, 95%CI(-11.85, 0.58), P=0.08;rotation MD=-5.80, 95%CI(-12.77, 1.17), P=0.10, radioulnar deviation MD=-2.86, 95%CI(-10.87, 5.15), P=0.48;complication rate RR=0.96, 95%CI(0.63, 1.46), P=0.83;Gartland-Werley clinical wrist score MD=0.13, 95%CI(-0.80, 1.06), P=0.78;excellent and good rate of Gartland-Werley wrist clinical score RR=0.93, 95%CI(0.87, 1.01), P=0.08;excellent and good rate of Cooney wrist score RR=0.99, 95%CI(0.62, 1.59), P=0.98;wrist DASH score MD=-4.67, 95%CI(-14.96, 5.62), P=0.37;the differences were not significant (P>0.05). CONCLUSION Compared with internal fixation with plate, external fixation can significantly reduce the amount of surgical bleeding, shorten the operation time, hospitalization time and fracture healing time, and its imaging anatomical indicators, wrist mobility, and complications can be significantly reduced in treating AO-C distal radius fractures. Rates and wrist function scores were equivalent.
Humans ; External Fixators ; Bone Plates ; Radius Fractures/surgery* ; Fracture Fixation/methods* ; Fracture Fixation, Internal ; Wrist Fractures

Cervical spine health issues not only seriously affect patients' quality of life but also impose a heavy burden on the social healthcare system. Existing guidelines lack sufficient clinical guidance on lifestyle and work habits, such as exercise, posture, daily routine, and diet, making it difficult to meet practical needs. To address this, relying on the China Association of Chinese Medicine, Wangjing Hospital of China Academy of Chinese Medical Sciences took the lead and joined hands with more than ten institutions to form a multidisciplinary guideline development group. For the first time, the group developed the Guidelines for Cervical Spine Health Intervention based on evidence-based medicine methods, strictly following the standardized procedures outlined in the World Health Organization Handbook for Guideline Development and the Guiding Principles for the Formulation/Revision of Clinical Practice Guidelines in China (2022 Edition). This proposal systematically explains the methods and steps for developing the guideline, aiming to make the guideline development process scientific, standardized, and transparent.
Humans ; Practice Guidelines as Topic/standards* ; Cervical Vertebrae ; China

A 12-year-old boy was admitted with symptoms of cough and fever lasting over a month, accompanied by weight loss 2 kg. Prior anti-infective treatments proved ineffective in alleviating the symptoms. Chest imaging revealed diffuse interstitial pulmonary edema in the right lung with obstructed lymphatic drainage. Combined with histopathological examinations, the diagnosis was confirmed as lung cancer with pulmonary lymphangitic carcinomatosis. The patient underwent chemotherapy with docetaxel and carboplatin, yet the disease progressively worsened, resulting in death three months after diagnosis. This case highlights lung cancer should not be overlooked in patients with persistent respiratory symptoms of unknown etiology. Early imaging examinations, along with necessary pathological evaluations, are crucial for timely detection and diagnosis. The presence of pulmonary lymphangitic carcinomatosis often indicates an advanced-stage of cancer, associated with a poor prognosis.
Humans ; Male ; Lung Neoplasms/complications* ; Child ; Carcinoma/drug therapy*