Tumor-associated macrophages(TAMs)are the predominant cell group in the tumor microenvironment(TME)and are the most important regulatory cells of immune system suppression and tumor cell proliferation in TIME.Src homology-2 domain-containing protein tyrosine phosphatase 2(SHP-2)is a non-receptor protein tyrosine phosphatase that plays an important role in the transmission of signals from the cell surface to the nucleus.SHP-2 is a key intracellular regulatory factor mediating cell proliferation and differentiation and is involved in a variety of growth factor and cytokine signaling pathways linking the cell surface to the nucleus.Recent studies have shown that SHP-2 is a key enzyme in determining the function of TAMs,but because of its variable function,it plays different or even opposite roles in different solid TMEs.This paper reviews the function of SHP-2 in TAMs and related solid tumors to provide a comprehensive reference for tumor immunity and targeted therapy research.

Malignant tumors are a major disease threatening human health with disability and mortality rates increasing yearly.Protein tyrosine phosphatase 2(SHP2)of Src homology 2,an important member of the protein tyrosine phosphatase family,has a wide range of functions,and its expression is elevated in a wide range of solid tumors.SHP2 plays an important regulatory role in invasion,metastasis,proliferation,apoptosis,and drug resistance.A large number of studies have shown that SHP2 plays a very important role in the genesis and development of many solid tumors,but no systematic studies have reported on the role of SHP2 in digestive system tumors.Here,we reviewed the biological functions and clinical significance of SHP2 in seven tumor types of the digestive system,explored its roles and mechanisms in cancer development stages,and summarized the development of SHP2 inhibitors to further search for potential targets for effective early diagnosis and gene therapy,which is of great significance to improvement the cancer patient survival rate.

Objective To investigate the effects of pterostilbene on human colon cancer LoVo cells and study the regulatory mechanism of nuclear factor E2-related factor 2(Nrf2)in the process of pterostilbene acting on LoVo cells.Methods LoVo cells were treated with different concentrations(5,10,20,40,60,80,100 panol/L)of pterostilbene.Cell viability,migration,invasion,and apoptosis were examined by CCK-8,scratch,Tran-swell,and TUNEL assays,respectively.The mitochondrial membrane potential was measured by the mitochon-drial membrane potential assay kit with JC-1.The reactive oxygen species level was measured by 2',7'-dichlo-rofluorescein diacetate.The protein levels of Nrf2,phosphorylated Nrf2,heme oxygenase 1,and apoptotic pro-teins(Bcl2 and Bax)were determined by Western blotting.In addition,cell viability,Nrf2 expression,and ap-optosis rate were determined after co-application of the Nrf2-specific agonist sulforaphane.Results Compared with the control group,40,60,80,100 μmol/L pterostilbene reduced the viability of LoVo cells(P=0.014,P＜0.001,P＜0.001,P＜0.001).Pterostilbene at 5,10,20 μmol/L did not show effects on cell viability but inhibited cell migration(P=0.008,P＜0.001,P＜0.001)and invasion(all P＜0.001).Pterostilbene at 40,60,80 μmol/L increased apoptosis(P=0.014,P＜0.001,P＜0.001),promoted mitochondrial membrane potential depolarization(P=0.026,P＜0.001,P＜0.001)and reactive oxygen species accumula-tion(all P＜0.001),and down-regulated the expression of phosphorylated Nrf2(P=0.030,P＜0.001,P＜0.001),heme oxygenase 1(P=0.015,P＜0.001,P＜0.001),and Bc12(P=0.039,P＜0.001,P＜0.001)in LoVo cells.Pterostilbene at 60,80 μmol/L down-regulated Nrf2 expression(P=0.001,P＜0.001)and up-regulated Bax expression(both P＜0.001).The application of sulforaphane reversed the effects of pterostilbene on cell viability(P＜0.001),apoptosis(P＜0.001),and Nrf2 expression(P=0.022).Conclusion Pterostilbene is a compound that can effectively inhibit colon cancer cells by inhibiting the Nrf2 pathway.

Objective:To evaluate the radiological and clinical outcomes of the aged patients with unstable proximal humeral fracture (UPHF) treated with a locking plate and an intramedullary titanium mesh.Methods:A retrospective study was conducted to analyze the 43 aged patients with UPHF who had been admitted to Department of Orthopedics, Zhongda Hospital Affiliated to Southeast University from January 2017 to July 2019. There were 13 males and 30 females with an age of (71.3±10.3) years (from 60 to 83 years). All patients were treated with a locking plate and an intramedullary titanium mesh to support. The postoperative imaging measurements included changes in humeral head height (HHH) and neck-shaft angle (NSA) (the difference between 3 years after surgery and the second day after surgery, taken as an absolute value); the postoperative clinical measurements included visual analogue scale (VAS), range of shoulder motion, Constant-Murley shoulder functional score (Constant score), American Shoulder and Elbow Surgeons (ASES) score, and incidence of complications.Results:All patients were followed up for (39.2±2.3) months after surgery. The change in HHH at 3 years after surgery was (1.5±1.1) mm, and the change in NSA at 3 years after surgery 3.3°±2.6°. At 3 years after surgery, the VAS score was (2.2±1.3) points, the Constant score (79.2±9.1) points, and the ASES score (78.9±9.2) points; the range of forward extension was 143.2°±20.8°, the range of outward extension 139.3°±23.1°, and the range of outward rotation 55.1°±4.7°. Complications after surgery were found in 6 patients, including humeral head necrosis in 2 cases, ectopic ossification in 1 case, and infection in 3 cases.Conclusion:In the treatment of the aged patients with UPHF, a locking plate combined with an intramedullary titanium mesh can help to restore the medial column support, leading to fine radiological and clinical outcomes.

Objective:To investigate the risk factors for preoperative hypoxemia in geriatric patients with hip fracture.Methods:A case-control study was used to analyze the clinical data of 99 geriatric patients with hip fracture admitted to Zhongda Hospital affiliated to Southeast University between November 2020 and August 2021. There were 29 males and 70 females, aged 67-96 years [(82.6±6.2)years]. The patients were divided into hypoxemia group ( n=51) and non-hypoxemia group ( n=48) using partial arterial partial pressure of oxygen (PaO 2)<80 mmHg while breathing room air at emergency as the reference standard. The two groups were compared in terms of sex, age, fracture types, body mass index (BMI), American Society of Anesthesiologists (ASA) classification, pulmonary diseases diagnosed by preoperative chest CT [atelectasis, pleural effusion, chronic obstructive pulmonary disease (COPD)], time from injury to visit, New York Heart Association (NYHA) classification, Barthel index, KATZ index, modified Medicine Research Council (mMRC) dyspnea scale, numeric rating scale (NRS), smoking, drinking, comorbidities (hypertension, diabetes mellitus, Parkinson′s disease, Alzheimer′s disease, cerebral infarction, coronary atherosclerotic heart disease), body temperature, blood routine test at first examination (erythrocyte count, leukocyte count, C-reactive protein, hemoglobin), biochemistry (serum albumin, blood glucose, blood creatinine, blood urea nitrogen), electrolyte (serum potassium, serum sodium), and other related examinations [D-dimer, brain natriuretic peptide (BNP), lactic acid]. Univariate analysis was performed to the correlation of those indicators with preoperative hypoxemia. Multivariate Logistic regression analysis was used to identify the independent risk factors for preoperative hypoxemia in geriatric patients with hip fracture. Results:Differences in sex, age, fracture types, BMI, pulmonary diseases diagnosed by preoperative chest CT, time from injury to visit, Barthel index, KATZ index, NRS, smoking, drinking, comorbidities, body temperature, first laboratory results of erythrocyte count, biochemistry, electrolyte and other related examinations were not statistically significant between the two groups (all P>0.05). The two groups showed statistical differences in ASA classification, NYHA classification, mMRC dyspnea scale, leukocyte count at first examination, C-reaction protein and hemoglobin (all P<0.05). Univariate analysis indicated that ASA classification, NYHA classification, mMRC dyspnea scale, leukocyte count at first examination and C-reaction protein were correlated with the occurrence of preoperative hypoxemia in geriatric patients with hip fracture (all P<0.05). Multivariate Logistic regressions analysis indicated that higher mMRC dyspnea scale ( OR=2.30, 95% CI 1.10-4.81, P<0.05), higher leukocyte count at first examination ( OR=1.24, 95% CI 1.05-1.45, P<0.05), higher level of C-reaction protein ( OR=1.02, 95% CI 1.01-1.03, P<0.05) and higher level of hemoglobin ( OR=1.04, 95% CI 1.01-1.07, P<0.05) were significantly correlated with the occurrence of preoperative hypoxemia in geriatric patients with hip fracture. Conclusion:Higher mMRC dyspnea scale, higher leukocyte count, higher level of C-reaction protein and higher level of hemoglobin are independent risk factors for preoperative hypoxemia in geriatric patients with hip fracture.

Objective:To investigate the clinical effects of retrograde anterolateral thigh perforator flaps assisted with computed tomography angiography (CTA) in repairing skin and soft tissue defects around the knee or in proximal lower leg.Methods:A retrospective cohort study was conducted. From May 2015 to October 2019, 17 patients with skin and soft tissue defects around the knee or in proximal lower leg were admitted to the Department of Orthopedics of Jizhong Energy Xingtai Mig General Hospital, including 12 males and 5 females, aged 16-65 years, with an average age of 35 years. The areas of skin and soft tissue defects after debridement ranged from 6.0 cm×3.0 cm to 15.0 cm×9.0 cm. The retrograde anterolateral thigh perforator flaps were designed according to the origin and distribution of the perforating branches in flaps and the length of the vascular pedicle examined with CTA and the condition of the wound to repair the wounds. The areas of resected flaps ranged from 6.5 cm×3.5 cm to 15.5 cm×9.5 cm. The wounds in donor sites of flaps were sutured directly or covered with medium-thickness skin grafts from healthy upper leg. The sources of the perforating branches in flaps were recorded. The lateral circumflex femoral artery, its branches, and the relative length of the vascular pedicle were compared between preoperative CTA detection and intraoperative observation. The survivals of the flaps were observed. At the last follow-up, the effects of flaps in repairing wounds were evaluated according to evaluation standard of efficacy satisfaction; the motion ranges of flexion and extension of the knee joint were measured, and the knee joint function was evaluated according to the Hohl knee joint function evaluation standard; the sensory function in the flap area was evaluated according to the sensory function evaluation standard formulated by the British Medical Research Council; the wound healing and the occurrence of complication affecting motor function of limb of flap donor sites was observed. Data were statistically analyzed with paired sample t test. Results:The perforating branches in flaps originated from descending branches, oblique branches, and rectus femoris branches of lateral circumflex femoral artery in 7, 6, and 4 patients, respectively. The flaps with blood supply from descending branches, oblique branches, and rectus femoris branches of lateral circumflex femoral artery were type 1, 2, and 3 retrograde anterolateral thigh perforator flaps, respectively. The preoperative CTA examination of lateral circumflex femoral artery and its branches were consistent with those observed during operation. The relative lengths of vascular pedicles of type 1, 2, and 3 retrograde anterolateral thigh perforator flaps calculated after CTA examination were 0.32±0.13, 0.56±0.07, and 0.56±0.15, which were close to 0.35±0.12, 0.52±0.10, and 0.53±0.12 measured and calculated during operation, respectively ( t=0.45, 0.80, 0.31, P>0.05). All flaps survived in 17 cases without vascular crisis. At the last follow-up, 16 patients were satisfied with effects of flaps in wound repair, with 1 patient feeling average about the effect; the flexion range of knee joint was 100-120°, and the extension range of knee joint was -2-0°; knee joint function was evaluated as excellent in 9 cases, good in 7 cases, and poor in 1 case; the sensory function of the flap area reached S 4 level in 2 cases, S 3 level in 8 cases, and S 2 level in 7 cases; the wounds in flap donor sites healed well; there was no adverse effect in motor function of limbs. Conclusions:Retrograde anterolateral thigh perforator flap is an effective method for repairing skin and soft tissue defects around the knee or in proximal lower leg. Preoperative CTA examination can fully show the anatomical characteristics of the branches of the lateral circumflex femoral artery and the perforating vessels of each branch, which can guide preoperative flap design and operation, thus shortening operation time and improving flap survival rate, with good clinical effects.

Objective:To explore the clinic effects of the head of second metatarsal bone and flap for bone and skin defect at lateral malleolus in children.Methods:Between July 2009 and May 2018, 4 children with ankle bone and skin and soft tissue defects in the Jizhong Energy Xingtai Mig General Hospital were selected, including 3 boys and 1 girl aged 4-13 years old. All cases were lateral malleolus defect with adjacent skin defect, the range of skin defect was 2.0 cm×2.0 cm -4.0 cm×5.0 cm, and the range of bone defect was 1.0-3.0 cm. The area of the flap was 2.5 cm×2.5 cm-4.5 cm × 5.5 cm, and the length of the second metatarsal head was 1.0-3.0 cm. The donor site was closed directly. After the operation, X-rays was performed to evaluate whether the ankle space and lateral malleolus longitudinal development was synchronized with the uninjured limb. Ankle joint function recovery was evaluated according to the American Orthopaedic Foot and Ankle Society (AOFAS). The outcomes of donor foot range of motion, weight-bearing, and walking were observed.Results:All the composite tissue flap survived with good blood circulation, and all the donor sites healed well. All the child patients were followed up for 0.5-2.0 years. The color and elasticity of the flaps were good, without cicatricial contracture. The patients had no inversion of ankle joint, with satisfying loading and walking function. Imaging evaluation showed that the space between ankle points and the longitudinal development of lateral malleolus were roughly synchronous with the healthy side. Two cases were graded as excellent and 2 as good according to the standard of the AOFAS.The donor's foot had normal flexion and extension function, without instability.Conclusions:The head of second metatarsal bone and flap can repair the epiphysis and soft tissue defect of lateral malleolus in children at one stage, and the reconstructed lateral malleolus can develop with the growth of children. It is a satisfactory method of reconstructing the traumatic defect of lateral malleolus in children.

Animals ; Biological Transport, Active/physiology* ; Centrioles/metabolism* ; Cilia/metabolism* ; Mice ; Mice, Mutant Strains ; N-Acetylglucosaminyltransferases/metabolism*

Objective:To explore the clinic effects of the head of second metatarsal bone and flap for bone and skin defect at lateral malleolus in children.Methods:Between July 2009 and May 2018, 4 children with ankle bone and skin and soft tissue defects in the Jizhong Energy Xingtai Mig General Hospital were selected, including 3 boys and 1 girl aged 4-13 years old. All cases were lateral malleolus defect with adjacent skin defect, the range of skin defect was 2.0 cm×2.0 cm -4.0 cm×5.0 cm, and the range of bone defect was 1.0-3.0 cm. The area of the flap was 2.5 cm×2.5 cm-4.5 cm × 5.5 cm, and the length of the second metatarsal head was 1.0-3.0 cm. The donor site was closed directly. After the operation, X-rays was performed to evaluate whether the ankle space and lateral malleolus longitudinal development was synchronized with the uninjured limb. Ankle joint function recovery was evaluated according to the American Orthopaedic Foot and Ankle Society (AOFAS). The outcomes of donor foot range of motion, weight-bearing, and walking were observed.Results:All the composite tissue flap survived with good blood circulation, and all the donor sites healed well. All the child patients were followed up for 0.5-2.0 years. The color and elasticity of the flaps were good, without cicatricial contracture. The patients had no inversion of ankle joint, with satisfying loading and walking function. Imaging evaluation showed that the space between ankle points and the longitudinal development of lateral malleolus were roughly synchronous with the healthy side. Two cases were graded as excellent and 2 as good according to the standard of the AOFAS.The donor's foot had normal flexion and extension function, without instability.Conclusions:The head of second metatarsal bone and flap can repair the epiphysis and soft tissue defect of lateral malleolus in children at one stage, and the reconstructed lateral malleolus can develop with the growth of children. It is a satisfactory method of reconstructing the traumatic defect of lateral malleolus in children.

Objective:To investigate the effects of hematopoietic progenitor kinase 1 (HPK1) overexpression by construction of lentiviral vector on the proliferation and apoptosis of breast cancer MCF-7 and MDA-MB-231 cells,and to elucidate its possible mechanism.Methods:The cells were infected with the lentivirus overxpressing HPK1,and the MCF-7-HPK1 and MDA-MB-231-HPK1 cell lines were stably expressed HPK1;each cell line was divided into three experimental groups:blank group (untreated),control group (empty vector) and HPK1-overexpression group.The expression levels of HPK1 mRNA and protein in breast cancer cells in each group were detected by RTPCR and Western blotting methods,respectively.The cell proliferation rate was detected by MTT assay.The cell cycle and apoptotic rate were detected by flow cytometry.Transwell assay was used to analyze the cell migration ability.Western blotting method was used to measure the expression levels of caspase 3,PTEN,MMP-9,MMP-2,Ki-67and HPK1 proteins.Results:Compared with blank groups and control groups,the expression levels of HPK1 mRNA and protein in the both cell lines in HPK1 overexpression groups were significantly up-regulated (P＜0.05),the proliferation rates were significantly decreased (P＜0.05) and the apoptotic rates were significantly increased (P＜0.05),the number of cells crossing matrigel was significantly reduced (P＜0.05),the cell cycle of MCF-7 was blocked in G1 phase (P＜0.05),the expression levels of caspase 3 and PTEN proteins in HPK1 overexpression group were significantly increased (P＜0.05),and the expression levels of MMP-2 and MMP-9 proteins were significantly decreased (P＜0.05).Conclusion:HPK1 overexpression can inhibit the proliferation and migration of MCF-7 and MDA-MB-231 cells and induce apoptosis,which may be related to the up-regulation of caspase 3 and PTEN and down-regulation of MMP-9,MMP-2 and Ki-67.