Head and neck squamous cell carcinoma(HNSCC)is a highly prevalent malignancy with poor prognosis.Treatment strategies to date have achieved limited success in significantly improving overall survival rates.γδ T cells,a unique subset of immune cells in the tumor microenvironment,can link adaptive and innate immune functions.While γδ T cells can effectively recognize and eliminate HNSCC tumor cells,certain subsets of these cells can secrete interleukin-17,contributing to tumor progression.Nevertheless,due to their remarkable cyto-toxic activity,γδ T cells have been identified as promising candidates for antitumor immunotherapy.This article reviews the biological back-ground of γδ T cells,their role in tumor immunity in HNSCC,and recent advances in γδ T cell immunotherapy,aiming to provide new in-sights into HNSCC diagnosis and treatment.

Objective:To evaluate the clinically curative effect of intervention treatment of electronic bronchoscope in treating tracheobronchial tuberculosis at clinical activity stage.Methods:Sixty patients with tracheobronchial tuberculosis at clinical activity stage(type I,II,III and VI)who admitted to Liuzhou People's Hospital from September 2020 to September 2023 were selected,and they were divided into drug group(anti-tuberculosis drug treatment)and combination group(anti-tuberculosis drug treatment+interventional treatment with electronic bronchoscope)by the random number table method,with 30 cases in each group.The curative effects of the two groups were observed,and the negative conversion rate of sputum bacteria,clinical symptom scores(cough symptom,expectoration symptom)before and after treatment,Modified British Medical Research Council Dyspnea Scale(mMRC)score between two groups were compared,and the differences in indicators of pulmonary function such as forced expiratory volume in the first second(FEV1),forced vital capacity(FVC)and maximum voluntary ventilation(MVV)between the two groups also were compared.And then,the incidence of complications was calculated.Results:During the 1,2 and 3 months of follow-up,there were respectively 21 cases,27 cases and 30 cases occurred negative conversion of sputum bacteria in 30 patients of the combination group,and there were respectively 15 cases,18 cases and 23 cases occurred negative conversion of sputum bacteria in 30 patients of the drug group.At the 1st month of follow-up,the negative conversion rate of sputum bacteria in combination group was higher than that in drug group,while there was no statistically significant difference between the two groups(P＞0.05).At the 2nd and 3rd month of follow-up,the negative conversion rate of sputum bacteria in the combination group was higher than that in the drug group,and the differences were statistically significant(x2=7.200,7.925,P<0.05).The effective rate of treatment of the combination group was 100%,which was higher than 80%of the drug group,and the difference of that between two groups was significant(x2=6.667,P<0.05).After 2 months of treatment,the mMRC score,cough symptom score and expectoration symptom score of the combination group were all lower than those of the drug group,and the differences were statistically significant(t=3.504,3.950,3.530,P<0.05).The improvement effects of FEV1,FVC and MVV of the combination group were all better than those of the drug group,and the differences were statistically significant(t=6.626,4.966,4.097,P<0.05).There was no significant difference in the incidence of complications between the two groups(P>0.05).Conclusion:Anti-tuberculosis drug therapy combined with electronic bronchoscopy intervention has a good therapeutic effect in clinically active tracheobronchial tuberculosis.

Objective To explore the mechanism of honey-processed Hedysari Radix in the regulation of intestinal immunity in rats with spleen qi deficiency,which was based on G protein-coupled receptor 41(GPR41)/GPR43-mediated mitogen-activated protein kinase(MAPK)signaling pathway.Methods The three-factor composite modeling method of eating disorder,diarrhea and fatigue was used to establish a model of spleen qi deficiency,and the rats were randomly divided into model,honey-processed Hedysari Radix,probiotics and blank groups with 15 rats per group.The honey-processed Hedysari Radix group was given by gavage 12.6 g·kg-1 aqueous extract of honey-processed Hedysari Radix.The probiotics group was given 0.625 g·kg-1 bifidobacterium triple viable solution by gavage.The blank and model groups were given the same dose of distilled water by gavage.Four groups were treated for 15 d with once a day.The expression levels of GPR41,GPR43,P38 MAPK,c-Jun N-terminal kinase(JNK)and extracellular regulatory protein kinase 1/2(ERK1/2)in colon tissues were detected by Western blotting.Results The relative expression levels of GPR41 in the blank,model,honey-processed Hedysari Radix and probiotics groups were 0.95±0.07,0.45±0.03,0.84±0.19 and 0.86±0.20;the relative expression levels of GPR43 were 1.17±0.11,0.41±0.06,0.66±0.03 and 0.57±0.01;the phosphorylated ERK1/2/ERK1/2 ratios were 0.16±0.01,0.43±0.01,0.39±0.01 and 0.36±0.02;the phosphorylated JNK/JNK ratios were 0.58±0.05,1.47±0.10,0.90±0.11 and 0.90±0.11;the phosphorylated P38 MAPK/P38 MAPK ratios were 1.77±0.33,3.19±0.03,2.01±0.17 and 2.23±0.59,respectively.Compared with the model group,the differences of above indexes were statistically significant in the honey-processed Hedysari Radix and probiotics groups(P＜0.05,P＜0.01).Conclusion The mechanism of honey-processed Hedysari Radix regulating intestinal immunity in rats with spleen qi deficiency is related to the regulation of GPR41/GPR43 mediated MAPK signaling pathway.

The pregnant woman was 30 years old,G2P0.This singleton pregnancy at 22 weeks of gestation was screened for second-trimester ultrasound malformations,suggesting fetal aortic valve atresia,aortic stenosis with reverse blood flow,mitral valve atresia,and markedly enlarged left ventricle,which was considered for the diagnosis of hypoplastic left heart syndrome(HLHS).The pregnancy was terminated at our hospital and subsequently underwent genetic testing with results of heterozygous variants in the NOTCH1 gene,which can cause aortic valve disease type 1.The findings of the fetal autopsy were aortic valve atresia,mitral valve widening and thickening,and left ventricular enlargement with myocardial infarction.This report focuses on the ultrasound characteristics of HLHS with left ventricular enlargement and its hemodynamic changes in order to improve clinicians'understanding of the progressive changes in the disease phenotype of HLHS.

Objective:To evaluate the clinically curative effect of intervention treatment of electronic bronchoscope in treating tracheobronchial tuberculosis at clinical activity stage.Methods:Sixty patients with tracheobronchial tuberculosis at clinical activity stage(type I,II,III and VI)who admitted to Liuzhou People's Hospital from September 2020 to September 2023 were selected,and they were divided into drug group(anti-tuberculosis drug treatment)and combination group(anti-tuberculosis drug treatment+interventional treatment with electronic bronchoscope)by the random number table method,with 30 cases in each group.The curative effects of the two groups were observed,and the negative conversion rate of sputum bacteria,clinical symptom scores(cough symptom,expectoration symptom)before and after treatment,Modified British Medical Research Council Dyspnea Scale(mMRC)score between two groups were compared,and the differences in indicators of pulmonary function such as forced expiratory volume in the first second(FEV1),forced vital capacity(FVC)and maximum voluntary ventilation(MVV)between the two groups also were compared.And then,the incidence of complications was calculated.Results:During the 1,2 and 3 months of follow-up,there were respectively 21 cases,27 cases and 30 cases occurred negative conversion of sputum bacteria in 30 patients of the combination group,and there were respectively 15 cases,18 cases and 23 cases occurred negative conversion of sputum bacteria in 30 patients of the drug group.At the 1st month of follow-up,the negative conversion rate of sputum bacteria in combination group was higher than that in drug group,while there was no statistically significant difference between the two groups(P＞0.05).At the 2nd and 3rd month of follow-up,the negative conversion rate of sputum bacteria in the combination group was higher than that in the drug group,and the differences were statistically significant(x2=7.200,7.925,P<0.05).The effective rate of treatment of the combination group was 100%,which was higher than 80%of the drug group,and the difference of that between two groups was significant(x2=6.667,P<0.05).After 2 months of treatment,the mMRC score,cough symptom score and expectoration symptom score of the combination group were all lower than those of the drug group,and the differences were statistically significant(t=3.504,3.950,3.530,P<0.05).The improvement effects of FEV1,FVC and MVV of the combination group were all better than those of the drug group,and the differences were statistically significant(t=6.626,4.966,4.097,P<0.05).There was no significant difference in the incidence of complications between the two groups(P>0.05).Conclusion:Anti-tuberculosis drug therapy combined with electronic bronchoscopy intervention has a good therapeutic effect in clinically active tracheobronchial tuberculosis.

Tumor drug resistance is an important problem in the failure of chemotherapy and targeted drug therapy, which is a complex process involving chromatin remodeling. SWI/SNF is one of the most studied ATP-dependent chromatin remodeling complexes in tumorigenesis, which plays an important role in the coordination of chromatin structural stability, gene expression, and post-translation modification. However, its mechanism in tumor drug resistance has not been systematically combed. SWI/SNF can be divided into 3 types according to its subunit composition: BAF, PBAF, and ncBAF. These 3 subtypes all contain two mutually exclusive ATPase catalytic subunits (SMARCA2 or SMARCA4), core subunits (SMARCC1 and SMARCD1), and regulatory subunits (ARID1A, PBRM1, and ACTB, etc.), which can control gene expression by regulating chromatin structure. The change of SWI/SNF complex subunits is one of the important factors of tumor drug resistance and progress. SMARCA4 and ARID1A are the most widely studied subunits in tumor drug resistance. Low expression of SMARCA4 can lead to the deletion of the transcription inhibitor of the BCL2L1 gene in mantle cell lymphoma, which will result in transcription up-regulation and significant resistance to the combination therapy of ibrutinib and venetoclax. Low expression of SMARCA4 and high expression of SMARCA2 can activate the FGFR1-pERK1/2 signaling pathway in ovarian high-grade serous carcinoma cells, which induces the overexpression of anti-apoptosis gene BCL2 and results in carboplatin resistance. SMARCA4 deletion can up-regulate epithelial-mesenchymal transition (EMT) by activating YAP1 gene expression in triple-negative breast cancer. It can also reduce the expression of Ca²⁺ channel IP3R3 in ovarian and lung cancer, resulting in the transfer of Ca²⁺ needed to induce apoptosis from endoplasmic reticulum to mitochondria damage. Thus, these two tumors are resistant to cisplatin. It has been found that verteporfin can overcome the drug resistance induced by SMARCA4 deletion. However, this inhibitor has not been applied in clinical practice. Therefore, it is a promising research direction to develop SWI/SNF ATPase targeted drugs with high oral bioavailability to treat patients with tumor resistance induced by low expression or deletion of SMARCA4. ARID1A deletion can activate the expression of ANXA1 protein in HER2+ breast cancer cells or down-regulate the expression of progesterone receptor B protein in endometrial cancer cells. The drug resistance of these two tumor cells to trastuzumab or progesterone is induced by activating AKT pathway. ARID1A deletion in ovarian cancer can increase the expression of MRP2 protein and make it resistant to carboplatin and paclitaxel. ARID1A deletion also can up-regulate the phosphorylation levels of EGFR, ErbB2, and RAF1 oncogene proteins.The ErbB and VEGF pathway are activated and EMT is increased. As a result, lung adenocarcinoma is resistant to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). Although great progress has been made in the research on the mechanism of SWI/SNF complex inducing tumor drug resistance, most of the research is still at the protein level. It is necessary to comprehensively and deeply explore the detailed mechanism of drug resistance from gene, transcription, protein, and metabolite levels by using multi-omics techniques, which can provide sufficient theoretical basis for the diagnosis and treatment of poor tumor prognosis caused by mutation or abnormal expression of SWI/SNF subunits in clinical practice.

Purpose: To investigate whether a new phospholipid-releasing soft contact lens can improve symptoms of dry eyes. Methods: The study used 2.5-3.0 kg New Zealand rabbits including both normal non-dry eye rabbits and dry eye rabbits, the latter having undergone electrocauterization of the meibomian glands to block the gland orifices. Each rabbit wore a control contact lens on one eye and a phospholipid-releasing contact lens on the other eye daily. Phospholipid-releasing and control contact lenses were provided by NEOVISION Co., Ltd. The parameters assessed included tear film break-up time, tear osmolarity, ocular surface staining, and central corneal thickness. After the experiment, the rabbits were euthanized and their conjunctival tissue was stained with Periodic Acid Schiff (PAS) to observe conjunctival goblet cells. Results: In both dry eye and normal non-dry eye rabbits, tear film break-up time was longer and tear osmolarity was lower when using the phospholipid-releasing contact lens compared to the control contact lens. The ocular surface remained unstained in normal non-dry eye rabbits while staining was observed in dry eye rabbits. There was no significant difference in central corneal thickness between the control and phospholipid-releasing contact lenses in either group. PAS staining showed no difference in conjunctival goblet cell density between the two lens types in normal non-dry eye rabbits. However, in dry eye rabbits, the conjunctival goblet cell density tended to be slightly higher with the phospholipid-releasing contact lens compared to the control lens. Conclusions Phospholipid-releasing contact lenses may help reduce dry eye symptoms and minimize contact lens-related complications by stabilizing the tear film and lowering tear osmolarity.

Accurate timing of myelination is crucial for the proper functioning of the central nervous system. Here, we identified a de novo heterozygous mutation in TMEM63A (c.1894G>A; p. Ala632Thr) in a 7-year-old boy exhibiting hypomyelination. A Ca²⁺ influx assay suggested that this is a loss-of-function mutation. To explore how TMEM63A deficiency causes hypomyelination, we generated Tmem63a knockout mice. Genetic deletion of TMEM63A resulted in hypomyelination at postnatal day 14 (P14) arising from impaired differentiation of oligodendrocyte precursor cells (OPCs). Notably, the myelin dysplasia was transient, returning to normal levels by P28. Primary cultures of Tmem63a^-/- OPCs presented delayed differentiation. Lentivirus-based expression of TMEM63A but not TMEM63A_A632T rescued the differentiation of Tmem63a^-/- OPCs in vitro and myelination in Tmem63a^-/- mice. These data thus support the conclusion that the mutation in TMEM63A is the pathogenesis of the hypomyelination in the patient. Our study further demonstrated that TMEM63A-mediated Ca²⁺ influx plays critical roles in the early development of myelin and oligodendrocyte differentiation.
Animals ; Cell Differentiation/physiology* ; Oligodendroglia/metabolism* ; Mice, Knockout ; Mice ; Male ; Myelin Sheath/metabolism* ; Humans ; Child ; Cells, Cultured ; Oligodendrocyte Precursor Cells/metabolism*

Type 2 diabetes mellitus(T2DM) is a prevalent metabolic and endocrine disorder. Long-term hyperglycemia can lead to severe chronic complications, imposing substantial economic burdens on both society and patients. Despite the availability of various hypoglycemic agents for clinical use, these agents often fail to meet the therapeutic needs of T2DM and its complications. Consequently, there is an urgent need for novel therapeutic strategies and drugs. Lithocarpus litseifolius(L. litseifolius), commonly referred to as "cordyceps on trees", has a long history of use in traditional medicine and can be applied in tea, sugar, and medicine. Research indicates that L. litseifolius extracts are rich in dihydrochalcones, including trilobatin, phloridzin, and phloretin, which exhibit a range of pharmacological activities, such as anti-inflammatory, antioxidant, hypoglycemic, hypolipidemic, hepatoprotective, and cardioprotective effects. These properties suggest potential applications in the treatment of T2DM and its complications. This review systematically compiled and organized the relevant literature from the past decade on dihydrochalcones(trilobatin, phloridzin, and phloretin) from L. litseifolius extracts. It highlighted recent research progress regarding their role in treating T2DM and its complications through mechanisms such as reducing insulin resistance, regulating glucose transport, improving glucose and lipid metabolism, modulating enzyme activity, regulating gut microbiota, and alleviating inflammation and oxidative damage. The purpose of this review is to provide a reference and basis for future research on the prevention and treatment of T2DM and its complications using dihydrochalcones(trilobatin, phloridzin, and phloretin) from L. litseifolius extracts.
Chalcones/chemistry* ; Diabetes Mellitus, Type 2/metabolism* ; Humans ; Animals ; Elaeocarpaceae/chemistry* ; Drugs, Chinese Herbal/therapeutic use* ; Hypoglycemic Agents/chemistry* ; Plant Extracts/chemistry*

This study investigates the mechanism by which Xintong Granules improve myocardial ischemia-reperfusion injury(MIRI) through the regulation of gut microbiota and their metabolites, specifically short-chain fatty acids(SCFAs). Rats were randomly divided based on body weight into the sham operation group, model group, low-dose Xintong Granules group(1.43 g·kg~(-1)·d~(-1)), medium-dose Xintong Granules group(2.86 g·kg~(-1)·d~(-1)), high-dose Xintong Granules group(5.72 g·kg~(-1)·d~(-1)), and metoprolol group(10 mg·kg~(-1)·d~(-1)). After 14 days of pre-administration, the MIRI rat model was established by ligating the left anterior descending coronary artery. The myocardial infarction area was assessed using the 2,3,5-triphenyltetrazolium chloride(TTC) staining method. Apoptosis in tissue cells was detected by the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling(TUNEL) assay. Pathological changes in myocardial cells and colonic tissue were observed using hematoxylin-eosin(HE) staining. The levels of tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β), interleukin-6(IL-6), creatine kinase MB isoenzyme(CK-MB), and cardiac troponin T(cTnT) in rat serum were quantitatively measured using enzyme-linked immunosorbent assay(ELISA) kits. The activities of lactate dehydrogenase(LDH), creatine kinase(CK), and superoxide dismutase(SOD) in myocardial tissue, as well as the level of malondialdehyde(MDA), were determined using colorimetric assays. Gut microbiota composition was analyzed by 16S rDNA sequencing, and fecal SCFAs were quantified using gas chromatography-mass spectrometry(GC-MS). The results show that Xintong Granules significantly reduced the myocardial infarction area, suppressed cardiomyocyte apoptosis, and decreased serum levels of pro-inflammatory cytokines(TNF-α, IL-1β, and IL-6), myocardial injury markers(CK-MB, cTnT, LDH, and CK), and oxidative stress marker MDA. Additionally, Xintong Granules significantly improved intestinal inflammation in MIRI rats, regulated gut microbiota composition and diversity, and increased the levels of SCFAs(acetate, propionate, isobutyrate, etc.). In summary, Xintong Granules effectively alleviate MIRI symptoms. This study preliminarily confirms that Xintong Granules exert their inhibitory effects on MIRI by regulating gut microbiota imbalance and increasing SCFA levels.
Animals ; Gastrointestinal Microbiome/drug effects* ; Rats ; Male ; Myocardial Reperfusion Injury/genetics* ; Drugs, Chinese Herbal/administration & dosage* ; Rats, Sprague-Dawley ; Apoptosis/drug effects* ; Humans ; Tumor Necrosis Factor-alpha/metabolism* ; Interleukin-6/genetics* ; Malondialdehyde/metabolism*