17ß-Estradiol inhibits hydrogen peroxide-induced senescence and apoptosis in human umbilical vein endothelial cells by regulating the THBS1/TGF-ß/Smad axis.

Before menopause, females exhibit a lower incidence of cardiovascular disease than age-matched males, possibly owing to the protective effects of sex hormones. 17ß-estradiol (17ß-E2) protects against oxidative stress-induced injury by suppressing thrombospondin-1 (THBS1) expression in endothelial cells. Here, we examined the role of 17ß-E2-mediated THBS1 suppression in preventing cell senescence and apoptosis. Human umbilical vein endothelial cells (HUVECs) were cultivated and treated with siRNA or overexpression plasmids to regulate THBS1. H2O2, estrogen-activity modulating drugs, and LY2109761 (a TGF-ß kinase inhibitor) treatments were applied. THBS1 knockdown repressed, and its overexpression aggravated, H2O2-induced cell injury, affecting cell death, proliferation, senescence, and apoptosis. 17ß-E2 inhibited THBS1 mRNA and protein expression time- and dose-dependently, by targeting ERß. THBS1 overexpression blocked 17ß-E2 from preventing H2O2-induced injury, significantly activating the TGF-ß/Smad pathway. 17ß-E2 inhibited H2O2-induced oxidative stress by downregulating THBS1 expression and TGF-ß/Smad signaling in HUVECs. The THBS1/TGF-ß/Smad axis could thus be a therapeutic target.

Double-stranded metallo-triangles: from anion-templated nonanuclear to cation-templated tetraicosanuclear dysprosium clusters.

Two double-stranded metallo-triangles, Dy9 and Dy24, with hexaple-C10H7PO32- bridges were constructed, and their magnetic properties were explored. Compared with the field-induced relaxation phenomenon of Dy9 templated with a chloride anion, Dy24 templated with a sodium cation exhibited zero-field single-molecule-magnet behavior.

Relationship between years since menopause and lipid variation in postmenopausal women: A cross-sectional study.

Lipid alteration in postmenopausal women is commonly due to hormonal changes. This study aimed to explore the association between the years since menopause and lipid profiles in postmenopausal women. In this cross-sectional study, a total of 1033 postmenopausal women were recruited from the Women's Hospital of Zhejiang University in China between 2015 and 2022. Each participant was interviewed using questionnaires regarding sociodemographic and reproductive data. Anthropometric measurements, lipid profiles, and reproductive hormone levels were assessed. Participants were divided into 3 groups based on the length of time since menopause: 2, 2 to 5.9, and 6 years. Differences in lipid profiles and reproductive hormones among the groups were compared. Logistic and linear regression analyses were used to examine the relationship between years after menopause and lipid profile. High-density lipoprotein cholesterol (HDL-C) and luteinizing hormone levels were significantly lower in postmenopausal women with time since menopause of ≥6 years than those <2 years (P < .05), whereas low-density lipoprotein cholesterol levels were significantly higher (P < .05). A longer time after menopause was independently associated with lower HDL-C levels (ß, -0.059, standard error, 0.023, P = .01) after adjustment for age, body mass index, and other confounders. Compared to women who had menopause for <2 years, those who were postmenopausal for >6 years had lower HDL-C levels after adjustment for age, body mass index, and other covariates (ß, -0.123, 95% confidence interval, [-0.221, -0.014], P = .014). Longer time since menopause was associated with an atherogenic lipid profile with appreciably low levels of HDL-C subfraction. Future multicenter studies are necessary to examine postmenopausal population and determine how differences in lipids influence the risk of cardiovascular disease in this group.

Clinical observation of menopause hormone therapy in postmenopausal women with euthyroid and mild subclinical hypothyroidism.

BACKGROUND: To evaluate the endocrine hormone and metabolic indices in postmenopausal women with euthyroid and mild subclinical hypothyroidism after menopause hormone therapy (MHT). METHODS: A retrospective study of 587 postmenopausal women receiving MHT was conducted. Median (25-75th percentile) age was 52 (49-54) years. According to thyroid stimulating hormone (TSH) levels at initial diagnosis, the patients were divided into three groups: I (euthyroid with low normal TSH range, n = 460), II (euthyroid with upper normal TSH range, n = 106) and III (mild subclinical hypothyroidism, n = 21). After a continuous oral MHT regimen using the same estradiol potency for 6-18 month cycles, serum endocrine hormone and metabolic indices were reassessed. RESULTS: Compared with baseline, serum TSH levels in groups I and II significantly changed but all values were within the normal range. No significant difference was observed in serum TSH levels in group III. After treatment, all serum free tri-iodothyronine and free thyroxine levels were within the normal range. Serum total cholesterol, triglyceride, fasting plasma glucose, fasting insulin levels and homeostasis model assessment of insulin resistance index had significantly decreased in group I. There were no significant differences in all observed lipid and glucose parameters in group III, before and after treatment. CONCLUSION: MHT did not affect thyroid function in postmenopausal women with euthyroid and mild subclinical hypothyroidism. MHT led to an improvement in lipid and glucose indicators in euthyroid women with low normal TSH range.

Association of Coenzyme Q10 with Premature Ovarian Insufficiency.

The aim of the study was to analyze the relationship between levels of coenzyme Q10 (CoQ10) and the risk of premature ovarian insufficiency (POI). In this cross-sectional case-control study, 32 women with POI and 58 women with normal menstrual cycles were recruited. The serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), anti-Müllerian hormone (AMH), CoQ10 and total cholesterol were measured. The association of CoQ10 with POI was assessed using binary logistic regression analysis. The CoQ10/total cholesterol ratio was significantly lower in the women with POI than in the women with normal menstrual cycles (120.94 ± 25.35 nmol/mmol vs 138.97 ± 39.19 nmol/mmol, P = 0.021). The serum CoQ10/total cholesterol ratio was inversely associated with POI (the unadjusted odds ratio (OR) = 0.984, 95% CI: 0.970-0.998, P = 0.027). The same trend was found after adjusting for confounding factors (such as age, body mass index, annual household income and education) (OR = 0.976, 95% CI: 0.956-0.996, P = 0.020). The serum CoQ10/total cholesterol ratio was inversely associated with POI, indicating that antioxidant deficiency may be a risk associated with the development of POI. CoQ10 may be a protective factor for ovarian tissue.

Occupational hazards and the onset of natural menopause.

OBJECTIVE: To identify occupational hazards associated with earlier onset of natural menopause. STUDY DESIGN: A national cross-sectional study was conducted to explore the reproductive health of Chinese female workers. The final sample size was 17,948. MAIN OUTCOME MEASURES: Participants completed a self-report instrument that recorded working conditions, chemical and physical agents in the occupational environment, socioeconomic factors, lifestyle, reproductive history, and occupational information. A Cox regression model was used to examine the association between each occupational hazard and onset of menopause. RESULTS: Abnormal workload (19.31 %), aromatic compounds (7.95 %), and noise (24.94 %) were the three most frequently self-reported occupational hazards in the three categories of working conditions, chemical agents, and physical agents, respectively. Abnormal workload (HR = 1.133, p = 0.038), noise (HR = 1.233, p < 0.001), and heat stress (HR = 1.178, p = 0.041) were associated with earlier age at natural menopause in the analyses of each hazard, after adjustment. Only noise (HR = 1.187, p = 0.003) remained statistically significant after including all possible occupational hazards. CONCLUSIONS: In a national survey of 17,948 female workers, this study investigated the association of age at natural menopause with multiple occupational hazards, some of which have not been addressed. Occupational noise was identified as a risk factor for reproductive senescence for the first time. However, further research is needed to confirm our findings.

Association between serum vitamin A levels and premature ovarian insufficiency: a case-control, cross-sectional survey study.

BACKGROUND: Although vitamin A is known to play an important role in ovarian function, its association with ovarian insufficiency has not been reported yet. Therefore, the aim of the study was to explore the association between serum vitamin A levels and premature ovarian insufficiency (POI). METHODS: This cross-sectional survey included women with POI (n = 47) and normo-ovulatory controls (n = 67) who were enrolled between December 2016 and May 2018 in Zhejiang, China. The serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), anti-Müllerian hormone (AMH), vitamin A, and total cholesterol (TC) were measured for each participant. The association of TC-adjusted vitamin A levels with the risk of POI was assessed using binary logistic regression analysis. RESULTS: Serum vitamin A levels appeared to be slightly higher in the POI group than in the control group, but there was no evidence of a statistically significant difference (728.00 ± 176.00 µg/L vs. 503.93 ± 145.64 µg/L, p = 0.13). After adjustment for serum lipid levels, the serum vitamin A/TC ratio was significantly lower in the POI group than in the control group (143.14 ± 35.86 vs. 157.56 ± 35.21 µg/mmol, p = 0.04). Further, the serum vitamin A/TC ratio was significantly and inversely associated with POI risk (unadjusted odds ratio [OR] = 0.988, 95% confidence interval [CI]: 0.977-0.999, p = 0.04). The association remained after adjusting for confounding factors (age, BMI, annual household income, and education) (OR = 0.986, 95% CI: 0.972-0.999, p = 0.04). CONCLUSIONS: Serum vitamin A/TC ratio was inversely associated with POI risk. Therefore, the serum vitamin A/TC ratio may serve as a predictive factor for POI, and vitamin A supplementation may play help prevent or treat POI.

Comprehensive pan-cancer analysis on CBX3 as a prognostic and immunological biomarker.

BACKGROUND: Increased evidence supports the relationship between chromobox protein homolog 3 (CBX3) and tumorigenesis of some cancers. However, the role of CBX3 in pan-cancers remains poorly defined. In the research, we aimed to investigate the prognostic value and the immunological functions of CBX3. RESULTS: We explored the potential oncogenic roles of CBX3 in mRNA and protein levels based on the diverse databases, including the expression, the correlation with prognosis, tumor microenvironment (TME), DNA methylation, protein phosphorylation and enrichment analysis across all TCGA tumors. The results show that CBX3 is overexpressed in multiple cancers, and significant correlations exist between high expression and adverse prognosis in most tumor patients. We observed an enhanced phosphorylation level in uterine corpus endometrial carcinoma, colon cancer and lung adenocarcinoma. A distinct relationship was also found between CBX3 expression and TME, including immune infiltration of tumor-infiltrating lymphocytes and cancer-associated fibroblasts, immune score or matrix score, immune checkpoints. The correlative transcription factors and miRNAs of CBX3-binding hub genes were analyzed to investigate the molecular mechanism. Moreover, alcoholism and alteration of DNA cellular biology may be involved in the functional mechanisms of CBX3. CONCLUSION: The first pan-cancer study offers a relatively comprehensive cognition on the oncogenic roles of CBX3 as a prognostic and immunological marker in various malignant tumors.

Change in metabolic parameters and reproductive hormones from baseline to 6-month hormone therapy.

ABSTRACT: Adequate evidence showed hormone therapy (HT) reduces the risk of new-onset diabetes in midlife women by decreasing fasting glucose and insulin. However, the improvement of these diabetic biomarkers varied with each individual in clinical observations. The objective of our study was to investigate potential baseline factors associated with the change of fasting glucose and insulin during HT.A retrospective cohort study was performed among 263 midlife participants aged 40 to 60 years with menopausal symptoms who have received 6-month individualized HT. Demographic information and laboratory indicators including reproductive hormone, lipid profiles, diabetic indicators were collected and measured at baseline and were followed-up. A series of statistical analyses were performed to confirm the effectiveness of HT and compare the baseline factors between participants with different glycemic or insulinemic response. Multivariable linear regression model with stepwise variable selection was further used to identify the associated factor with the change of fasting glucose and insulin.Of all participants, fasting glucose (P = .001) and fasting insulin (P < .001) were significantly decreased after individualized HT. Significant differences in baseline reproductive hormones were observed in participants with different glycemic response to HT (P < .001 for both follicle stimulating hormone [FSH] and estradiol). Stepwise linear regression model showed that in addition to baseline fasting glucose levels, baseline FSH was also independently associated with the change of fasting glucose (ß = -0.145, P = .019 for baseline FSH) but not fasting insulin. Greater reduction in fasting glucose in women with higher FSH levels was observed even though they have already been in better metabolic conditions (P = .037).Midlife women with higher baseline FSH levels have greater reduction in fasting glucose but not fasting insulin. FSH could be an independent predictor of glycemic response to HT in peri- and postmenopausal women.

Modulating the relaxation dynamics of the Na2Mn3 system via an auxiliary anion change.

This paper reports two closely related heteropentanuclear manganese complexes, namely, {Na2Mn3(opch)3(µ4-O)(µ2-N3) (µ2-AcO)(µ2-MeO)}·6CH3OH·0.5H2O (1) and {Na2Mn3(opch)3(µ4-O)(µ2-N3)2(µ2-AcO)}·2.5CH3OH·2H2O (2), where H2opch is (E)-N'-(2-hydroxy-3-methoxybenzylidene)pyrazine-2-carbohydrazide. Single-crystal X-ray diffraction analysis reveals that the trigonal bipyramidal skeletons in both complexes are comparable, where a perfect triangular Mn3 motif occupies the equatorial plane. Magnetic investigations suggest that overall antiferromagnetic coupling is present within the triangles of 1 and 2. However, their dynamic magnetic properties are drastically distinct. Indeed, complexes 1 and 2 show two kinds of dual slow magnetic relaxation processes that correspond to anisotropy barriers (Δ) of 9.2 cm-1 (11.4 cm-1 for 2) and 12.8 cm-1 (30.0 cm-1 for 2) for the low- and high-frequency domains, respectively. More importantly, a further comparative study of the structure and magnetism indicates that the coordination sphere of these two model complexes with the homologous hydrazone-based coordination sites undergoes an alteration from methoxide-O to azide-N upon a subtle change of the auxiliary anion accompanied by modulating octahedron geometries, leading to a further influence on different relaxation dynamics.

Effects of hormone replacement therapy on glucose and lipid metabolism in peri- and postmenopausal women with a history of menstrual disorders.

BACKGROUND: Previous studies have indicated that women with a history of menstrual disorders have an increased risk of metabolic and cardiovascular diseases. This has been attributed to the high proportion of polycystic ovary syndrome (PCOS) among this group. The favorable effects of hormone replacement therapy (HRT) on serum lipid profiles and glucose homeostasis in postmenopausal women is widely accepted. Whether HRT can also show positive effects on metabolic homeostasis in menopausal women with prior menstrual disorders (a putative PCOS phenotype) has not been reported yet. The aim of the study was to compare the effects of HRT on glucose and lipid metabolism in peri- and postmenopausal women with prior menstrual disorders and controls who did not have prior menstrual disorders. METHODS: A retrospective multicenter study was conducted including 595 peri- and postmenopausal women who received HRT at four hospitals in the Zhejiang Province from May 31, 2010 to March 8, 2021. Participants were divided into the Normal menstruation group and the Menstrual disorders group according to their prior usual menstrual cycle pattern. Glucose and lipid metabolism indicators were assessed at baseline and after HRT. The results were compared between and within the groups, and data from peri- and postmenopausal women were analyzed separately. RESULTS: HRT significantly decreased fasting insulin and homeostasis model assessment of insulin resistance in perimenopausal users, and fasting plasma glucose levels in postmenopausal users with prior menstrual disorders, compared with baseline. Furthermore, HRT decreased low-density lipoprotein cholesterol, total cholesterol, fasting insulin, fasting plasma glucose and homeostasis model assessment of insulin resistance in both peri- and postmenopausal controls, compared with baseline. Nevertheless, no significant differences were observed in any of the glucose or lipid metabolism indicators at baseline and follow-up, as well as changes from baseline levels between menopausal women with and without prior menstrual disorders. CONCLUSIONS: HRT shows more obvious within-group improvements in glucose and lipid metabolism in controls, but there is no significant between-group difference. Further prospective studies are required for confirmation.

Metabolic profile of women with premature ovarian insufficiency compared with that of age-matched healthy controls.

OBJECTIVE: . To compare the metabolic profile of women with spontaneous premature ovarian insufficiency (POI) with that of age-matched healthy controls. STUDY DESIGN: . A cross-sectional case-control study was conducted using 1:1 matching by age. Women below the age of 40 with spontaneous POI who did not receive any medication (n = 303) and age-matched healthy women (n = 303) were included in this study. MAIN OUTCOME MEASURES: . Metabolic profiles, including serum levels of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), glucose, uric acid, urea and creatinine, were compared between women with POI and controls. For women with POI, factors associated with the metabolic profile were analyzed. RESULTS: . Women with POI were more likely to exhibit increased serum levels of TG (ß, 0.155; 95% CI, 0.086, 0.223) and glucose (0.067; 0.052, 0.083), decreased levels of HDL-C (-0.087; -0.123, -0.051), LDL-C (-0.047; -0.091, -0.003) and uric acid (-0.053; -0.090, -0.015), and impaired kidney function (urea [0.070; 0.033, 0.107]; creatinine [0.277; 0.256, 0.299]; eGFR [-0.234; -0.252, -0.216]) compared with controls after adjusting for age and BMI. BMI, parity, gravidity, FSH and E2 levels were independent factors associated with the metabolic profile of women with POI. CONCLUSION: . Women with POI exhibited abnormalities in lipid metabolism, glucose metabolism, and a decrease in kidney function. In women with POI, early detection and lifelong management of metabolic abnormalities are needed.

Associations of age at natural menopause and occupations in Chinese female workers: A cross-sectional study.

AIMS: To investigate the impact of occupation types on age at natural menopause. METHODS: This is a nation-wide cross-sectional study based on 17,948 female workers aged over 40, who come from different industries or organizations. A face-to-face standardized questionnaire was conducted in all participants with the help of occupational hygienists. Occupational titles were coded according to the International Standard Classification of Occupations (2008) (ISCO08). Cox regression model was used to assess the association between each independent occupation and menopausal timing. Models were adjusted for marriage, education, average annual family income, parity, cigarette smoking, alcohol consumption. RESULTS: Higher risks of earlier age at natural menopause was found among legislators and senior officials (ISCO Minor group:111, HR = 2.328, P < 0.001), among other health associated professionals (ISCO Minor group: 325, HR = 1.477, P = 0.003), the workers involved in mining and mineral processing (ISCO Minor group: 811, HR = 1.515, P = 0.048) and metal processing and finishing (ISCO Minor group: 812, HR = 1.722, P < 0.001). Reduced risks of earlier age at natural menopause, including: finance professionals (ISCO Minor group: 241, HR = 0.751, P = 0.021), manufacturing and construction supervisors (ISCO Minor group: 312, HR = 0.477, P = 0.002), administrative and specialized secretaries (ISCO Minor group: 334, HR = 0.788, P = 0.045), cleaners and helpers (ISCO Minor group: 911, HR = 0.633, P = 0.01). CONCLUSIONS: This is the first study to address the influence of occupation types on reproductive aging, showing some specific occupations could be associated with age at natural menopause. Further investigations are necessary to clarify whether it is chance finding or a true association.

The relationship between vitamin E level and premature ovarian insufficiency.

AIM: The aim of this study is to investigate the role of vitamin E in the etiology of premature ovarian insufficiency (POI). METHODS: This study included a total of 96 matched cases and controls, including the case group composed of 40 women with POI, and the control group composed of 56 women with normal menstrual cycles. Serum levels of vitamin E (also known as α-tocopherol), total cholesterol, follicle stimulating hormone (FSH), luteinizing hormone (LH) and anti-Müllerian hormone (AMH) were determined. The relationship of α-tocopherol with FSH, LH and AMH levels in women were evaluated using regression models. RESULTS: We found a negative association of α-tocopherol levels with FSH and LH levels, and a positive correlation between a-tocopherol and AMH levels in the whole study population. In this study, α-tocopherol levels were significantly lower in women with POI than those in women with normal menstrual cycles. CONCLUSION: Vitamin E levels showed significantly statistical difference between the POI and control group (P < 0.001). Therefore, vitamin E is correlated to POI.

Menopausal symptoms in women with premature ovarian insufficiency: prevalence, severity, and associated factors.

OBJECTIVE: To comprehensively investigate and evaluate the prevalence, severity, and associated factors of menopausal symptoms in women with premature ovarian insufficiency (POI). In this study, the specific symptomatology experienced by women with POI and women with natural menopause was also compared. METHODS: In this cross-sectional study, 293 Chinese women with POI from an outpatient clinic were recruited between June 2014 and January 2019. The prevalence and severity of menopausal symptoms were assessed with modified Kupperman Menopausal Index. Participants completed a structured questionnaire, including medical history, menstrual characteristics, and sociodemographic data. Serum levels of reproductive hormones were measured. RESULTS: Among 293 women with POI (33.76 ±â€Š5.47 y), the most prevalent symptoms were mood swings (73.4%), insomnia (58.7%), sexual problems (58.7%), and fatigue (57.3%). Moderate-to-severe mood swings were most frequently reported (23.9%), followed by formication (17.4%) and hot flashes/sweating (17.1%). Compared with women with natural menopause, women with POI exhibited significantly higher risks for fatigue (odds ratio  = 1.42; 95% confidence interval, 1.04-1.94), melancholia (3.12; 1.94-5.01), mood swings (3.57; 2.33-5.45), insomnia (1.41; 1.02-1.96), and significantly lower risks for moderate-to-severe sexual problems (0.40; 0.23-0.69), any and moderate-to-severe muscle/joint pain (0.41; 0.27-0.62 and 0.45; 0.25-0.78, respectively). Living in urban areas and higher gravidity were independently associated with menopausal symptoms in women with POI. CONCLUSIONS: Women with POI experienced a high prevalence of menopausal symptoms, particularly related to psychological and sexual domains. Furthermore, women with POI tended to have more distressing menopausal symptoms compared with women with natural menopause.

Ring-forming transformation associated with hydrazone changes of hexadecanuclear dysprosium phosphonates.

{Dy16(µ6-C10H7PO3)2(µ5-C10H7PO3)8(spch)8(µ3-OH)2(µ2-OH)2(µ2-AcO)6(µ3-COO)2(DMF)2(H2O)6}·0.5CH3OH·4.5H2O (1) and {Dy16(µ5-C10H7PO3)4(µ3-C10H7PO3)12(µ2-C10H7PO3H)8(opch)4(DMF)8(MeOH)4}·2.5CH3OH·3H2O (2), where H2spch is ((E)-N'-(2-hydroxybenzylidene)pyrazine-2-carbohydrazide, C10H7PO3H2 is 1-naphthylphosphonic acid and H2opch is (E)-N'-(2-hydroxy-3-methoxybenzylidene)pyrazine-2-carbohydrazide, were successfully synthesized by varying the hydrazone ligands in the Dy-phosphonate system. It is important that the ellipsoidal core experiences a ring forming structural transformation to the supramolecular square motif upon the incorporation of an ortho-methoxy substituent into the hydrazone. Alternating-current (ac) magnetic susceptibility studies of 1 and 2 suggest that similar single molecule magnet behaviors occur for these two complexes. The result represents an effective molecular assembly tactic to develop highly complicated lanthanide coordination clusters through the multicomponent self-assembly of the coalescence of phosphonate- and hydrazone-based ligands and metal salts.

Usefulness of [18F]fluorodeoxyglucose PET/CT for evaluating the PD-L1 status in nasopharyngeal carcinoma.

PURPOSE: To explore the relationship between [18F]fluorodeoxyglucose (18F-FDG uptake) and PD-L1 expression and determine the usefulness of 18F-FDG PET/CT for evaluating the PD-L1 status in tumour cells (TCs) and tumour-infiltrating immune cells (TIICs) in patients with nasopharyngeal carcinoma (NPC). METHODS: We retrospectively evaluated the records of 84 eligible patients who received an initial histopathological diagnosis of NPC between December 2016 and March 2019. All tissue specimens and PET/CT images were collected prior to treatment. High PD-L1 expression in TCs and TIICs was defined as ≥ 50% of stained cells. RESULTS: There was a significant difference in 18F-FDG uptake according to the PD-L1 status in TCs and TIICs. Univariate analysis showed that PD-L1 expression in TCs was associated with tumour maximum standardized uptake value (SUVmax) (P < 0.001), primary tumour total lesion glycolysis (TLG; P < 0.001), and T stage (P = 0.044), but not with plasma Epstein-Barr virus (EBV) load (P = 0.816), whereas PD-L1 expression in TIICs was related to SUVmax (P = 0.011), TLG (P = 0.001), T stage (P = 0.028), and plasma EBV load (P = 0.003). In multivariate logistic regression, PD-L1 expression in TCs was positively associated with SUVmax (P = 0.003) and TLG (P = 0.001), and in TIICs, negatively associated with SUVmax (P = 0.038) and plasma EBV load (P = 0.025). CONCLUSIONS: 18F-FDG uptake in NPC lesions was positively correlated with PD-L1 expression in TCs and negatively correlated with PD-L1 expression in TIICs. Thus, 18F-FDG PET/CT may be useful for evaluating the PD-L1 status in patients with NPC.

Concordance of PD-L1 Status Between Image-Guided Percutaneous Biopsies and Matched Surgical Specimen in Non-Small Cell Lung Cancer.

OBJECTIVE: Programmed death-ligand 1 (PD-L1) expression status is a crucial index for identifying patients who will benefit from anti-programmed cell death protein 1 (PD-1)/PD-L1 therapy for non-small cell lung cancer (NSCLC). However, the concordance of Tumor Proportion Score (TPS) between biopsies and matched surgical specimens remains controversial. This study aims to evaluate the concordance of PD-L1 expression between image-guided percutaneous biopsies and matched surgical specimens. METHOD: We evaluated 157 patients diagnosed with operable NSCLC on both surgical tissue sections and matched lung biopsies retrospectively. The patients underwent either regular computed tomography (CT)-guided biopsy (n = 82) or positron emission tomography (PET)/CT-guided biopsy (n = 75). The concordance between surgical specimens and lung biopsies for PD-L1 TPS was evaluated using Cohen's kappa (κ) coefficient. RESULTS: Immunohistochemical expression of PD-L1 was evaluated in both surgical resected specimens and matched biopsies in the eligible 138 patients. The concordance rate of PD-L1 expression between surgical tissue sections and matched biopsies was fairly high at 84.1% (116/138), and the κ value was 0.73 (95% CI: 0.63-0.83, P < 0.001). The concordance rate was higher for tissue sections from PET/CT-guided biopsy than for tissue sections from CT-guided biopsy [88.6% (62/70, κ value: 0.81) vs 79.4% (54/68, κ value: 0.66)]. CONCLUSION: PD-L1 TPS was strongly concordant between surgical specimens and matched lung biopsies. Thus, the routine evaluation of PD-L1 expression in diagnostic percutaneous biopsies could be reliable for identifying patients who will benefit from anti-PD-1/PD-L1 immunotherapy.