Objective To gain insights into the biological characteristics of different populations of Culex tritaeniorhynchus within and around the Yellow Sea wetland from the perspective of the occurrence of resistance, we investigated the levels of resistance to deltamethrin and kdr gene mutation in the wetland and its peripheral areas. Methods Specimens were collected from Cx. tritaeniorhynchus populations at two monitoring sites in the Rare Bird National Nature Reserve and Tiaozi Ni Wetland Scenic Area, and also from two populations in Yancheng City and the Liuhe District of Nanjing, and the resistance of these mosquitoes to deltamethrin was determined using the CDC biotest bottle method. For each concentration of deltamethrin assessed, a random subset of exposed specimens was selected for amplification of the kdr gene fragment, followed by Sanger sequencing to identify and analyze resistance-associated mutations. Results The LC50 levels of deltamethrin among mosquitoes from the four populations in Luhe, Yancheng, the Rare Bird National Nature Reserve and the Tiaozi Ni Wetland Scenic Area were 2.048 5, 7.798 2, 3.473 3, and 17.695 5 mg/mL, respectively, with corresponding concentrations of deltamethrin ranging from 0.005 to 5.000,0.050 to 50.000,0.050 to 25.000 and 0.050 to 50.000 mg/mL, respectively. Furthermore, the ranges of the KT50 values were 11.76-107.43, 67.05-216.30,29.77-107.43 and 28.40-329.51 min; the 1-h knockdown rates were 34.58%-99.15%, 9.52%-43.80%, 55.09%-73.01%, and 10.09%-68.07%; and the 24-h mortality rates were 12.15%-67.52%,9.52%-79.56%,13.17%-82.21%, and 11.01%-78.99%, respectively. With respect to kdr gene mutation, we assayed a total of 63,70,59, and 57 mosquitoes for the four populations, for which we detected L1014F mutation frequencies of 14.29%, 35.00%, 20.34%, and 31.58%, respectively, with a majority of these mutations being heterozygous for resistance. In addition, five adult mosquitoes were identified has having synonymous mutations at site 1011[i. e. , AAT(asparagine)mutation to AAC(asparagine)]. Conclusions Our findings revealed the clear resistance of Cx. tritaeniorhynchus to deltamethrin in the Yancheng region of the Yellow Sea wetland, and the resistance phenotype and kdr frequency of Cx. tritaeniorhynchus in the wetland environment were comparable to those of Cx. tritaeniorhynchus in the wetland environment, thereby indicating that the resistance of different populations of Cx. tritaeniorhynchus was homogeneous under the pressure of different insecticide selection within and around the wetland. However, the underlying mechanisms need to be further studied.

The neonatal mammalian heart has a remarkable regenerative capacity, while the adult heart has difficulty to regenerate. A metabolic reprogramming from glycolysis to fatty acid oxidation occurs along with the loss of cardiomyocyte proliferative capacity shortly after birth. In this study, we sought to determine if and how metabolic reprogramming regulates cardiomyocyte proliferation. Reversing metabolic reprogramming by carnitine palmitoyltransferase 1 (CPT1) inhibition, using cardiac-specific Cpt1a and Cpt1b knockout mice promoted cardiomyocyte proliferation and improved cardiac function post-myocardial infarction. The inhibition of CPT1 is of pharmacological significance because those protective effects were replicated by etomoxir, a CPT1 inhibitor. CPT1 inhibition, by decreasing poly(ADP-ribose) polymerase 1 expression, reduced ADP-ribosylation of dual-specificity phosphatase 1 in cardiomyocytes, leading to decreased p38 MAPK phosphorylation, and stimulation of cardiomyocyte proliferation. Our present study indicates that reversing metabolic reprogramming is an effective strategy to stimulate adult cardiomyocyte proliferation. CPT1 is a potential therapeutic target for promoting heart regeneration and myocardial infarction treatment.

OBJECTIVE: To investigate the association between long-term glycemic control and cerebral infarction risk in patients with diabetes through a large-scale cohort study. METHODS: This prospective, community-based cohort study included 12,054 patients with diabetes. From 2006 to 2012, 38,272 fasting blood glucose (FBG) measurements were obtained from these participants. FBG trajectory patterns were generated using latent mixture modelling. Cox proportional hazards models were applied to assess the subsequent risk of cerebral infarction associated with different FBG trajectory patterns. RESULTS: At baseline, the mean age of the participants was 55.2 years. Four distinct FBG trajectories were identified based on FBG concentrations and their changes over the 6-year follow-up period. After a median follow-up of 6.9 years, 786 cerebral infarction events were recorded. Different trajectory patterns were associated with significantly varied outcome risks (Log-Rank P < 0.001). Compared with the low-stability group, Hazard Ratio ( HR) adjusted for potential confounders were 1.37 for the moderate-increasing group, 1.23 for the elevated-decreasing group, and 2.08 for the elevated-stable group. CONCLUSION Sustained high FBG levels were found to play a critical role in the development of ischemic stroke among patients with diabetes. Controlling FBG levels may reduce the risk of cerebral infarction.
Humans ; Cerebral Infarction/blood* ; Middle Aged ; Male ; Female ; Blood Glucose/analysis* ; Fasting/blood* ; Aged ; Prospective Studies ; Risk Factors ; Diabetes Mellitus/blood* ; Adult ; Proportional Hazards Models

Objective:To explore the diagnostic value of total bilirubin to albumin ratio(B/A ratio)combined with alpha-fetoprotein(AFP)and abnormal prothrombin induced by vitamin K absence-Ⅱ(PIVKA-Ⅱ)for hepatocellular carcinoma(HCC).Methods:35 HCC patients(HCC group),35 cirrhosis patients(cirrhosis group),35 HCC patients post-transcatheter arterial chemoembolization(TACE)(TACE postoperative group),and 35 healthy volunteers(healthy control group)were selected in our hospital from October 2023 to October 2024.The serum B/A ratio,AFP,and PIVKA-Ⅱ levles were measured and compared across the groups.The correlations between serum B/A ratio,AFP,and PIVKA-Ⅱ in the HCC group were analyzed.The B/A ratio,AFP,PIVKA-Ⅱ were compared across different clinical and pathological features in HCC patients.The serum B/A ratio,AFP,and PIVKA-Ⅱ levels were compared pre and post operation in the HCC group.The diagnostic value of B/A ratio,AFP,PIVKA-Ⅱ alone and in combination for HCC were analyzed by receiver operating characteristic(ROC)curves.Results:The serum B/A ratio,AFP,and PIVKA-Ⅱ levels in HCC group and TACE postoperative group were significantly higher than those in the cirrhosis group and healthy control group,and the HCC group was higher than that in the TACE postoperative group(P＜0.05).Pearson correlation analysis results showed that,B/A ratio in the HCC group was positively correlated with AFP(r=0.352,P=0.001),B/A ratio was positively correlated with PIVKA-Ⅱ(r=0.327,P=0.003),and AFP was positively correlated with PIVKA-Ⅱ(r=0.285,P=0.008).Higher TNM stage,larger tumor diameter,presence of vascular invasion,and lower differentiation degree of HCC patients,who had higher B/A ratio,AFP,and PIVKA-Ⅱ levels(P＜0.05).Serum B/A ratio,AFP,and PIVKA-Ⅱ levels in the HCC group post operation were significantly lower than those in pre operation(P＜0.05).ROC curve analysis results showed that,when B/A ratio,AFP,and PIVKA-Ⅱ were detected separately,the area under the curve(AUC)was 0.785,0.756,and 0.802,respectively.The AUC for joint detection was 0.925.The AUC in combination was greater than that of individual detection of each indicator.Conclusion:The combination of B/A ratio,AFP,and PIVKA-Ⅱ testing significantly improves the diagnostic efficiency for HCC,which is worthy of clinical application.

This study aims to explore the effects of Buzhong Yiqi Decoction(BYD) on the cyclic guanosine monophosphate-adenosine monophosphate synthase(cGAS)-stimulator of interferon genes(STING) signaling pathway in the mouse model of autoimmune thyroiditis(AIT) and the mechanism of BYD in alleviating the immune injury. Forty-eight NOD.H-2~(h4) mice were assigned into normal, model, low-, medium-, and high-dose BYD, and selenium yeast tablets groups(n=8). Mice of 8 weeks old were treated with 0.05% sodium iodide solution for 8 weeks for the modeling of AIT and then administrated with corresponding drugs by gavage for 8 weeks before sampling. High performance liquid chromatography was employed to measure the astragaloside Ⅳ content in BYD. Hematoxylin-eosin staining was employed to observe the pathological changes in the mouse thyroid tissue. Enzyme-linked immunosorbent assay was employed to measure the serum levels of thyroid peroxidase antibody(TPO-Ab), thyroglobulin antibody(TgAb), and interferon-γ(IFN-γ). Flow cytometry was employed to detect the distribution of T cell subsets in the spleen. The immunohistochemical method was used to detect the expression of cGAS, STING, TANK-binding kinase 1(TBK1), and interferon regulatory factor 3(IRF3). Real-time PCR and Western blot were employed to determine the mRNA and protein levels, respectively, of markers related to the cGAS-STING signaling pathway in the thyroid tissue. The results showed that the content of astragaloside Ⅳ in BYD was(7.06±0.08) mg·mL~(-1). Compared with the normal group, the model group showed disrupted structures of thyroid follicular epithelial cells, massive infiltration of lymphocytes, and elevated levels of TgAb and TPO-Ab. Compared with the model group, the four treatment groups showed intact epithelial cells, reduced lymphocyte infiltration, and lowered levels of TgAb and TPO-Ab. Compared with the normal group, the model group showed increases in the proportions of Th1 and Th17 cells, a decrease in the proportion of Th2 cells, and an increase in the IFN-γ level. Compared with the model group, the four treatment groups presented decreased proportions of Th1 and Th17 cells and lowered levels of IFN-γ, and the medium-dose BYD group showed an increase in the proportion of Th2 cells. Compared with the normal group, the modeling up-regulated the mRNA levels of cGAS, STING, TBK1, and IRF3 and the protein levels of cGAS, p-STING, p-TBK1, and p-IRF3. Compared with the model group, the four treatment groups showed reduced levels of cGAS, STING, TBK1, and IRF3-positive products, down-regulated mRNA levels of cGAS, STING, and TBK1, and down-regulated protein levels of cGAS and p-STING. The high-dose BYD group showed down-regulations in the mRNA level of IRF3 and the protein levels of p-TBK1 and p-IRF3. The above results indicate that BYD can repair the imbalance of T cell subsets, alleviate immune injury, and reduce thyroid lymphocyte infiltration in AIT mice by inhibiting the cGAS-STING signaling pathway.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Signal Transduction/drug effects* ; Thyroiditis, Autoimmune/metabolism* ; Mice ; Membrane Proteins/metabolism* ; Mice, Inbred NOD ; Humans ; Female ; Nucleotidyltransferases/metabolism* ; Male ; Disease Models, Animal

The aim of this study was to investigate the trend in testicular volume changes after orchiopexy in children with cryptorchidism. The clinical data of 854 children with cryptorchidism who underwent orchiopexy between January 2013 and December 2016 in Shenzhen Children's Hospital (Shenzhen, China) were retrospectively analyzed. The mean (standard deviation) age of the patients was 2.8 (2.5) years, and the duration of follow-up ranged from 1 year to 5 years. Ultrasonography was conducted preoperatively and postoperatively. The variables analyzed included age at the time of surgery, type of surgical procedure, laterality, preoperative testicular position, preoperative and postoperative testicular volumes, and the testicular volume ratio of them. The average testicular volumes preoperatively and at 1 year, 2 years, 3 years, and 5 years postoperatively were 0.27 ml, 0.38 ml, 0.53 ml, 0.87 ml, and 1.00 ml, respectively ( P < 0.001). The corresponding testicular volume ratios were 0.67, 0.76, 0.80, 0.83, and 0.84 ( P < 0.001). The mean volume of the undescended testes was significantly smaller than the mean normative value ( P < 0.001, lower than the 10 th percentile). The postoperative testicular volumes in children with cryptorchidism were generally lower than those in healthy boys but were still greater than the 10 th percentile and exhibited an increasing trend. The older the child is at the time of surgery, the larger the gap in volume between the affected and normal testes. Although testicular volume tends to gradually increase after orchiopexy for cryptorchidism, it could not normalizes. Earlier surgery results in affected testicular volumes closer to those of healthy boys.
Humans ; Male ; Cryptorchidism/diagnostic imaging* ; Orchiopexy ; Child, Preschool ; Testis/surgery* ; Retrospective Studies ; Organ Size ; Ultrasonography ; Infant ; Child ; Postoperative Period ; Follow-Up Studies

Objective:To explore the diagnostic value of total bilirubin to albumin ratio(B/A ratio)combined with alpha-fetoprotein(AFP)and abnormal prothrombin induced by vitamin K absence-Ⅱ(PIVKA-Ⅱ)for hepatocellular carcinoma(HCC).Methods:35 HCC patients(HCC group),35 cirrhosis patients(cirrhosis group),35 HCC patients post-transcatheter arterial chemoembolization(TACE)(TACE postoperative group),and 35 healthy volunteers(healthy control group)were selected in our hospital from October 2023 to October 2024.The serum B/A ratio,AFP,and PIVKA-Ⅱ levles were measured and compared across the groups.The correlations between serum B/A ratio,AFP,and PIVKA-Ⅱ in the HCC group were analyzed.The B/A ratio,AFP,PIVKA-Ⅱ were compared across different clinical and pathological features in HCC patients.The serum B/A ratio,AFP,and PIVKA-Ⅱ levels were compared pre and post operation in the HCC group.The diagnostic value of B/A ratio,AFP,PIVKA-Ⅱ alone and in combination for HCC were analyzed by receiver operating characteristic(ROC)curves.Results:The serum B/A ratio,AFP,and PIVKA-Ⅱ levels in HCC group and TACE postoperative group were significantly higher than those in the cirrhosis group and healthy control group,and the HCC group was higher than that in the TACE postoperative group(P＜0.05).Pearson correlation analysis results showed that,B/A ratio in the HCC group was positively correlated with AFP(r=0.352,P=0.001),B/A ratio was positively correlated with PIVKA-Ⅱ(r=0.327,P=0.003),and AFP was positively correlated with PIVKA-Ⅱ(r=0.285,P=0.008).Higher TNM stage,larger tumor diameter,presence of vascular invasion,and lower differentiation degree of HCC patients,who had higher B/A ratio,AFP,and PIVKA-Ⅱ levels(P＜0.05).Serum B/A ratio,AFP,and PIVKA-Ⅱ levels in the HCC group post operation were significantly lower than those in pre operation(P＜0.05).ROC curve analysis results showed that,when B/A ratio,AFP,and PIVKA-Ⅱ were detected separately,the area under the curve(AUC)was 0.785,0.756,and 0.802,respectively.The AUC for joint detection was 0.925.The AUC in combination was greater than that of individual detection of each indicator.Conclusion:The combination of B/A ratio,AFP,and PIVKA-Ⅱ testing significantly improves the diagnostic efficiency for HCC,which is worthy of clinical application.

Objective:To investigate the safety and efficacy of laparoscopic simultaneous bilateral adrenalectomy in treating ectopic ACTH syndrome (ACTH)caused by medullary thyroid carcinoma(MTC).Methods:A 56-year-old male patient was admitted after MTC surgery and 7 months of general fatigue. The patient had a history of two open thyroid surgeries for medullary thyroid carcinoma, with previous pathological reports indicating lymph node metastasis in the upper mediastinum and mediastinum, accompanied by weak cytoplasmic expression of ACTH and negative CRH staining. After the operation, the patient developed diabetes, hypertension, and hypokalemia. Upon admission, the patient presented with a blood pressure reading of 200/95 mmHg (1 mmHg = 0.133 kPa), a weight of 61.5 kg, a height of 160 cm, a body mass index (BMI)of 24.02 kg/cm 2, and a waist circumference of 83 cm. Laboratory tests revealed the following: blood potassium level of 2.71 mmol/L, blood calcium level of 1.47 mmol/L, parathyroid hormone level of 6.0 pg/ml, fasting blood glucose level of 10.51 mmol/L, glycated hemoglobin level of 8.2%, blood calcitonin level exceeding 2 000 pg/ml, and blood CEA level of 70.8 μg/L. The plasma ACTH levels at 8∶00, 16∶00, and 24∶00 were 189.0, 125.0, and 65.0 pg/ml, respectively. Serum cortisol levels at 08∶00, 16∶00, and 24∶00 were 429.30, 408.14, and 446.61 μg/L, respectively. The 24-hour urine free cortisol measurement was 1 200 μg, and after the midnight 1mg dexamethasone suppression test at 8∶00, the plasma ACTH level was 183.0 pg/ml, and the serum cortisol level was 538.27 μg/L. The aldosterone level in standing position after 2 hours was 8.2 pg/ml. There were no significant abnormality in catecholamine hormone detection or thyroid function in blood and urine samples. An 18F-FDG-PET/CT examination showed multiple lymph node metastases in the neck, while an abdominal CT scan revealed bilateral adrenal hyperplasia. Enhanced MRI revealed pituitary gland thinning, and lung CT and sputum culture examinations showed scattered multiple lung infections. After a multidisciplinary discussion, the patient was diagnosed with EAS, postoperative MTC metastasis, diabetes, hypertension, hypokalemia, pulmonary infection, mild anemia, liver dysfunction, hypoparathyroidism, and hypocalcemia. The patient were accepted laparoscopic bilateral adrenalectomy via an abdominal approach under general anesthesia. The left adrenal gland was removed first, followed by the right adrenal gland after repositioning. Results:The surgery was successful with a surgical duration of approximately 60 minutes and an intraoperative bleeding volume of about 20 ml. No surgical complications occurred during the perioperative period. Pathological examination confirmed nodular hyperplasia of the adrenal cortex and bilateral adrenal medullary hyperplasia with negative ACTH staining. After a 3-month postoperative follow-up, blood calcitonin levels remained above 2000 pg/ml. The blood ACTH levels at 1 week, 1 month, and 3 months after surgery were 183.0, 220.0, and 731.0 pg/ml, respectively. However, hypertension, diabetes, and hypokalemia rapidly improved. One month after surgery, blood pressure was 100/80 mmHg, fasting blood glucose was 4.4 mmol/L, and blood potassium was 3.87 mmol/L. Pulmonary infection showed improvement, and no adrenal crisis occurred. Glucocorticoid replacement therapy consisted of 20 mg of hydrocortisone tablets in the morning and 10 mg in the afternoon, and thyroid hormone replacement therapy involved daily administration of 100 μg of levothyroxine. Genetic testing revealed heterozygous mutations in the Ret gene. The patient is currently undergoing clinical trial treatment with Ret inhibitors.Conclusions:Based on the data from this case and existing literature reports, laparoscopic simultaneous bilateral adrenalectomy might be safe and effective treatment option for EAS caused by unresectable MTC metastasis. It can correct hypertension, diabetes, and hypokalemia and increase the opportunity for MTC treatment.

Objective To investigate the clinical effect of modified suspension reduction method combined with percuta-neous vertebroplasty in the treatment of osteoporotic thoracolumbar compression fractures.Methods From February 2020 to October 2021,92 patients with thoracolumbar osteoporotic compression fracture were treated by percutaneous vertebroplasty.According to different treatment methods,they were divided into the observation group and the control group.The observation group was treated with modified suspension reduction and then percutaneous vertebroplasty,while the control group was treated with percutaneous vertebroplasty alone.The observation group(47 cases),including 20 males and 27 females,the age ranged from 59 to 76 years old with an average of(69.74±4.50)years old,fractured vertebral bodies:T10(2 cases),T11(7 cases),T12(19 cases),L1(14 cases),L2(5 cases);the control group(45 cases),including 21 males and 24 females,the age ranged from 61 to 78 years old with an average of(71.02±3.58)years old,fractured vertebral bodies:T10(3 cases),T11(8 cases),T12(17 cas-es),L1(12 cases),L2(5 cases);The leakage of bone cement were observed,the visual analogue scale(VAS),Oswestry lumbar dysfunction index(ODI),anterior vertebrae height(AVH),Cobb angle of kyphosis and the amount of bone cement injected before and after operation were recorded and compared between the two groups.Results All patients were followed up,ranged from 6 to1O with an average of(8.45±1.73)months.Two patients ocurred bone cement leakage in observation group and 3 pa-tients in control group.AVH of observation group increased(P＜0.05)and Cobb angle of injured vertebrae decreased(P＜0.05).Cobb angle of injured vertebrae and AVH of the control group were not significantly changed(P＞0.05).Cobb angle of injured vertebrae of the observation group was lower than that of control group(P＜0.05)and AVH was higher than that of the control group(P＜0.05).In the observation group,VAS before operation and 1 week,3 and 6 months after operation respective-ly were(7.32±1.05)scores,(3.56±1.18)scores,(1.83±0.67)scores,(1.27±0.34)scores,and ODI were(40.12±14.69)scores,(23.76±10.19)scores,(20.15±6.39)scores,(13.45±3.46)scores.In the control group,VAS before operation and 1 week,3 and 6 months after operation respectively were(7.11±5.26)scores,(3.82±0.68)scores,(1.94±0.88)scores,(1.36± 0.52)scores,and ODI were(41.38±10.23)scores,(25.13±14.22)scores,(20.61±5.82)scores,(14.55±5.27)scores.The scores of VAS and ODI after operation were lower than those before operation(P＜0.05),but there was no significant difference between the two groups(P＜0.05).Conclusion Modified suspension reduction method combined with PVP surgery for osteo-porotic thoracolumbar compression fractures has achieved good clinical results,which can effectively relieve lumbar back pain,restore vertebral height,correct kyphosis,improve lumbar function and patients'quality of life.

Objective To investigate the preliminary clinical effect of closed reduction and cannulated nail internal fixa-tion for femoral neck fracture assisted by robot navigation and positioning system.Methods From July 2019 to January 2020,16 cases of femoral neck fracture(navigation group)were treated with closed reduction and internal fixation guided by robot system,including 7 males and 9 females,aged 25 to 72 years old with an average of(53.61±5.45)years old;Garden classification of fracture:3 cases of type Ⅰ,3 cases of type Ⅱ,8 cases of type Ⅲ,2 cases of type Ⅳ.Non navigation group(control group):20 cases of femoral neck fracture were treated with closed reduction and hollow nail internal fixation,8 males and 12 females,aged 46 to 70 years old with an average of(55.23±4.64)years old;Garden type Ⅰ in 2 cases,type Ⅱ in 4 cases,type Ⅲ in 11 cases,type Ⅳ in 3 cases.The operation time,fluoroscopy times,guide needle drilling times,screw adjustment times,intraoperative bleeding volume and other indicators of two groups were evaluated.Results Both groups were followed up for 12 to 18 months with an average of(15.6±2.8)months.The fractures of both groups were healed without delayed union and nonunion.There was no significant difference in healing time between two groups(P=0.782).There was no significant differ-ence in Harris scores between two groups at the last follow-up(P=0.813).There was no significant difference in operation time between two groups(P＞0.05).There were significant differences between two groups in fluoroscopy times,guide needle drilling times,hollow screw replacement times,and intraoperative bleeding volume(P＜0.05).Conclusion Closed reduction and hollow screw internal fixation assisted by robot navigation system for femoral neck fracture has the advantages of minimally invasive operation,precise screw placement,and reduction of X-ray radiation damage during operation.