IntroductionA previous study using 1996 Medical Expenditure Panel Survey (MEPS) data identified disparities in primary care experiences by health insurance status. This study examined changes in these disparities following substantial expansions in health insurance coverage.MethodsWe conducted survey-weighted logistic regression analyses using 2021–2022 MEPS data among noninstitutionalized U.S. residents younger than 65 years and compared the findings with those of a previous study using 1996 data. Five primary care attributes were examined, including having a usual source of care (USC), USC location, waiting time, telephone accessibility, and evening or weekend office hours.ResultsThe uninsured proportion decreased from 19% in 1996 to 8% in 2021–2022, while public insurance coverage increased from 12% to 23%. The proportion of individuals with a USC declined from 93% to 71%. Insured individuals had significantly higher odds of having a USC than uninsured individuals in both 1996 (OR 3.40, 95% CI 2.91–3.97) and 2021–2022 (OR 3.92, 95% CI 2.74–5.62). Among privately versus publicly insured individuals, the odds ratio for being seen within 30 minutes decreased from 1.77 (95% CI 1.51–2.06) to 1.02 (95% CI 0.51–2.03), and the odds ratio for evening or weekend office hours decreased from 1.68 (95% CI 1.48–1.91) to 0.98 (95% CI 0.59–1.63).DiscussionDespite improvements in insurance coverage, disparities in primary care experiences persisted, particularly between insured and uninsured individuals. Some findings suggested reduced disparities between privately and publicly insured individuals, especially in waiting times and evening or weekend office hours. Further targeted efforts to improve equitable access to primary care are warranted.
Lactic acid, as a novel epigenetic regulator, participates in the regulation of gene transcription through lactylation. In the pathological context of PCOS, its core TCM pathogenesis—“the mutual entanglement of phlegm and blood stasis”—aligns closely with metabolic disorders and chronic low-grade inflammation in modern medicine. These conditions collectively drive the abnormal accumulation of lactate, which in turn acts as a substrate to drive lactylation, thereby continuously influencing the expression of genes related to ovarian granulosa cell function, follicular development, and endometrial receptivity. Abnormally accumulated lactate may not only represent the microscopic manifestation of “phlegm-dampness” but may also act as a signalling molecule that exacerbates the “blood stasis” state characterised by inflammation and tissue damage. Therefore, from the perspective of TCM's phlegm-blood stasis framework, it is essential to thoroughly investigate whether abnormalities in lactate metabolism and dysregulation of lactylation serve as common molecular nodes for key pathological processes in PCOS—such as insulin resistance (IR), chronic inflammation, and impaired follicular development. We also aim to explore the potential value of traditional Chinese medicine (TCM) and integrated Chinese-Western medicine strategies—guided by the therapeutic principle of “resolving phlegm and removing stasis”—in targeting the lactate metabolic network, with the goal of providing molecular-level evidence and new insights for the prevention and treatment of PCOS through integrated Chinese-Western medicine.
BackgroundFollicular thyroid carcinoma (FTC) is difficult to distinguish from benign follicular lesions before surgery. This study examined heat shock protein family A member 5 (HSPA5), an endoplasmic reticulum chaperone, and its association with ferroptosis-related transcriptional programs and cellular phenotypes in FTC.MethodsFive public transcriptomic cohorts were integrated for candidate discovery, external characterization, and paired-tissue evaluation. HSPA5 was silenced with two short-hairpin RNA constructs in FTC-238 and FTC-133 cells. Knockdown, metabolic activity, DNA synthesis, wound closure, migration, and invasion were evaluated using molecular and cell-based assays.ResultsIn exploratory analyses, HSPA5 correlated with ferroptosis-driver and lipid-peroxidation scores (Spearman rho = 0.709 and 0.791; false-discovery rates = 0.023 and 0.013). Expression was higher in eight patient-matched primary FTC samples than in adjacent thyroid (P = 0.0078). External discrimination between FTC and follicular adenoma was limited (area under the receiver-operating-characteristic curve = 0.51). In both FTC-238 and FTC-133 cells, HSPA5 silencing reduced the 24-h Cell Counting Kit-8 (CCK-8) signal and the numbers of migrating and invading cells, but increased the 5-ethynyl-2'-deoxyuridine (EdU)-positive fraction.ConclusionHSPA5 is associated with ferroptosis-related transcriptional programs, and its depletion reduces 24-h CCK-8 signals and Transwell cell counts in FTC models. The role of HSPA5 in ferroptotic cell death requires functional validation.
BackgroundNeutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are inexpensive inflammatory markers derived from routine blood counts. However, their value for assessing amputation risk in patients with diabetic foot ulcers (DFUs) remains uncertain. This meta-analysis aims to evaluate the associations and discriminatory performance of baseline NLR and PLR for DFU-related amputation.Material and methodsPubMed, Embase, the Cochrane Library, and Web of Science were searched from inception to July 2026 for English-language observational studies. Eligible studies reported baseline NLR or PLR according to amputation status or their area under the receiver operating characteristic curve (AUC) for amputation. Random-effects models were used to pool standardized mean differences (SMD) and AUC with 95% confidence intervals (CI). Risk of bias and certainty of evidence were assessed using the QUIPS tool and GRADE framework, respectively.ResultsThirteen studies involving 3,667 patients were included. Baseline NLR was higher in patients who underwent any amputation than in those managed with limb salvage (SMD 0.69, 95% CI 0.42–0.97; I2 = 85.5%) and showed moderate discriminatory performance (AUC 0.713, 95% CI 0.665–0.757; I2 = 0%). NLR was also higher in patients undergoing major amputation (SMD 0.97, 95% CI 0.18–1.77), whereas the minor-amputation comparison was not statistically significant (SMD 0.24, 95% CI −0.04 to 0.51). PLR was higher in patients undergoing any amputation (SMD 0.55, 95% CI 0.17–0.93) and showed a pooled AUC of 0.664 (95% CI 0.631–0.697; I2 = 0%). The certainty of evidence was moderate for both the associations of NLR and PLR with any amputation and their discriminatory performance assessed by AUC. Higher PLR was observed in the minor- and major-amputation groups, but both analyses were exploratory and included only two studies. Evidence certainty was moderate for minor amputation and low for major amputation.ConclusionsHigher baseline NLR and PLR were associated with DFU-related amputation, with more consistent evidence for NLR. These markers may complement clinical risk assessment but are insufficient for stand-alone decision-making. Prospective multicenter studies are needed to validate standardized thresholds and determine their added value within established classification systems.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/view/CRD420261461714, PROSPERO CRD420261461714.
BackgroundSerplulimab is the first anti-PD-1 monoclonal antibody to receive marketing approval for the first-line treatment of extensive-stage small-cell lung cancer (ES-SCLC) worldwide. To date, only sporadic cases of immune-induced adverse events (irAEs) secondary to serplulimab have been reported. Herein, we report a case of a man who suffered from a toxic epidermal necrolysis-like reaction after treatment with serplulimab and was successfully treated with comprehensive therapy. Additionally, we review the literature on toxic epidermal necrolysis (TEN) associated with serplulimab and provide a detailed description of the clinical symptoms, underlying mechanisms, and treatment for a more comprehensive understanding of immune-related TEN for the first time.Case summaryA 76-year-old man diagnosed with ES-SCLC developed sporadic red maculopapular eruptions 7 days after the first cycle of serplulimab infusion, which rapidly progressed to blisters and ulceration, ultimately deteriorating to extensive epidermal detachment within a short time. A diagnosis of a TEN-like reaction was conservatively made due to the lack of a skin biopsy. The patient was successfully treated with a multifaceted management approach consisting of immune suppression using a combination of corticosteroids and intravenous immunoglobulin (IVIG), anti-infection treatment based on susceptibility testing, personalized wound care, and nutritional support.ConclusionDespite serplulimab having reshaped the treatment landscape of ES-SCLC, the occurrence of rare but potentially fatal TEN secondary to serplulimab should not be ignored.This case illustrates that serplulimab can induce a rare but potentially fatal TEN-like reaction within a short time and underscores the importance of vigilant monitoring of skin and mucous membranes and early recognition during treatment. In addition, we highlight that a multidimensional treatment approach consisting of immune suppression, anti-infection treatment, wound care, and nutritional support is pivotal for recovery.
