Lung cancer is the malignant tumor with the highest incidence and mortality rates globally. Current treatment methods for lung cancer primarily include surgery， chemotherapy， targeted therapy， and immunotherapy. However， the main limitations of these treatments are their side effects， the drug resistance， and the economic burden they impose. As a critical cancer pathway， the Janus kinase （JAK）/signal transducer and activator of transcription （STAT） signaling pathway regulates tumor occurrence and development through multiple mechanisms by influencing various downstream targets. Consequently， the JAK/STAT signaling pathway offers a promising avenue for lung cancer treatment research. Numerous studies have demonstrated that the JAK/STAT signaling pathway plays a key role in the proliferation and growth of lung cancer cells， angiogenesis， epithelial-mesenchymal transition （EMT）， metabolic alterations， remodeling of the immune microenvironment， and the development of treatment resistance. Traditional Chinese medicine （TCM） has garnered increasing attention due to its minimal side effects， low economic burden， and its potential to enhance efficacy and reduce toxicity when used in conjunction with Western medicine. In addition to traditional Chinese medicine compounds， a growing number of Chinese medicine monomers have come into the spotlight because of their more targeted effects. Numerous studies investigating the regulation of the JAK/STAT signaling pathway by TCM in the treatment of lung cancer have demonstrated that TCM can inhibit the proliferation and invasion of lung cancer cells， tumor angiogenesis， and EMT， improve the inflammatory and immunosuppressive microenvironments， and enhance treatment sensitivity by intervening in the JAK/STAT signaling pathway， thereby impeding the progression of lung cancer. In recent years， the research on the regulation of this pathway by TCM in the treatment of lung cancer has been updated rapidly. However， the summary of these studies has not been updated in time. This review summarizes and reflects on the recent research findings regarding the regulation of the JAK/STAT signaling pathway by TCM to intervene in lung cancer from three aspects， introducing the JAK/STAT pathway， elaborating the mechanism of this pathway in lung cancer， and exploring the intervention of TCM in the treatment of lung cancer through this pathway， to provide more reference for the treatment of lung cancer in the future.

OBJECTIVES: To explore the effect of A. muciniphila gavage on intestinal microbiota and gut-brain interaction disorders (DGBIs) in gp120tg transgenic mouse models of HIV-associated neurocognitive disorder (HAND). METHODS: Intestinal microbiota was detected by 16S rRNA gene sequencing in 6-, 9-, and 12-month-old wild-type (WT) mice and gp120tg transgenic mice. The 12-month-old WT and transgenic mice were divided into 2 groups for daily treatment with PBS or A.muciniphila gavage (2×10⁸ CFU/mouse) for 6 weeks. After the treatment, immunohistochemistry, ELISA and qPCR were used to detect changes in colonic expression levels of glycosylated mucins, MBP and IL-1β, eosinophil infiltration, serum lipopolysaccharide (LPS) levels, and colonic expressions of occludin, ZO-1, IL-10, TNF-α and INF-γ mRNA. Morris water maze test and immunofluorescence assay were used to assess learning and spatial memory abilities and neuronal damage of the mice. RESULTS: Compared with WT mice, the transgenic mice exhibited significantly lowered Simpson's diversity of the intestinal microbiota with reduced abundance of Akkermansia genus, increased serum LPS levels and decreased colonic expression of glycosylated mucin. A.muciniphila gavage obviously ameliorated the reduction of glycosylated mucin in the transgenic mice without causing significant changes in body weight. The 12-month-old gp120tg mice had significantly decreased cdonic expressions of Occludin and ZO-1 with increased eosinophil infiltration and TNF-β, INF-γ and IL-1β levels and obviously lowered IL-10 level; all these changes were significantly mitigated by A.muciniphila gavage, which also improved cognitive impairment and neuronal loss in the hippocampus and cortex of the transgenic mice. CONCLUSIONS The gp120tg mice have lower intestinal microbiota richness and diversity than WT mice. The 12-month-old gp120tg mice have significantly reduced Akkermansia abundance with distinct DGBIs-related indexes, and A. muciniphila gavage can reduce intestinal barrier injury, colonic inflammation and eosinophil activation, cognitive impairment and brain neuron injury in these mice.
Animals ; Mice, Transgenic ; Gastrointestinal Microbiome ; Mice ; Brain ; HIV Envelope Protein gp120/genetics* ; Akkermansia ; Disease Models, Animal

Neck dissection and reconstruction are two important aspects of oral cancer treatment.There are various surgical methods for neck dissection and reconstruction,but all of them are performed by open surgery.This article reports a full endoscopic neck dis-section through the retroauricular hairline approach,the radical resection of the intraoral tumor and the repair of the defect by superfi-cial circumflex iliac artery perforator flap with in situ vascular anastomosis intraorally.The incision is located in the hairline,hidden and invisible,and there is no exposed surgical scar on the neck after surgery.This paper introduces the technique of scarless neck dissection combined with free skin flap repair for the treatment of oral cancer and discusses its advantages and disadvantages.

Objective:To explore the biomarkers of radiochemotherapy sensitivity and potential mechanisms in esophageal squamous cell carcinoma (ESCC), and validate the screened biomarkers at human tissue, animal and cellular levels.Methods:Based on bioinformatics system, clinical and transcriptome data of ESCC were obtained from The Cancer Genome Atlas (TCGA) and GEO databases. HUB genes related to chemoradiotherapy sensitivity were identified by weighted correlation network analysis (WGCNA) and cytoscape software and survival differences were analyzed. CellMiner database was used to predict and screen drugs with strong correlation with HUB genes. The expression levels of HUB genes in clinical tissues was detected by real-time reverse transcription PCR (qRT-PCR). Then, oe-AKR1C1 mouse model, cisplatin-resistant cells and radiation-resistant cells were constructed, and the effects of HUB genes on tumor size and mass, and cell proliferation ability were analyzed.Results:A total of 5 HUB genes were identified, among which NAD(P)H quinone dehydrogenase 1 (NQO1), AKR1C1 and NADH: ubiquinone oxidoreductase core subunit S2 (NDUFS2) were significantly correlated with ESCC survival (all P<0.05). Dacarbazine, alectinib and obatoclax were the anti-tumor drugs predicted to have a strong correlation with HUB genes in this study. Human tissue test results showed that the expression levels of NQO1, AKR1C1 and NDUFS2 were up-regulated in patients with chemoradiotherapy resistance, and AKR1C1 and NDUFS2 had statistical significance (both P<0.05). The results of mouse tumor bearing experiment showed that the tumor volume and mass of oe-AKR1C1 mice after radiotherapy and chemotherapy were significantly higher than those in the control group (both P<0.05). The cell experiment results showed that the expression levels of AKR1C1 and NDUFS2 in radiation-resistant cells and cisplatin-resistant cells were significantly higher than those in control cells ( P<0.05), while there was no statistically significant difference in the relative expression level of NQO1. Conclusion:NQO1, AKR1C1 and NDUFS2 are HUB genes significantly related to the survival of ESCC, which can be used as important therapeutic tumor targets for ESCC.

Purpose: Patients with advanced biliary tract cancer (BTC) have a poor survival. We aim to evaluate the efficacy and safety of nab-paclitaxel plus gemcitabine and cisplatin regimen in Chinese advanced BTC patients. Materials and Methods: Eligible patients with locally advanced or metastatic BTC administrated intravenous 100 mg/m2 nab-paclitaxel, 800 mg/m2 gemcitabine, and 25 mg/m2 cisplatin every 3 weeks. The primary endpoint was progression-free survival (PFS). The secondary endpoints included overall survival (OS) and adverse events, while exploratory endpoint was the association of biomarkers with efficacy. Results: After the median follow-up of 25.0 months, the median PFS and OS of 34 enrolled patients were 7.1 months (95% confidence interval [CI], 5.4 to 13.7) and 16.4 months (95% CI, 10.9 to 23.6), respectively. The most common treatment-related adverse events at ≥ 3 grade were neutropenia (26.5%) and leukopenia (26.5%). Survival analyses demonstrated that carcinoembryonic antigen (CEA) levels could monitor patients’ survival outcomes. A significant increase in the number of infiltrating CD4+ cells (p=0.008) and a decrease in programmed death-1–positive (PD-1+) cells (p=0.032) were observed in the response patients. Conclusion In advanced BTC patients, nab-paclitaxel plus gemcitabine and cisplatin regimen showed therapeutic potential. Potential prognostic factors of CEA levels, number of CD4+ cells and PD-1+ cells may help us maximize the efficacy benefit.

Objective:To investigate frailty in older patients with comorbidities and explore related risk factors.Methods:A cross-sectional study was conducted with an enrollment of 746 patients aged 65 years or older with comorbidities in the Wanshoulu Road area of Beijing from April 2019 to December 2020.A total of 617 patients with comorbidities were finally included, aged(85.6±4.8)years, including 358 women(58.0%); According to the FRAIL scale, 617 patients with comorbidities were divided into a frail group(156 cases, 25.3%)and a non-frail group(461 cases, 74.7%). Demographic data and information on comorbidities were collected.Univariate and multivariate Logistic regression analyses of risk factors were conducted.Results:Among 617 patients with comorbidities, the common chronic diseases in descending order were hypertension(497 cases, 80.6%), coronary heart disease(375 cases, 60.8%), osteoporosis(357 cases, 57.9%), osteoarthritis(281 cases, 45.5%), type 2 diabetes(211 cases, 34.2%), stroke and/or transient ischemic attack(193 cases, 31.3%), chronic lung disease(144 cases, 23.3%), tumor(133 cases, 21.6%), chronic kidney disease(92 cases, 14.9%), and heart failure(58 cases, 9.4%). Univariate logistic regression analysis showed that age, type 2 diabetes, coronary heart disease, heart failure, chronic lung disease, stroke/transient ischemic attack, cancer and osteoarthritis were influencing factors for frailty( P<0.05). Multivariate logistic regression analysis showed that age, type 2 diabetes, heart failure, chronic lung disease, cancer and osteoarthritis were risk factors for frailty( OR=1.076, 1.806, 3.275, 3.371, 1.640, 2.227, all P<0.05). Conclusions:Old age, type 2 diabetes, heart failure, chronic lung disease, tumor and osteoarthritis are closely related to frailty in elderly patients with comorbidities.Proactive and effective prevention and intervention should be instituted to target risk factors for frailty to reduce the occurrence of adverse outcomes.

Objective:To investigate the correlation between serum insulin-like growth factor 1 (IGF-1), thyroid stimulating hormone (TSH), degree of insulin resistance and thyroid nodule imaging reporting and data system (TI-RADS) grading in patients with type 2 diabetes mellitus (T2DM).Methods:The clinical data of 120 patients with T2DM from February 2020 to November 2021 in Kunshan Hospital of Integrated Traditional Chinese and Western Medicine were retrospectively analyzed. Among them, 56 patients had no thyroid nodules (non-thyroid nodule group), all patients were TI-RADS grade 1; 64 patients had thyroid nodules (thyroid nodule group), including 7 cases of TI-RADS grade 2, 12 cases of TI-RADS grade 3, 20 cases of TI-RADS grade 4, and 25 cases of TI-RADS grade 5. The levels of IGF-1 and TSH were measured by automated biochemical analyzer, the homeostatic model assessment insulin resistance index (HOMA-IR) was calculated. Spearman method was used for correlation analysis; multivariate Logistic regression was used to analyze the independent risk factors of TI-RADS grading in patients with T2DM combined with thyroid nodules; the receiver operating characteristic (ROC) curve was drawn to analyze the efficacy of IGF-1, TSH and HOMA-IR in predicting TI-RADS grading in patients with T2DM combined with thyroid nodules.Results:The IGF-1, TSH and HOMA-IR in thyroid nodule group were significantly higher than those in non-thyroid nodule group: (185.35 ± 45.08) ng/L vs. (168.36 ± 30.25) ng/L, (2.98 ± 0.85) mU/L vs. (2.69 ± 0.35) mU/L and 3.25 ± 0.75 vs. 2.95 ± 0.44, and there were statistical differences ( P<0.05 or <0.01). In patients with T2DM combined with thyroid nodules, with the increase of TI-RADS classification, the IGF-1, TSH and HOMA-IR gradually increased, and there were statistical differences ( P<0.05). Spearman correlation analysis result showed that the levels of IGF-1, TSH and HOMA-IR were positive correlation with TI-RADS grading ( r = 0.918, 0.906 and 0.920; P<0.05). Multivariate Logistic regression analysis result showed that the IGF-1, TSH and HOMA-IR were independent risk factors for TI-RADS grading in patients with T2DM combined with thyroid nodule ( OR = 1.684, 1.044 and 1.851; 95% CI 0.674 to 6.665, 0.032 to 0.055 and 1.212 to 2.298; P<0.01 or <0.05). ROC curve analysis result show that the area under the curve of IGF-1, TSH and HOMA-IR for predicting the TI-RADS grading patients with T2DM combined with thyroid nodule were 0.946, 0.983 and 0.975, with all sensitivity of 100.00%, and specificity of 82.14%, 91.07% and 89.29%. Conclusions:There is a correlation between IGF-1, TSH, HOMA-IR and TI-RADS grading in patients with T2DM combined with thyroid nodule, which has some guiding value for clinical monitoring of thyroid nodule changes.

Objective:To investigate the clinical effect of programmed death receptor-1 (PD-1)/programmed death receptor ligand-1 (PD-L1) immunotherapy combined with concurrent radiotherapy and chemotherapy in the treatment of locally advanced cervical cancer (LACC).Methods:From November 2018 to October 2019, 51 LACC patients in Qinhuangdao First Hospital who received anti-PD-1/PD-L1 immunotherapy (pembrolizumab) combined with concurrent radiotherapy and chemotherapy [intensity modulated radiotherapy (IMRT)+ TP (taxol+ carboplatin) chemotherapy] were selected as the observation group. 51 LACC patients who received concurrent chemotherapy and radiotherapy were selected as the control group. The objective remission rate, disease control rate, tumor markers [squamous cell carcinoma antigen (SCCAg), soluble cytokeratin 19 fragment (CYFRA21-1), and carcinoembryonic antigen (CEA), carbohydrate antigen 125 (CA125)], proliferation and apoptosis indicators [survivin (Survivin), B-cell lymphoma-2 (Bcl-2), Caspase-3 (Caspase-3), apoptosis-promoting substance (Bax)], PD-1/PD-L1 [soluble PD-L1 (sPD-L1), CD4 + T cell surface PD-1 expression (PD-1 CD4 + T cells), CD8 + T cell surface PD-1 expression (PD-1 CD8 + T cell) and CD14 + monocyte surface PD-L1 expression (PD-L1 CD14 + monocyte)], safety and survival rate within 1 year were compared between the two groups. Results:(1) Disease control and safety: the objective response rate and disease control rate of the observation group were 80.39%(41/51) and 92.16%(47/51), respectively, which were higher than those of the control group by 39.22%(20/51) and 70.59%(36/51) (all P<0.05), but there was no significant difference in the incidence of side effects between the groups (all P>0.05). (2) Tumor markers and proliferation and apoptosis indexes: compared with those before treatment, the levels of serum SCCAg, CYFRA21-1, CEA, CA125, survivin and Bcl-2 in the two groups after treatment were significantly lower, and the levels of Caspase-3 and Bax were significantly higher; the above indexes in the observation group were better than those in the control group after treatment (all P<0.05). (3) PD-1/PD-L1: after treatment, sPD-L1, PD-1 CD4 + T cells, PD-1 CD8 + T cells and PD-L1 CD14 + monocytes in the observation group were significantly lower than those before treatment (all P<0.05). After treatment, the sPD-L1, PD-1 CD4 + T cells, PD-1 CD8 + T cells, PD-L1 CD14 + monocytes in the observation group were lower than those in the control group (all P<0.05). (4) Survival: the survival rate of the observation group was higher than that of the control group within 1 year ( P<0.05). Conclusions:The clinical effect of anti-PD-1/PD-L1 immunotherapy combined with concurrent radiotherapy and chemotherapy in the treatment of LACC is significant. It can effectively inhibit the progression of the disease by regulating tumor markers, proliferation and apoptosis indicators and PD-1/PD-L1 expression without increasing the risk of treatment, and has a positive effect on improving the survival rate of patients.

Objective:To investigate the relationship between CD8 +FoxP3 +CD25 + T cell subsets and the therapeutic effect of programmed death receptor 1 (PD-1) inhibitor pembrolizumab in treatment of uterine cervical cancer. Methods:The data of 105 patients with uterine cervical cancer who received pemblizumab therapy based on chemotherapy in the First Hospital of Qinhuangdao from January 2018 to January 2020 were retrospectively analyzed. Flow cytometry was used to detect the ratio of CD8 +FoxP3 +CD25 + T cell in peripheral blood of patients. The efficacy and safety were analyzed. According to the efficacy, all patients were divided into remission group (complete remission + partial remission) and non-remission group (stable disease + progressive disease). The clinical characteristics and CD8 +FoxP3 +CD25 + T cell ratio of the two groups were compared. Multivariate logistic regression model was used to analyze the influencing factors for the efficacy. The efficacy of CD8 +FoxP3 +CD25 + T cell ratio predicting the therapeutic effect of patients was analyzed by using receiver operating characteristic (ROC) curve. Results:The objective remission rate of all patients was 17.14% (18/105), and the incidence of adverse reaction was 39.05% (41/105). The proportion of patients with a family history of cervical cancer in the remission group was lower than that than in the non-remission group [5.56% (1/18) vs. 34.48% (30/87)], and the difference was statistically significant ( χ2=6.00, P=0.014). The proportion of CD8 +FoxP3 +CD25 + T cell of 105 patients before and after treatment was (0.83±0.21)% and (0.77±0.10)%, respectively; the proportion of CD8 +FoxP3 +CD25 + T cell before and after treatment in the remission group was (0.55±0.26)%, (0.31±0.12)%, respectively; the proportion of CD8 +FoxP3 +CD25 + T cell before and after treatment in the non-remission group was (0.89±0.30)%, (0.87±0.28)%, respectively. The proportion of CD8 +FoxP3 +CD25 + T cell after treatment in the remission group was lower than that before treatment ( P < 0.05); there was no statistically significant difference in the proportion of CD8 +FoxP3 +CD25 + T cell before and after treatment in the non-remission group ( P>0.05). The proportion of CD8 +FoxP3 +CD25 + T cell before and after treatment in the non-remission group was higher than that in the remission group (all P<0.001). The proportion of CD8 +FoxP3 +CD25 + T cell higher than the mean value of both groups before treatment and the proportion of CD8 +FoxP3 +CD25 + T cell higher than the mean value of both groups after treatment were independent risk factor of disease remission ( OR=2.542, 95% CI 1.649-3.918, P<0.001; OR=2.936, 95% CI 2.154-4.002, P<0.001). ROC curve analysis showed that the area under the curve of CD8 +FoxP3 +CD25 + T cell ratio predicting the disease remission before treatment was 0.720, and its best cut-off value was 0.77%, the senfitivity was 77.78%, the specificity was 70.11%. Conclusions:Early detection of CD8 +FoxP3 +CD25 + T cell ratio helps to predict the effect of PD-1 inhibitor pembrolizumab therapy for uterine cervical cancer.

BACKGROUND: Changes in thyroid hormone levels are commonly recognized characters among the elderly, which were reported to potentially influence incident frailty. Therefore, we examined the cross-sectional associations of thyroid hormones (THs) with frailty as well as the five components characterizing frailty (fatigue, resistance, ambulation, number of illnesses, and loss of weight) among the oldest-old. METHODS: Four hundred and eighty-seven community-dwelling oldest-old from a local community in Haidian District, Beijing, participated in our recruitment campaign between April 2019 and May 2020. The primary outcomes were a definitive diagnosis of frailty according to the FRAIL scale (Fatigue, Resistance, Ambulation, Illnesses, Loss of weight) and a positive score for each frailty subdomain. Demographic information (age, sex, marital status, and educational status), comorbidities, and details on the participants' lifestyles were recorded. Serum THs including free triiodothyronin (fT3), triiodothyronine (T3), free thyroxine (fT4), and thyroxine (T4) and thyroid stimulating hormone (TSH) levels were also measured at the beginning of our study. Logistic regressions were conducted to screen for potential risk factors for frailty and its subdomains. RESULTS: Among the total 487 subjects at enrollment, 60 (12.23%) of them were diagnosed with subclinical hypothyroidism and 110 (22.59%) of the total population scored positive for frailty. Logistic regression analyses adjusted for all potential confounders, showed that frailty was significantly associated with the serum TSH concentration (odds ratio [OR]: 1.06), fT3 concentration (OR: 0.54), and subclinical hypothyroidism score (OR: 2.18). The association between fT4 and frailty was absent in our observational study. The fT3/fT4 ratio characterizing peripheral hormone conversion was also tested to be correlated with frailty. CONCLUSION Subclinical hypothyroidism, higher TSH level, lower fT3 level, and decreased fT3/fT4 ratio were all associated with frailty assessed by the FRAIL scale among the community-dwelling oldest-old, suggesting a relevant role of thyroid function in aging. Future longitudinal studies are warranted to determine the casual relationship between thyroid dysfunction and frailty in the oldest-old.
Humans ; Aged, 80 and over ; Aged ; Thyroxine ; Cross-Sectional Studies ; Thyrotropin ; Frailty ; Independent Living ; Triiodothyronine ; Thyroid Function Tests ; Thyroid Hormones ; Hypothyroidism ; Fatigue