Liver cancer, one of the most common primary malignancies in humans, is a malignant tumor characterized by multifactorial induction, polygenic involvement, and intricate molecular mechanisms. This disease is characterized by its treatment challenges and poor prognosis, which are closely related to its unique tumor microenvironment composition. The tumor microenvironment of liver cancer is a dynamic ecosystem composed of heterogeneous cellular populations, soluble cytokines, and remodeled extracellular matrix. In recent years, significant progress has been made in the study of the tumor microenvironment of liver cancer, revealed an important role in the occurrence, development, and treatment of liver cancer. The key regulatory elements of the tumor microenvironment in liver cancer were systematically summarized, such as activation of hepatic stellate cells, dysfunction of immune cells, abnormalities of platelet, and remodeling of the extracellular matrix, which provided theoretical foundations for prevention and treatment strategies against liver cancer.

Objective To observe the therapeutic effect and mechanism of external application with Shilian Powder combined with oral administration of Shumai Capsules for the treatment of rats with diabetic foot ulcer(DFU).Methods Eight male rats with successfully modeled foot ulcer(DF)were used as the control group.While 24 male rats with successfully modeled DFU were randomly divided into DFU group,Shumai Capsules group and Shilian Powder combined with Shumai Capsules group,with eight rats in each group.After the corresponding interventions,we determined the wound healing rate,histopathological changes of wound,levels of inflammatory factors such as interleukin(IL)-6,IL-1β and vascular endothelial growth factor(VEGF)in serum,levels of Apelin and Relaxin,and protein expressions of phosphatidylinositol 3-kinase(PI3K),protein kinase B(AKT)and VEGF in wound tissue,as well as mRNA expressions of PI3K,AKT,Relaxin and Apelin.Results Compared with the control group,the DFU group showed a significant decrease in wound healing rate,VEGF level in serum and wound,wound Relaxin level,protein and mRNA levels of wound AKT(P<0.05),and a significant increase in serum IL-6 and IL-1β levels,wound Apelin level,wound PI3K protein and mRNA levels(P<0.05),and the reduced wound granulation tissue and formation of new capillaries and increased inflammatory cell infiltration were seen under the microscope.Compared with the DFU group,the wound healing rate,VEGF level in serum and wound,wound Relaxin and Apelin levels,protein and mRNA levels of wound PI3K and AKT in the Shumai Capsules group and Shilian Powder combined with Shumai Capsules group were significantly increased(P<0.05),and serum IL-6 and IL-1β levels were significantly decreased(P<0.05),and the increased wound granulation tissue and formation of new capillaries and reduced inflammatory cell infiltration were seen under the microscope.Compared with the Shumai Capsules group,the wound healing rate,wound VEGF level,wound Relaxin and Apelin levels,protein and mRNA levels of wound PI3K and AKT in Shilian Powder combined with Shumai Capsules group were significantly increased(P<0.05),and the serum IL-6 and IL-1β levels were significantly decreased(P<0.05),and the increased wound granulation tissue and formation of new capillaries and reduced inflammatory cell infiltration were seen under the microscope.Conclusion External application with Shilian Powder combined with oral administration of Shumai Capsules can promote the wound healing in rats with DFU,its mechanism is related to the activation of PI3K/AKT/Relaxin/Apelin signaling pathway.

Objective To analyze the correlation of inflammatory indicators of neutrophil-to-lymphocyte ratio(NLR),platelet-to-lymphocyte ratio(PLR),monocyte-to-lymphocyte ratio(MLR),and systemic immune-inflammation index(SII)with traditional Chinese medicine(TCM)syndrome types and Chinese version of Thyroid Imaging Reporting and Data System(C-TIRADS)classification and properties of nodules in the patients with thyroid nodules(TN),thus to provide evidence for guiding TCM syndrome differentiation and treatment,and for assessing C-TIRADS classification and properties of the nodules in patients with TN.Methods A retrospective analysis was carried out in 140 inpatients who were diagnosed as TN and had underwent thyroidectomy during the period of January 2021 to January 2024 in the Department of General Surgery of Guangzhou Integrated Chinese and Western Medicine Hospital Affiliated to Guangzhou University of Chinese Medicine(Guangzhou Hospital of Integrated Traditional and West Medicine).The patients were allocated to various group with reference to TCM syndrome types,C-TIRADS classification,and the properties of TN.The correlation of each clinical indicator with TCM syndrome types and C-TIRADS classification and properties of TN was analyzed.The Spearman correlation coefficient was employed for evaluating the correlation of clinical indicators with the C-TIRADS classification and properties of TN,receiver operating characteristic curve(ROC)was used to analyze the predictive value of NLR,MLR,PLR,and SII for the properties of nodules in patients with TN,and the Youden's Index was used to determine the cutoff value for optimal prediction.Results(1)According to the criteria of TCM syndrome differentiation,72 cases were differentiated as qi stagnation and phlegm obstruction syndrome,65 cases as phlegm accumulation and blood stasis syndrome,and 3 cases as heart-liver yin deficiency syndrome.For the number of cases of heart-liver yin deficiency syndrome was too small,only the first two syndromes were included for the analysis.(2)The levels of free T3(FT3)and free T4(FT4)in the patients of qi stagnation and phlegm obstruction syndrome were higher,and the levels of anti-thyroid peroxidase antibody(A-TPO),anti-thyroglobulin antibody(A-TG),neutrophil(NEU),NLR,and SII were lower than those in the patients of phlegm accumulation and blood stasis syndrome,the differences being all statistically significant(P<0.05 or P<0.01).(3)The levels of NLR,PLR,and SII in the patients with C-TIRADS3 classification were lower than those in the patients with C-TIRADS4 classification,the differences being all statistically significant(P<0.05 or P<0.01);no statistically significant difference of MLR was presented between the patients with C-TIRADS3 classification and those with C-TIRADS4 classification(P>0.05).(4)The levels of NLR,PLR,MLR,and SII in patients with benign nodules were lower than those in patients with malignant nodules,the differences being statistically significant(P<0.05 or P<0.01).(5)The Spearman correlation analysis showed that NLR,PLR,and SII were positively correlated with the C-TIRADS classification of the nodules,and NLR,PLR,MLR,and SII were positively correlated with the properties of the nodules,the differences being all statistically significant(P<0.05 or P<0.01).(6)The levels of NLR,MLR,PLR,and SII in patients with high-risk TN exerted a certain predictive value for the properties of the nodules,and their area under the curve(AUC)was 0.645,0.641,0.604,and 0.716,respectively,the differences being statistically significant(P<0.05 or P<0.01).For the prediction of nodule properties by NLR,MLR,PLR,and SII levels in patients with high-risk TN,their cutoff values and the corresponding sensitivities and specificities were 2.261(0.551,0.791),138.108(0.735,0.527),5.132(0.714,0.495),493.114(0.776,0.615),respectively;and their Youden's Index was 0.342,0.262,0.209,0.391,respectively.Conclusion The results indicated that in patients with TN,the FT3 and FT4 levels are positively correlated with the qi stagnation and phlegm obstruction syndrome;the values of A-TPO,A-TG,NEU,NLR,and SII are positively correlated with the phlegm accumulation and blood stasis syndrome;NLR,PLR and SII values are positively correlated with C-TIRADS classification;NLR,PLR,PLR,SII values are positively correlated with malignant TN.NLR,MLR,PLR,SII values exert high efficiency for the prediction of the properties of nodules in patients with TN.

Intrahepatic cholangiocarcinoma is a malignant tumor with an extremely poor prognosis， and its pathogenesis is complex and remains unclear. In recent years， more and more studies have focused on the role of bile-gut axis in the development and progression of intrahepatic cholangiocarcinoma. Bile-gut axis refers to the complex interaction between bile and gut microbiota， including bile salt metabolism， dynamic changes of microbiota， inflammatory response， and immune system regulation. This article elaborates on the potential mechanisms of bile-gut axis in intrahepatic cholangiocarcinoma， especially gut microbiota dysbiosis， abnormal bile salt metabolism， chronic inflammatory response， and immune system interaction， this article aims to provide new perspectives and possible therapeutic targets for future research and promote the early diagnosis and effective treatment of intrahepatic cholangiocarcinoma.

Pancreatic cancer is characterized by nerve invasion and a high mortality rate， and its pathological process depends on the complex interaction network between tumor and the nervous system. Based on the concept of “pancreatic cancer neuroecology”， this article analyzes the mechanism of action of peripheral motor nerve， sensory nerve， and central nerve in tumorigenesis， pain regulation， and cachexia formation and emphasizes the synergistic regulatory role of immune cells， Schwann cells， and extracellular matrix in the microenvironment of perineural invasion. At the same time， this article further elaborates on the metabolic interaction and chemotaxis between neuraxis and tumor， the effect on promoting chemotherapy resistance， and the dynamic relationship between neuroplasticity and tumor adaptability. In clinical practice， this article summarizes the key value of perineural invasion in prognostic evaluation， preoperative evaluation， and the selection of surgical strategy. In addition， this article reviews the basic research advances in the biomarkers and potential targets associated with perineural invasion in pancreatic cancer and points out the limitations of current model and transformation research. In the future， systematically analyzing the nerve-tumor-immune network and targeting its key nodes may provide multi-dimensional strategies and new breakthroughs for the precise intervention of pancreatic cancer， the reversal of drug resistance， and the relief of symptoms.

ObjectiveTo observe the clinical efficacy and safety of hot ironing with Haitongpi Formula （海桐皮方， HF） in the treatment of lumbar disc herniation （LDH） of cold-dampness obstruction type. MethodsA total of 70 patients with cold-dampness obstruction type LDH were randomly divided into a treatment group and a control group， with 35 cases in each group. Both groups received three movements technique of Qinggong Spinal Manipulation （QSM） as the basis for treatment. In addition， the treatment group received hot ironing with HF， while the control group applied Diclofenac Sodium Gel externally. The treatment duration for both groups was 14 days. The clinical efficacy was compared between groups. Japanese Orthopedic Association （JOA） score， visual analog scale （VAS） for pain， pain pressure threshold （PPT） for lumbar positive response points， and traditional Chinese medicine （TCM） symptom scores were compared， on day 7， and day 14 of treatment， as well as on day 7 and day 14 of follow-up. The lumbar curvature index （LCI） was also compared before treatment and on day 14 of treatment. Adverse reactions during the study were recorded for both groups. ResultsA total of 35 patients in the treatment group and 34 patients in the control group were included for final analysis. The clinical total effective rate of the treatment group （91.43%， 32/35） was significantly higher than that of the control group （82.35%， 28/34， P＜0.05）. Both the JOA score and PPT of the two groups increased on day 7 and day 14 of treatment， and on day 7 and day 14 of follow-up. VAS scores and TCM symptom scores both decreased. The LCI of both groups increased on day 14 of treatment （P＜0.01）. Compared with the control group at the same time points， on day 14 of treatment and day 7 and day 14 of follow-up， the treatment group had higher JOA scores and PPT， and lower VAS scores and TCM symptom scores. The LCI of the treatment group increased on day 14 of treatment （P＜0.05 or P＜0.01）. One case in the control group showed mild skin allergy， with no other adverse reactions observed in either group. ConclusionBased on three movements technique of QSM， hot ironing with HF shows better clinical efficacy than external Diclofenac Sodium Gel in the treatment of cold-dampness obstruction type LDH. It can significantly reduce lumbar pain， increase pain pressure threshold， improve clinical symptoms， lumbar function， and lumbar curvature， with good safety.

Objective:To investigate the factors influencing the metastasis of right-sided lymph nodes posterior to right recurrent laryngeal nerve (LN-prRLN) in patients with papillary thyroid microcarcinoma (PTMC) at cN 0 stage, to construct a nomogram prediction model for metastasis of right-sided LN-prRLN in patients with PTMC at cN 0 stage and to provide the decision reference for the dissection of right-sided LN-prRLN. Methods:A retrospective case-controlled study was conducted. The clinical data of patients receiving right-sided LN-prRLN dissection in Baoding No.1 Central Hospital between January 2023 and June 2024 were collected. All patients were divided into the metastatic group and the normal group according to whether metastasis of right-sided LN-prRLN would happen after the postoperative pathological examination. The differences in the clinicopathological characteristics between the 2 groups were compared, and multivariate logistic regression model was used to screen out the independent risk factors influencing right-sided LN-prRLN. A nomogram prediction model for metastasis of right-sided LN-prRLN based on independent risk factors was built; taking the postoperative pathological examination results as the gold standard, the receiver operating characteristic (ROC) curve was used to evaluate the efficacy of the model in determining the metastasis of right-sided LN-prRLN. Bootstrap internal validation method was used for random sampling to calculate the consistency index (CI) of the model. The calibration curves and clinical decision curves were drawn to respectively verify the calibration degree of the model and the clinical application ability of the model.Results:All 235 patients included 57 males (24.3%) and 178 females (75.7%). The age was (39±13) years old and 47 cases (20.0%) out of 235 patients had the metastasis of right-sided LN-prRLN. The proportion of patients characterized by male, right-sided tumors, tumor diameter > 0.5 cm, extrathyroidal invasion, metastasis of right-sided lymph nodes anterior to right recurrent laryngeal nerve (LN-arRLN) in the metastatic group was higher than that in the normal group, and the differences were statistically significant (all P < 0.05). Multivariate logistic regression analysis showed that male ( OR = 3.705, 95% CI: 1.133-12.116, P = 0.030), right-sided tumors ( OR = 5.610, 95% CI: 1.811-17.381, P = 0.003), the increased tumor diameter ( OR = 3.504, 95% CI: 1.169-10.507, P = 0.025), extrathyroidal invasion ( OR = 2.812, 95% CI: 1.026-7.708, P = 0.044) and right-sided LN-arRLN metastasis ( OR = 10.522, 95% CI: 3.237-34.199, P < 0.001) were independent risk factors of the metastasis of LN-prRLN in PTMC patients at cN 0 stage; based on the above independent risk factors, a nomogram prediction model was established. The ROC curve showed that the area under the curve of the nomogram prediction model for determining the metastasis of right-sided LN-prRLN in PTMC patients at cN 0 stage was 0.864 (95% CI: 0.794-0.935), Youden index was 0.735, the optimal cut-off value was 4.562, the corresponding sensitivity was 87.0%, and the corresponding specificity was 86.5%, which indicated a high predictive value of the nomogram model. Bootstrap test internal validation showed that the CI was 0.810 (95% CI: 0.763-0.917). Calibration curves showed that bias-corrected line was close to the ideal line, indicating a good consistency ( P = 0.347). Decision curve showed a good clinical efficacy. Conclusions:Male, right-sided tumors, the increased tumor diameter, extrathyroidal invasion and right-sided LN-arRLN metastasis are independent risk factors for right-sided LN-prRLN metastases in patients with PTMC at cN 0 stage. The nomogram prediction model based on the above factors has a good predictive performance, which is helpful for surgeons to make clinical decisions.

Objective:To analyze the epidemiological information of oral leukoplakia and explore the relationship between clinical characteristics and different degrees of epithelial dysplasia.Methods:A total of 430 patients with oral leukoplakia confirmed by pathology in the Department of Oral Medicine, Shanghai Ninth People′s Hospital, Shanghai Jiao Tong University School of Medicine from February 2013 to May 2021 were enrolled. Epidemiological information was recorded, and univariate and multivariate Logistic regression analysis were performed on age, gender, smoking, drinking, lesion size, lesion site and lesion type to evaluate the correlation between the risk factors and the degree of epithelial dysplasia in oral leukoplakia.Results:A total of 430 valid samples were included in this study, among which 23 patients were diagnosed with oral leukoplakia with concurrent cancer. The age of all patients was (52.9±12.9) years (22-85 years); 213 were male and 217 were female. One hundred and seventy-six cases (40.9%) had lesions on the lateral and ventral tongue, and 254 cases (59.1%) had lesions in other locations. Three hundred and two cases (70.2%) had homogeneous lesions, and 128 cases (29.8%) had heterogeneous lesions. The degrees of epithelial dysplasia included none [11.9% (51/430)], mild [51.9% (223/430)], moderate [24.4% (105/430)], severe [6.5% (28/430)], and concurrent cancer [5.3% (23/430)]. Smoking, drinking, and gender were correlated with the degree of epithelial dysplasia in some binary classification systems, while tongue (border and ventral) and non-homogeneous damage were significantly correlated with higher degrees of epithelial dysplasia in all binary classification systems ( P<0.05). Conclusions:Lesions on the lateral or ventral tongue and heterogeneous lesions are significantly associated with higher degrees of dysplasia, suggesting that clinicians should pay more attention to these types of oral leukoplakia during the follow-up monitoring process.

Objective To investigate the effect of active muscle response on mechanical responses and injuries of human neck under high Gx loading.Methods A refined finite element model of the head and neck with active muscle response was established and validated based on the existing post-crash volunteer experiments.The effects of active muscle action on the kinematic and biomechanical responses of the neck were investigated under different G-value loads and at each tilting angle using this model.Results The stress distribution of vertebrae under high Gx load was dispersed from C4-7 to the whole vertebrae,and the active muscle action reduced the stress change,and the effect was significant under 8 G acceleration,which reduced the peak vertebral bone stress by 23.6％and 11.6％,and the peak intervertebral disc stress by 42.3％and 63.4％under 8 G and 10 G conditions,respectively.The maximum stress difference of 34.3 MPa was achieved by the active muscle action at 15° backward tilting.Conclusions The neck showed better stability by the active muscle action under the impact of high Gx loading.At different tilting angles,the active muscle action was more obvious in the backward tilting posture compared with the forward tilting and upright seated postures,and the backward tilting posture was safer to meet the impact when the same active muscle action was applied.The results can provide a reference for the subsequent studies related to the neck injury.

Objective:To investigate risk factors for permanent hypoparathyroidism (PHPP) after total thyroidectomy in patients with differentiated thyroid carcinoma (DTC).Methods:The clinical data of 316 DTC patients who underwent total thyroidectomy at our hospital from Jan 2020 to Jan 2023 were retrospectively analyzed. Patients were divided into normal parathyroid function group (284 cases) and hypoparathyroidism group (32 cases) according to whether parathyroid function was decreased. The clinical examination, intraoperative conditions and postoperative pathological data of the two groups were statistically analyzed.Results:Logistic regression analysis showed that: serum calcium on the first postoperative day ( OR=0.163, P<0.05), parathyroid hormon (PTH) on the first postoperative day ( OR=0.958, P<0.05), bilateral lymph node dissection ( OR=3.138, P<0.05), accidental resection of parathyroid (PG) ( OR=2.614, P<0.05), posterior capsule tumor invasion ( OR=3.336, P<0.05) and multiple cancer foci ( OR=2.664, P<0.05) were independent risk factors for PHPP after total thyroidectomy. Conclusion:Postoperative day 1 serum calcium, postoperative day 1 PTH, bilateral lymph node dissection, accidental resection of PG, posterior capsule invasion and multiple cancer foci are independent risk factors for PHPP after total thyroidectomy.