It is believed that the occurrence and development of squamous cell carcinoma （SCC） is closely associated with inflammatory responses. The theory of fire and heat， advocated by LIU Wansu， provides significant clinical guidance for understanding the pathogenesis and treatment of SCC. Based on this theory， the pathological mechanisms and clinical characteristics of SCC at different stages were analyzed. In the precancerous and early stages， the primary pathogenesis is qi stagnation leading to internal generation of constrained heat； in post-surgery， the condition shifts to qi deficiency with latent yin fire； during the treatment phase， the pathogenesis involves accumulation of pathogenic factors， excess toxins， and severe heat toxicity； in the late stage， the main pathology is yin deficiency with toxic heat， and phlegm-stasis obstruction of the internal organs. Corresponding stage-based treatment strategies are proposed. In the early stage， regulating qi movement to dissipate constrained heat； for post-surgery， tonifying qi and raising yang to dispel latent fire； during treatment stage， clearing heat and detoxifying to eliminate cancerous toxins； and in the late stage， nourishing yin and unblocking the bowels to clear deficiency heat.

AIM: To identify the primary active components and underlying mechanisms of Yijing Decoction(YJD)in treating early diabetic retinopathy(DR)based on liquid chromatography-mass spectrometry and network pharmacology.METHODS: Active components of YJD were characterized through LC-MS. Components with optimal ADME(absorption, distribution, metabolism, excretion)properties were selected as key bioactive candidates. Network pharmacology approaches were employed to predict YJD-DR therapeutic targets. Protein-protein interaction(PPI)networks, gene ontology(GO)enrichment analysis, and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis were subsequently conducted to predict core targets and networks. Critical targets and pathways were experimentally validated through Western blot.RESULTS: Ten core therapeutic targets were identified, including TNF, Alb, EGFR, STAT3, PTGS2, ESR1, PPAR, MMP9, TLR4, and MAPK. YJD was related to cancer-related signaling, fluid shear stress and atherosclerosis, and neurodegenerative diseases, encompassing key biological processes such as inflammatory response regulation, programmed cell death activation, and enhanced cell migration. Furthermore, Western blot analysis confirmed that YJD significantly inhibited high glucose-induced phosphorylation of STAT3(P-STAT3/STAT3)and ERK(P-ERK/ERK)in rat retinal microvascular endothelial cells.CONCLUSION: This study revealed YJD's pharmacodynamical basis and its multi-component, multi-target, and multi-paths pharmacology. YJD exerts therapeutic effects on DR by coordinately regulating critical signaling pathways and alleviating intraocular inflammation, thus preserving retinal vascular endothelial cells, maintaining blood-retinal barrier integrity, and facilitating retinal neurovascular repair.

Background::T-cell-mediated immunity is crucial for the effective clearance of viral infection, but the T-cell-mediated immune responses that are induced by booster doses of inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines in people living with human immunodeficiency virus (PLWH) remain unclear.Methods::Forty-five PLWH who had received antiretroviral therapy (ART) for more than two years and 29 healthy controls (HCs) at Beijing Youan Hospital were enrolled to assess the dynamic changes in T-cell responses between the day before the third vaccine dose (week 0) and 4 or 12 weeks (week 4 or week 12) after receiving the third dose of inactivated SARS-CoV-2 vaccine. Flow cytometry, enzyme-linked immunospot (ELISpot), and multiplex cytokines profiling were used to assess T-cell responses at the three timepoints in this study.Results::The results of the ELISpot and activation-induced marker (AIM) assays showed that SARS-CoV-2-specific T-cell responses were increased in both PLWH and HCs after the third dose of the inactivated SARS-CoV-2 vaccine, and a similar magnitude of immune response was induced against the Omicron (B.1.1.529) variant compared to the wild-type strain. In detail, spike-specific T-cell responses (measured by the ELISpot assay for interferon γ [IFN-γ] release) in both PLWH and HCs significantly increased in week 4, and the spike-specific T-cell responses in HCs were significantly stronger than those in PLWH 4 weeks after the third vaccination. In the AIM assay, spike-specific CD4 + T-cell responses peaked in both PLWH and HCs in week 12. Additionally, significantly higher spike-specific CD8 + T-cell responses were induced in PLWH than in HCs in week 12. In PLWH, the release of the cytokines interleukin-2 (IL-2), tumour necrosis factor-alpha (TNF-α), and IL-22 by peripheral blood mononuclear cells (PBMCs) that were stimulated with spike peptides increased in week 12. In addition, the levels of IL-4 and IL-5 were higher in PLWH than in HCs in week 12. Interestingly, the magnitude of SARS-CoV-2-specific T-cell responses in PLWH was negatively associated with the extent of CD8 + T-cell activation and exhaustion. In addition, positive correlations were observed between the magnitude of spike-specific T-cell responses (determined by measuring IFN-γ release by ELISpot) and the amounts of IL-4, IL-5, IL-2 and IL-17F. Conclusions::Our findings suggested that SARS-CoV-2-specific T-cell responses could be enhanced by the booster dose of inactivated COVID-19 vaccines and further illustrate the importance of additional vaccination for PLWH.

Objective:To summarize the distributional characteristics of postoperative occurrence of multi-drug resistant organism (MDRO) infections and their risk factors in simultaneous pancreas-kidney transplantation (SPK) recipients and examine the impact of MDRO infections on the survival of SPK recipients.Method:From January 2016 to December 2022, the relevant clinical data were retrospectively reviewed for 218 SPK recipients. The source of donor-recipient specimens and the composition percentage of MDRO pathogens were examined. According to whether or not MDRO infection occurred post-transplantation, they were assigned into two groups of MDRO (98 cases) and non-MDRO (120 cases). The clinical data of two groups of donors and recipients were analyzed. And the risk factors for an onset of MDRO infection were examined by binary Logistic regression. The survival rate of two recipient groups was compared by Kaplan-Meier method.Result:A total of 98/218 recipients (45%) developed MDRO infections. And 46 (46.9%) of sputum and 34 (34.7%) of urine were cultured positively and 49 (50%) pathogens expressed extended spectrum beta-lactamase. There were pneumonia (46 cases, 46.9%), urinary tract infections (34 cases, 34.7%), abdominal infections (16 cases, 16.3%) and bloodstream infections (2 cases, 2.0%). Univariate regression analysis revealed that length of renal failure ( P=0.037), length of hospitalization ( P<0.001), length of antibiotic use ( P<0.001), novel antibiotics ( P=0.014), albumin ( P<0.001) and leukocyte count ( P<0.001) were risk factors for an onset of MDRO infections. The results of multifactorial regression indicated that low albumin ( OR=0.855, 95% CI: 0.790~0.925, P<0.001) and leukopenia ( OR=0.656, 95% CI: 0.550~0.783, P<0.001) were independent risk factors for an onset of MDRO infections. The survival rates of recipients in MDRO group at Year 1/3 post-operation were 92.9% (91/98) and 89.8% (88/98). And the survival rate of recipients in non-MDRO group was 96.7% (116/120) at Year 1/3 post-operation. Inter-group difference was not statistically significant in 1-year survival rate of two recipient groups ( P=0.201); statistically significant inter-group difference in 3-year survival rate between two recipient groups ( P=0.041) . Conclusion:Low albumin and leukopenia are risk factors for MDRO infection. Infection with MDRO has some impact on the survival of recipients.

Objective:To explore the clinical effect of perforator pedicled propeller flap (PPPF) in reconstruction of soft tissue defect in ankle and foot, as well as the role of preoperative ultrasonography in assistance of the location of perforators in donor site.Methods:From January 2017 to June 2023, the Department of Microorthopedics of the Second Affiliated Hospital of Luohe Medical College of Higher Education applied PPPF to reconstruct small and medium-sized soft tissue defects in the ankle and foot for 26 patients. The patients were 17 males, 9 females, aged 18 to 68 years old with 46 years old in average. The defect sites were 3 in forefoot and 6 in midfoot and combined with different degrees of tendon and bone exposure, 17 in ankle and heel and combined with various degrees of bone exposure, 12 with ankle open injury and 5 with Achilles tendon exposure. The area of soft tissue defects ranged from 2.5 cm×1.5 cm to 16.0 cm × 6.5 cm. The width of injury was measured before surgery, and a HHD was used to detect the perforators proximal to the defect site, and then high-frequency CDU was used to locate and confirm the location of the perforator and its alignment, blood flow and diameter. The line drawn between the 2 perforators was set as the axis of flap. The donor site was assessed by a "pinching and lifting" method to determine a direct closure of donor site or to have it closed by a flap transfer. The sizes of flap were from 2.8 cm×1.5 cm to 24.0 cm×7.5 cm. Twenty-two donor sites were directly closed and 4 received flap transfers. Four flaps had sutures with the skin nerves in the recipient site. Masquelet technique was performed in 6 patients with bone defects in the surgery. Patients received outpatient reviews with 1-2 weeks of intervals in the first 2 months after surgery, and X-ray reviews per 1-2 months for those with bone implants until bone healing.Results:All flaps survived successfully without any special treatment after surgery, except 1 flap that had blood vessel congestion and showed swelling and poor blood supply to the distal flap at 24 hours after surgery. The blood vessel congestion was revised by removal of part of the suture at the tip of flap pedicle. One week later, the tip of the flap remained with a small area of necrosis, which was then healed after dressing changes. A total of 21 patients were included in postoperative follow-up with 4 months to 3 years. All of the flaps had satisfactory appearance, colour and texture, and without any ulceration. Three cases of nerve suture were also included in follow-up. According to the assessment criteria of British Medical Research Council (BMRC), the sensory recovery of the flaps was found of S 2 in 1 flap and S 3 in 2 flaps. According to the American Orthopaedic Foot and Ankle Society (AOFAS), the ankle-hindfoot function scores, there were excellent in 16 patient and good in 5 patients. Conclusion:With the assistance of ultrasound, the PPPF can be effectively used in reconstruction of soft tissue defects in ankle and foot.

Objective:To explore the involvement of miR-126 and the role of mammalian target of rapamycin (mTOR)/hypoxia-induced factor 1 α (HIF-1 α) pathway in regulating human umbilical cord mesenchymal stem cells (hUCMSCs) exosomes (Exo) on vascular endothelial growth factor (VEGF)-A levels in high glucose-induced human retinal vascular endothelial cells (HRECs).Methods:The hREC was cultured in EGM-2-MV endothelial cell culture medium with 30 mmol/L glucose and placed in hypoxic cell incubator by 1% oxygen concentration. The cell model of high glucose and low oxygen was established. After modeling, divided HRECs into Exo group, phosphate buffer saline (PBS) group, PBS+anti-miR126 group, Exo+anti-miR126 group, PBS+anti-mTOR group, and PBS+anti-HIF-1 α group. High-glucose and hypoxia-induced hREC in the PBS and Exo groups were respectively co-cultured with PBS and 100 μg/ml hUCMSC Exo. PBS+anti-mTOR group, PBS+anti-HIF-1 α group: 500 nmol/L mTOR inhibitor ADZ2014, 25 μmol/L HIF-1 α inhibitor YC-1 pretreatment for hREC 12 h, and then co-culture with PBS after High-glucose and hypoxia-induced. PBS+anti-miR126 group, Exo+anti-miR126 group: miR-126 LNA power inhibitor probe was transfected with high glucose, and co-cultured with PBS and hUCMSC Exo 6 h after transfection. Real-time polymerase chain reaction (qPCR) measured miRNA-126 expression levels in PBS, and Exo groups for 0, 8, 16 and 24 h. After 24 h of co-culture, the levels of mTOR and HIF-1 α in the cells of PBS and Exo groups were detected by immunofluorescence, Western blot and qPCR, respectively. Western blot, qPCR detection of VEGF-A expression levels in cells of the PBS+anti-mTOR and PBS+anti-HIF-1 α groups. The expression of VE GF-A, mTOR, and HIF-1 α mRNA was measured in cells of PBS+anti-miR126 group and Exo+anti-miR126 group by qPCR. Comparison between two groups was performed by t-test; one-way ANOVA was used for comparison between multiple groups. Results:At 0, 8, 16 and 24 h, the relative mRNA expression of miR-126 gradually increased in the Exo group ( F=95.900, P<0.05). Compared with the PBS group, The mTOR, HIF-1 α protein ( t=3.466, 6.804), mRNA in HRECs in the Exo group, VEGF-A mRNA expression ( t=8.642, 7.897, 6.099) were all downregulated, the difference was statistically significant ( P<0.05). The relative expression level of VEGF-A protein ( t=3.337, 7.380) and mRNA ( t=8.515, 10.400) was decreased in HRECs of the anti-mTOR+PBS group and anti-HIF-1 α+PBS group, differences were statistically significant ( P<0.05). The relative expression of VEGF-A, mTOR, and HIF-1 α mRNA was significantly increased in the cells of the Exo+anti-miR126 group, the differences were all statistically significant ( t=4.664, 6.136, 6.247; P<0.05). Conclusions:miR-126 plays a role in regulating the effect of hUCMSCs exosomes on VEGF-A levels in high glucose-induced HRECs via mTOR-HIF-1 α pathway.

Objective:To analyze the assessment effect and reliable indicators of multimodal magnetic resonance imaging(MRI)for axillary lymph node metastasis(ALNM)of breast cancer.Methods:A total of 152 female patients with breast cancer who were diagnosed and received surgical treatment in Handan First Hospital from January 2020 to November 2021 were selected.According to the pathological results of postoperative axillary lymph node,45 cases with ALNM were selected as ALNM group,and 107 cases without ALNM were selected as non-ALNM group.Dynamic contrast enhanced-magnetic resonance imaging(DCE-MRI),T2weighted image(T2WI)and diffusion-weighted imaging(DWI)were used to determine breast cancer ALNM.Results:The diagnostic sensitivity,specificity,positive predictive value and negative predictive value and diagnostic consistent rate of multimodal MRI were respectively 82.22%,96.26%,90.24%,92.79%and 92.11%.Logistic regression analysis showed that the maximum tumor size and ADC value were closely correlated with lymph node metastasis.The receiver operating characteristic(ROC)curve analysis showed that the area under curve(AUC)of the maximum tumor diameter was 0.797(95%CI=0.694～0.842,P<0.01),and the diagnostic sensitivity and specificity were respectively 77.4%and 60.7%when the optimal cut-off value was 1.96cm.The AUC of ADC value was 0.844(95%CI=0.808-0.915,P<0.01),and the diagnostic sensitivity and specificity were respectively 82.1%and 71.2%when the optimal cutoff value was 1.122×10-3mm2/s.The AUC value of the combined diagnosis of maximum tumor diameter and AUC value was 0.952(95%CI:0.904-0.991,P<0.01),and the sensitivity and specificity were respectively 88.6%and 81.4%under the optimal cutoff value.The AUC value of the combined indicators was higher than that of the maximum tumor diameter(Z=3.982,P<0.05)and ADC value(Z=3.014,P<0.05),respectively.Conclusion:Multimodal MRI has a good diagnostic effect on breast cancer ALNM,in which the maximum tumor diameter and AUC value are important reference indicators,and the combination of them can improve the diagnostic efficiency.

BACKGROUND:The elastic modulus of traditional bone implants is large and does not match the elastic modulus of human bone,which will cause a stress shielding effect and lead to bone resorption.The trabecular scaffold of the triply periodic minimal surface with radial gradient has elastic modulus matching with human cancellous bone,and its yield strength is greater than that of human cortical bone,which provides a new choice for the design of bone scaffold. OBJECTIVE:Triply periodic minimal surface structure with radial gradient was constructed by the implicit surface method.The sample was manufactured by laser selective melting technology,and the quasi-static compression test was carried out to obtain trabecular scaffolds with mechanical properties matching human bones. METHODS:Four types of the trabecular scaffolds of the triply periodic minimal surface with a radial gradient of G,I,P and D were established by the implicit surface method.Samples were manufactured by laser selective melting technology.We observed the surface morphology of the molded sample,evaluated the molding quality,conducted a quasi-static compression test,and evaluated the mechanical properties of the samples. RESULTS AND CONCLUSION:The quasi-static compression test results showed that compared with the four triply periodic minimal surface scaffolds,the platform stress of the G scaffold had less fluctuation and no failure or fracture,indicating that the G scaffold had the best plasticity.The mechanical properties of the G scaffolds with 45%,55%and 65%porosities were analyzed.It was found that the elastic modulus of G scaffolds with 55%porosity was within the range of elastic modulus of human cancellous bone(0.022-3.7 GPa),and the yield strength was close to the maximum yield strength of human cortical bone(187.7-222.3 MPa).In conclusion,G triply periodic minimal surface scaffold with 55%porosity can reduce the stress shielding effect,bear a higher body load,improve the stability of the implant,and prolong the service life of the implant.

BACKGROUND:Vertebral compression fracture is a common disease in the current orthopedic field.However,the occurrence of re-fracture in neighboring vertebrae after surgery is a problem that cannot be ignored,which has a serious impact on the normal life of patients. OBJECTIVE:The aim of this study is to establish four postoperative models with different recovery heights using computed tomography images.By using finite element analysis,we derived the stresses on the neighboring vertebrae at different recovery heights and further explored the importance of postoperative recovery of the height of the injured vertebrae. METHODS:A finite element model of the thoracolumbar spine(T11-L3)was established and validated,on the basis of which four postoperative finite element models of L1 with different recovery heights of 100%,80%,60%,and 40%were constructed,in which the cement capacity varied with the recovery height.The specific models are as follows:Model 1 was the postoperative model with normal recovery height,and the cement capacity was 8.3 mL.Model 2 was the postoperative model in which 20%of the anterior height of the L1 was removed and the posterior convexity angle became 10.41°,and the cement capacity was 6.9 mL.Model 3 was the postoperative model in which 40%of the anterior height of the L1 was removed and the posterior convexity angle became 20.17°,and the cement capacity was 4.7 mL.Model 4 was a postoperative model with 60%of the L1 anterior height removed and the posterior convexity angle changed to 28.85°,with a cement capacity of 3.6 mL.For evaluation of the postoperative model,we applied a moment of 7 Nm and an axial force of 500 N.The followings were recorded and analyzed:peak stresses in the L2 upper endplate and T12 lower endplate;peak stresses in the L2 and T12 cancellous bone. RESULTS AND CONCLUSION:(1)The highest peak stresses for each condition of the L2 upper endplate,T12 lower endplate,L2 cancellous bone,and T12 cancellous bone occurred in Model 1 and Model 4.In particular,the T12 lower endplate,except for the posterior extension condition,the anterior flexion,left and right lateral bending,and left and right rotation conditions all reached their highest peak stresses in Model 4,with stresses of 50.3,33.1,44.9,34.3,and 31.9 MPa.(2)Based on the peak stresses in the adjacent vertebral endplates and cancellous bone,after excluding Model 1 and Model 4,the minimum peak stresses for most of the conditions appeared in the Model 2,and the minimum peak stresses appeared in the Model 2 in 66.6%of the cases,especially in the upper endplates of the L2 and cancellous bone except for the posterior extension condition,the minimum peak stresses all appeared on the Model 2.(3)Therefore,controlling the recovery height at about 100%and 40%of the original height was a dangerous recovery height,which had a greater impact on the neighboring vertebrae.Controlling the recovery height at about 80%of the original height may be a more ideal choice.With a recovery height of about 80%of the original height,the adjacent vertebrae are subjected to less stress,thus reducing the risk of re-fracture of the adjacent vertebrae in the patient.

Objective:To compare and evaluate the difference in maxillary dentition position using an anatomical facebow and jaw movement analyzer.Methods:From March to May 2023, 15 medical interns from Yantai Stomatological Hospital were recruited, including 9 males and 6 females, aged 20-25 years. Digital models and plaster models of maxillary dentition were obtained from the 15 medical interns. The anatomical facebow group (AFB) and jaw movement analyzer group (JMA) were used to transfer the position of the maxillary dentition to the virtual articulator. The virtual occlusal articulator module of exocad denture design software was used to measure the inclination angle of the occlusal plane of the two groups, the distance between the mesio-incisal angle of the left maxillary central incisor and the lateral center point of the lateral condylar sphere of the virtual occlusal articulator, the distance between the mesial buccal cusp of the maxillary first molar and the lateral center point of the lateral condyle sphere of the virtual articulator. The same marks (mesial incisor point of left maxillary central incisor and mesial buccal cusp point of both maxillary first molars) were measured in two groups of maxillary dentition, and the root-mean-square error between 3 points was calculated.Results:The occlusal plane inclination angle in AFB group (9.11°±3.85°) was significantly larger than that in JMA group (4.94°±2.69°) ( t=10.45, P<0.001). There were significant differences between AFB and JMA groups. The distances from the mesial cusp of the left first molar to the lateral center of the left condylar, from the mesial cusp of the left maxillary central incisor to the lateral center of the left condylar[(91.75±3.05), (129.09±4.60) mm]were significantly smaller than those in the JMA group[(95.68±5.45), (132.41±5.64) mm]( t=-4.48, P=0.001; t=-4.21, P=0.001). In both groups of models, the distance of the mesial cusp of the left maxillary central incisor was (8.81±2.56) mm, and the distance between mesial buccal cusp of maxillary left first molar was (7.56±2.49) mm, the distance between mesial buccal cusp of maxillary right first molar was (7.13±2.77) mm; the root mean square error was (7.93± 2.94) mm. Compared with 0, the difference was statistically significant ( t=10.45, P<0.001). Conclusions:There were differences between the two methods (anatomical facebow and the jaw movement analyzer) for transferring the maxillary dentition position to the three-dimensional space position of the virtual articulator.