ObjectiveTo summarize the biological function and molecular regulation mechanism of serine threonine tyrosine kinase 1 (STYK1) in tumor occurrence and development. MethodThe relevant literature about STYK1 and tumor progression in recent years was searched and reviewed. ResultsThe expression of STYK1 was up-regulated in a variety of tumors and was related to the prognosis. STYK1 might regulate the proliferation, apoptosis, migration, metastasis, aerobic glycolysis, drug resistance and other biological functions of tumor cells through MEK/ ERK, PI3K/AKT, JAK/STAT and their targeting proteins, and promote the malignant progress of tumors. Conclusion STYK1is expected to become a new target for the treatment of malignant tumors, but the molecular mechanism of its regulation of tumor progression and its upstream regulators need to be further explored.
ObjectiveTo systematically elucidate the resistance mechanism of targeted drug therapy for breast cancer and to discuss future direction of optimized treatment strategies. MethodA literature review on targeted therapy for breast cancer had been conducted based on recent domestic and international research. ResultsContemporary breast cancer targeted therapies mainly comprised human epidermal growth factor receptor 2 (HER2)-directed agents, CDK4/6 inhibitors, phosphatidylinositol 3-kinase/protein kinase B/mechanistic target of rapamycin pathway blockers, poly (ADP-ribose) polymerase inhibitors, and immune checkpoint modulators, etc. While these agents had conferred subtype-specific survival benefits, resistance developed through target mutations, compensatory signaling, epigenetic alterations, drug efflux pumps, among other mechanisms. Emerging strategies for reversing drug resistance included dual-targeted approaches (such as trastuzumab in combination with pertuzumab), dynamic monitoring of drug-resistant gene mutations by liquid biopsy, epigenetic modulators, etc. ConclusionsDrug resistance remains a key bottleneck limiting long-term efficacy of breast cancer targeted therapy. Future research should integrate multi-omics approaches to decipher tumor heterogeneity, implement combinatorial multi-target inhibition with real-time monitoring of multidimensional interventions, and leverage artificial intelligence to predict resistance evolution. This integrated strategy is expected to enable personalized combination therapies, ultimately overcoming drug resistance and improving patient survival outcomes.
Objective To summarize the papers about the research status and prospects of ferroptosis in hepatocellular carcinoma (HCC) and its drug resistance in recent years in order to provide directions and ideas for the treatment of HCC. Method The relevant literatures at home and abroad in recent years about ferroptosis in HCC and its drug resistance were reviewed. Results The mechanism of ferroptosis in the development and drug resistance of HCC was complicated, involving multiple protein and molecular pathways. Ferroptosis played an important role in improving chemotherapy and sorafenib resistance, and it had a broad application prospect in HCC. Conclusions The molecular mechanism of ferroptosis in HCC and its drug resistance has not been fully elucidated. Further research on the mechanism of ferroptosis in HCC may provide new molecular therapeutic targets for HCC. Ferroptosis has a broad application prospect in the treatment of HCC.
ObjectiveTo investigate role and mechanism of protein tyrosine phosphatase 1B (PTP1B) in jejunoileal bypass to treating rats with type 2 diabetes mellitus (T2DM).
MethodsTwenty-four T2DM SD rats and 24 normal SD rats were selected randomly by using random number table, then the SD rats with T2DM were randomly divided into jejunoileal bypass operation (DJBO, n=12) group and sham operation (DSO, n=12) group, the SD rats with normal food diet were randomly divided into jejunoileal bypass operation (NJBO, n=12) group and sham operation (NSO, n=12) group. Subsequently, fasting body weight (FBW), fasting plasma glucose (FPG), fasting insulin (FINS), and homeostasis model-insulin resistant (HOMA-IR) index of rats in each group were tested at different time points (before operation, on week 4 and 8 after operation). In addition, expression of PTP1B protein in skeletal muscle was determined by immunohistochemical staining and Western blot method respectively.
Results① The FBW before making T2DM model had no significant difference between the rats with high-fat diet and with normal diet (P > 0.05), which on week 4 or 8 after making T2DM model in the rats with high-fat diet was significantly heavier than that in the rats with normal diet (P < 0.05). ② Before jejunoileal bypass operation, the FBW, FPG, FINS, and HOMA-IR index in the DJBO group and the DSO group were significantly higher than those in the NJBO group and the NSO group (P < 0.05), respectively, which had no significant differences between the DJBO group and the DSO group (P > 0.05) and between the NJBO group and the NSO group (P > 0.05). ③ Compared with the values before jejunoileal bypass operation, the FBW, FPG, FINS, and HOMA-IR index on week 4 or 8 after jejunoileal bypass operation were significantly decreased in the DJBO group (P < 0.05); the FBW was significantly increased on week 4 or 8 after jejunoileal bypass operation in the DSO group and the NSO group (P < 0.05), and on week 8 after jejunoileal bypass operation in the NJBO group (P < 0.05). The other indexes had no significant differences between before and after jejunoileal bypass operation in the DSO group, the NSO group, or the NJBO group (P > 0.05). ④ On week 8 after jejunoileal bypass operation, the expression of PTP1B protein in the DSO group was significantly higher than that in the DJBO group, the NSO group or the NJBO group (P < 0.05), which in the DJBO group was significantly higher than that in the NSO group (P < 0.05) or the NJBO group (P < 0.05), which had no significant difference between the NJBO group and the NSO group (P > 0.05).
ConclusionJejunoileal bypass could effectively improve insulin resistance and decrease FPG level and FBW of T2DM rats through inhibiting expression of PTP1B protein in skeletal muscle of rat with T2DM.
ObjectiveTo investigate the condensate pollution in the pipeline of severe pneumonia patients undergoing mechanical ventilation.MethodsFrom January 2017 to January 2019, 120 patients with severe pneumonia treated by mechanical ventilation in our hospital were collected continuously. The lower respiratory tract secretions were collected for bacteriological examination. At the same time, the condensed water in the ventilator exhaust pipe was collected for bacteriological examination at 4, 8, 12, 16, 20 and 24 hours after tracheal intubation and mechanical ventilation. The bacterial contamination in the condensed water at different time points was analyzed and separated from the lower respiratory tract. The consistency of bacteria in secretion and drug resistance analysis of bacterial contamination in condensate water were carried out.ResultsOf the 120 patients with severe pneumonia after mechanical ventilation, isolates were cultured in the lower respiratory tract secretions of 102 patients. One strain was cultured in 88 cases, two strains were cultured in 10 cases, and three strains were cultured in 4 cases. The isolates were mainly Gram-negative bacteria (57.5%) and Gram-positive bacteria (42.5%). The most common isolates were Pseudomonas aeruginosa, Staphylococcus aureus and Acinetobacter baumannii. The contamination rate of condensate water was 5.0% at 4 hours, 37.5% at 8 hours, 60.0% at 12 hours, 76.7% at 16 hours, 95.0% at 20 hours, and 100.0% at 24 hours, respectively. The bacterial contamination rate in condensate water at different time points was statistically significant (P=0.000). The pollution rate at 4 hours was significantly lower than that at 8 hours (P=0.000). Gram-negative bacteria accounted for 57.5% and Gram-positive bacteria accounted for 42.5%. The most common isolates were Staphylococcus aureus, Pseudomonas aeruginosa and Acinetobacter baumannii. The consistency of bacteria in lower respiratory tract and condensate water was 83.3% in severe pneumonia patients undergoing mechanical ventilation. The overall resistance of Pseudomonas aeruginosa, Acinetobacter baumannii and Staphylococcus aureus was higher, but the resistance to imipenem/cilastatin was lower.ConclusionsThe bacterial contamination in the condensate of patients with severe pneumonia during mechanical ventilation is serious. The pollution rate is low within 4 hours. It is consistent with the bacterial contamination in lower respiratory tract and the bacterial resistance is high.
Objective To summarize the roles of tumor initiating cells （TICs） and epithelial-mesenchymal transition （EMT） in tumor metastasis and drug resistance. Methods Domestic and international publications online which involving TICs，EMT，and its roles in tumor metastasis and drug resistance in recent years were reviewed. Results TICs were self-renewal cells and had the ability to give rise to more differentiated cell types，and played an important role in tumor metastasis and drug resistance. Various markers had been used to identify TICs，such as CD133，CD44，and so on. EMT was the process by which epithelial cells losed polarity and detach from the epithelial sheet， and acquired a motile mesenchymal phenotype，usually observed in embryo development and wound healing. It also could promote tumor progression and metastasis，and may also be responsible for the ability of tumors to evade the body’s immune response. EMT may be the reasons of TICs that drived tumor metastasis and recurrence. TICs or EMT as a target for treatments may effectively prevent tumor recurrence and improve patient’s survival. Conclusions EMT is probably the mechanism that TICs promote tumor metastasis and drug resistance. More effective target therapies for cancer may be found if we know more about TICs and EMT.
ObjectiveTo summarize the latest research progress and related mechanisms of cancer-associated fibroblasts (CAFs) in invasion, metastasis and drug resistance of breast cancer, so as to seek the best treatment strategy for patients with breast cancer metastasis and drug resistance. MethodThe literatures about CAFs research in breast cancer in recent years were searched and summarized. ResultsCAFs was the main stromal cell in tumor microenvironment (TME). By changing TME, the biological characteristics of CAFs could be changed and the growth and invasion of breast cancer cells could be induced. CAFs in breast cancer promotes the invasion and metastasis of breast cancer cells by interacting with inflammatory factors and promoting the formation of pre-transplantation ecosystems, and CAFs also mediates chemotherapy resistance to breast cancer, target resistance, endocrine resistance, and radiation resistance through the secretion of various cellular factors. ConclusionsAt present, some progress has been made in the research of CAFs in breast cancer, but there is still a certain gap to clinical application CAFs has a variety of functional phenotypes, so it is necessary to identify and characterize specific CAFs subtypes when studying new anti-CAFs therapeutic strategies. It has been proved that CAFs has great potential as a specific target for breast cancer treatment, but CAFs still lacks specific biomarkers. Therefore, an in-depth understanding of the biological characteristics and heterogeneity of CAFs can provide a reliable theoretical basis for developing drugs targeting CAFs.
ObjectiveTo systematically evaluate the changes in placental protein expressions in gestational diabetes mellitus (GDM) and their correlations with maternal insulin resistance (IR). Methods PubMed, Cochrane Library, Scopus, Web of Science, Embase, China National Knowledge Infrastructure, VIP database, Wanfang Database and CBMdisc were searched for case-control studies published from January 2009 to November 2021, which reported the placental protein expressions in GDM and their correlations with IR. Two researchers independently reviewed the literature, extracted data and evaluated the literature quality. RevMan 5.4 software was used for meta-analysis, and descriptive analysis was performed on data that cannot be combined. ResultsA total of 19 studies were included, comprising 2 012 patients. The results of meta-analysis showed that: the expression level of retinol binding protein 4 (RBP4) [standard mean difference=2.11, 95% confidence interval (CI) (1.64, 2.58), P<0.000 01] and the positive rate of protein tyrosine phosphatase-1B (PTP1B) [relative risk (RR)=1.56, 95%CI (1.29, 1.88), P<0.000 01] were up-regulated, and the positive rate of insulin receptor substrate 1 (IRS-1) [RR=0.69, 95%CI (0.60, 0.78), P<0.000 01] was down-regulated. The protein expression levels of RBP4 (P<0.000 01) and PTP1B (P<0.000 01) were positively correlated with homeostasis model assessment of insulin resistance (HOMA-IR), while the protein expression levels of IRS-1 (P<0.000 01) and APN (P=0.002) were negatively correlated with HOMA-IR, and glucose transporter 4 (GLUT 4) was not correlated with HOMA-IR (P=0.79). Descriptive analysis found that the expression levels or positive rates of adipocytokines (leptin, resistin), oxidative stress markers (xanthione oxidase, malondialdehyde, 8-isoprostaglandin),inflammatory factors (tumor necrosis factor α, Toll-like receptor 4, Galectin-3, Galectin-2, migration inhibitory factor),fetuin-A, forkhead box transcription factor 1, forkhead box transcription factor 3a and estrogen receptor α in GDM placenta were up-regulated and all were positively correlated with HOMA-IR. The expression levels or positive rates of insulin signaling pathway proteins [phosphoinositide 3-kinase (PI3K), protein kinases B (AKT), phospho-protein kinases B (p-AKT), GLUT 4] were down-regulated, PI3K and AKT were negatively correlatedwith HOMA-IR, while p-Akt had no correlation with HOMA-IR. ConclusionsThe dysregulation of placental protein expressions may mediate maternal IR exacerbation, thus promote the occurrence and development of GDM and other pregnancy complications. The causal relationship and regulatory mechanism are still unclear, which need to be further studied.
Objective
To detect the difference of periostin expression in small cell lung cancer (SCLC) cell, and explore its effect on chemoresistance of SCLC patients.
Methods
The expression of periostin in mRNA and protein was detected by RT-PCR and Western blot analysis in SCLC H69 and multidrug resistant strain H69AR. The expression of periostin was up-regulated by recombinant plasmid-periostin in H69 cell. The survival rate in the transfected group was different from that of the negative control group and uninterrupted group.
Results
The expression of periostin mRNA and protein in the sensitive strain H69 was lower than that of the multidrug resistant strain H69AR (P<0.05). The recombinant periostin-plasmid was transfected into H69 cells and at the same concentration of chemotherapeutic drugs (cisplatin, etoposide) the survival rate increased significantly (P<0.05). The positive expression rate of periostin in SCLC tissues was 67.44%, and the sensitivity of the chemotherapy group was lower than that of the drug resistant group (P<0.05).
Conclusion
The expression of periostin in SCLC cell H69 is significantly lower than that of the multidrug resistant strain H69AR and overexpression of periostin increases resistance of the sensitive strain H69 and hence periostin may be involved in SCLC chemoresistance.
Objective To explore the effect of low-load resistance training on physical fitness in aged adults. Methods Select the aged adults who will go to the outpatient Department of Rehabilitation Medicine of Peking Union Medical College Hospital between June 1, 2020 and May 31, 2021. The aged adults were randomly divided into three groups by using the method of random number table: medium intensity aerobic training group (aerobic training group), standard-load resistance training group (standard-load group) and low-load resistance training group (low-load group). The basic information, exercise endurance (peak power, peak oxygen uptake), exercise cardiopulmonary function [peak heart rate, predicted peak heart rate, peak minute ventilation (VE), ventilatory equivalent for carbon dioxide at anaerobic threshold (EqCO2 during AT)], muscle strength, and muscle oxygen related indexes were collected blindly before the first exercise and after 12 weeks of training, respectively. To compare the differences of the indexes before and after training. Results A total of 90 patients were enrolled, 30 in each group. There was no significant difference in age, sex, height, weight and body mass index among the three groups (P>0.05). There was no significant difference in cardiopulmonary endurance, cardiopulmonary function, muscle strength, muscle oxygen related indexes between the groups before and after training (P>0.05). Except for the indexes related to cardiac function (peak heart rate, predicted peak heart rate) and resting muscle oxygen level (P>0.05), other indexes related to pulmonary function, cardiopulmonary endurance, muscle strength, and time of muscle oxygen falling to the valley in the three groups were statistically significant compared with those before training (P<0.05). Except for peak power, peak oxygen uptake and time of muscle oxygen falling to the valley (P>0.05), the difference of muscle strength before and after training in the three groups was statistically significant (P<0.05), including grip strength, chest push, sitting rowing, leg extension, hip abduction, body bending and horizontal push and push, and the low-load group was better than the aerobic training group (P<0.05), but the improvement of body bending and horizontal push and push in the standard-load group was better than the low-load group (P<0.05). Conclusions Low-load resistance training, standard-load resistance training and aerobic training have almost the same effect on improving the physical fitness of the elderly. Low-load resistance training is superior to medium intensity aerobic training in improving muscle strength, which is an effective method to improve the physical fitness of the aged adults.
