Advances in predictive biomarkers associated with immunotherapy in extensive-stage small cell lung cancer.

Small cell lung cancer (SCLC) is a highly malignant and poor-prognosis cancer, with most cases diagnosed at the extensive stage (ES). Amidst a landscape marked by limited progress in treatment modalities for ES-SCLC over the past few decades, the integration of immune checkpoint inhibitors (ICIs) with platinum-based chemotherapy has provided a milestone approach for improving prognosis, emerging as the new standard for initial therapy in ES-SCLC. However, only a minority of SCLC patients can benefit from ICIs, which frequently come with varying degrees of immune-related adverse events (irAEs). Therefore, it is crucial to investigate predictive biomarkers to screen potential beneficiaries of ICIs, mitigate the risk of side effects, and improve treatment precision. This review summarized potential biomarkers for predicting ICI response in ES-SCLC, with a primary focus on markers sourced from tumor tissue or peripheral blood samples. The former mainly included PD-L1 expression, tumor mutational burden (TMB), along with cellular or molecular components related to the tumor microenvironment (TME) and antigen presentation machinery (APM), molecular subtypes of SCLC, and inflammatory gene expression profiles. Circulating biomarkers predominantly comprised circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), cytokines, plasma autoantibodies, inflammation-related parameters, and blood TMB. We synthesized and analyzed the research progress of these potential markers. Notably, investigations into PD-L1 expression and TMB have been the most extensive, exhibiting preliminary predictive efficacy in salvage immunotherapy; however, consistent conclusions have yet to be reached across studies. Additionally, novel predictive markers developed based on TME composition, APM, transcriptomic and genomic features provide promising tools for precision immunotherapy. Circulating biomarkers offer the advantages of convenience, non-invasiveness, and a comprehensive reflection of tumor molecular characteristics. They may serve as alternative options for predicting immunotherapy efficacy in SCLC. However, there is a scarcity of studies, and the significant heterogeneity in research findings warrants attention.

Current challenges and therapeutic advances of CAR-T cell therapy for solid tumors.

The application of chimeric antigen receptor (CAR) T cells in the management of hematological malignancies has emerged as a noteworthy therapeutic breakthrough. Nevertheless, the utilization and effectiveness of CAR-T cell therapy in solid tumors are still limited primarily because of the absence of tumor-specific target antigen, the existence of immunosuppressive tumor microenvironment, restricted T cell invasion and proliferation, and the occurrence of severe toxicity. This review explored the history of CAR-T and its latest advancements in the management of solid tumors. According to recent studies, optimizing the design of CAR-T cells, implementing logic-gated CAR-T cells and refining the delivery methods of therapeutic agents can all enhance the efficacy of CAR-T cell therapy. Furthermore, combination therapy shows promise as a way to improve the effectiveness of CAR-T cell therapy. At present, numerous clinical trials involving CAR-T cells for solid tumors are actively in progress. In conclusion, CAR-T cell therapy has both potential and challenges when it comes to treating solid tumors. As CAR-T cell therapy continues to evolve, further innovations will be devised to surmount the challenges associated with this treatment modality, ultimately leading to enhanced therapeutic response for patients suffered solid tumors.

Light plays a critical role in the accumulation of chlorogenic acid in Lonicera macranthoides Hand.-Mazz.

Light has important effects on plant metabolism. However, the relationship between the chlorogenic acid (CGA) content and light in plants remains unclear. Here, we investigated the effects of shading treatment on gene expression and CGA content in Lonicera macranthoides Hand.-Mazz. (LM), a widely used medicinal plant. A total of 1891 differentially expressed genes (DEGs) were obtained in flower buds and 819 in leaves in response to light in shading treatment compared to the control sample by RNA-Seq. After shading treatment, the content of CGA in LM leaves decreased significantly by 1.78-fold, the carotenoid content increased, and the soluble sugar and starch contents significantly decreased. WGCNA and the expression of related genes verified by qRT‒PCR revealed that CGA synthesis pathway enzyme genes form a co-expression network with genes for carbohydrate synthesis, photosynthesis, light signalling elements, and transcription factor genes (TFs) that affect the accumulation of CGA. Through a virus-induced gene silencing (VIGS) system and CGA assay in Nicotiana benthamiana (NB), we determined that downregulation of NbHY5 expression decreased the CGA content in NB leaves. In this study, we found that light provides energy and material for the accumulation of CGA in LM, and light affects the expression of CGA accumulation-related genes. Our results show that different light intensities have multiple effects on leaves and flower buds in LM and are able to coregulate LmHY5 expression and CGA synthesis.

One-stage freehand minimally invasive pedicle screw fixation combined with mini-access surgery through OLIF approach for the treatment of lumbar tuberculosis.

OBJECTIVE: To compare one-stage freehand minimally invasive pedicle screw fixation (freehand MIPS) combined with mini-access surgery through OLIF approach with posterior approach for treatment of lumbar tuberculosis (TB), and evaluate its feasibility, efficacy and safety in debridement, bone graft fusion and internal fixation. METHODS: 48 patients with single segment lumbar TB from June 2014 to June 2017 were included. Among them, 22 patients underwent one-stage freehand MIPS combined with mini-access surgery through OLIF approach (group 1), 26 patients were treated with posterior open surgery (group 2). Duration of operation, blood loss, and stay time in hospital were compared. Pre- and postoperative visual analog scale (VAS) pain scores, Oswestry disability index (ODI), erythrocyte sedimentation rate, complications and images were also recorded. RESULTS: Patients in group 1 showed significantly less blood loss (165 ± 73 ml vs 873 ± 318 ml, P < 0.001), shorter stay time in hospital (6/4-8 days vs 12/8-15 days, P < 0.001), while longer duration of operation (185 ± 14 min vs 171 ± 12 min, P < 0.001) than group 2 did. VAS scores significantly decreased after surgery in both groups, however, VAS scores of group 1 were significantly lower than that of group 2 immediately after surgery and during follow-ups (P < 0.001). ODI of group 1 was also significantly lower than that of group 2 at 12-month after surgery (P < 0.001). CONCLUSION: One-stage freehand MIPS combined with mini-access surgery through OLIF approach is a feasible, efficient and safe method in treating single segment lumbar TB. It shows advantages of less surgical trauma and faster postoperative recovery.

Efficacy and safety of anterior cervical discectomy and fusion (ACDF) through mini-incision and posterior laminoplasty (LAMP) for treatment of long-level cervical spondylosis: a retrospective cohort study.

BACKGROUND: The efficacy and safety of anterior cervical discectomy and fusion (ACDF) through mini-incision and posterior laminoplasty for long-level cervical spondylosis were investigated. METHOD: From January 2018 to September 2019, clinical patients data with 3-4 segments (C3-7) cervical spondylotic radiculopathy, cervical spondylotic myelopathy, or mixed cervical spondylosis who received ACDF (42 cases) throughwith mini-incision or LAMP (36 cases) treatment were retrospectively collected and analyzed. The operative time, bleeding volume, incisive length, and hospital stay were recorded. Moreover, the intervertebral height, functional segment height, cervical lordosis, cervical hyperextension and hyperflexion range-of-motion (ROM) and ROM in all directions of the cervical spine before and after the operation were measured. Additionally, all relevant postoperative complications were also recorded. Then, the therapeutic effects of both surgical methods were investigated. RESULTS: Patients in the ACDF group had less bleeding, shorter incision, and fewer hospitalization days than the LAMP group. There was no significant difference in JOA, VAS score of the upper limb, NDI score after surgery between two groups. Postoperative intervertebral height and functional segment height in the ACDF group were significantly higher than those before the operation, and postoperative functional segment height of the ACDF group was significantly higher than that of the LAMP group. Moreover, the postoperative cervical lordosis angle in the ACDF group was significantly larger than the LAMP group. There was no significant difference between preoperative and postoperative ROM in all directions of the cervical spine for the two groups. CONCLUSIONS: Both ACDF through mini-incision and LAMP are effective treatments for long-level cervical spondylosis. However, ACDF through mini-incision shows minor trauma, less bleeding, fast recovery, and it is beneficial for cervical lordosis reconstruction.

Influence of distal radius fractures involving the intermediate column on forearm rotation.

BACKGROUND: The objective of the study was to compare the radiologic and clinical outcome of patients with distal radius fractures involving the intermediate column and distal radial metaphyseal fractures treated conservatively. METHODS: Two cohorts of 52 matched patients with distal radius fractures treated conservatively, one with a fracture involving the intermediate column and the other with no intermediate column fracture, were retrospectively analyzed by examining the data. Patients were matched for age, sex, fracture side, and AO fracture type. The two groups were analyzed for differences in wrist motion; grip strength; Gartland and Werley score; Disabilities of the Arm, Shoulder and Hand (DASH) score; and visual analogue scale (VAS) score at 12 months. The differences in continuous variables were compared using the paired t test. Linear regression analyses or Pearson correlation analyses were used to evaluate the associations of radiological parameters with clinical outcomes. RESULTS: The analysis showed significant differences in the range of motion (ROM) for pronation (p = 0.000) and supination (p = 0.008) in the paired groups. There was a significant difference in DASH scores (p = 0.024) in the paired groups. Using Pearson correlation analysis, negative correlations (r = - 0.360, p = 0.000) were observed between articular step-off and ROM for pronation. Linear regression analyses also indicated that ROM for pronation had negative relationships (ß = - 6.327, p = 0.001) with articular step-off. CONCLUSIONS: Distal radius fractures involving the intermediate column had an adverse effect on forearm rotation after distal radius fractures treated conservatively.

Targeted salinomycin delivery with EGFR and CD133 aptamers based dual-ligand lipid-polymer nanoparticles to both osteosarcoma cells and cancer stem cells.

We previously developed salinomycin (sali)-entrapped nanoparticles labeled with CD133 aptamers which could efficiently eliminate CD133+ osteosarcoma cancer stem cells (CSCs). However, sufficient evidences suggest that the simultaneous targeting both CSCs and cancer cells is pivotal in achieving preferable cancer therapeutic efficacy, due to the spontaneous conversion between cancer cells and CSCs. We hereby constructed sali-entrapped lipid-polymer nanoparticles labeled with CD133 and EGFR aptamers (CESP) to target both osteosarcoma cells and CSCs. The cytotoxicity of CESP in osteosarcoma cells and CSCs was superior to that of single targeting or nontargeted sali-loaded nanoparticles. Administration of CESP in vivo showed the best efficacy in inhibiting tumor growth than other controls in osteosarcoma-bearing mice. Thus, CESP was demonstrated to be capable of efficiently targeting both osteosarcoma CSCs and cancer cells, and it represents an effective potential approach to treat osteosarcoma.

Association between Paraoxonase 1 polymorphisms and risk of esophagogastric junction adenocarcinoma: a case-control study involving 2,740 subjects.

Esophagogastric junction adenocarcinoma (EGJA) is a serious public health problem with high mortality in China. In this study, we assessed the association between Paraoxonase 1 (PON-1) rs662 C>T, rs854560 A>T polymorphisms and EGJA risk. This case-control study enrolled 2,740 participants of Asians origin from the Eastern Chinese Han populations. SNPscanTM genotyping assay was harnessed to determine the genotyping of PON1 polymorphisms. The PON-1 rs854560 A>T and rs662 C>T genotypes distribution accorded with Hardy-Weinberg equilibrium. We found that there was no difference in the frequency of PON-1 rs662 C>T, rs854560 A>T genotypes between the overall EGJA cases and controls. In the subgroup analyses, the results indicated that PON-1 rs662 C>T polymorphism might be associated with a significantly decreased risk of EGJA in ever smoking group (TT vs. CC/CT: adjusted OR = 0.58, 95% CI 0.35-0.95, P = 0.029). In conclusion, our study highlights PON-1 rs662 C>T polymorphism may decrease the risk of EGJA, which interacts with the tobacco using. In the future, a fine-mapping case-control study with detailed gene-environmental data is needed to further assess these potential relationship.

[Effectiveness analysis of surgical treatment of Schatzker type â £ tibial plateau fractures].

Objective: To introduce a surgical protocol based on the location and orientation of the apex of the medial condylar fracture line for the treatment of Schatzker type Ⅳ tibial plateau fractures and report the preliminary effectiveness. Methods: The clinical data of 18 patients with Schatzker type Ⅳ tibial plateau fractures underwent open reduction and internal fixation between March 2012 and April 2016 were retrospectively analysed. There were 6 males and 12 females, aged 36-74 years (mean, 45 years). The causes of injury included traffic accident in 2 cases, falling in 14 cases, bruise injury in 1 case, and crush injury of heavy object in 1 case. All cases were fresh closed fractures, without injury of nerves and blood vessels. According to sub type of Wahlquist tibial plateau type Ⅳ fracture classification, there were 1 case of type A, 5 cases of type B, and 12 cases of type C. The interval of injury and operation was 6-16 days (mean, 9.5 days). The location of the apex of the medial condylar fracture line was determined the surgical approach. After operation, reduction of tibial plateau fractures was evaluated by the DeCoster score evaluation criteria. The knee joint function was assessed by short Musculoskeletal Function Assessment (SMFA) score and Hospital for Special Surgery (HSS) score. Results: The incisions all healed by first intension after operation without surgery related complications. All the patients obtained satisfactory exposure and reduction during operation. According to DeCoster score evaluation criteria, the results were excellent in 13 cases and fair in 5 cases. All the patients were followed up 12-30 months (mean, 18 months). X-ray films showed that all fractures healed at 10-16 weeks (mean, 12 weeks) after operation. There was no plate displacement, screw loosening, and other complications occurred during follow-up. At last follow-up, the SMFA score was 15-48 (mean, 28.5). The HSS score was 52-94 (mean, 81.1), and the results were excellent in 10 cases, good in 5 cases, fair in 2 cases, and poor in 1 case with an excellent and good rate of 83.3%; the main clinical manifestation was severe traumatic osteoarthritis symptom in 1 case with the fair result. Conclusion: The surgical program should be developed based on the location and orientation of the apex of the medial condylar fracture line. Open reduction and internal fixation for treating Schatzker type Ⅳ fractures can achieve satisfactory effectiveness.

Downregulation of CRKL expression can inhibit tumorigenesis in colon cancer.

CRKL, as a "switch" factor on several oncogenic pathways, plays vital roles in multiple cancers. However, little is known about CRKL in gastrointestinal cancers. Here, we showed that CRKL is involved in colon cancer, which is the most common form of cancer of the digestive system. Immunohistochemistry analysis showed that CRKL expression in colon tumor tissue is significantly higher than normal tissue and CRKL level is associated with tumor differentiation. Suppression of CRKL in colon cancer cells inhibited cell proliferation, migration and invasion, while induced apoptosis. Colon cancer cells xenografts in nude mice showed that CRKL promoted tumorigenesis. Our results suggest that CRKL has the ability to regulate colon cancer malignancy and CRKL has the potential to serve as a diagnosis and prognosis marker and a therapy target of colon cancer.