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.

ObjectiveTo analyze the output and efficiency of chronic disease management services for hypertension and diabetes in community health service institutions in Shanghai, to evaluate the allocation and efficiency of chronic disease management resources, and to provide references for improving the efficiency of chronic disease management in Shanghai’s communities. MethodsA total of 73 community health institutions from 15 districts of Shanghai were selected. Based on the chronic disease management resource data of community health institutions in 2019, 2021, and 2023, descriptive methods and the BCC model in Data Envelopment Analysis (DEA) were used to analyze the resource allocation, service output, and the efficiency of chronic disease management services in community health institutions in Shanghai. ResultsFrom 2019 to 2023, the indicators of resource allocation and service output of community health service institutions in Shanghai all showed upward trends. In terms of service efficiency, the average number of chronic disease patients managed by each health technician decreased from 237 to 231, and the number of patients served per 1 000 working hours decreased from 54 to 44. DEA efficiency analyses showed that the average overall efficiency increased from 0.867 in 2019 to 0.886 in 2021 and then decreased to 0.811 in 2023. The average technical efficiency decreased from 0.901 to 0.847, which was the main reason for the decline in overall efficiency. The average scale efficiency showed an initial increase followed by a decrease, rising from 0.961 in 2019 to 0.977 in 2021 and dropping back to 0.955 in 2023. The number of strong effective districts (overall efficiency=1.000) decreased from 6 in 2019 to 3 in 2023, and the efficiency differences between districts expanded. The range of overall efficiency widened from 0.622‒1.000 to 0.513‒1.000, indicating a decline in overall efficiency and an increase in inter-district heterogeneity. ConclusionFrom 2019 to 2023, the total volume of resource allocation and service output for chronic disease management in community health service institutions in Shanghai increased continuously. However, both the service output efficiency and the overall resource allocation efficiency declined, driven primarily by a decrease in technical efficiency, and accompanied by widening inter‑district disparities.

Tumor immunotherapy has attracted worldwide attention in cancer treatment because of its obvious advantages such as strong specificity and long curative effect.It is found that activation of STING signaling pathway in cells is one of directions to effec-tively realize tumor immunotherapy.However,due to low response rate of related drugs,difficult degradation,certain toxic and side effects,its clinical application has been seriously hindered.Nano-drug delivery system can achieve targeted drug delivery,improve drug stability,delivery rate,osmotic effect and long-term retention effect,reduce drug side effects,and show significant advantages in tumor immunotherapy.In this paper,research progress of nano-drug delivery system activating STING pathway in tumor immunother-apy in recent years is reviewed,and many nano-drug delivery systems that can activate STING signal pathway and their application ex-amples after loading drugs are listed,including nucleotide-based drug delivery system,non-nucleotide-based drug delivery system and metal-based drug delivery system,providing reference for application of nano-drugs in tumor immunotherapy.

Tumor immunotherapy has attracted worldwide attention in cancer treatment because of its obvious advantages such as strong specificity and long curative effect.It is found that activation of STING signaling pathway in cells is one of directions to effec-tively realize tumor immunotherapy.However,due to low response rate of related drugs,difficult degradation,certain toxic and side effects,its clinical application has been seriously hindered.Nano-drug delivery system can achieve targeted drug delivery,improve drug stability,delivery rate,osmotic effect and long-term retention effect,reduce drug side effects,and show significant advantages in tumor immunotherapy.In this paper,research progress of nano-drug delivery system activating STING pathway in tumor immunother-apy in recent years is reviewed,and many nano-drug delivery systems that can activate STING signal pathway and their application ex-amples after loading drugs are listed,including nucleotide-based drug delivery system,non-nucleotide-based drug delivery system and metal-based drug delivery system,providing reference for application of nano-drugs in tumor immunotherapy.

Objective:To evaluate the role of the CC chemokine ligand 2/CC chemokine receptor 2 (CCL2/CCR2) signaling pathway in electroacupuncture (EA)-induced reduction of spinal cord injury (SCI) in rats.Methods:Sixty clean-grade healthy adult female Sprague-Dawley rats, weighing 210-250 g, were divided into 5 groups ( n=12 each) using a random number table method: sham operation group (group S), group SCI, SCI+ Anti-CCL2 group (group SCI+ A), SCI+ EA group (group SCI+ EA), and spinal cord injury+ EA+ rCCL2 group (group SCI+ EA+ R). The SCI model was established using the Allen method in anesthetized animals. Group S only underwent spinous process and laminectomy without damaging the spinal cord. In SCI+ A group, CCL2 neutralizing antibody 50 μg/kg was intrathecally injected at 0, 3 and 6 days after successful development of the SCI model. On the 7th day after the successful development of the SCI model, Jiaji, Dazhui and Mingmen acupoints were stimulated with a depth of 2 mm, voltage of 12-15 mV and frequency of 2 Hz for 30 min once a day for 7 consecutive days in SCI+ EA group. In SCI+ EA+ R group, recombinant rat CCL2 2.5 μg/kg was intrathecally injected at the site of injury at 0, 3 and 6 days after successful development of the SCI model, and the remaining treatments were similar to those in SCI+ EA group. At 1 day before developing the model, 0, 3, 7, 14, 21 and 28 days after developing the model, the mechanical paw withdraw threshold (MWT) and thermal paw withdrawal latency (TWL) were measured, and the motor function was assessed by BBB score. The rats were sacrificed after the final behavioral testing, and their spinal cord tissues were obtained for determination of the expression of CCL2 and CCR2 protein and mRNA (by Western blot or quantitative real-time polymerase chain reaction), the expression of GFAP (by immunofluorescence), contents of tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1β) and IL-6 (by enzyme-linked immunosorbent assay) and for examination of the pathological changes (using HE staining). Results:Compared with S group, the MWT and BBB scores were significantly decreased and the TWL was shortened at each time point after developing the model, the expression of CCL2 and CCR2 protein and mRNA and GFAP was up-regulated, and the contents of TNF-α, IL-1β and IL-6 were increased in SCI group ( P<0.05). Compared with SCI group, the MWT and BBB scores were significantly increased, and the TWL was prolonged at 7 days after developing the model in SCI+ A group, the MWT and BBB scores were significantly increased, and the TWL was prolonged at 14 days after developing the model in SCI+ EA group, and the expression of CCL2 and CCR2 protein and mRNA and GFAP was significantly down-regulated, and the contents of TNF-α, IL-1β and IL-6 were decreased in SCI+ A and SCI+ EA groups ( P<0.05). Compared with SCI+ EA group, the MWT and BBB scores were significantly decreased at 14 days after developing the model, the TWL was shortened, the expression of CCL2 and CCR2 protein and mRNA and GFAP was up-regulated, and the contents of TNF-α, IL-1β and IL-6 were increased in SCI+ EA+ R group ( P<0.05). Compared with SCI+ A and SCI+ EA groups, the histopathological injury were significantly attenuated in SCI group, and the histopathological injury was aggravated in SCI+ EA+ R group. Conclusions:The CCL2/CCR2 signaling pathway is involved in the process by which EA reduces SCI, and the mechanism is related to the inhibition of astrocyte activation, thereby reducing the inflammatory response.

Objective To investigate the anatomical structure and surface location of the Lieque(LU7)acupoint.Methods Firstly,the anatomical localization descriptions of the Lieque(LU7)acupoint from classical medical literature were reviewed and summarized.A total of 21 participants were recruited from Shandong Provincial Hospital Affiliated to Shandong First Medical University from January to March 2025.A Cartesian coordinate system was established over the Lieque(LU7)region on the right forearm.Following standardized manual pressure stimulation,the coordinates of the participant′s reported acupoint sensations were recorded.Based on surface pressure mapping result,10 participants were arbitrarily selected for acupuncture intervention.Upon elicitation of acupoint sensation,the ultrasound imaging was used for real-time visualization of anatomical spatial relationships between the needle tip and distal radial osseous landmarks.Five red latex-perfused adult upper limb specimens were selected for microdissection of the Lieque(LU7)regions pre-localized via ultrasonography,achieving definitive structural characterization of its anatomical strata.Another 10 participants were arbitrarily selected to find the physical structure of the Lieque(LU7)acupoint using ultrasound,and the similarities and differences of acupoint sensation responses were verified using acupuncture needle insertions into both the demarcated zone and peripheral tissues.Results The descriptions of the localization of the Lieque(LU7)acupoint in ancient books can be summarized as"one and a half cun above the wrist side"longitudinally,and"at the intersection head,between two tendons and two bones in the hollow"transversely.During surface pressure application,the sites of the participant′s elicited acupoint sensation were anatomically concentrated in the proximal depression adjacent to the radiopalmar ridge,specifically at the transitional interface between the extensor pollicis brevis tendon and scaphoid bone.During acupuncture-induced acupoint sensation,ultrasound imaging demonstrated that the location of the needle tip was located within the proximal depression adjacent to the radiopalmar ridge,accompanied by arterial hemodynamic perfusion signals into adjacent osseous interfaces.Microdissection findings revealed perforating branches of the radial artery traversing the cortical bone interface within the Lieque(LU7)acupoint region.Acupuncture stimulation at the proximal depression adjacent to the radiopalmar ridge elicited consistent acupoint sensations in all 10 participants,and the acupoint sensations differed from those of other surrounding tissues.Conclusion The anatomical structure of Lieque(LU7)acupoint is located within the proximal depression adjacent to the radiopalmar ridge,characterized by the presence of"hilus of bone"structure.

OBJECTIVE: Rhei Radix et Rhizoma has five types of products, namely, raw rhubarb (RR), wine rhubarb (WR), vinegar rhubarb (VR), cooked rhubarb (CR), and rhubarb charcoal (RC). However, Rhei Radix et Rhizoma is easily contaminated with fungi and mycotoxins if not harvested or processed properly. Here, we intend to analyze how microbiome assemblies and co-occurrence patterns are influenced by sampling locations and processing methods. METHODS: High-throughput sequencing and internal transcribed spacer 2 (ITS2) were carried out to study the diversities (α- and β-diversity), composition (dominant taxa and potential biomarkers), and network complexitity of surface fungi on RR, WR, VR, CR, and RC collected from Gansu and Sichuan provinces, China. RESULTS: The phyla Ascomycota and Basidiomycota; the genera Kazachstania, Malassezia, and Asterotremella; and the species Kazachstania exigua, Asterotremella pseudolonga, and Malassezia restricta were the dominant fungi and exhibited differences in the two provinces and the five processed products. The α-diversity and network complexity were strongly dependent on processing methods. Chao 1, the Shannon index, and network complexity and connectivity were highest in the CR group. The α-diversity and network complexity were influenced by sampling locations. Chao 1 and network complexity and connectivity were highest in the Gansu Province. CONCLUSION The assembly and network of the surface microbiome on Rhei Radix et Rhizoma were shaped by processing methods and sampling locations. This paper offers a comprehensive understanding of microorganisms, which can provide early warning for potential mycotoxins and ensure the safety of drugs and consumers.

OBJECTIVE: The investigation of the correlation between ecological factors and the genetic characteristics or metabolites of plants offers valuable insights into the regional causes of genetic and metabolic diversity. Here, Gastrodia elata, a medicinal plant, is employed as a model to explore the environmental factors that influence its genetic characteristics and metabolic accumulations. METHODS: A total of 23 G. elata populations from six cultispecies and 11 cultivated regions were selected based on the predictions of the global geographic information system. The genetic characteristics of these populations were evaluated using highly polymorphic simple sequence repeat markers. Additionally, the metabolic accumulations and antioxidant capacity of mature tubers were measured employing colorimetry and high performance liquid chromatography (HPLC). Ecological data of each region were obtained from the WorldClim-global climate database and harmonized world soil database. To assess the influence of ecological factors on the genetic characteristics and metabolic profiles of G. elata, Pearson's correlation analysis was conducted. RESULTS: Genetic variation among G. elata populations exceeded that within populations. Genetic diverisity, distance and structure manifested regional and species-specific patterns. Metabolic profiling and antioxidant capacity exhibited regional variations. Notably, the Lueyang region demonstrated that a content range of total polysaccharide, total protein, and phenolic glycosides was 9.34%-189.67% higher than the average. Similarly, in the Hubei region, total phenolic content, p-hydroxybenzyl alcohol content, and antioxidant indicators were observed to be higher than the average levels, by 106.57%, 136.47% and 12.50%-91.14%, respectively. Furthermore, ecological factors had a significant comprehensive impact on G. elata genetic characteristics (r > 0.256 and P < 0.05). Multivariate metabolite accumulations in G. elata were influenced by dominant ecological factors. Temperature notably impacted the accumulation of total protein (|r| > 0.528 and P < 0.05). Moisture, encompassing precipitation and soil content, significantly affected the production of phenolic glycosides (|r| > 0.503 and P < 0.05). CONCLUSION The genetic characteristics of G. elata manifested regional and species-specific patterns, with the metabolic accumulations and antioxidant capacity of mature tubers exhibited regional variations. Specifically, multivariate ecological factors comprehensively influenced genetic characteristics. Temperature and moisture played pivotal roles in regulating the accumulations of proteins and phenolic glycosides, respectively. These findings underscore the significant impact of ecological factors on the shaping of G. elata, highlighting their crucial role in enhancing the quality of Chinese medicinal materials.

Objective To investigate the anatomical structure and surface location of the Lieque(LU7)acupoint.Methods Firstly,the anatomical localization descriptions of the Lieque(LU7)acupoint from classical medical literature were reviewed and summarized.A total of 21 participants were recruited from Shandong Provincial Hospital Affiliated to Shandong First Medical University from January to March 2025.A Cartesian coordinate system was established over the Lieque(LU7)region on the right forearm.Following standardized manual pressure stimulation,the coordinates of the participant′s reported acupoint sensations were recorded.Based on surface pressure mapping result,10 participants were arbitrarily selected for acupuncture intervention.Upon elicitation of acupoint sensation,the ultrasound imaging was used for real-time visualization of anatomical spatial relationships between the needle tip and distal radial osseous landmarks.Five red latex-perfused adult upper limb specimens were selected for microdissection of the Lieque(LU7)regions pre-localized via ultrasonography,achieving definitive structural characterization of its anatomical strata.Another 10 participants were arbitrarily selected to find the physical structure of the Lieque(LU7)acupoint using ultrasound,and the similarities and differences of acupoint sensation responses were verified using acupuncture needle insertions into both the demarcated zone and peripheral tissues.Results The descriptions of the localization of the Lieque(LU7)acupoint in ancient books can be summarized as"one and a half cun above the wrist side"longitudinally,and"at the intersection head,between two tendons and two bones in the hollow"transversely.During surface pressure application,the sites of the participant′s elicited acupoint sensation were anatomically concentrated in the proximal depression adjacent to the radiopalmar ridge,specifically at the transitional interface between the extensor pollicis brevis tendon and scaphoid bone.During acupuncture-induced acupoint sensation,ultrasound imaging demonstrated that the location of the needle tip was located within the proximal depression adjacent to the radiopalmar ridge,accompanied by arterial hemodynamic perfusion signals into adjacent osseous interfaces.Microdissection findings revealed perforating branches of the radial artery traversing the cortical bone interface within the Lieque(LU7)acupoint region.Acupuncture stimulation at the proximal depression adjacent to the radiopalmar ridge elicited consistent acupoint sensations in all 10 participants,and the acupoint sensations differed from those of other surrounding tissues.Conclusion The anatomical structure of Lieque(LU7)acupoint is located within the proximal depression adjacent to the radiopalmar ridge,characterized by the presence of"hilus of bone"structure.

Objective:To evaluate the role of the CC chemokine ligand 2/CC chemokine receptor 2 (CCL2/CCR2) signaling pathway in electroacupuncture (EA)-induced reduction of spinal cord injury (SCI) in rats.Methods:Sixty clean-grade healthy adult female Sprague-Dawley rats, weighing 210-250 g, were divided into 5 groups ( n=12 each) using a random number table method: sham operation group (group S), group SCI, SCI+ Anti-CCL2 group (group SCI+ A), SCI+ EA group (group SCI+ EA), and spinal cord injury+ EA+ rCCL2 group (group SCI+ EA+ R). The SCI model was established using the Allen method in anesthetized animals. Group S only underwent spinous process and laminectomy without damaging the spinal cord. In SCI+ A group, CCL2 neutralizing antibody 50 μg/kg was intrathecally injected at 0, 3 and 6 days after successful development of the SCI model. On the 7th day after the successful development of the SCI model, Jiaji, Dazhui and Mingmen acupoints were stimulated with a depth of 2 mm, voltage of 12-15 mV and frequency of 2 Hz for 30 min once a day for 7 consecutive days in SCI+ EA group. In SCI+ EA+ R group, recombinant rat CCL2 2.5 μg/kg was intrathecally injected at the site of injury at 0, 3 and 6 days after successful development of the SCI model, and the remaining treatments were similar to those in SCI+ EA group. At 1 day before developing the model, 0, 3, 7, 14, 21 and 28 days after developing the model, the mechanical paw withdraw threshold (MWT) and thermal paw withdrawal latency (TWL) were measured, and the motor function was assessed by BBB score. The rats were sacrificed after the final behavioral testing, and their spinal cord tissues were obtained for determination of the expression of CCL2 and CCR2 protein and mRNA (by Western blot or quantitative real-time polymerase chain reaction), the expression of GFAP (by immunofluorescence), contents of tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1β) and IL-6 (by enzyme-linked immunosorbent assay) and for examination of the pathological changes (using HE staining). Results:Compared with S group, the MWT and BBB scores were significantly decreased and the TWL was shortened at each time point after developing the model, the expression of CCL2 and CCR2 protein and mRNA and GFAP was up-regulated, and the contents of TNF-α, IL-1β and IL-6 were increased in SCI group ( P<0.05). Compared with SCI group, the MWT and BBB scores were significantly increased, and the TWL was prolonged at 7 days after developing the model in SCI+ A group, the MWT and BBB scores were significantly increased, and the TWL was prolonged at 14 days after developing the model in SCI+ EA group, and the expression of CCL2 and CCR2 protein and mRNA and GFAP was significantly down-regulated, and the contents of TNF-α, IL-1β and IL-6 were decreased in SCI+ A and SCI+ EA groups ( P<0.05). Compared with SCI+ EA group, the MWT and BBB scores were significantly decreased at 14 days after developing the model, the TWL was shortened, the expression of CCL2 and CCR2 protein and mRNA and GFAP was up-regulated, and the contents of TNF-α, IL-1β and IL-6 were increased in SCI+ EA+ R group ( P<0.05). Compared with SCI+ A and SCI+ EA groups, the histopathological injury were significantly attenuated in SCI group, and the histopathological injury was aggravated in SCI+ EA+ R group. Conclusions:The CCL2/CCR2 signaling pathway is involved in the process by which EA reduces SCI, and the mechanism is related to the inhibition of astrocyte activation, thereby reducing the inflammatory response.