Objective: To investigate the trends in incidence and mortality of thyroid cancer in cancer registration areas of Zhengzhou City, Henan Province from 2016 to 2021, so as to provide evidence for developing targeted thyroid cancer prevention and treatment strategies. Methods: Data on incidence and mortality of thyroid cancer with qualified registration quality were collected from cancer registration offices in Zhengzhou City. Crude incidence and crude mortality were calculated. The Chinese population-standardized incidence and world population-standardized incidence were calculated using the standard age structure from the Fifth National Population Census in 2 000 and Segi's world standard population structure, respectively. The average annual percentage change (AAPC) was used to analyze the trends in the incidence and mortality of thyroid cancer in Zhengzhou City from 2016 to 2021 across different gender, age, and urban-rural area. Results: In 2021, the crude incidence, Chinese population-standardized incidence and world population-standardized incidence of thyroid cancer in Zhengzhou City were 42.55/105, 37.43/105, and 32.56/105, respectively. The crude mortality, Chinese population-standardized mortality and world population-standardized mortality were 1.07/105, 0.77/105, and 0.71/105, respectively. The Chinese population-standardized incidence and mortality in females were 2.64 times and 2.83 times those in males, respectively; those in urban areas were 2.25 times and 1.51 times those in rural areas, respectively. The crude incidence peaked in the group aged 55-<60 years at 92.52/105. From 2016 to 2021, the crude incidence and Chinese population-standardized incidence of thyroid cancer showed an upward trend (AAPC=21.797%, 22.725%, both P<0.05), with trends consistent across different genders and urban-rural areas with the total population. The crude incidence showed upward trends in the groups aged 20-<30 years, 30-<40 years, 40-<50 years, 50-<60 years, and 60-<70 years (AAPC=17.237%, 31.026%, 21.289%, 23.010%, and 11.752%, all P<0.05). From 2016 to 2021, the Chinese population-standardized mortality of thyroid cancer showed an upward trend (AAPC=15.196%, P<0.05), while the trend in crude mortality was not statistically significant (P>0.05). The crude mortality (AAPC=21.078%, 25.669%) and Chinese population-standardized mortality (AAPC=24.122%, 28.865%) in females and rural areas showed upward trends (all P<0.05). Conclusions From 2016 to 2021, the Chinese population-standardized incidence and mortality of thyroid cancer in cancer registration areas of Zhengzhou City showed an upward trend. Females, urban residents, and middle-aged and young populations are key groups for thyroid cancer prevention and control.

OBJECTIVE: To explore the correlation between albumin (Alb) combined with diuretic treatment and the mortality risk of septic patients with pre-existing congestive heart failure based on the United States Critical Care Medical Information Database-IV (MIMIC-IV), and to conduct the external validation. METHODS: A retrospective cohort study was conducted. The clinical data of septic patients with pre-existing congestive heart failure admitted to the intensive care unit (ICU) from 2008 to 2019 in the MIMIC-IV 2.0 were extracted, including demographic characteristics, comorbidities, laboratory indicators on the first day of ICU admission, severity of illness, treatment measures, etc. For external validation, clinical data were collected from septic patients with pre-existing congestive heart failure admitted to the ICU of the Second People's Hospital of Shenzhen from October 2022 to December 2023. The patients were divided into Alb alone group and Alb combined with diuretic group. The ICU mortality was defined as the primary outcome event, and the 30-day and 60-day mortality were defined as the secondary outcomes. Multivariate Cox proportional hazard regression analysis was conducted to investigate the relationship between Alb combined with diuretic treatment and the mortality risk of ICU and 30 days in septic patients with pre-existing congestive heart failure, and subgroup analysis was performed. Kaplan-Meier survival curve was plotted to compared the 60-day cumulative survival rate between the Alb alone group and Alb combined with diuretic group. RESULTS: (1) Analysis results of data from MIMIC-IV: a total 1 754 patients were enrolled, of which 378 in the Alb alone group, and 1 376 in the Alb combined with diuretic group. Compared with the Alb alone group, the patients in the Alb combined with diuretic group had significantly lower ICU, 30-day, and 60-day mortality [ICU mortality: 19.11% (263/1 376) vs. 30.42% (115/378), 30-day mortality: 18.90% (260/1 376) vs. 32.54% (123/378), 60-day mortality: 24.49% (337/1 376) vs. 39.15% (148/378), all P < 0.05]. Based on the multivariate Cox proportional hazard regression adjusted models considering demographic characteristics, comorbidities, laboratory indicators, severity of illness, and treatment measures, it was shown that the use of Alb combined with diuretic was significantly associated with a reduced risk death of ICU and 30 days [ICU mortality risk: hazard ratio (HR) = 0.597, 95% confidence interval (95%CI) was 0.460-0.774, P < 0.001; 30-day mortality risk: HR = 0.557, 95%CI was 0.433-0.716, P < 0.001]. Subgroup analysis revealed that after adjusting for variables, regardless of gender, age, and whether or not patients had comorbidities such as hypertension, diabetes, severe liver disease, acute renal insufficiency, and sequential organ failure assessment (SOFA) score, the ICU mortality risk was significantly reduced in patients treated with Alb combined with diuretic (all HR < 1, P < 0.05), with no interaction observed (all P > 0.05). Kaplan-Meier survival curve showed the 60-day cumulative survival rate of patients in the Alb combined with diuretic group was significantly higher than that in the Alb alone group (Log-rank test: χ ² = 49.62, P < 0.05). (2) External validation: a total of 385 patients were enrolled, of which 144 in the Alb alone group, and 241 in the Alb combined with diuretic group. Compared with the Alb alone group, the patients of the Alb combined with diuretic group had significantly lower ICU, 30-day, and 60-day mortality [ICU mortality: 19.92% (48/241) vs. 31.25% (45/144), 30-day mortality: 19.09% (46/241) vs. 28.47% (41/144), 60-day mortality: 24.07% (58/241) vs. 34.03% (49/144), all P < 0.05]. The results of multivariate Cox proportional hazard regression analysis, subgroup analysis, and Kaplan-Meier survival curve analysis were consistent with the data analysis of the MIMIC-IV database. CONCLUSIONS Combination therapy of Alb and diuretic was associated with reduced mortality risk in septic patients with pre-existing congestive heart failure.
Humans ; Heart Failure/mortality* ; Retrospective Studies ; Sepsis/drug therapy* ; Intensive Care Units ; Diuretics/therapeutic use* ; Male ; Female ; Aged ; Middle Aged ; Proportional Hazards Models ; Hospital Mortality

Objective To explore the magnetic resonance(MR)imaging characteristics of joint damage caused by Chikungunya virus(CHIKV)and its correlation with pain severity,and analyze the value of T2-Mapping in asse-ssing the severity and prognosis of such damage.Methods A multicenter retrospective study design was adopted,and patients with CHIKV infection accompanied by joint pain were included in analysis.Multi-joint MR scans were performed to assess joint effusion,synovial thickening,bone marrow edema,and cartilage damage.T2-Mapping values were measured.Pain severity was assessed using the Visual Analog Scale(VAS),and imaging findings were independently assessed by two radiologists.Results A total of 131 patients were included in the study.The inci-dence of joint cavity and/or synovial sac effusion was the highest(77.1％,n=101),with knee and ankle joint effu-sion accounting for 81.2％(severe,mild-moderate were 17 and 65 cases,respectively),other joint effusion were mild.78 cases had synovial thickening(14 and 64 were severe and mild-moderate cases,respectively),27 cases had tenosynovitis,21 cases had bone marrow edema(primarily in the knee and ankle joints).19 cases had cartilage damage,114 cases presented muscle soft tissue edema(17 and 97 were severe and mild-moderate cases,respective-ly),28 cases had Kager's fat pad edema.Patients with elevated T2-Mapping values exhibited more pronounced chronic joint pain,with T2-Mapping values in the cartilage damage site increasing by 40％-60％compared with normal cartilage site(19 cases in total).The T2-Mapping value for severely damaged soft tissue was(52.3+6.7)ms,while for mildly to moderately damaged soft tissue was(42.3±5.2)ms,both significantly higher than normal refe-rence values(＜35 ms,both P＜0.05).Among 17 patients with severe soft tissue damage,12 experienced persistent pain for over one month,with statistically significant differences in T2 values compared with those with mild-mode-rate damage(P＜0.05).This further suggested that the degree of elevation in T2-Mapping values was closely related to the duration of pain and the severity of damage.After one-month follow-up,103 patients had pain relief.Among the 28 patients with ongoing pain,17 developed into subacute bone joint pain.Bone marrow edema(81.0％),ele-vation of T2-Mapping value of cartilage(89.5％),and severe synovial thickening(71.4％)were high-risk MR manifestations of subacute bone joint pain.The incidences of subacute joint cavity/sac effusion and subacute tenosy-novitis were 3.0％and 7.4％,respectively.Conclusion MR can clearly display the inflammatory and structural changes in CHIKV joint damage,and T2-Mapping values may serve as a potential imaging measurement parameter for assessing severity and prognosis of damage.

Objective To explore the magnetic resonance(MR)imaging characteristics of joint damage caused by Chikungunya virus(CHIKV)and its correlation with pain severity,and analyze the value of T2-Mapping in asse-ssing the severity and prognosis of such damage.Methods A multicenter retrospective study design was adopted,and patients with CHIKV infection accompanied by joint pain were included in analysis.Multi-joint MR scans were performed to assess joint effusion,synovial thickening,bone marrow edema,and cartilage damage.T2-Mapping values were measured.Pain severity was assessed using the Visual Analog Scale(VAS),and imaging findings were independently assessed by two radiologists.Results A total of 131 patients were included in the study.The inci-dence of joint cavity and/or synovial sac effusion was the highest(77.1％,n=101),with knee and ankle joint effu-sion accounting for 81.2％(severe,mild-moderate were 17 and 65 cases,respectively),other joint effusion were mild.78 cases had synovial thickening(14 and 64 were severe and mild-moderate cases,respectively),27 cases had tenosynovitis,21 cases had bone marrow edema(primarily in the knee and ankle joints).19 cases had cartilage damage,114 cases presented muscle soft tissue edema(17 and 97 were severe and mild-moderate cases,respective-ly),28 cases had Kager's fat pad edema.Patients with elevated T2-Mapping values exhibited more pronounced chronic joint pain,with T2-Mapping values in the cartilage damage site increasing by 40％-60％compared with normal cartilage site(19 cases in total).The T2-Mapping value for severely damaged soft tissue was(52.3+6.7)ms,while for mildly to moderately damaged soft tissue was(42.3±5.2)ms,both significantly higher than normal refe-rence values(＜35 ms,both P＜0.05).Among 17 patients with severe soft tissue damage,12 experienced persistent pain for over one month,with statistically significant differences in T2 values compared with those with mild-mode-rate damage(P＜0.05).This further suggested that the degree of elevation in T2-Mapping values was closely related to the duration of pain and the severity of damage.After one-month follow-up,103 patients had pain relief.Among the 28 patients with ongoing pain,17 developed into subacute bone joint pain.Bone marrow edema(81.0％),ele-vation of T2-Mapping value of cartilage(89.5％),and severe synovial thickening(71.4％)were high-risk MR manifestations of subacute bone joint pain.The incidences of subacute joint cavity/sac effusion and subacute tenosy-novitis were 3.0％and 7.4％,respectively.Conclusion MR can clearly display the inflammatory and structural changes in CHIKV joint damage,and T2-Mapping values may serve as a potential imaging measurement parameter for assessing severity and prognosis of damage.

Objective To compare the efficacy and safety of vedolizumab(VDZ)and infliximab(IFX)for moderate to severe ulcerative colitis(UC)patients through a multicenter retrospective cohort study.Methods All patients with moderate to severe UC who were naive to biologic agents and treated with IFX or VDZ for at least 14 weeks at 3 hospitals in Southwest China between January 2021 and January 2023 were retrospectively enrolled.The efficacy evaluation indicators,including steroid-free clinical remission rates,clinical remission rates and endoscopic remission rates at weeks 14 and 52 were compared between the 2 groups.The occurrence of adverse events during treatment were recorded.Taking whether mucosal healing could be achieved after 14 and 52 weeks of treatment as the dependent variable,firstly,univariate analysis was performed to analyze the risk factors affecting mucosal healing at weeks 14 and 52,and then multivariate logistic regression analysis was applied to identify the independent risk factors of mucosal healing at the 2 time points.Results A total of 151 patients with moderate to severe UC were included,after propensity score matching(PSM),each group included 57 patients.There were no significant differences in the steroid-free clinical remission rate and clinical remission rate between the 2 groups at weeks 14 and 52(P＞0.05).The endoscopic remission rate at week 14 was significantly higher in the VDZ group than the IFX group[40.4％(23/57)vs 22.8％(13/57),P=0.044],but no such difference was observed at week 52[64.5％(20/31)vs 59.5％(22/37),P=0.669].Multivariate logistic regression analysis showed that left-sided disease(E2)[vs pancolitis(E3)](OR=0.46,95％CI:0.21～0.98,P=0.045)was independent risk factor for mucosal healing at week 14 and a disease duration ≥36 months(OR=0.25,95％CI:0.09～0.66,P=0.005)was independent risk factor for mucosal healing at week 52.No statistical difference was observed in the incidence of adverse events between the 2 groups(1.8％vs 7.0％,P=0.360).Conclusion VDZ and IFX have similar efficacy and safety,and both can be used as first-line options for patients with moderate to severe UC.

AIM:This study aimed to observe the analgesic effects of Hegu acupoint catgut embedding in a rat model of labor and investigate its influence on biomarkers such as calcitonin gene-related peptide(CGRP)signals at the Hegu acupoint.METHODS:Thirty-six pregnant rats were randomly divided into three groups:control group,Hegu acu-puncture group,and Hegu catgut embedding group.Pain threshold changes were assessed using the tail immersion test and paw withdrawal thermal latency at four time points:pre-induction,before the onset of labor,at the onset of labor,and at the mid-stage of labor.Tissue samples from the Hegu acupoint were collected at the mid-stage of labor to detect the ex-pression of CGRP,substance P(SP),and mast cells using immunofluorescence.The concentrations of ATP and ade-nosine were measured using ELISA.RESULTS:Before labor induction,there was no significant difference in tail immer-sion test and paw withdrawal thermal latency among the three groups(P>0.05).Before the onset of labor,both the acu-puncture and catgut embedding groups exhibited significantly higher tail-flick times and paw withdrawal latencies com-pared to the control group(P<0.05).At labor initiation and mid-labor,the catgut embedding group had significantly higher tail-flick times and paw withdrawal latencies compared to both the control and acupuncture groups(P<0.05).During mid-labor,the expression of CGRP,SP,mast cells,ATP,and adenosine concentrations in the catgut embedding group was significantly higher than that in the control and acupuncture groups(P<0.05),with co-expression of CGRP,SP,and mast cells observed.CONCLUSION:Hegu acupoint catgut embedding effectively alleviates labor pain,and its mechanism may involve increased local expression of CGRP and SP,promoting mast cell degranulation,and increasing ATP release and its conversion to adenosine.

Objective Screening for sensitive biomarkers for predicting and analyzing drug-induced renal toxicity,accelerates drug early development.Methods Focuses on epithelial cells of proximal convoluted tubules in human renal cortex(human kidney-2,HK-2)cells as the research object,screening for highly sensitive biomarkers using three nephrotoxic drugs(cisplatin,gentamicin,and aristolochic acid Ⅰ).Results The sensitivity of biomarkers in intracellular fluid is higher than in extracellular fluid,compared to detecting a single biomarker in the intracellular fluid.The combined detection of β2-microglobulin(β2-MG)and neutrophil gelatinase-associated lipocalin(NGAL)improved the accuracy of renal toxicity evaluation.Conclusion Based on the HK-2 cell model,the combined detection of β2-MG and NGAL in intracellular fluid can be used to predict renal toxicity in the drug's early development stage.

Objective: To investigate the current status and real performance of the detection of RUNX1-RUNX1T1 fusion transcript levels and WT1 transcript levels in China through interlaboratory comparison. Methods: Peking University People’s Hospital (PKUPH) prepared the samples for comparison. That is, the fresh RUNX1-RUNX1T1 positive (+) bone morrow nucleated cells were serially diluted with RUNX1-RUNX1T1 negative (-) nucleated cells from different patients. Totally 23 sets with 14 different samples per set were prepared. TRIzol reagent was added in each tube and thoroughly mixed with cells for homogenization. Each laboratory simultaneously tested RUNX1-RUNX1T1 and WT1 transcript levels of one set of samples by real-time quantitative PCR method. All transcript levels were reported as the percentage of RUNX1-RUNX1T1 or WT1 transcript copies/ABL copies. Spearman correlation coefficient between the reported transcript levels of each participated laboratory and those of PKUPH was calculated. Results: ①RUNX1-RUNX1T1 comparison: 9 samples were (+) and 5 were (-) , the false negative and positive rates of the 20 participated laboratories were 0 (0/180) and 5% (5/100) , respectively. The reported transcript levels of all 9 positive samples were different among laboratories. The median reported transcript levels of 9 positive samples were from 0.060% to 176.7%, which covered 3.5-log. The ratios of each sample’s highest to the lowest reported transcript levels were from 5.5 to 12.3 (one result which obviously deviated from other laboratories’ results was not included) , 85% (17/20) of the laboratories had correlation coefficient ≥0.98. ②WT1 comparison: The median reported transcript levels of all 14 samples were from 0.17% to 67.6%, which covered 2.6-log. The ratios of each sample’s highest to the lowest reported transcript levels were from 5.3-13.7, 62% (13/21) of the laboratories had correlation coefficient ≥0.98. ③ The relative relationship of the reported RUNX1-RUNX1T1 transcript levels between the participants and PKUPH was not always consistent with that of WT1 transcript levels. Both RUNX1-RUNX1T1 and WT1 transcript levels from 2 and 7 laboratories were individually lower than and higher than those of PKUPH, whereas for the rest 11 laboratories, one transcript level was higher than and the other was lower than that of PKUPH. Conclusion The reported RUNX1-RUNX1T1 and WT1 transcript levels were different among laboratories for the same sample. Most of the participated laboratories reported highly consistent result with that of PKUPH. The relationship between laboratories of the different transcript levels may not be the same.

With the rapid development and wide application of traditional Chinese medicine injection (TCMI), a number of adverse events of some TCMIs have incessantly been reported and have drawn broad attention in recent years. Establishing effective and practical analytical methods for safety evaluation and quality control of TCMI can help to improve the safety of TCMIs in clinical applications. In this study, a sensitive and rapid high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method has been developed and validated for the quantitative determination of potentially harmful substance 5,5'-oxydimethylenebis (2-furfural, OMBF) in TCMI samples. Chromatographic separation was performed on a C18 reversed-phase column (150 mm × 2.1 mm, 5 µm) by gradient elution, using methanol-water containing 0.1% formic acid as mobile phase at the flow rate of 0.3 mL/min. MS/MS detection was performed on a triple quadrupole mass spectrometer with positive electrospray ionization in the multiple reaction-monitoring mode. The method was sensitive with a limit of quantification of 0.3 ng/mL and linear over the range of 0.3-30 ng/mL (=0.9998). Intra- and inter-day precision for analyte was <9.52% RSD with recoveries in the range 88.0-109.67% at three concentration levels. The validated method was successfully applied to quantitatively determine the compound OMBF in TCMIs and glucose injections. Our study indicates that this method is simple, sensitive, practicable and reliable, and could be applied for safety evaluation and quality control of TCMIs and glucose injections.

Objective: To evaluate the efficacy and safety of ivabradine for the treatment of Chinese patients with chronic heart failure based on the Chinese subgroup data of the systolic heart failure treatment with the I_f inhibitor ivabradine trial (SHIFT). Method: A total of 6 558 stable outpatients who presented symptoms of heart failure, with a left ventricular ejection fraction (LVEF) ≤35%, sinus rhythms with a heart rate ≥70 bpm participated in the randomized, double-blind, placebo-controlled, international multicenter clinical study.The subset of Chinese patients with heart rate ≥75 bpm was enrolled in the post-hoc subgroup analyses.Patients were randomly allocated by computer-generated assignment through a telephone interactive voice response system to ivabradine group (starting dose 5 mg bid, which was then uptitrated to the maximum 7.5 mg bid) or matched placebo group.The clinical baseline characteristics of participants were obtained and analyzed.The primary outcome endpoint was a composite endpoint of cardiovascular death or hospitalization resulting from worsening HF.The primary safety endpoint included total incidence of adverse events during the study, bradycardia, and adverse visual reaction (phosphenes). Results: A total of 49 Chinese centers enrolled a total of 225 patients with chronic heart failure, of whom, 106 patients were randomized to the ivabradine group and the other 119 patients to the placebo group, and the mean follow-up time was (15.6±5.1) months.By the end of the study, mean heart rate (71.0 bpm vs. 80.3 bpm, P<0.05) and incidence of the primary endpoint events (18.9% (20/106) vs. 31.9%(38/119), HR=0.56, 95%CI 0.33-0.97, P=0.039) were significantly lower, while the percentage of patients with improvement in heart functional class NYHA (53.8% (56/106) vs. 34.5% (41/119), P=0.006 1) was significantly higher in the ivabradine group than in the placebo group.The total number of adverse events (129 events, 49.6% PY) in the ivabradine group was lower than that in the placebo group (203 events, 50.8% PY). In the ivabradine group and the placebo group, there were respectively 2 patients (1.9%) and 0 patients experienced bradycardia, 3 patients (2.9%) and 1 patient (0.8%) experienced adverse visual reaction (phosphenes). Conclusions: Ivabradine significantly reduced heart rate and improved the clinical outcomes and NYHA function class in Chinese patients with chronic heart failure, these beneficial effects are achieved without inducing remarkable adverse reactions.The results of Chinese subgroup analysis were thus consistent with the overall results of the SHIFT study. Clinical Trial Registry International standard randomized controlled trials registry, ISRCTN 70429960.