Vasorin (VASN) overexpression promotes pulmonary metastasis and resistance to adjuvant chemotherapy in patients with locally advanced rectal cancer.

BACKGROUND: LARC patients commonly receive adjuvant therapy, however, hidden micrometastases still limit the improvement of OS. This study aims to investigate the impact of VASN in rectal cancer with pulmonary metastasis and understand the underlying molecular mechanisms to guide adjuvant chemotherapy selection. METHODS: Sequencing data from rectal cancer patients with pulmonary metastasis from Sun Yat-sen University Cancer Center (SYSUCC) and publicly available data were meticulously analyzed. The functional role of VASN in pulmonary metastasis was validated in vivo and in vitro. Coimmunoprecipitation (co-IP), immunofluorescence, and rescue experiments were conducted to unravel potential molecular mechanisms of VASN. Moreover, VASN expression levels in tumor samples were examined and analyzed for their correlations with pulmonary metastasis status, tumor stage, adjuvant chemotherapy benefit, and survival outcome. RESULTS: Our study revealed a significant association between high VASN expression and pulmonary metastasis in LARC patients. Experiments in vitro and in vivo demonstrated that VASN could promote the cell proliferation, metastasis, and drug resistance of colorectal cancer. Mechanistically, VASN interacts with the NOTCH1 protein, leading to concurrent activation of the NOTCH and MAPK pathways. Clinically, pulmonary metastasis and advanced tumor stage were observed in 90% of VASN-positive patients and 53.5% of VASN-high patients, respectively, and VASN-high patients had a lower five-year survival rate than VASN-low patients (26.7% vs. 83.7%). Moreover, the Cox analysis and OS analysis indicated that VASN was an independent prognostic factor for OS (HR = 7.4, P value < 0.001) and a predictor of adjuvant therapy efficacy in rectal cancer. CONCLUSIONS: Our study highlights the role of VASN in decreasing drug sensitivity and activating the NOTCH and MAPK pathways, which leads to tumorigenesis and pulmonary metastasis. Both experimental and clinical data support that rectal cancer patients with VASN overexpression detected in biopsies have a higher risk of pulmonary metastasis and adjuvant chemotherapy resistance.

[Effect of plasminogen activator urokinase receptor gene on the activation and apoptosis of neutrophil].

Objective: To investigate the effect of plasminogen activator urokinase receptor (PLAUR) gene on neutrophil activation and apoptosis in neutrophil-like cell model. Methods: Human acute myeloid leukemia cell line HL60 was cultured in vitro and induced to differentiate into neutrophil-like cells by all-trans retinoic acid (ATRA). Lentiviral vectors interfering with human PLAUR gene was constructed and transfected into neutrophil-like cells (siRNA group). The phosphate buffer saline (PBS) group (untransfected neutrophil-like cells) and normal blank control group (NC group) (neutrophil-like cells transfected with blank plasmid) were used as controls (n=3). After starvation culture and addition of interleukin-17 afterwards in these 3 groups, the expression of CD11b on the cell membrane was detected by flow cytometry, and the levels of myeloperoxide (MPO) and extracellular neutrophil traps (NETs) in the supernatant were detected by enzyme-linked immunosorbent assay (ELISA) to investigate the activation of neutrophil-like cells. The apoptosis was detected by flow cytometry with annexin V/propidium iodide (PI) double staining and the expressions of apoptosis-related proteins caspase-3, bax and bcl-2 were detected by Western blotting. Results: The expression of CD11b in siRNA group (32.37±8.17) was lower than that in PBS group (46.27±1.54) and NC group (53.07±8.14) (P<0.05) by flow cytometry. The levels of MPO and NETs (33.37±1.11, 57.69±3.03) in the supernatant of siRNA group were significantly lower than those in PBS group (41.64±2.20, 77.60±4.33) and NC group (40.84±5.11, 76.15±2.10) (P<0.05). Flow cytometry with annexin V/PI showed that the expression of apoptosis in siRNA group (20.42%±2.45%) was significantly higher than that in PBS group (11.91%±2.23%) and NC group (11.13%±2.56%) (P<0.05). The relative expression of caspase-3 protein and bax protein (0.84±0.05, 0.83±0.04) in siRNA group was significantly higher than that in PBS group (0.68±0.02, 0.63±0.08) and NC group (0.71±0.01, 0.66±0.10) (P<0.05), and the relative expression of anti-apoptosis protein bcl-2 decreased in siRNA group (0.38±0.02) than in PBS group (0.73±0.05) and NC group (0.69±0.06) (P<0.05). Conclusion: PLAUR promotes the activation of neutrophil-like cells and inhibits the apoptosis.

[Analysis of the characteristics of MRI T2 value changes of the muscles around the knee joint before and after the race in amateur marathon runners based on T2 mapping].

Objective: To evaluate the characteristics of MRI T2 value changes of muscles around the knee joint in amateur marathon athletes based on T2 mapping. Methods: A total of 12 amateur marathon runners (5 males and 7 females) were recruited as the marathon group, aged from 21 to 37(27.5±5.4) years. MRI examination of bilateral knee joint was performed one week before the race, within 12 hours after the race and two months after the race, respectively. Fifteen healthy volunteers (5 males and 10 females) were recruited as the control group, aged from 24 to 27(24.9±1.0) years, and underwent MRI examination of both knee joints. The T2 mapping imaging sequence was used to measure the T2 values of the sartorius, vastus medialis, biceps femoris, semimembranosus, medial head of gastrocnemius and lateral gastrocnemius head on the post-processing platform, and analyzed the marathon group before and after the race. The differences in the T2 value of each muscle of the marathon group before and after the race within 12 hours, before and 2 months after the race, and between the control group and the marathon group before the marathon were analyzed. Results: All subjects had not knee joint pain during the examination. Routine MRI examination showed that there was no obvious abnormality in the shape and signal of the muscles around the knee joint. The T2 value of the semimembranosus [(34.3±2.8) ms vs (35.5±2.5) ms, P=0.008], medial head of gastrocnemius [(34.1±3.4) ms vs (37.7±3.1) ms,P<0.001] and lateral head of gastrocnemius [(35.2±2.9) ms vs (37.2±3.9) ms,P=0.011] increased after the competition compared with that of pre-competition in the marathon group, while the T2 value of the remaining muscles showed no significant difference compared with that of pre-competition(P>0.05). At the follow-up of 2 months, the T2 value of semimembranosus remains higher than before the marathon [(34.3±2.8) ms vs (35.4±2.5) ms,P=0.043], and the T2 value of the medial head of the gastrocnemius and lateral head of gastrocnemius showed no statistically difference compared with pre-competition (P>0.05). Compared with the control group, the T2 value of the lateral head of the gastrocnemius in the marathon group was decreased [(35.3±3.0) ms vs (38.5±4.1) ms,P=0.007]. There was no significant difference in the T2 value of the remaining muscles in the marathon group (P>0.05). Conclusions: After the marathon, the changes in the T2 value of the muscles around the knee joint is reversible. T2 mapping imaging sequence can indirectly reflect the changes of skeletal muscle microstructure to a certain extent.

[Meta-analysis of the therapeutic value of plasma exchange simple or combined with dual plasma molecular adsorption system for liver failure].

Objective: To systematically analyze the serological parameters, effective rate and survival rate of patients with liver failure after simple plasma exchange treatment and half-dose plasma exchange combined with dual plasma molecular adsorption system. Methods: Randomized controlled trials published in the full-text articles of Pubmed, Embase, Web of Science, The Cochrane Library, Wanfang, Weipu, CNKI, and other journals from June 2020 were retrieved. Revman 5.3 software was used to conduct the meta-analysis after the literature quality evaluation. Results: A total of 10 studies involving 884 cases were selected. Among them, 425 and 459 were treated with combination and simple plasma exchange therapy. The levels of TBIL (MD=-28.58, 95% CI: -37.42～-19.75, P<0.000 01) and ALB (MD=-2.00, 95%CI:-2.61～-1.39, P<0.000 01) were lower in the combined treatment group than those in the simple treatment group, and the difference was statistically significant. HGB (MD=5.96, 95%CI: 1.52-10.40, P=0.009), effective rate (OR=1.92, 95%CI: 1.29-2.85, P=0.001), and survival rate (OR=1.63, 95%CI: 1.13-2.36, P=0.009) were higher in the combined treatment group than those in the simple treatment group, and the difference was statistically significant.The two treatment methods had good curative effects for the improvement of ALT, AST, DBIL, PTA, INR, and PLT levels (P＜0.05), and there was no statistically significant difference between them (P＞0.05). Conclusion: Half-dose plasma exchange combined with dual plasma molecular adsorption system therapy not only effectively improves hyperbilirubinemia, efficacy, and survival rate while significantly reducing plasma dosage, but it also has fewer adverse effects on hemoglobin depletion in patients with liver failure than simple plasma exchange therapy.

[Oligometastatic and oligoprogressive esophageal squamous cell carcinoma:clarifying conceptions and surgery perspectives].

The oligometastatic and oligoprogressive state has been a hot issue in cancer research. Its indolent tumor behavior, representing a novel therapeutic opportunity, has been identified as a clinical subtype in several malignancies. However, the clinical implications of the oligometastatic and oligoprogressive state in esophageal squamous cell carcinoma (ESCC) have not been thoroughly elucidated. There are still controversies regarding the existence of the oligometastatic state in ESCC, if the solitary regional lymph node metastasis should be viewed as oligoprogressive disease after esophagectomy, and the role of surgery and radiotherapy in ESCC oligometastatic disease. Despite many exciting contributions to the literature on these, further exploration is warranted. Thus, fostering the advance of research and scientific knowledge on the biological and prognostic characteristics scrupulously would facilitate personalizing treatment strategy for better outcomes.

[The application of scales and characteristics of disability in the common genotypes of Charcot-Marie-Tooth disease].

Objective: To analyze the correlations among different common scales for evaluating the severity of the first-visit Charcot-Marie-Tooth disease (CMT), and explore the cross-sectional characteristics of neurological dysfunction in patients with four common genotypes (CMT1A, CMT1X, CMT2A and MPZ-related CMT) at their first visits. Methods: A total of 117 genetically confirmed CMT patients (aged ≥10 years) from the Department of Neurology of the Third Xiangya Hospital from 2009 to 2019 were included in the study, which consisted of 45 CMT1A, 41 CMT1X, 19 CMT2A, and 12 MPZ-related CMT patients. Clinical data of these patients at first visits were collected and neurological deficits were evaluated by Charcot-Marie-Tooth Neuropathy Score (CMTNS), Charcot-Marie-Tooth Examination Score (CMTES), Overall Neuropathy Limitation Scale (ONLS) and Functional Disability Scale (FDS). Spearman's correlation was performed to analyze the relationship between CMTNS, CMTES, ONLS and FDS. The age of onset, duration of disease, scores of CMTNS, CMTES, ONLS and FDS were compared among four genotypes. Results: In the 117 CMT patients, the male to female ratio was 1.79/1, and the age of onset was (19±13) years. The duration of disease was 10(3, 15) years, and the scores of CMTNS, CMTES, ONLS and FDS were 11.4±6.2, 8.8±5.7, 2.7±1.4 and 2.6±1.3, respectively. There was a significant correlation between CMTES, ONLS, FDS and CMTNS in the overall CMT patients and four subtypes respectively (r≥0.40, P<0.05). CMTNS, CMTES and ONLS scores of four subtypes showed positive correlations with duration of disease (P<0.05), but FDS scores of CMT1A, CMT1X and MPZ-related CMT patients exhibited no correlation with duration of disease (P>0.05) at their first visits. The age of onset in CMT2A patients was younger than that of the patients with the other three genotypes (P<0.05), furthermore, the scores of four scales in early-onset CMT2A patients were higher than those of adult-onset type CMT2A patients (CMTNS: P=0.031, CMTES: P=0.048, ONLS: P=0.042, FDS: P=0.047). In CMT1X patients, the males had higher scores than those of females for all four scales (CMTNS: P=0.028, CMTES: P=0.014, ONLS: P=0.023, FDS: P=0.002). Conclusions: CMTNS, CMTES and ONLS could be used in natural history studies and clinical trials according to the different clinical situations. In the four genotypes, CMT2A patients have younger age of onset, and the earlier the age of onset, the severer the dysfunction. Moreover, male CMT1X patients relatively have severer neurological dysfunction than female patients.

Uncoupling DAPK1 from NMDA receptor GluN2B subunit exerts rapid antidepressant-like effects.

Several preclinical studies have reported the rapid antidepressant effects of N-methyl-D-aspartate receptor (NMDAR) antagonists, although the underlying mechanisms are still unclear. Death-associated protein kinase 1 (DAPK1) couples GluN2B subunits at extrasynaptic sites to regulate NMDAR channel conductance. In the present study, we found that chronic unpredictable stress (CUS) induced extracellular glutamate accumulation, accompanied by an increase in the DAPK1-NMDAR interaction, the high expression of DAPK1 and phosphorylated GluN2B at Ser1303, a decrease in phosphorylated DAPK1 at Ser308 and synaptic protein deficits in the rat medial prefrontal cortex (mPFC). CUS also enhanced GluN2B-mediated NMDA currents and extrasynaptic responses that were induced by bursts of high-frequency stimulation, which may be associated with the loss of astrocytes and low expression of glutamate transporter-1 (GLT-1). The blockade of GLT-1 in the mPFC was sufficient to induce depressive-like behavior and cause similar molecular changes. Selective GluN2B antagonist, DAPK1 knockdown by adeno-associated virus-mediated short-hairpin RNA or a pharmacological inhibitor, and the uncoupling of DAPK1 from the NMDAR GluN2B subunit produced rapid antidepressant-like effects and reversed CUS-induced alterations in the mPFC. The inhibition of DAPK1 and its interaction with GluN2B subunit in the mPFC also rescued CUS-induced depressive-like behavior 7 days after treatment. A selective GluN2B antagonist did not have rewarding effects in the conditioned place preference paradigm. Altogether, our findings suggest that the DAPK1 interaction with the NMDAR GluN2B subunit acts as a critical component in the pathophysiology of depression and is a potential target for new antidepressant treatments.

[Analysis of differences in epidemiology and clinical features of Guillain-Barré syndrome between rural and urban areas of southern China].

Objective: To explore the differences in epidemiology and clinical features of Guillain- Barré syndrome (GBS) between rural and urban areas of southern China. Methods: The clinical data of 759 hospitalized GBS patients from 31 hospitals of 13 provinces/cities in southern China, between January 1st, 2013 and September 30th, 2016, were collected and analyzed retrospectively. Results: The risk of GBS was higher for males than females in rural and urban areas and the median age was 49 and 48 years, respectively. Seasonal clustering in winter and spring was noted in both rural and urban areas, and the seasonal trend was more markedly in rural areas, but the differences showed no statistical significance. There were 70.37% of patients in rural areas and 73.69% in urban areas who had antecedent respiratory infection. The median time from onset to nadir was 7 days, and Hughes Disability Scale at admission, nadir and discharge were (2.95±1.10 vs 2.84±1.15), (3.25±1.11 vs 3.14±1.21), (2.02±1.24 vs 2.00±1.31) in rural and urban areas respectively. Albuminocytologic dissociation was present in 84.34% of patients in rural areas and 84.62% of cases in urban areas. There were 8.65% and 10.94% of cases in rural and urban areas who required mechanical ventilation during hospitalization, respectively. Demyelinating GBS accounted for 53.29% and 48.77%, respectively, in patients with findings of nerve conduction studies available in rural and urban areas. Conclusions: GBS in rural areas of southern China showed male predominance and a peak of spring and winter occurrence, with respiratory infection as the predominated preceding events and demyelinating GBS being main clinical subtype. Winter and spring showed a higher incidence of GBS in rural and urban areas. There were no significant differences of sex, age, preceding events, season trend, progression of disease, clinical subtypes and cerebrospinal fluid investigations in GBS patients between rural and urban areas.

[Comparison of the etiological constitution of two and three or more recurrent miscarriage].

Objective: To compare the etiological constitution of recurrent miscarriage (RM) between patients with consecutive two and three or more miscarriages through combining the routine examination results and embryonic karyotype. Methods: Patients with a history of two or more consecutive clinical miscarriages (≤12 weeks of gestation) consulting in the RM clinic of the First Affiliated Hospital of Sun Yat-sen University from March 2011 to January 2016 were collected. Six hundred and ninety-six with detailed history recorded, routine clinical examinations of RM and at least once embryonic karyotype were ultimately enrolled in this study. Their etiological constitution of RM were analyzed in groups of consecutive two and three or more miscarriage. The etiologies of RM in analysis consisted of women age, body mass index (BMI) , chromosome abnormalities of couples, uterine abnormalities, endocrinology abnormalities and antiphospholipid syndrome (APS) . Results: (1) Among 696 patients, the abnormal embryonic karyotypes was 60.6% (422/696) and routine RM etiologies was 32.2% (224/696) , leaving the ratio of unexplained RM was only 29.0% (202/696). (2) A total of 717 embryo karyotype were found in 696 patients, included21 cases with twice embryo karyotype results the percentage of normal embryo was 39.7% (285/717) , while abnormal ones was 60.3% (432/717). Among the types of abnormal karyotype, the most common ones (>10%) were trisomy 16 (19.2%, 83/432) , monosome X (11.3%, 49/432) and trisomy 22 (10.9%, 47/432). (3) Among the 696 RM patients, the number of two and three or more miscarriages were respectively 446 (64.1%, 446/696) and 250 (35.9%, 250/696). Comparing groups of three or more miscarriages with two miscarriages, there were significant differencein older age as well as uterine adhesion (P<0.05). But no difference was found in body mass index (BMI) , the rates of chromosome abnormalities of couples, uterine abnormalities except uterine adhesion, endocrinology abnormalities and APS (all P>0.05) between two groups. Conclusions: The abnormal embryonic karyotype is the most common cause of first-trimester RM. The etiological constitution of two and three or more recurrent miscarriages is accordant, suggesting that routine clinical examination and the embryonic karyotype should be started following two consecutive clinical early miscarriages.

Phenotypes and cellular effects of GJB1 mutations causing CMT1X in a cohort of 226 Chinese CMT families.

The aim of this study is to explore the phenotypic and genotypic features of X-linked Charcot-Marie-Tooth (CMT) disease in the mainland of China and to study the cellular effects of six novel Gap junction protein beta-1 variants. We identified 25 missense and 1 non-sense mutations of GJB1 in 31 unrelated families out of 226 CMT families. The frequency of GJB1 mutations was 13.7% of the total and 65% of intermediate CMT. Six novel GJB1 variants (c.5A>G, c.8G>A, c.242T>C, c.269T>C, c.317T>C and c.434T>G) were detected in six unrelated intermediate CMT families. Fluorescence revealed that HeLa cells transfected with EGFP-GJB1-V74M, EGFP-GJB1-L81P or EGFP-GJB1-L90P had diffuse endoplasmic reticulum staining, HeLa cells transfected with EGFP-GJB1-L106P had diffuse intracellular staining, and HeLa cells transfected with EGFP-GJB1-N2S had cytoplasmic and nuclear staining. The distribution of Cx32 in HeLa cells transfected with EGFP-GJB1-F145C was similar to that of those transfected with wild-type (WT). These six variants resulted in a higher percentage of apoptosis than did WT as detected by flow cytometry and Hoechst staining. In conclusion, mutation screening should be first performed in intermediate CMT patients, especially those with additional features. The novel GJB1 variants c.5A>G, c.8G>A, c.242T>C and c.269T>C are considered pathogenic, and c.317T>C and c.434T>G are classified as probably pathogenic.

[Correlation between mismatch repair proteins status and clinicopathological characteristics in sporadic colorectal cancer patients].

Objective: To explore the expression of mismatch repair (MMR) proteins in sporadic colorectal cancer (SCRC) patients, and its association with clinicopathological characteristics of SCRC. Methods: Patients with histologically confirmed colorectal cancer were consecutively recruited between December 2011 and June 2015 at Sun Yat-sen University Cancer Center. The exclusion criteria included multiple primary colorectal tumors, hereditary colorectal cancer (including Lynch syndrome, familial adenomatous polyposis), and the patients without the MMR proteins status tested. A total of 2 684 patients were included. Correlations of MMR proteins status and patients' demographics (including gender, age), tumor characteristics (site and differentiation) and TNM staging (excluding 315 SCRC patients receiving neoadjuvant therapy) were investigated. Results: The percentage of deficient MMR (dMMR) in these SCRC patients was 10.2%, and that of proficient MMR (pMMR) was 89.8%. The dMMR was more likely to be detected in younger (≤59 old years) SCRC patients compared to the elderly (>59 years) [12.7%(179/1 406)vs 7.5%(96/1 278), P<0.001]. The dMMR rate in right colon cancer was significantly higher than that in left colon cancer and rectal cancer [22.7%(151/664)vs 7.2%(69/956)vs 5.2%(55/1 064), P<0.001]. Among the various pathological types of SCRC, mucinous adenocarcinoma showed the highest rate of dMMR (24.4%), and neuroendocrine carcinoma the lowest rate of dMMR (0) (P<0.001). In addition, the proportions of dMMR in stage Ⅰ, stage Ⅱ, stage Ⅲ and stage Ⅳ SCRC were 9.7%, 16.5%, 8.5%, and 3.9%, respectively (P<0.001). There is no significant difference in the proportion of dMMR between male and female (11.0% vs 9.1%, P=0.114). Conclusion: dMMR status may be most likely to exist in younger (≤59 years) patients with stage Ⅱ right colon mucinous adenocarcinoma among SCRC.

Oral Chinese herbal medicine as maintenance treatment after chemotherapy for advanced non-small-cell lung cancer: a systematic review and meta-analysis.

BACKGROUND: The concept of maintenance therapy in cancer treatment is currently under debate because of modest survival benefits, added toxicity, economic considerations, and quality-of-life concerns. Traditional Chinese Medicine (tcm) is widely used in China for cancer patients, offering the advantages of low toxicity and enhancement of quality of life. However, no systematic reviews or meta-analyses have assessed the role of tcm as maintenance treatment for non-small-cell lung carcinoma. METHODS: We searched the Chinese Biomedical Literature Database, the China National Knowledge Infrastructure, PubMed, embase, and the Cochrane Library databases for all eligible studies. The endpoints were overall survival (os), progression-free survival (pfs), the 1-year and 2-year survival rates, and performance status. Our meta-analysis used a fixed-effects model and a random-effects model for heterogeneity in the Stata software application (version 11.0: StataCorp LP, College Station, TX, U.S.A.), with the results expressed as hazard ratios (hrs) or risk ratios (rrs), with their corresponding 95% confidence intervals (95% cis). RESULTS: Sixteen randomized studies representing 1150 patients met the inclusion criteria. Compared with best supportive care, observation, or placebo, tcm as maintenance treatment was associated with a significant increase in os (hr: 0.49; 95% ci: 0.35 to 0.68; p < 0.001), pfs (hr: 0.66; 95% ci: 0.51 to 0.84; p = 0.001), and 2-year survival rate (rr: 0.63; 95% ci: 0.44 to 0.92, p = 0.017), and a significant improvement in performance status (rr: 0.68; 95% ci: 0.61 to 0.75; p < 0.001). CONCLUSIONS: For patients who show non-progression-including stable disease, partial response, or complete response-after first-line chemotherapy, including those with poor quality of life, oral Chinese herbal medicine can be considered an efficient and safe maintenance therapy strategy.

Neurodegenerative diseases in a dish: the promise of iPSC technology in disease modeling and therapeutic discovery.

The study of stem-cell biology has been a flourishing research area because of its multi-differentiation potential. The emergence of induced pluripotent stem cells (iPSCs) open up the possibility of addressing obstructs, such as the limited cell source, inherent complexity of the human brain, and ethical constrains. Though still at its infancy phase, reprogramming of somatic cells has been demonstrating the ability to enhance in vitro study of neurodegenerative diseases and potential treatment. However, iPSCs would not thoroughly translate to the clinic before limitations are addressed. In this review, by summarizing the recent development of iPSC-based models, we will discuss the feasibility of iPSC technology on relevant diseases depth and illustrate how this new tool applies to drug screening and celluar therapy.

Effects of autologous SCF- and G-CSF-mobilized bone marrow stem cells on hypoxia-inducible factor-1 in rats with ischemia-reperfusion renal injury.

To explore the mechanism whereby stem cell factor (SCF) and granulocyte colony-stimulating factor (G-CSF) jointly mobilize bone marrow stem cells (BMSCs) and promote kidney repair, male Sprague-Dawley rats were randomly assigned into 4 groups. In the treatment control group, rats were administered SCF (200 µg·kg(-1)·day(-1)) and G-CSF (50 µg·kg-1·day-1) for 5 days. In the treatment group, RIRI models were established, and 6 h later, SCF (200 µg·kg(-1)·day(-1)) and G-CSF (50 µg·kg(-1)·day(-1)) were administered for 5 days. In the model and treatment groups, tubular epithelial cell degeneration and necrosis were noticed, but the extent of repair in the treatment group was significantly better than in the model group. Five days after the operation, renal tissue CD34+ cells significantly increased in the model and treatment groups compared with the control and treatment control groups. HIF-1α, VEGF, and EPO expression in treatment groups increased significantly compared with the other groups. HIF- 1α, VEGF, EPO expression in the treatment control group increased significantly compared with the control group. Joint use of SCF and G-CSF increased the number of BMSCs in damaged kidney tissue and reduced the degree of renal tissue damage. BMSCs promote increased HIF-1α expression in renal tissue. Increased kidney tissue HIF- 1α and its target gene products VEGF and EPO expression possibly induce SCF and G-CSF to promote acute tubular necrosis repair.

Long-term survival of non-small-cell lung cancer patients with EGFR inhibitor treatment.

The epidermal growth factor receptor (EGFR) inhibitors gefitinib and erlotinib are effective in the treatment of advanced non-small-cell lung cancer (NSCLC), but the median survival of patients is short. Here, we describe 2 patients with NSCLC receiving conventional chemotherapy and alternative treatment with gefitinib or erlotinib as second-line therapy. The first patient was alive at 8 years with alternative conventional chemotherapy and gefitinib, and the second patient was alive at long-term follow-up with conventional chemotherapy and gefitinib or erlotinib. Gefitinib, erlotinib, and conventional chemotherapy can be combined for satisfactory therapy for NSCLC.

[Advances in the application of minimal residual disease in non-metastatic colorectal cancer].

In recent years, the application of minimal residual disease (MRD) in solid tumors has gained widespread attention. MRD typically refers to the presence of residual cancer cells that remain undetectable by imaging after curative treatments, such as surgical resection. The presence of MRD post-surgery is significantly associated with an increased risk of tumor recurrence. In colorectal cancer, circulating tumor DNA (ctDNA) serves as an effective marker for assessing MRD, particularly in non-metastatic (stages I-III) colorectal cancer. As a real-time, accurate, and convenient biomarker, ctDNA can effectively predict tumor recurrence, guide postoperative adjuvant chemotherapy decisions, and provide crucial information for recurrence monitoring. The application prospects of ctDNA detection technology are vast, promising more precise and individualized treatment plans for colorectal cancer patients. This article comprehensively analyzes the progress in the application of ctDNA for detecting MRD in non-metastatic colorectal cancer patients, elaborates on its guiding role in clinical treatment decisions, and envisions the future development directions in this field.

Osteoarthritis pain mechanisms: basic studies in animal models.

OBJECTIVE: Osteoarthritis (OA) is a complex and painful disease of the whole joint. At present there are no satisfying agents for treating OA. To promote OA research and improved treatment, this review summarizes current preclinical evidence on the development of OA. METHODS: Preclinical OA research was searched and key findings are summarized and commented. RESULTS: Mechanisms of OA-associated pain have been studied in rodent knee OA models produced by intra-knee injection of the chondrocyte glycolytic inhibitor mono-iodoacetate (MIA), surgery, or spontaneous development in some species. These models are clinically relevant in terms of histological damage and functional changes, and are used to study mechanisms underlying mechanical, thermal, ambulatory, body weight supporting-evoked, and ongoing OA pain. Recent peripheral, spinal, and supraspinal biochemical and electrophysiological studies in these models suggest that peripheral pro-inflammatory mediators and neuropeptides sensitize knee nociceptors. Spinal cytokines and neuropeptides promote OA pain, and peripheral and spinal cannabinoids inhibit OA pain respectively through cannabinoid-1 (CB1) and CB1/CB2 receptors. TRPV1 and metalloproteinases contribute and supraspinal descending facilitation of 5-hydroxytryptamine (5-HT)/5-HT 3 receptors may also contribute to OA pain. Conditioned place preference tests demonstrate that OA pain induces aversive behaviors, suggesting the involvement of brain. During OA, brain functional connectivity is enhanced, but at present it is unclear how this change is related to OA pain. CONCLUSION: Animal studies demonstrate that peripheral and central sensitization contributes to OA pain, involving inflammatory cytokines, neuropeptides, and a variety of chemical mediators. Interestingly, brainstem descending facilitation of 5-HT/5-HT3 receptors plays a role OA pain.

[Optimization of perioperative treatment strategies for locally advanced esophageal squamous cell carcinoma from the perspective of tumor heterogeneity].

Recent advances in multimodality treatment offer excellent opportunities to rethink the paradigm of perioperative management for locally advanced esophageal squamous cell carcinoma. One treatment clearly doesn't fit all in terms of a broad disease spectrum. Individualized treatment of local control of bulky primary tumor burden (advanced T stage) or systemic control of nodal metastatic tumor burden (advanced N stage) is essential. Given that clinically applicable predictive biomarkers are still awaited, therapy selection guided by diverse phenotypes of tumor burden (T vs. N) is promising. Potential challenges regarding the use of immunotherapy may also boost this novel strategy in the future.

[Advances of immunotherapy-related biomarker in esophageal carcinoma].

Esophageal carcinoma is one of the most common malignant tumors in the world, with incidence and mortality rankings of 7th and 6th, respectively. In recent years, immunotherapy represented by immune checkpoint inhibitors of programmed death-1 and programmed death ligand 1 (PD-L1) has been introduced into clinical practice and has changed the treatment status of esophageal cancer. Although immunotherapy has provided long-term survival benefits for patients with advanced esophageal cancer and high pathological response rates in the neoadjuvant therapy, only a few of the patients have satisfactory therapeutic outcomes. Therefore, effective biomarkers for predicting immunotherapeutic effects are urgently needed to identify those patients who could benefit from immunotherapy. In this paper, we mainly discuss recent research advances of biomarkers related to the immunotherapy of esophageal cancer and the clinical application prospects of these biomarkers.