With the continuous innovation of genomics,proteomics and molecular biological detection technol-ogy,the treatment of non-small cell lung cancer(NSCLC)has changed from traditional chemotherapy to immunotherapy and targeted therapy.Among them,molecular tumor markers targeting tyrosine kinase pathways play more important roles in clinical practice.For advanced NSCLC patients with positive epidermal growth factor receptor(EGFR)mutations,there are many first-line drugs on the market and they could bring significant efficacy,thus completely subverting the treatment pattern of advanced NSCLC.Common mutations of EGFR in Chinese patients are located on exons 19,20 and 21,of which exons 19 and 21 mutations are the more common types.Besides,there is also a subtype of EGFR mutations,known as EGFR 20 exon insertion(EGFR 20ins)mutation.The authors summarized the treatment of a lung adenocarcinoma patient with EGFR 20ins mutation accepting Furmonertinib mesylate,in order to provide effective references for clinical diagnosis and treatment.

Objective To analyze the stresses in implanted titanium solid and bone trabecular prosthesis hip replacements.Methods A femur model was built inversely based on Mimics software,and optimized using Geomagic software,and then materialized by SolidWorks software.The osteotomized femur was assembled with the metal femoral stem to form a model,and then the model was imported into ABAQUS for finite element calculation.The upper femur was divided into four regions in different states of integration:medial proximal point(small trochanter region),lateral proximal region(large trochanter region),proximal point of the femoral stem(region around the mid-portion of the styloid process)and distal region(around the end of the styloid process and distal portion).Calculations were carried out over the femoral stresses before and after implantation of titanium solid and trabecular prostheses under gait and stair-climbing loads and the interfacial stresses when the region was unintegrated.The type of deformation at the bone interface was analyzed by means of a stress ellipsoid.Results At the small trochanter region,the stress shielding rates of the trabecular prosthesis under gait and stair climbing loads were reduced by 20.5％and 14.7％compared to the titanium solid prosthesis,respectively.In case of different integration states of the titanium solid prosthesis,the interface tensile stresses under the gait and stair climbing loads were up to 10.842 MPa and 12.900 MPa,and the shear stresses reached 7.050 MPa and 6.805 MPa,respectively;in case of different integration states of the trabecular prosthesis,the interface tensile stresses under the gait and stair climbing loads were up to 3.858 MPa and 4.389 MPa,and the shear stresses reached 4.156 MPa and 3.854 MPa,respectively.Under the 2 different loads,the inboard shear stress ellipsoid of the interface opened toward the sides and the bone interface showed tensile deformation;the outboard shear stress ellipsoid of the interface opened up and down and had compressive deformation.Conclusion After total hip arthroplasty,the overall performance of the trabecular prosthesis is better than that of the titanium solid prosthesis.The unintegrated edges of the prosthesis-bone interface are susceptible to stress concentrations and distortion which may result in occurrence of failures.[Chinese Medical Equipment Journal,2024,45(3):29-35]

Intramedullary needle(IMN)has the advantages of high healing rate and low incidence of complications in treatment of tibial fracture,and has become one of the most commonly used fixation methods for the treatment of tibial fracture.However,due to the patient's own factors,fracture location and fracture type,infection and surgical treatment,bone nonunion after IMN still occurs in clinic.Bone nonunion leads to the increase of medical cost and prolonged the hospitalization time of patients,which causes great pain to patients,and also brings great challenges to the treatment of orthopedic surgeons.Therefore,this paper reviews the influencing factors of bone nonunion after IMN for tibial fracture,in order to provide reference for clinical treatment.

Objective:To optimize the technical parameters related to the preparation of novel frozen human platelets and formulate corresponding protocol for its preparation.Methods:Novel frozen human platelets were prepared with O-type bagged platelet-rich plasma(PRP),the key technical parameters(DMSO addition,incubation time,centrifugation conditions,etc.)of the preparation process were optimized,and the quality of the frozen platelets was evaluated by routine blood tests,apoptosis rate,platelet activation rate and surface protein expression level.Results:In the preparation protocol of novel frozen human platelets,the operation of centrifugation to remove supernatant was adjusted to before the procedure of platelets freezing,and the effect of centrifugation on platelets was minimal when the centrifugation condition was 800 xg for 8 min.In addition,platelets incubated with DMSO for 30 min before centrifugation exhibited better quality after freezing and thawing.The indexes of novel frozen human platelets prepared with this protocol remained stable after long-term cryopreservation.Conclusion:The preparation technique of novel frozen human platelets was established and the protocol was formulated.It was also confirmed that the quality of frozen platelets could be improved by incubating platelets with DMSO for 30 min and then centrifuging them at 800 ×g for 8 min in the preparation of novel frozen human platelets.

Objective:To investigate the mechanism of benzyl isothiocyanate(BITC) in the treatment of anaplastic thyroid cancer(ATC).Methods:Using network pharmacological analysis, key targets of BITC and ATC were screened, followed by GO and KEGG enrichment analysis. In order to validate the findings, AutoDock software was used to dock BITC and ATC key targets. BITC was applied to two ATC cell lines(8505C and CAL-62). Flow cytometry was used to analyze cell apoptosis. Autophagy inhibitors hydroxychloroquine sulfate(HCQ) and 3-methyladenine(3MA) were used in combination with BITC. Real-time quantitative PCR was conducted to detect the gene level of LC3B, while Western blotting was utilized to examine the expression of NF-κB, LC3B Ⅱ, Beclin-1, and Bcl-2. In animal experiments, a mouse tumor model was constructed using CAL-62 cells, treated with intraperitoneal injections of BITC(100 mg/kg) and normal saline respectively, administered every other day for a total of 21 days. Immunoblotting of tumor tissue was performed to detect the expression of LC3B Ⅱ, Bcl-2, Beclin-1, and NF-κB.Results:A total of 10 key targets with binding energies≤-4.0 kcal/mol were identified. KEGG analysis showed that these genes are mainly involved in NF-κB signaling pathway and apoptosis. BITC inhibited ATC cells with IC50 values of 27.56 μmol/L for 8505C and 28.30 μmol/L for CAL-62. The expression levels of NF-κB, Beclin-1, and Bcl-2 decreased, while LC3B Ⅱ and LC3B gene expression increased. Combining 3MA with BITC enhanced cell inhibition LC3B Ⅱ expression. HCQ increased LC3B Ⅱ expression without enhancing cell and viability inhibition. In the mouse tumor model, compared to the control group, the treatment group had higher LC3B Ⅱ and lower Bcl-2, Beclin-1, and NF-κB levels.Conclusion:BITC could inhibit the growth of ATC cells in vitro and in vivo, disrupt the autophagy degradation, and inhibit the NF-κB pathway.

Objective:To investigate the effect of neutrophils on cell pyroptosis and its mechanisms in mice with early brain injury (EBI) following subarachnoid hemorrhage (SAH).Methods:Seventy six male C57BL/6J mice were randomly divided into sham-operated group, SAH group, SAH+vehicle group, and SAH+anti-ly6G group ( n=19). SAH models in the latter 3 groups were established by modified endovascular perforation. Mice in the SAH+vehicle group and SAH+anti-ly6G group received intravenous injection of equal normal saline or anti-ly6G antibody (4 mg/kg) 24 h before SAH. At 24 h after SAH, immunofluorescent staining was used to detect the locations/expressions of neutrophils, S100 calcium binding protein A8 (S100A8) and gasdermin D (GSDMD); FJC staining was performed to assess the neuronal injury; modified Garcia test and rotarod test were used to evaluate the neurological functions, and brain water content test was applied to evaluate the brain edema; Western blotting was used to detect the expressions of S100A8, Toll-like receptor 4 (TLR4), NOD-like receptor thermal protein domain associated protein 3 (NLRP3), cleaved cysteinyl aspartate specific proteinase-1 (cleaved-caspase1), and cleaved N-terminal gasdermin D (GSDMD-N). Results:(1) Compared with those in the sham-operated group, neutrophil infiltration at the damaged cortex with highly expressed S100A8 in neutrophils was observed in the SAH group, and increased GSDMD expression at the damaged cortex and GSDMD co-localization in astrocytes, microglia and neurons were observed in the SAH group. (2) Compared with the sham-operated group, the SAH group and SAH+vehicle group had significantly increased numbers of infiltrated neutrophils and FJC-positive neurons, significantly decreased falling latency in the modified Garcia score and rotarod test, significantly increased brain water content, and significantly elevated expressions of S100A8, TLR4, NLRP3, cleaved-caspase1 and GSDMD-N ( P<0.05); the SAH+anti-ly6G group had statistically decreased numbers of infiltrated neutrophils and FJC-positive neurons, statistically increased falling latency in the modified Garcia score and rotarod test, statistically decreased brain water content, and statistically decreased expressions of S100A8, TLR4, NLRP3, cleaved-caspase1 and GSDMD-N compared with the SAH group and SAH+vehicle group ( P<0.05). Conclusion:Inhibition of neutrophils can down-regulate the S100A8 expression after SAH and attenuate TLR4/NLRP3 activation-mediated cell pyroptosis, thereby improving EBI.

AIM:To explore the correlation and consistency of three tear assessment methods in the diagnosis of dry eye, which include the Schirmer Ⅰ test(SⅠt), tear meniscus height(TMH)measurement and a new generation of tear detection technology-Strip meniscometry tube(SMTube).METHODS: A diagnostic test study. A total of 183 dry eye outpatients(183 right eyes)in the Dry Eye Center of Henan Eye Hospital were enrolled from May to June 2021. The SⅠt, TMH and SMTube were performed on all patients, and the correlation and consistency of the measurement results were analyzed.RESULTS:The ocular surface disease index(OSDI)of all included patients was 43.75(31.25, 58.33), noninvasive breakup time(NIBUT)was 7.26(4.97, 9.37)s, and the results of SⅠt, TMH and SMTube were 6(2, 12)mm/5min, 0.18(0.14, 0.22)mm and 5(3,8)mm/5s, respectively; The results of correlation analysis: TMH was positively correlated with SMTube(rs=0.751, P<0.001), however, SⅠt had no correlation with TMH(rs=0.139, P=0.060)and SMTube(rs=0.019, P=0.799). The results of consistency analysis: TMH showed good consistency with SMTube(Kappa=0.794, P=0.044), however, SⅠt showed poor consistency with TMH(Kappa=0.271, P=0.074)and SMTube(Kappa=0.193, P=0.070)respectively.CONCLUSION:SMTube is a new, simple and convenient tool for evaluating tear volume. It has a good correlation and consistency with TMH measurement results. Therefore, it can replace TMH measurement, but cannot replace SⅠt in clinical application.

There are inconsistencies in treatment outcomes, measurement instruments, and criteria for assessing clinical effectiveness in studies related to distal radius fractures (DRF), resulting in potential biases and failing to provide high-quality clinical evidence. To address these challenges, international researchers have reached a consensus on developing the core outcome indicator set for distal radius fractures(COS-DRF). However, it's important to note that the existing COS-DRF framework could not reflect the unique characteristics of Traditional Chinese Medicine (TCM) treatment. Currently, there are no established standards for treatment outcomes and measurement instruments specific to TCM clinical research, nor has a COS-DRF been established for TCM clinical studies in China. In light of these gaps, our research team aims to construct a core set of treatment outcomes for TCM clinical research on distal radius fractures. This involves compiling a comprehensive list of treatment outcomes and measurement instruments, initially derived from a thorough literature review and expert consensus, which will then undergo further refinement and updates based on real-world clinical experiences, incorporating feedback from 2 to 3 rounds of expert consensus or Delphi questionnaire surveys. Our goal is to establish a COS-DRF or CMS-DRF that aligns with the principles and practices of TCM, and provide high-quality evidence for clinical practice.
Humans ; China ; Consensus ; East Asian People ; Outcome Assessment, Health Care ; Wrist Fractures/therapy* ; Medicine, Chinese Traditional ; Review Literature as Topic ; Fracture Fixation/standards*

ObjectiveTo investigate the role of bile acid receptor TGR5 activation in renal fibrosis induced by unilateral ischemia reperfusion injury and contralateral nephrectomy （uIRIx） model. MethodsIn vivo： C57BL/6J mice were randomly divided into Sham group， uIRIx group and uIRIx+ lithcholic acid （LCA） group with 6 mice in each group. Kidney fibrosis was induced by uIRIx model， kidney function was evaluated by blood and urine biochemical indexes， and the degree of kidney injury was evaluated by HE staining. Masson staining and immunohistochemistry were used to evaluate the degree of renal fibrosis， and Western Blotting was used to detect the expression of related index proteins of renal cortical fibrosis. Sham group and uIRIx group were set in TGR5^+/+ mice and TGR5^-/- mice respectively， with 6 mice in each group. The degree of renal fibrosis in each group was detected by Western Blotting. In vitro： TGF-β1 was administered to induce pro-fibrosis response in human renal tubular epithelial cell line （HK2 cells）， LCA was used for drug intervention， cytoskeleton was labeled with phalloidin-FITC staining and the expression of fibrosis related indicator protein in HK2 cells was detected by Western Blotting. ResultsIn vivo： Compared with the Sham group， plasma creatinine level （P=0.007） and urinary albumin/creatinine ratio （P=0.041） in uIRIx group were significantly increased， renal cortical protein TGR5 expression （P=0.002） was decreased， Fibronectin expression （P=0.020） and COL1A1 expression （P<0.001） were increased. At the same time， the kidney structure was damaged and collagen deposition was aggravated. LCA intervention effectively improved the kidney function and alleviated the degree of kidney injury and fibrosis. TGR5 gene knockout increased uIRIx-induced Fibronectin expression （P<0.001） and COL1A1 expression （P=0.001） compared with TGR5^+/+ mice. In vitro： TGF-β1 induced morphological changes of HK2 cells， cytoskeletal depolymerization and recombination， and promoted the up-regulation of fibrosis index protein. LCA effectively inhibited the morphological changes and skeletal depolymerization induced by TGF-β1， and down-regulated the expression of fibrosis related indicator proteins. ConclusionsLCA alleviated renal fibrosis induced by uIRIx model， and knockout of TGR5 gene aggravated uIRIx induced renal fibrosis； In HK2 cells， LCA alleviated fibrogenic reaction induced by TGF-β1. This indicates that activation of TGR5 alleviates renal fibrosis induced by uIRIx.

Humans ; Thoracoscopy ; Spine/surgery* ; Neoplasms ; Thoracic Vertebrae/surgery*