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 thyroid gland is the largest endocrine organ in the human body， and its dysfunction can cause varying degrees of liver injury， leading to liver failure in severe cases. Patients with hyperthyroidism have a relatively high incidence rate of liver dysfunction， manifesting as hepatocellular injury or cholestatic liver injury， while hypothyroidism is closely associated with metabolic dysfunction-associated fatty liver disease. Autoimmune thyroid diseases， including Hashimoto’s thyroiditis and subacute thyroiditis， are commonly comorbid with autoimmune liver disease. In addition， medications such as antithyroid drugs， amiodarone， and immune checkpoint inhibitors can cause severe liver injury through direct toxicity or immune-mediated mechanisms. Although significant progress has been achieved in related diagnosis and treatment techniques in recent years， there are still many challenges in pathogenesis， individualized treatment strategies， early warning， and prognostic evaluation. This article systematically reviews the research advances in liver injury associated with thyroid dysfunction and proposes the directions for future research， in order to provide guidance for clinical diagnosis and treatment.

Objective: To prepare the erythrocyte-liposome drug delivery system to enhance the therapeutic effect of drugs on tumors and inhibit tumor metastasis. Methods: This study prepared and characterized paclitaxel (PTX)-plerixafor (AMD3100) liposomes (Lips), developed the erythrocyte-liposome drug delivery system, and evaluated its targeting efficiency and therapeutic efficacy through a series of in vitro cellular and in vivo animal experiments. Results: The particle size of PTX-AMD-Lips was (186.4±0.83) nm. Drug encapsulation efficiency of PTX-AMD-Lips was (75.50±5.27)% for PTX and (88.31±2.45)% for AMD. The Binding efficiency between RBC and liposomes in the drug delivery system was (69.93±2.55)%. Vitro cellular experiments revealed that PTX-AMD-Lips significantly inhibited tumor cell migration. In vivo animal experiments, the erythrocyte-liposome drug delivery system significantly increased drug accumulation in the lungs. At the experimental endpoint, the quantitative fluorescence signal of tumor size measured (4.04±0.44)×10 for the PTX-Lips group, and (5.14±3.40)×10 for the RBC-PTX-AMD-Lips group. Conclusion: The erythrocyte-liposome drug delivery system could enhance the lung-specific targeting capability of liposomes, kill tumor cells and suppress further metastasis effectively.

BACKGROUND:The diabetic microenvironment can cause excessive M1 polarization of macrophages,and this hyperglycemic inflammatory state can inhibit osteogenic differentiation of bone marrow mesenchymal stem cells,thus affecting the healing of diabetic bone defects.Studies have indicated that mogroside V possesses anti-inflammatory,antioxidant,and hypoglycemic properties.However,its potential to modulate M1 polarization of macrophages and osteogenic differentiation of bone marrow mesenchymal stem cells under high glucose and inflammatory condition remains unclear. OBJECTIVE:To explore the effect of mogroside V on regulating M1 macrophage polarization and its effect on osteogenic differentiation of bone marrow mesenchymal stem cells under high glucose and inflammatory condition. METHODS:Murine diabetic models were established using C57BL/6 mice.Bone marrow-derived macrophages were isolated from tibia and fibula of normal and diabetic mice,and cultured in low-glucose and high-glucose media.Then M1 polarization of bone marrow-derived macrophages was induced using lipopolysaccharide and interferon-γ.Bone marrow-derived macrophages were treated with 160,320,and 640 μmol/L mogroside V.Flow cytometry was employed to determine the proportion of F4/80+CD86+cells.qRT-PCR was utilized to assess mRNA expression levels of inducible nitric oxide synthase,interleukin 1β,and interleukin 6.ELISA was employed to evaluate tumor necrosis factor-α secretion in bone marrow-derived macrophage supernatants.Bone marrow mesenchymal stem cells were isolated from tibia and fibula of C57BL/6 suckling mice,and induced osteogenic differentiation using low-or high-glucose osteogenic induction medium.Bone marrow mesenchymal stem cells were treated with M1 macrophage-conditioned mediums with or without 320 μmol/L mogroside V in osteogenic differentiation process.qRT-PCR was employed to assess the mRNA expression of alkaline phosphatase,Runt-related factor 2,osteocalcin,and osteopontin on day 14 after osteogenic induction.Alizarin red staining and quantitative analysis were conducted to evaluate calcium deposition on day 21 after osteogenic induction. RESULTS AND CONCLUSION:(1)Flow cytometry results showed that with the treatment of 320 and 640 μmol/L mogroside V,the proportion of F4/80+CD86+bone marrow-derived macrophages was significantly lower than that in the high-glucose control group(P<0.05).(2)qRT-PCR results showed that with the treatment of 160,320,and 640 μmol/L mogroside V,the mRNA expression levels of inducible nitric oxide synthase and interleukin 6 were significantly lower than that in the high-glucose control group(P<0.05).With the treatment of 320 and 640 μmol/L mogroside V,the mRNA expression level of interleukin 1β was significantly lower than that in the high-glucose control group(P<0.05).(3)ELISA results exhibited that with the treatment of 160,320,and 640 μmol/L mogroside V,the tumor necrosis factor-α secretion level was significantly lower than that in the high-glucose control group(P<0.05).(4)With the treatment of 320 μmol/L mogroside V,calcium salt deposition was increased in bone marrow mesenchymal stem cells under high glucose and inflammatory conditions(P<0.05),and the mRNA relative expression levels of alkaline phosphatase,Runt-related factor 2,and osteopontin were increased(P<0.05).These findings indicate that mogroside V can promote osteogenic differentiation of bone marrow mesenchymal stem cells by inhibiting the M1 polarization of bone marrow-derived macrophages under high glucose and inflammatory conditions and reducing the generation of inflammatory factors.

[Objective] To investigate the effect of Shenmai injection on the preservation quality of suspended red blood cells of high hemoglobin population in Xizang plateau. [Methods] Whole blood (400 mL, n=8) collected by the Xizang Autonomous Region Blood Center was centrifuged at 3 000 g for 10 minutes to remove most of the plasma, followed by the addition of 100 mL of MAP preservation solution to obtain plateau suspended red blood cells, which were then divided into three equal portions. One portion was the control group, and another part had 15 mL of MAP preservation solution added, which was the dosage group. The third portion involved diluting Shenmai injection with MAP, followed by addition of 15 mL of MAP preservation solution containing Shenmai to the red blood cells, resulting in a final concentration of Shenmai injection of 1%, which was the Shenmai group. Blood routine, pH value, electrolytes, glucose, lactate, free Hb, adenosine triphosphate (ATP), P50, phosphatidylserine (PS) and other indicators were detected at day 1, 21 and 35, respectively. [Results] The Hb concentration and Hct of the dosage group and the Shenmai group were significantly lower than those of the control group, with values of (179.3±17.8) vs (181.0±17.1) vs (199.1±19.5) g/L for Hb concentration and (53.2±2.6)% vs (53.3±2.5)% vs (58.4±3.1)% for Hct. The three groups maintained this pattern until the end of storage. In the middle and late stages of preservation, the glucose and Na⁺ contents in the dosage group and the Shenmai group were higher than those in the control group, while the lactate and K⁺ contents were lower than those in the control group. At the end of storage, the glucose and Na⁺ content of the Shenmai group was higher than that of the dosage group, while the lactate and K⁺ content were lower than that of the dosage group. From day 1 to day 35 of storage, the hemolysis rate of the Shenmai group was significantly lower than that of the control group and the dosage group. On day 21 and 35 of storage, the PS expression rate in the Shenmai group was significantly lower than that in the control group and the dosage group, which were (6.52±0.40)% vs (7.24±0.91)% vs (8.27±0.93)% and (7.29±0.53)% vs (9.37±0.82)% vs (8.39±0.76)%, respectively. [Conclusion] The hemolysis rate and PS of suspended red blood cells of Xizang high altitude prepared by adding Shenmai injection were significantly lower than those in the control group and the dosage group, which was conducive to reducing hemolysis and slowing down the aging of red blood cells, and had a certain improvement on the preservation quality of suspended red blood cells in Xizang plateau people.

[Objective] To use Chitosan Methacryloyl (CSMA) loaded with artificial platelet-derived exosomes (aPexos) as the needle body material, and gelatin and carboxymethyl chitosan (CMCS) loaded with Epigallocatechin gallate(EGCG) as the backing material to prepare microneedles, aims to investigate the therapeutic effect and mechanism of aPexos-EGCG microneedles in the treatment of burn wound healing. [Methods] First, aPexos were extracted using ultrasound and gradient ultracentrifugation. The concentration, morphology, and growth factor content (TGF-β1, PDGF-BB, VEGF) of the exosomes were assessed using NTA, transmission electron microscopy, and ELISA kits. The aPexos and EGCG were then dissolved in the needle body and backing materials, respectively. The aPexos and EGCG were loaded into the needle body and backing layer, respectively. The morphology, mechanical properties, and puncture performance of the microneedles were examined, and the preparation conditions for the microneedles loaded with aPexos-EGCG were optimized. Finally, animal experiments and tissue staining were conducted to assess the efficacy of the aPexos-EGCG microneedles in promoting burn wound healing in rats. [Results] The size distribution of aPexos was mainly in the range of 50-150 nm, with an average diameter of 132.7±3.8 nm and an average concentration of approximately 2.88×10¹³±3.62×10¹² particles/mL. The concentrations of TGF-β1, PDGF-BB, and VEGF were approximately 1 363±135.9 ng/mL, 63.5±14.8 ng/mL, and 1 606.0±77.5 pg/mL, respectively. Mechanical property testing of the microneedles indicated that, compared with the blank microneedles, the drug-loaded microneedles had sufficient piercing ability to penetrate the stratum corneum of the skin. The results of the rat burn wound healing experiment showed that the wound healing rates of the d 3, d 7, aPexos-EGCG microneedle group compared to the control group showed significant differences, with respective values of (47.64±12.5)% vs (18.11±6.40)%, (87.45±5.57)% vs (79.85±5.03)%(P<0.05). Hematoxylin-eosin (HE) staining revealed more intact epidermal layers in the aPexos-EGCG microneedle group. Masson staining showed that the collagen deposition percentage in the aPexos-EGCG microneedle group was higher than in the control group. Immunofluorescence staining results indicated that the aPexos-EGCG microneedle group had a reduced content of M1-type macrophages and an increased content of M2-type macrophages. Additionally, the vascular markers CD31 and α-SMA showed elevated expression in this group, with significant differences compared to the other groups (P<0.05). [Conclusion] The aPexos-EGCG microneedle developed in this study exhibits good mechanical properties, capable of successfully penetrating the skin's stratum corneum and delivering aPexos and EGCG. aPexos promotes wound repair, while EGCG regulates the ratio of M1 and M2 macrophages at the wound site and suppresses the inflammatory response. This microneedle can effectively promote wound healing in rats with burn injuries, offering a novel approach for tissue repair.

Objective:To explore the application value of P1 response threshold of cortical auditory evoked potential（CAEP） in evaluating the rehabilitation effect of cochlear implant in young children. Methods:Thirty-three young children after cochlear implantation were divided into groups according to hearing age: Group A（hearing age 1-<2 years old） 10 people; Group B（hearing age 2-<3 years old） 13 people; Group C（hearing age 3-<4 years old） 10 people. The subjective assessment was carried out using the assessment tool for hearing-impaired children- "Criteria and Methods for assessing Auditory and language ability of hearing-impaired children" and objective electrophysiological examination was carried out using CAEP to evaluate the rehabilitation effect. SPSS 25.0 software was used for statistical analysis. Results:The results of subjective assessment of auditory ability and language ability in each group showed an increasing trend with the increase of auditory age. In this study, the P1 response threshold of CAEP in CI implanted children had a significant positive correlation with the 2 kHz hearing threshold after intervention, and the P1 response threshold of CAEP was negatively correlated with many items in subjective auditory ability and language ability assessment. Conclusion:The P1 response threshold of CAEP has a stable correlation with the results of speech audiometry, which can effectively and objectively evaluate the postoperative rehabilitation effect of young children with cochlear implantation.
Humans ; Child, Preschool ; Infant ; Male ; Female ; Evoked Potentials, Auditory ; Cochlear Implantation/rehabilitation* ; Cochlear Implants ; Auditory Threshold

Cyclin-dependent kinase 9 (CDK9) is a member of the transcription CDK subfamily and plays a role in transcriptional regulation. Selective CDK9 degraders possess potent clinical advantages over reversible CDK9 inhibitors. Herein, we report the first ATG101-recruiting selective CDK9 degrader, AZ-9, based on the hydrophobic tag kinesin degradation technology. AZ-9 showed significant degradation effects and selectivity toward other homologous cell cycle CDKs in vitro and in vivo, which could also affect downstream related phenotypes. Mechanism research revealed that AZ-9 recruits ATG101 to initiate the autophagy-lysosome pathway, and forms autophagosomes through the recruitment of LC3, which then fuses with lysosomes to degrade CDK9 and the partner protein Cyclin T1. These dates validated the existence of non-proteasomal degradation pathway of hydrophobic driven protein degradation strategy for the first time, which might provide research ideas for chemical induction intervention on other types of pathogenic proteins.

Cemental tear is a rare and indetectable condition unless obvious clinical signs present with the involvement of surrounding periodontal and periapical tissues. Due to its clinical manifestations similar to common dental issues, such as vertical root fracture, primary endodontic diseases, and periodontal diseases, as well as the low awareness of cemental tear for clinicians, misdiagnosis often occurs. The critical principle for cemental tear treatment is to remove torn fragments, and overlooking fragments leads to futile therapy, which could deteriorate the conditions of the affected teeth. Therefore, accurate diagnosis and subsequent appropriate interventions are vital for managing cemental tear. Novel diagnostic tools, including cone-beam computed tomography (CBCT), microscopes, and enamel matrix derivatives, have improved early detection and management, enhancing tooth retention. The implementation of standardized diagnostic criteria and treatment protocols, combined with improved clinical awareness among dental professionals, serves to mitigate risks of diagnostic errors and suboptimal therapeutic interventions. This expert consensus reviewed the epidemiology, pathogenesis, potential predisposing factors, clinical manifestations, diagnosis, differential diagnosis, treatment, and prognosis of cemental tear, aiming to provide a clinical guideline and facilitate clinicians to have a better understanding of cemental tear.
Humans ; Dental Cementum/injuries* ; Consensus ; Diagnosis, Differential ; Cone-Beam Computed Tomography ; Tooth Fractures/therapy*

BACKGROUND: The use of inserted sham acupuncture as a placebo in randomized controlled trials (RCTs) is controversial, because it may produce specific effects that cause an underestimation of the effect of acupuncture treatment. OBJECTIVE: This systematic survey investigates the magnitude of insert-specific effects of sham acupuncture and whether they affect the estimation of acupuncture treatment effects. SEARCH STRATEGY: PubMed, Embase and Cochrane Central Register of Controlled Trials were searched to identify acupuncture RCTs from their inception until December 2022. INCLUSION CRITERIA: RCTs that evaluated the effects of acupuncture compared to sham acupuncture and no treatment. DATA EXTRACTION AND ANALYSIS: The total effect measured for an acupuncture treatment group in RCTs were divided into three components, including the natural history and/or regression to the mean effect (controlled for no-treatment group), the placebo effect, and the specific effect of acupuncture. The first two constituted the contextual effect of acupuncture, which is mimicked by a sham acupuncture treatment group. The proportion of acupuncture total effect size was considered to be 1. The proportion of natural history and/or regression to the mean effect (PNE) and proportional contextual effect (PCE) of included RCTs were pooled using meta-analyses with a random-effect model. The proportion of acupuncture placebo effect was the difference between PCE and PNE in RCTs with non-inserted sham acupuncture. The proportion of insert-specific effect of sham acupuncture (PIES) was obtained by subtracting the proportion of acupuncture placebo effect and PNE from PCE in RCTs with inserted sham acupuncture. The impact of PIES on the estimation of acupuncture's treatment effect was evaluated by quantifying the percentage of RCTs that the effect of outcome changed from no statistical difference to statistical difference after removing PIES in the included studies, and the impact of PIES was externally validated in other acupuncture RCTs with an inserted sham acupuncture group that were not used to calculate PIES. RESULTS: This analysis included 32 studies with 5492 patients. The overall PNE was 0.335 (95% confidence interval [CI], 0.255-0.415) and the PCE of acupuncture was 0.639 (95% CI, 0.567-0.710) of acupuncture's total effect. The proportional contribution of the placebo effect to acupuncture's total effect was 0.191, and the PIES was 0.189. When we modeled the exclusion of the insert-specific effect of sham acupuncture, the acupuncture treatment effect changed from no difference to a significant difference in 45.45% of the included RCTs, and in 40.91% of the external validated RCTs. CONCLUSION The insert-specific effect of sham acupuncture in RCTs represents 18.90% of acupuncture's total effect and significantly affects the evaluation of the acupuncture treatment effect. More than 40% of RCTs that used inserted sham acupuncture would draw different conclusions if the PIES had been controlled for. Considering the impact of the insert-specific effect of sham acupuncture, caution should be taken when using inserted sham acupuncture placebos in RCTs. Please cite this article as: Luo XC, Liu JL, Yao MH, Chen YM, Fan AY, Liang FR, Zhao JP, Zhao L, Zhou X, Zhong XY, Yang JH, Li B, Zhang Y, Sun X, Li L. Specific effect of inserted sham acupuncture and its impact on the estimation of acupuncture treatment effect in randomized controlled trials: A systematic survey. J Integr Med. 2025; 23(6):630-640.
Acupuncture Therapy/methods* ; Humans ; Randomized Controlled Trials as Topic ; Placebo Effect ; Placebos ; Treatment Outcome