The theoretical source and development of subclinical state in Traditional Chinese Medicine were explored in order to establish the theoretical basis of the modern preventive medicine for subclinical state and provide the theoretical foundation for study of it. The preventive idea of subclinical state origined from the theory of treating disease before it onset in HuangdiNeijin Internal Canon of Medicine of the Yellow Emperor. The preventive measures of treating disease before it onset such as taking preventive measures and treating the disease before it onset taking acupuncture before the disease onset observing the principle of mental concentration doing nothing with any excessive fatigue and eating foods with proper tastes etc. were all supplied the guiding principle for treatment of TCM and acupuncture and keeping in good health and dietetic therapy. Since the dynasty of Han Tang Ming and Qing the TCM has given full play to and developed the preventive ideas in treating subclinical state from many field such as keeping in good health and treating in the early stage and observing standard life style.
Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are effective treatments for non-small cell lung cancer (NSCLC) patients with activating EGFR mutations. There are many uncommon and rare mutations in the EGFR gene. The efficacy of the EGFR-TKIs is largely unknown for cancers harboring uncommon or rare EGFR mutations.A 69-year-old woman was diagnosed with adenocarcinoma cT4N2M1c, stage IVB. Next-generation sequencing (NGS) confirmed a rare EGFR V786M mutation. During chemotherapy, immune checkpoint inhibitor (ICI), and anti-angiogenic treatment, no radiological response was observed. Subsequent third-generation EGFR TKI showed a remarkable therapeutic effect. Structural prediction revealed that the V786M mutation induces conformational change at the dimer interface, without altering the ATP binding to the EGFR tyrosine kinase domain (TKD). Consistently, docking simulations indicated that the affinity of ATP to the V786M mutant was not disturbed, which explained the TKI sensitivity.Our data confirmed the activating role on EGFR V786M mutation. Together with structural predictions and clinical evidence for activity of TKIs against EGFR V786M mutations, these findings warrant further investigation.
To investigate the effects of diffuse brain injury on activity an d expression of nitric oxide synthase(NOS) in hippocampus of rats and the rela tionship between the activity of NOS in subfields of hippocampus and time points Methods:All Wistar rat models with diffuse brain injury were randomly divided into 6 groups:a control group,a sham operated group and 4 other groups kille d at 6,12,24 and 48 hours after injury respectively NADPH d histochemistry a nd ABC immunohistochemistry were used to measure the activity and expression of NOS Results:With NADPH d histochemistry,the number of neuronal NOS positive cells in hippocampal formation was the highest at 6 hours after injury,then it gradually decreased The number in the group killed at 24 or 48 hours after inj ury was lower than that in the sham operated group (P0 05) With ABC immuno histochemistry,the numbers in CA1,CA3 subfields and dentate gyrus in the group s killed at 24 and 48 hours after injury were lower than that in the sham opera ted group(P0 01) Conclusion:After diffuse brain injury in rats,the activi ty of NOS changes in the subfields of hippocampus,which might be related to sec ondary brain injury
Objective To investigate the relationship between the effects of lithium on cholecystokinin(CCK) positive neurons of dentate gyrus,and the learning and memory ability in lead-exposed rats.Methods Wistar rats were randomly divided into control group,lead group,and a four lead +(3,30,300,3 000 mg/kg) groups LiCl.Four lead + LiCl groups were fed with food containing 3,30,300,3 000 mg/kg LiCl,respectively.Lead + LiCl groups and lead group were given distilled water containing 0.2% lead acetate.Y-maze test was employed to study the effects of lead on learning and memory ability of rats;ABC immunohistochemistry was used to investigate the changes in CCK positive neurons in dentate gyrus of lead-exposed rats.Results Compared with the control group,the learning and memory ability of lead-exposed rats were significantly decreased(P0.05).The number of CCK positive neurons in dentate gyrus lead-exposed rats fed with lithium(3,30,300 mg/kg) were significantly increased,compared with lead-exposed rats(P0.05).Conclusion Lead damages the learning-memory ability of rats,which may be related to the changes in CCK positive neurons of dentate gyrus in lead-exposed rats.Lower dose of lithium plays an important role in preventing lead-induced damages.
4009 Background: Integrating immunotherapy with trastuzumab and chemotherapy has shown a significant improvement in overall response rate (ORR) and progression-free survival (PFS) in HER2-overexpression gastric or gastroesophageal junction cancer (GC/GEJC). However, the overall survival (OS) did not achievestatistical significance, and there was no benefit in patients with a PD-L1 combined positive score (CPS) <1. RC48, an antibody-drug conjugate drug, has proven its effect in advanced HER2-positive (HER2 3+ or 2+ by IHC, regardless of FISH positivity) GC/GEJC in later-line treatment setting. This trial was to assess the efficacy and safety of combining RC48, immunotherapy (Tislelizumab), and S-1 as a first-line treatment for HER2-overexpressing GC/GEJC. Methods: This was a single-arm, multi-center, phase II trial conducted in patients with HER2-overexpressing metastatic or unresectable GC/GEJC for first-line treatments. Participants received RC48 (2.5 mg/kg), Tislelizumab (200 mg), and S-1 (40-60 mg BID for 14 days) every 3 weeks until disease progression or intolerable toxicities. The primary endpoint was ORR, while the secondary endpoints included disease control rate (DCR), PFS, OS, and safety. Results: A total of 47 patients were enrolled from 8 centers, median 65 (39 ~ 81) years old, 37 male, 37 GC and 8 GEJC, and all adenocarcinoma. Of them, 30 (63.8%) were HER2 IHC 3+, 11 (23.4%) HER2 IHC 2+/FISH+, and 6 (12.8%) IHC 2+/FISH-. Patients with PD-L1 CPS≥5, ≥1 accounted for 14.9%, 36.2% respectively. With a median follow-up duration of 116.5 days, patients received a median of 5.0 treatment cycles. As of January 20, 2024, 40 patients were included for efficacy analysis, and 44 patients for safety. The ORR reached 95.0% (38/40, 95% CI: 83.1-99.4%), clinical Complete Response rate was 20.0% (5/40, 95% CI: 4.2-26.8%), and the DCR was 100.0% (95% CI: 91.2-100.0%). The median PFS and OS were not reached, while the 6-month and 9-month PFS rates were 100.0% and 80.8%, the 6-month and 9-month OS rates were 100.0% and 83.8%. ORR among the HER2 IHC 3+, IHC 2+/FISH+, and IHC 2+/FISH- groups showed no significant difference (93.3%, 100.0%, 100.0%). ORR for patients with CPS≥1 or < 1 were 100.0%, 92.9%, respectively. One stage IVA GC patient (cT4bN3M0, HER2 3+, CPS 0) and another stage IVB GEJC one (cT3N2M1, HER2 2+/FISH+, CPS≥5) received radical surgery and both achieved pathological complete response. Grade 3/4 treatment-related adverse events occurred in 40.9% of patients, notably neutropenia, fatigue, and diarrhea. Conclusions: The combination of RC48, Tislelizumab, and S-1 showed notable efficacy with manageable safety in the first-line treatment of advanced HER2-overexpressing GC/GEJC patients. These findings support further exploration in this context. Clinical trial information: NCT05586061 .
The rearranged during transfection (RET) gene is one of the receptor tyrosine kinases and cell-surface molecules responsible for transmitting signals that regulate cell growth and differentiation. In non-small cell lung cancer (NSCLC), RET fusion is a rare driver gene alteration associated with a poor prognosis. Fortunately, two selective RET inhibitors (sRETi), namely pralsetinib and selpercatinib, have been approved for treating RET fusion NSCLC due to their remarkable efficacy and safety profiles. These inhibitors have shown the ability to overcome resistance to multikinase inhibitors (MKIs). Furthermore, ongoing clinical trials are investigating several second-generation sRETis that are specifically designed to target solvent front mutations, which pose a challenge for first-generation sRETis. The effective screening of patients is the first crucial step in the clinical application of RET-targeted therapy. Currently, four methods are widely used for detecting gene rearrangements: next-generation sequencing (NGS), reverse transcription-polymerase chain reaction (RT-PCR), fluorescence in situ hybridization (FISH), and immunohistochemistry (IHC). Each of these methods has its advantages and limitations. To streamline the clinical workflow and improve diagnostic and treatment strategies for RET fusion NSCLC, our expert group has reached a consensus. Our objective is to maximize the clinical benefit for patients and promote standardized approaches to RET fusion screening and therapy.
The fibroblast growth factor receptor (FGFR) is a crucial receptor tyrosine kinase involved in essential biological processes, including growth, development, and tissue repair. However, FGFR gene mutations, including amplification, fusion, and mutation, can disrupt epigenetics, transcriptional regulation, and tumor microenvironment interactions, leading to cancer development. Targeting these kinase mutations with small molecule drugs or antibodies has shown clinical benefits. For example, erdafitinib is approved for treating locally advanced or metastatic urothelial cancer patients with FGFR2/FGFR3 mutations, and pemigatinib is approved for treating cholangiocarcinoma with FGFR2 fusion/rearrangement. Effective screening of FGFR variant patients is crucial for the clinical application of FGFR inhibitors. Various detection methods, such as polymerase chain reaction, next-generation sequencing, fluorescence in situ hybridization, and immunohistochemistry, are available, and their selection should be based on diagnostic and treatment decision-making needs. Our developed expert consensus aims to standardize the diagnosis and treatment process for FGFR gene mutations and facilitate the practical application of FGFR inhibitors in clinical practice.
Supplementary Figures Legends 1-3 from <i>CMTM3</i>, Located at the Critical Tumor Suppressor Locus 16q22.1, Is Silenced by CpG Methylation in Carcinomas and Inhibits Tumor Cell Growth through Inducing Apoptosis
Objective We surveyed the exponent of Ca 2+ in blood platelet of the patients with cerebral infarction to study the therapy method. Methods We used flow cytometry instrument to detect the exponent of Ca 2+. Results The exponents of Ca 2+ in blood platelet of the the patients with cerebral infarction were higher than the group of control(P 0.01). The exponents of groups of moderate and serious disease patients were higher than mild patients(P 0.01), and exponent in male patient was higher than in female patient;P 0.05. Conclusion The exponent of Ca 2+ in blood platelet increasing may induce cerebral ischemic injury.
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