Retrospective assessment of neoadjuvant camrelizumab combined with induction chemotherapy: efficacy in laryngeal preservation for advanced hypopharyngeal and laryngeal squamous cell carcinoma.

BACKGROUND: Hypopharyngeal and laryngeal squamous cell carcinoma (SCC) account for 25-30% of head and neck SCC. Total laryngectomy, while effective, compromises the quality of life. Immune checkpoint inhibitors such as Camrelizumab offer potential in laryngeal preservation. The study investigated Camrelizumab combined with TP regimen as a neoadjuvant therapy for laryngeal preservation in advanced hypopharyngeal and laryngeal SCC. METHODS: A retrospective study was conducted at Sun Yat-sen University Cancer Center on patients diagnosed with locally advanced SCC of the hypopharynx and larynx from October 1, 2019, to October 25, 2022. The efficacy of a first-line treatment combining Camrelizumab (200 mg) and TP regimen (Albumin-bound paclitaxel at 260 mg/m2 and Cisplatin at 60 mg/m2) was evaluated using RECIST 1.1 criteria. Outcomes included overall survival (OS), progression-free survival (PFS), laryngectomy-free survival (LFS), and response rates. RESULTS: Of the 71 included patients, the median age was 60.7 years. Post the first-line treatment, 90.1% demonstrated an overall response. The one-year and two-year OS rates were 91.5% and 84.3%, respectively. One-year and two-year PFS rates were 92.9% and 83.9%, respectively, with LFS at 85.6% and 73.2%. The initial T4 stage as significantly associated with reduced OS and LFS. Skin reaction was the predominant adverse event. CONCLUSION: The Camrelizumab-TP regimen demonstrated promising results for advanced hypopharyngeal/laryngeal SCC patients, exhibiting high response rates, OS, and LFS, positioning it as a potential primary option for laryngeal preservation. Further comprehensive, randomized controlled studies are imperative to validate these initial observations and elucidate the regimen's full clinical efficacy in optimizing laryngeal outcomes.

Mouse islet-derived stellate cells are similar to, but distinct from, mesenchymal stromal cells and influence the beta cell function.

AIMS: Evidence is accumulating of the therapeutic benefits of mesenchymal stromal cells (MSCs) in diabetes-related conditions. We have identified a novel population of stromal cells within islets of Langerhans - islet stellate cells (ISCs) - which have a similar morphology to MSCs. In this study we characterize mouse ISCs and compare their morphology and function to MSCs to determine whether ISCs may also have therapeutic potential in diabetes. METHODS: ISCs isolated from mouse islets were compared to mouse bone marrow MSCs by analysis of cell morphology; expression of cell-surface markers and extracellular matrix (ECM) components; proliferation; apoptosis; paracrine activity; and differentiation into adipocytes, chondrocytes and osteocytes. We also assessed the effects of co-culture with ISCs or MSCs on the insulin secretory capacity of islet beta cells. RESULTS: Although morphological similar, ISCs were functionally distinct from MSCs. Thus, ISCs were less proliferative and more apoptotic; they had different expression levels of important paracrine factors; and they were less efficient at differentiation down multiple lineages. Co-culture of mouse islets with ISCs enhanced glucose induced insulin secretion more effectively than co-culture with MSCs. CONCLUSIONS: ISCs are a specific sub-type of islet-derived stromal cells that possess biological behaviors distinct from MSCs. The enhanced beneficial effects of ISCs on islet beta cell function suggests that they may offer a therapeutic target for enhancing beta cell functional survival in diabetes.

Microbiological Distribution, Antimicrobial Susceptibility and Risk Factors of Polymicrobial Infections in Diabetic Foot.

BACKGROUND: Diabetic foot infection (DFI) leads to poor prognosis and polymicrobial infections are usually the main cause. The study is to explore the microbiological distribution, antimicrobial drug susceptibility, and risk factors of polymicrobial infections in hospitalized patients with DFI. METHODS: This retrospective study included 160 patients with DFI in Wagner's grades 2, 3, and 4. Deep necrotic tissue was used to acquire specimens for microbiological culture. VITEK-2 system and MALDI-TOF mass spectrometry were used to identify the bacterial isolates. The Kirby Bauer method was used for drug susceptibility tests. RESULTS: A total of 202 pathogens were isolated. The proportion of gram-negative bacilli (GNB, 62.4%, 126 of 202) was higher than that of gram-positive cocci (GPC, 37.6%, 76 of 202). The most prevalent GPC was Staphylococcus aureus in every Wagner grade, while the most common GNB varied in different Wagner grades. Linezolid was the most effective antibiotic for GPC in different Wagner grades. Imipenem was the most effective antibiotic for GNB in Wagner grade 2. Amikacin was the most effective antibiotic for GNB in Wagner grades 3 and 4. Polymicrobial infections existed only in Wagner grades 3 and 4 and increased the risk of amputation (p < 0.01). History of antibiotics, duration of diabetic foot, CRP, and lower extremity arterial disease were the independent risk factors of polymicrobial infections (p < 0.05). CONCLUSIONS: Clinicians should adjust the antibiotic as needed based on the results of drug susceptibility and clinical treatment effect among different Wagner grades. Particular attention should be given to the treatment of polymicrobial infections.

Gasless robot-assisted transaxillary hemithyroidectomy (RATH): learning curve and complications.

PURPOSE: Gasless robot-assisted transaxillary hemithyroidectomy (RATH) is regarded as an alternative surgical option for thyroid operations. However, the associated steep learning curve is a clinical concern. This study evaluated the learning curve of RATH for surgeons without experience of endoscopic surgery and the early surgical outcomes of RATH. METHODS: We conducted a retrospective study of patients who underwent gasless RATH and conventional hemithyroidectomy (CH) at Sun Yat-sen University Cancer Center, Guangzhou, China, from June 2021 to August 2022. The learning curve and early surgical outcomes of gasless RATH were evaluated. And the early surgical outcomes of gasless RATH were compared to CH. RESULTS: In total, 105 patients who underwent gasless RATH and 104 patients who underwent CH were matched and assessed. The cumulative sum techniques (CUSUM) analysis showed that the peak point of gasless RATH operative time occurred at the 31st case. No clear single peak was identified in the CUSUM plot for drainage amount and blood loss. No significant difference in perioperative complications was observed between these two groups. Moreover, the number of postoperative patients who got sense of thyroid area traction were fewer in the gasless RATH group (n = 11, 10.5%) than in the CH group (n = 32, 30.8%). CONCLUSION: Gasless RATH can be considered as an alternative approach to the conventional open procedure, as it is an easy remote access technique, with shorter learning curves and certain advantage such as less sense of thyroid area traction.

Evaluation of a new low-cost negative pressure wound therapy in the treatment of diabetic foot ulcers.

OBJECTIVE: To investigate the effectiveness of a new and low-cost negative pressure wound therapy (LC-NPWT) in the treatment of diabetic foot ulcers (DFUs). METHOD: In this retrospective cohort study, patients from our inpatient clinic with Wagner grade 3 DFUs were given LC-NPWT or conventional wound dressings. The primary outcome was the wound healing rates. Complete wound healing, defined as complete re-epithelialisation of the wound, was recorded during the two months of follow-up. The definition of complete epidermis of the wound was that the skin was closed (100% re-epithelialisation), with no drainage or dressing. The secondary outcomes were the number of inpatient days and surgical procedures, and outcomes after hospital discharge. The wound score from the Bates-Jensen wound assessment tool and the levels of the inflammation factors procalcitonin (PCT), C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were compared between the two groups. The Kaplan-Meier survival estimate was used to examine the cumulative wound healing rate. RESULTS: The study cohort comprised 41 patients. The two-month wound healing rate was higher in patients in the LC-NPWT group than in the control group (15/21 (71.4%) versus 8/20 (40.0%), respectively; p=0.043). At the end of the two-month follow-up period, the cumulative wound healing rate was higher in the LC-NPWT group than in the control group (p=0.032). Patients in the LC-NPWT group had fewer inpatient days (19.3±3.84 versus 25.05±4.81; p<0.001) and shorter duration of antibiotic use (32.14±3.89 days versus 36.10±5.80 days; p=0.014) than those who received conventional wound dressings. There were significant improvements in mean wound score between the LC-NPWT group and the control group (p<0.001). After one week of treatment, the blood levels of PCT (0.03±0.30ng/ml versus 0.07±0.08ng/ml; p=0.039), CRP (14.55±13.40mg/l versus 24.71±18.10mg/l; p=0.047) and ESR (42.05±29.29mm/h versus 61.65±22.42mm/h; p=0.021) were lower in patients who received LC-NPWT than those who received conventional wound dressings. CONCLUSION: LC-NPWT is effective in the treatment of DFUs and provides a cheaper alternative for patients with DFUs that could potentially alleviate the economic distress these patients endure.

Evaluation of neoadjuvant chemotherapy combined with PD-1 inhibitors in patients with oropharyngeal and hypopharyngeal squamous cell carcinoma: a comparative study of antitumor activity.

PURPOSE: To assess the antitumor activity of neoadjuvant chemotherapy in conjunction with PD-1 inhibitors (neoadjuvant chemoimmunotherapy) among patients with oropharyngeal and hypopharyngeal squamous cell carcinoma (OPHSCC) and compare its efficacy with neoadjuvant chemotherapy alone. METHODS: We conducted a retrospective analysis using data from patients diagnosed with OPHSCC and treated at the Sun Yat-sen University Cancer Center between September 2012 and August 2022. We included patients who received neoadjuvant chemotherapy alone or combined with PD-1 inhibitors. We assessed the clinical response using the Response Evaluation Criteria in Solid Tumors and evaluated progression-free survival (PFS) and overall survival (OS). RESULTS: Preliminary results demonstrate that neoadjuvant chemoimmunotherapy exhibited robust antitumor activity in OPHSCC, with an impressive overall response rate (ORR) of 81.0%. Complete response and partial response rates were 14.9% and 65.9%, respectively. Notably, neoadjuvant chemoimmunotherapy demonstrated superior PFS and OS to neoadjuvant chemotherapy alone. The 1-year PFS rate was 80.7%, and the 2-year rate was 61.1%. Additionally, the 1-year OS rate reached 92.3%. Finally, a multivariate analysis identified the American Joint Committee on Cancer stage reduction post-treatment as a favorable predictor of PFS. CONCLUSION: Our results underscore the promising potential of neoadjuvant chemoimmunotherapy in enhancing antitumor activity in patients with OPHSCC. The robust ORR, along with improved PFS and OS, supports the utility of this combined approach. These results pave the way for further investigations to validate and refine the application of neoadjuvant chemoimmunotherapy in this challenging clinical context.

PD-1 Inhibitors combined with paclitaxel (Albumin-bound) and cisplatin for larynx preservation in locally advanced laryngeal and hypopharyngeal squamous cell carcinoma: a retrospective study.

BACKGROUND: laryngeal and hypopharyngeal squamous cell carcinoma (SCC) is a common head and neck cancer with significant impact on quality of life due to its crucial roles in vocalization, airway protection, and swallowing. This retrospective study aims to evaluate the efficacy and larynx organ preservation of neoadjuvant treatment with PD-1 inhibitors in combination with paclitaxel (Albumin-bound) and cisplatin for locally advanced laryngeal and hypopharyngeal SCC. METHODS: Medical records of consecutive patients diagnosed with histologically or cytologically confirmed locally advanced SCC of the larynx and hypopharynx, who received PD-1 inhibitor therapy at a single tertiary care center, were reviewed from January 1, 2019, to December 15, 2022. The patients were treated with a combination of PD-1 inhibitors, paclitaxel (Albumin-bound) 260mg/m2, and cisplatin 60mg/m2 (TP) as their first-line therapy. Survival outcomes, laryngectomy-free survival (LFS) rates and response rates were assessed. RESULTS: The study cohort comprised 156 patients, predominantly male, with a median age of 60.4 years. The estimated one-year overall survival (OS) rate was 94.1%, two-year OS rate was 82.5%, one-year progression-free survival (PFS) rate was 80.4%, and two-year PFS rate was 66.3%. The one-year LFS was 86.4%, and the two-year LFS rate was 73.0%. The overall response rate after TP + PD-1 inhibitors therapy was 88.5%. Common treatment-associated adverse events included rash, thyroid function abnormalities, myelosuppression, and colitis. CONCLUSION: Neoadjuvant therapy with PD-1 inhibitors in combination with paclitaxel (Albumin-bound) and cisplatin showed promising efficacy and tolerability for larynx preservation in locally advanced laryngeal and hypopharyngeal SCC. The high response rates and favorable survival outcomes suggest this approach as a potential treatment option. Prospective randomized controlled trials are needed to further validate these findings and establish the role of immunotherapy in larynx preservation.

Birth weight is associated with obesity and T2DM in adulthood among Chinese women.

BACKGROUND: Previous studies have indicated an association between birth weight (BW) and type 2 diabetes mellitus (T2DM), but few studies have explored this relationship under different conditions of obesity in adulthood. METHODS: A total of 4,005 individuals from ten provinces of China were randomly selected to participate in this study. We used a questionnaire to collect age, BW, current weight, height, T2DM history, age at T2DM diagnosis, and other variables. The participants were divided into three groups were according to BW trisection (BW ≤ 2500 g for the lower BW group, 2500 g < BW ≤ 3500 g for the normal BW group, and BW > 3500 g for the higher BW group). The cutoff of overweight and obesity were 25 kg/m2 and 28 kg/m2, respectively. RESULTS: The prevalence rates of T2DM among women with lower BW, normal BW and higher BW were 5.2%, 3.6% and 2.0%, respectively. The obesity prevalence rates in the lower BW, normal BW and higher BW groups were 8.1%, 6.7% and 9.0%, respectively. In the obese population, we did not find a relationship between BW and T2DM, but in the nonobese population, we found that with increasing BW, the risk of developing T2DM was reduced. Obese status in adulthood modified the association between BW and the risk of T2DM. CONCLUSION: There is a "U" shape association between BW and risk of adulthood obesity in Chinese women, but this trend is not existed between BW and risk of developing T2DM. In non-overweight females, the risk of developing T2DM decreased with increasing BW, but this trend was not observed in overweight females.

Laryngeal function-preserving of frontolateral vertical partial laryngectomy (FLVPL) for selected T4a glottic cancer with thyroid cartilage invasion adherence to the anterior commissure: an innovative attempt.

OBJECTIVE: To evaluate the feasibility and efficacy in selected T4a glottic cancer (thyroid cartilage invasion adherence to the anterior commissure) treated with frontolateral vertical partial laryngectomy (FLVPL) and laryngeal framework reconstruction using titanium mesh. METHODS: Six patients with the limited T4a glottic cancer with thyroid cartilage destruction adherence to the anterior commissure, underwent FLVPL from 2009 to 2016 in Sun Yat-Sen University Cancer Center. All patients were followed up postoperatively. RESULTS: All patients comprised radical tumor resection and favorable functional outcomes, and no aspiration and laryngeal stenosis were observed. According to postoperative pathology, four patients should go through postsurgical radiotherapy with a mean dose of 66 Gy. But one of them refused to undergo postoperative radiotherapy, who observed local recurrence in postcricoid area underwent total laryngectomy (TL) and ipsilateral selected neck dissection in post-surgery two year. During follow-up period, all patients were still alive, and five patients without local recurrence and distant metastases. CONCLUSION: FLVPL and laryngeal framework reconstruction using titanium mesh is one viable surgical procedure to obtain adequate oncologic and functional outcomes.

Six-year follow-up study on the association between white blood cell count and fasting blood glucose level in Chinese adults: A community-based health examination survey.

BACKGROUND: Pre-diabetes is considered to be an important reversible stage of type 2 diabetes (T2DM); thus, early identification of pre-diabetes may help in the prevention of T2DM. This study aimed to explore the relationship between white blood cell (WBC) counts and the cumulative risk of impaired fasting glucose (IFG) regulation at 6 years. METHODS: A community-based health examination survey was conducted among individuals who were randomly selected from 1300 residents living in China in 2010 to 2016. The participants were divided into four groups according to WBC baseline level. This study initially conducted a cross-sectional analysis of the population who underwent physical examination to explore the relationship between WBC count and FBG levels. Then, a follow-up study was conducted on the population who underwent IFG normal physical examination to explore the relationship between baseline WBC count and changes in FBG levels and the cumulative risk of 6-year IFG. RESULTS: During the 6-year cohort follow-up, 17.2% of the participants developed IFG, and the cumulative incidence rates of IFG in the four groups were 14.7%, 16.3%, 15.8%, and 22.2%. By Cox multiple regression equation the hazard ratio (HR) of the IFG increased by 18.7% for each additional unit of baseline WBC count with no adjustment of any factor. After adjusting factors, HR increased by 8.4%. CONCLUSION: Increased WBC counts are associated with risk of IFG, suggesting chronic inflammation may be involved in the development and progression of IFG.

Clinical application of supraclavicular flap for head and neck reconstruction.

PURPOSE: To assess the efficacy and clinical application of a supraclavicular flap for head and neck reconstruction. METHOD: A pedicled supraclavicular flap was used on 26 patients at Sun Yat-Sen University Cancer Center between July 2017 and November 2018, including 16 cases with oral cancer defects, 7 cases with laryngeal cancer and hypopharyngeal carcinoma defects, 1 case with parotid gland cancer defects, 1 case with external auditory canal cancer defects, and 1 case with tracheal esophageal fistula. The time required to harvest the flap, the amount of intraoperative blood loss, the duration of postoperative drainage tube placement, the outcome of the flap, and the healing observed at the donor site are reported. RESULT: The sizes of the flaps were 6-20 × 4-6.5 cm. The time required to harvest the supraclavicular flap ranged from 25 to 35 min and averaged 30 min. The amount of intraoperative blood loss ranged from 20 to 100 ml and averaged 58.8 ml. The duration of postoperative drainage tube placement ranged from 3 to 8 days and averaged 5.9 days. A total of 23 flaps survived. In two cases, the distal blood supply of the flaps was poor, but the flaps survived after debridement and suturing. One flap had partial necrosis, but survived after conservative treatment. All donor area defects were directly sewed and stitched without complications. CONCLUSION: There are multiple advantages of the supraclavicular flap, including simple preparation technique, reliable repair of the defects, and without the need for performing microvascular anastomosis. It can be safely used in head and neck reconstruction after surgery.

Decreased expression of protein tyrosine kinase 6 contributes to tumor progression and metastasis in laryngeal squamous cell carcinoma.

BACKGROUND: PTK6 is involved in cell proliferation, invasion and migration. Patients with lower PTK6 expression predicts poor prognosis of LSCC. However, the mechanism of PTK6 in LSCC progression remains unclear. We investigated the role of PTK6 in the pathogenesis of LSCC. METHODS: Human LSCC tissues and paired adjacent non-tumor tissues were obtained to evaluate PTK6 expression. The biological function of PTK6 in LSCC was determined by overexpression of PTK6 in Hep-2 cells in vitro and in nude mice. The potential PTK6 target factors and signaling pathways were identified by Western blotting assay and immunohistochemical staining. RESULTS: PTK6 was downregulated in tissues of human LSCC. Biological function investigation of PTK6 demonstrated that overexpression of PTK6 significantly decreased cell growth, clonogenicity, invasion and migration capacity in vitro and suppressed xenograft tumor growth as well as lung metastasis in vivo. PTK6 suppresses LSCC proliferation mainly by inhibiting c-myc and cyclinD1 expression. In addition, PTK6 promotes cell apoptosis in LSCC. Moreover, PTK6 mitigated LSCC invasion and migration through regulating EMT and MMP-9. CONCLUSION: PTK6 plays a tumor suppressor role in LSCC by regulating c-myc and cyclinD1 expression, cell apoptosis, EMT and MMP-9.

The operation experience of endoscopic thyroidectomy by areola and axilla approach.

To explore the feasibility of endoscopic thyroidectomy via breast areola and axilla approach. The clinical data of 36 cases that underwent endoscopic thyroidectomy via breast areola and axilla approach from February 2012 to December 2013 were reviewed. All cases were completed, the mean operation time was 136.3 min (95-183 min), intraoperative blood loss was 15.8 ml (5-60 ml). The average hospitalization time was 5 days (4-6 days). There were no conversions to open surgery, no permanent nerve injuries, and no cases of hypoparathyroidism. Three patients had postoperative subcutaneous ecchymosis who were cured spontaneously after 1 month. Endoscopic thyroidectomy is safe and feasible for patients with thyroid diseases with good cosmetic results, and is worthy of being widely applied for patients who have cosmetic demand.

The CDKAL1 gene is associated with impaired insulin secretion and glucose-related traits: the Cardiometabolic Risk in Chinese (CRC) study.

OBJECTIVE: Insulin secretion and insulin resistance, which affect metabolic homoeostasis, each have a significant genetic component. Cyclin- dependent kinase 5 (CDK5) regulatory subunit-associated protein 1-like 1 (CDKAL1) rs10946398, a novel body mass index (BMI)-associated locus specifically in the Asian population, may impair insulin secretion and may be associated with insulin resistance and type 2 diabetes. Our objective was to investigate the impact of the rs10946398 polymorphism of CDKAL1 on insulin secretion, insulin resistance and glucose-related traits in the Chinese population. SUBJECTS AND METHODS: The study samples were based on a community-based health examination survey conducted in central China. Indices of insulin resistance and insulin secretion were derived from fasting glucose measurements and oral glucose tolerance tests (OGTTs). Using multivariate linear regression models, the relationships between the rs10946398 polymorphism of CDKAL1 and insulin secretion, insulin resistance and quantitative glucose-related traits were investigated in 2313 participants. RESULTS: The CDKAL1 rs10946398 C allele showed a significant association with decreased insulin secretion (ß = -0·05, P < 0·0005), but not with insulin resistance (ß = 0·02, P = 0·08). We also found that the CDKAL1 rs10946398 C allele was significantly associated with glucose-related traits (fasting glucose, fasting insulin, 2-h glucose and HbA1c). There was no significant relationship between rs10946398 and other metabolic traits. CONCLUSIONS: rs10946398 of CDKAL1 was associated with markers of impaired insulin secretion. It is reasonable to infer that the relationship between CDKAL1 and metabolic diseases is mediated by its effect on glucose-related traits.

Relationship between white blood cells and hypertension in Chinese adults: the Cardiometabolic Risk in Chinese (CRC) study.

Increased blood pressure was associated with increased white blood cell count (adjusted p < 0.001) in a community-based health examination survey of adults in China (n = 39 282; aged 18-93 years). Adjusted odds ratios (95% confidence intervals) for hypertension across white blood cell count quintiles were 1.00, 0.99 (0.89-1.09), 1.11 (1.01-1.22), 1.09 (0.99-1.20), and 1.19 (1.08-1.31) (p for trend < 0.001). Body mass index and white blood cell count had an additive effect on systolic blood pressure (p for interaction = 0.047). Therefore, white blood cell count could independently predict hypertension in Chinese adults.

Neck circumference and early stage atherosclerosis: the cardiometabolic risk in Chinese (CRC) study.

BACKGROUND: Neck circumference (NC) has been previously related to cardiometabolic risk factors. In this study we examined the association between NC and early stage atherosclerosis in Chinese adults. METHODS: The study samples were from a community-based health examination survey in central China. In total 2,318 men and women (18-64 y) were included in the final analyses. Carotid radial pulse wave velocity (crPWV), carotid femoral PWV (cfPWV), carotid artery dorsalis pedis PWV (cdPWV) and NC were measured. RESULTS: After adjustment for age, sex, lipids, glucose, blood pressure, heart rate, body mass index (BMI), high NC was significantly associated with an increasing trend of cfPWV, cdPWV and crPWV (P = 0.001, 0.049, and 0.038; respectively). In addition, we found significant interaction between hypertension status and NC level in relation to cfPWV, adjusted for age, sex, BMI, fasting glucose, lipids and heart rate(P for interaction = 0.034). The associations between NC and cfPWV were significant (P = 0.02) among those with hypertension, but not significant among those without hypertension. CONCLUSIONS: Our data showed that high NC was associated with an increased risk of early stage atherosclerosis in Chinese adults, independent of other metabolic risk factors. Hypertension might modify the association between NC and cfPWV.

The relationships between biological novel biomarkers Lp-PLA2 and CTRP-3 and CVD in patients with type 2 diabetes mellitus.

BACKGROUND: Cardiovascular disease (CVD) is recognized as a primary and severe comorbidity in patients with type 2 diabetes mellitus (T2DM) and is also identified as a leading cause of mortality within this population. Consequently, the identification of novel biomarkers for the risk stratification and progression of CVD in individuals with T2DM is of critical importance. METHODS: This retrospective cohort study encompassed 979 patients diagnosed with T2DM, of whom 116 experienced CVD events during the follow-up period. Clinical assessments and comprehensive blood laboratory analyses were conducted. Age- and sex-adjusted Cox proportional hazard regression analysis was utilized to evaluate the association between lipoprotein-associated phospholipase A2 (Lp-PLA2), C1q/tumor necrosis factor-related protein 3 (CTRP-3), and the incidence of CVD in T2DM. The diagnostic performance of these biomarkers was assessed through receiver operating characteristic (ROC) curve analysis and the computation of the area under the curve (AUC). RESULTS: Over a median follow-up of 84 months (interquartile range: 42 [32-54] months), both novel inflammatory markers, Lp-PLA2 and CTRP-3, and traditional lipid indices, such as low-density lipoprotein cholesterol and apolipoprotein B, exhibited aberrant expression in the CVD-afflicted subset of the T2DM cohort. Age- and sex-adjusted Cox regression analysis delineated that Lp-PLA2 (hazard ratio [HR] = 1.007 [95% confidence interval {CI}: 1.005-1.009], p < 0.001) and CTRP-3 (HR = 0.943 [95% CI: 0.935-0.954], p < 0.001) were independently associated with the manifestation of CVD in T2DM. ROC curve analysis indicated a substantial predictive capacity for Lp-PLA2 (AUC = 0.81 [95% CI: 0.77-0.85], p < 0.001) and CTRP-3 (AUC = 0.91 [95% CI: 0.89-0.93], p < 0.001) in forecasting CVD occurrence in T2DM. The combined biomarker approach yielded an AUC of 0.94 (95% CI: 0.93-0.96), p < 0.001, indicating enhanced diagnostic accuracy. CONCLUSIONS: The findings suggest that the biomarkers Lp-PLA2 and CTRP-3 are dysregulated in patients with T2DM who develop CVD and that each biomarker is independently associated with the occurrence of CVD. The combined assessment of Lp-PLA2 and CTRP-3 may significantly augment the diagnostic precision for CVD in the T2DM demographic.

A Case of 17q12 Microdeletion Syndrome in a MODY5 Type Diabetes with HNF-1ß Gene Mutation Accompanied.

Maturity Onset Diabetes of the Young (MODY) is an autosomal dominant inherited disorder prevalent among adolescents. Typically, it manifests with hyperglycemia before the age of 25. MODY5 is attributed to a mutation in the Hepatocyte Nuclear Factor-1ß (HNF-1ß) gene. A complete absence of HNF-1ß is observed in 50% of those with MODY5. The 17q12 microdeletion syndrome closely linked with MODY5. Its incidence in the general population is around 1 in 14,500 and is linked with facial deformities, diabetes, polycystic kidneys, pancreatic hypertrophy, liver anomalies, and neuropsychological impairments. The most primary clinical signs are predominantly associated with the HNF-1ß gene deletion. We chronicle the case of a male of 19 years of age diagnosed with diabetes, who, alongside persistent liver damage and polycystic kidneys, was referred from a community hospital to the Xuzhou Central Hospital. His clinical presentation included diabetes, liver dysfunction, polycystic kidneys, lipid irregularities, insulin resistance, and fatty atrophy. Subsequent genetic screening unveiled a 17q12 chromosomal deletion and an absence of the Hepatocyte Nuclear Factor-1ß (HNF-1ß) gene. Hence, for adolescent patients lacking a familial diabetes history but exhibiting symptoms like polycystic kidneys, liver damage, lipid irregularities, and fatty atrophy, a thorough assessment for the 17q12 microdeletion syndrome becomes imperative.

Follow-up study to explore the relationship between Neutrophil to lymphocyte ratio and impaired fasting glucose-using the group-based trajectory modeling.

Previous studies have indicated a link between neutrophil to lymphocyte ratio (NLR) and impaired fasting glucose (IFG), but the findings have been disputed. By conducting a real-world follow-up study, we can monitor the development of diseases and confirm the connection between NLR and IFG. A total of 1168 patients without IFG or T2DM were followed up for six years. At baseline, participants' NLR levels, fasting plasma glucose and other clinical characteristics were recorded. During the follow-up period, NLR levels and the prevalence of IFG were recorded. Ultimately, 45 individuals were lost to follow-up, leaving 1,123 participants for analysis. Using Group-Based Trajectory Modeling (GBTM), the sample was divided into three groups. The prevalence of IFG in the three groups was 12.1%, 19.4%, and 20.85%, respectively. Compared with the low-level NLR group, the hazard ratio of IFG in the moderate-level NLR group and high-level NLR group were 1.628 (1.109-2.390) and 1.575 (1.001-2.497), respectively. There was a significant interaction effect of BMI and NLR on the risk of IFG (P < 0.001). In this real-world follow-up study, we observed a positive association between NLR and the risk of IFG, with this relationship being exacerbated by obesity status.

PD-1 inhibitor combined with paclitaxel and cisplatin in the treatment of recurrent and metastatic hypopharyngeal/laryngeal squamous cell carcinoma: efficacy and survival outcomes.

Objective: This retrospective study analyzed the efficacy of PD-1 inhibitors combined with albumin-bound paclitaxel and cisplatin (TP regimen) in the treatment of recurrent and metastatic hypopharyngeal/laryngeal squamous cell carcinoma (RMHSCC/RMLSCC). Methods: Patients diagnosed and treated at the Sun Yat-sen University Cancer Center from August 1, 2020, to August 15, 2023, with histologically confirmed RMHSCC/RMLSCC were included. All patients received PD-1 inhibitors combined with albumin-bound paclitaxel (260mg/m2) and cisplatin (60mg/m2) for 3-4 cycles. The primary endpoints were overall survival (OS) and progression-free survival (PFS). Results: A total of 50 patients with RMHSCC/RMLSCC who received TP+PD-1 inhibitor therapy were included, with an objective response rate (ORR) of 56.0% (28/50). The 1-year and 2-year OS rates were 80.2% (95% CI: 69.3%-92.9%) and 68.6% (95% CI: 52.6%-89.5%), respectively, while the 1-year and 2-year PFS rates were 44.7% (95% CI: 31.9%-62.5%) and 26.0% (95% CI: 12.6%-53.4%), respectively. Treatment-related adverse events mainly included rash, myelosuppression, gastrointestinal reactions, and hypothyroidism. Conclusion: In the treatment of RMHSCC/RMLSCC with TP + PD-1 inhibitors, survival rates of patients can be improved while ensuring the safety of the treatment regimen.