Background Di(2-ethylhexyl) phthalate (DEHP) is the most prevalent environmental endocrine disruptor among phthalate acid esters (PAEs) worldwide. Previous studies have indicated that exposure to DEHP may disrupt glucose metabolism. Objective To investigate the impact of DEHP on glucose homeostasis in rats, focusing on oxidative stress-induced impairment of autophagy in islet β cells. Methods Forty male SD rats were randomly assigned to four groups, receiving DEHP doses of 0, 187, 375, and 750 mg·kg⁻¹ for 12 weeks. Oral glucose tolerance (OGTT) and insulin tolerance tests (ITT) were conducted 24 h after the final exposure. Pancreatic microstructural alterations were assessed using hematoxylin and eosin (HE) staining and transmission electron microscopy (TEM). Commercial ELISA kits were employed to quantify the levels of insulin, adenosine triphosphate (ATP), and adenosine monophosphate (AMP) in rat serum, as well as the protein expression level of activated caspase-3 in pancreatic tissue. Additionally, commercial microplate kits were utilized to measure the concentration of reduced glutathione (GSH) in serum, the activity of superoxide dismutase (SOD) using water-soluble tetrazolium salt-1, the content of malondialdehyde (MDA) by thiobarbituric acid method, and the level of reactive oxygen species (ROS) in pancreatic tissue by chemical fluorescence method. Reverse transcription polymerase chain reaction (RT-PCR) was used to measure sequestosome1 (SQSTM1/p62), Beclin1, microtubule-associated protein 1 light chain 3 (LC3), and cysteinyl aspartate specific proteinase-8 (Caspase-8) mRNA levels. Western blot analysis was applied to detect the protein relative expression levels of p62, Beclin-1, LC3-I, LC3 II, AMPK, p-AMPK, mTOR, p-mTOR, ULK1, and Caspase-8. Results Compared to the 0 mg·kg⁻¹ DEHP group, the 750 mg·kg⁻¹ DEHP group exhibited a significant increase in fasting blood glucose levels at 2, 4, 6, and 12 weeks (P<0.05). The OGTT showed that, following high-glucose gavage, the 187 mg·kg⁻¹ DEHP group had elevated blood glucose at 30 min (P<0.05), the 375 mg·kg⁻¹ DEHP group showed increased glucose levels at 15, 30, and 180 min (P<0.05), and the 750 mg·kg⁻¹ DEHP group exhibited elevated levels at 15, 30, 60, and 180 min (P<0.05). The 375 and 750 mg·kg⁻¹ DEHP groups demonstrated significantly increased OGTT area under the curve (AUC) values (P<0.05). In contrast, ITT results indicated no significant differences in blood glucose levels or AUC among the DEHP exposure groups at all time points (P>0.05). Compared to the 0 mg·kg⁻¹ DEHP group, the 750 mg·kg⁻¹ DEHP group exhibited significantly higher HOMA-IR levels and markedly lower HOMA-ISI values (P<0.05). HE and TEM showed that in each DEHP exposure group, the number of islet cells decreased, the islet area reduced, and chromatin condensation occurred. The endocrine granules in the cytoplasm of islet β cells decreased, and there were varying degrees of widening of the nuclear membrane gap, flattening and expansion of the Golgi complex, and expansion of the endoplasmic reticulum. Ribosome separation was observed, and autophagosomes were visible. In the 375 and 750 mg·kg⁻¹ DEHP groups, the mitochondria were deformed to varying degrees, and some cristae structures disappeared, presenting vacuolization. Moreover, the chromatin condensation in the nuclei was more severe in the 750 mg·kg⁻¹ DEHP group. The serum SOD activity was significantly elevated in the 750 mg·kg⁻¹ DEHP group (P<0.05). Both the 375 mg·kg⁻¹ and 750 mg·kg⁻¹ DEHP groups exhibited a significant increase in the relative ROS content in pancreatic tissue (P<0.05). In DEHP-treated groups, the MDA content increased (P<0.05), while the GSH content decreased (P<0.05). Additionally, in the 750 mg·kg⁻¹ DEHP group, the AMP/ATP ratio in serum was significantly raised (P<0.05), and the expression of cleaved Caspase-3 protein in pancreatic tissue was also significantly increased (P<0.05). The relative mRNA levels of p62, Beclin-1, LC3, and Caspase-8 in the pancreatic tissue of rats exposed to DEHP were significantly elevated (P<0.05). The relative expression levels of p-AMPK/AMPK, p-ULK1/ULK1, and Beclin-1 proteins in the DEHP-treated groups were significantly increased (P<0.05). In the 375 mg·kg⁻¹ and 750 mg·kg⁻¹ DEHP treatment groups, the relative expression levels of p62, LC3 II/LC1, and Caspase-8 proteins were significantly increased (P<0.05), while the relative expression level of p-mTOR/mTOR was significantly decreased (P<0.05). Conclusion DEHP can disrupt glucose homeostasis by inducing oxidative stress, which subsequently activates autophagy via the ROS/AMPK/ULK1 pathway, impairing autophagic flux and promoting apoptosis of islet β cells, ultimately decreasing their function and number.

Objective:To explore the genetic etiology of a child featuring multiple fractures and congenital insensitivity to pain (CIP).Methods:A child who had presented at the West China Hospital of Sichuan University on March 16, 2023 for recurrent fractures and CIP was selected as the study subject. Peripheral blood samples of the child and his parents was collected. Trio-whole exome sequencing was carried out. Candidate variants were verified by Sanger sequencing and bioinformatic analysis. This study has been approved by the Medical Ethics Committee of West China Hospital of Sichuan University (No. 2019-772).Results:Trio-whole exome sequencing revealed that the child has harbored compound heterozygous variants of the SCN9A gene, namely c. 560delC (p.P187Rfs*15) and c. 829C>T (p.R277*), which were respectively inherited from his father and mother. Homozygous c. 829C>T variant had been demonstrated as pathogenic among CIP patients, whilst the c. 560delC (p.P187Rfs*15) variant was unreported previously and predicted to be pathogenic based on the guidelines of the American College of Medical Genetics and Genomics (ACMG). Conclusion:The child was diagnosed with CIP due to the compound heterozygous variants of the SCN9A gene. Above finding has enabled genetic counselling and reproductive guidance for this family.

Objective:Preliminary explore the safety and efficacy of using only vitamin K antagonists without antiplatelet therapy after left ventricular assist devices (LVAD) implantation.Methods:This is a cohort study. Patients who underwent HeartCon LVAD implantation in TEDA International Cardiovascular Hospital from September 2020 to September 2022 were included. Oral warfarin sodium was given on postoperative days 1 to 2, with the target international standardized ratio (INR) of 2.0 to 2.5. Follow-up until September 2022, survival, INR level and occurrence of bleeding and thrombosis were recorded. Survival analysis was performed by the Kaplan-Meier method (censored for heart transplantation).Results:A total of 22 patients, including 16 male patients (72.7%), aged (51.0±13.3) years, were included. The duration of HeartCon LVAD support was (458±166) days and the INR during support was 2.28±0.26. One patient underwent the heart transplant at 307 d after implantation. One patient (4.5%) occured cardiac tamponade, two patients (9.1%) occured hemorrhagic stroke, five patients (22.7%) occured gastrointestinal bleeding, four patients (18.2%) occured gingival hemorrhage, two patients (9.1%) occured epistaxis, one patient (4.5%) occurred ischemic stroke, one patient (4.5%) occured pump thrombosis, and one patient (4.5%) occured aortic valve thrombosis. The survival rates were 100%, 95%, 95%, and 95% at 3 months, 6 months, 1 year, 2 years after implantation respectively.Conclusion:The single antithrombotic strategy using warfarin (target INR 2.0-2.5) without antiplatelet for patients with implantations of HeartCon type LVAD may be safe and effective.

Objective:To discuss the effects of moxibustion combined with acupuncture on nasal resistance and quality of life in allergic rhinitis (AR) patients with lung qi deficiency and cold syndrome.Methods:Randomized controlled trial was conducted. Totally 82 patients of AR were divided into two groups according to random number table method, with 41 cases in each group. The control group received routine intervention, and the observation group received moxibustion combined with acupuncture intervention on the basis of routine intervention. The treatment for both groups lasted for 4 weeks. The severity of nasal symptoms was evaluated using the Total Nasal Symptom Score (TNSS) before and after treatment. The Rhinoconjunctival Quality of Life Questionnaire (RQLQ) was used to evaluate the quality of life, patient nasal resistance was measured, and clinical efficacy was evaluated.Results:The total effective rate was 95.12% (39/41) in the observation group and 75.61% (31/41) in the control group, with statistical significance ( χ2=4.78, P=0.029). The scores and total scores of nasal itching, sneezing, runny nose and congestion in the observation group after treatment were lower than those in the control group ( t values were 4.45, 4.73, 4.64, 4.68, 9.09, respectively, P<0.01). The scores of daily activities, sleep, non-nasal/eye symptoms, behavioral problems, nasal symptoms, eye symptoms, and emotion were lower than those in the control group ( t values were 4.83, 4.63, 4.50, 5.32, 5.56, 5.29, 4.84, respectively, P<0.01). The nasal resistance of the observation group after treatment [(0.15±0.03) Pa/(cm?s) vs. (0.21±0.03) Pa/(cm?s), t=9.06] was lower than that of the control group ( P<0.001). Conclusion:Moxibustion combined with acupuncture in patients with AR can further reduce nasal resistance and improve their quality of life and clinical efficacy.

Objective:To compare with video-fluoroscopic swallowing function test(VFSS),so as to evaluate the application value of ultrasonography in the test of dysphagia after stroke.Methods:A total of seventy-two patients with dysphagia after stroke who admitted to The Second Affiliated Hospital of Hainan Medical University from January 2022 to July 2023 were selected as cases group,and a total of 45 healthy aged with normal swallowing function were selected as healthy control group at the same time.All of them underwent video X-ray fluoroscopic examination of swallowing function and quantitative assessment of ultrasound.Quantitative assessment of ultrasound was performed by twice to compare the internal consistency of ultrasound test.Meanwhile,the correlation between ultrasound and VFSS results was tested to verify the validity of ultrasound quantitative assessment.The VFSS was used as gold standard to analyze the sensitivity and specificity of ultrasound assessment.The differences of abnormal grade of Geniohyoid muscle;movement time,movement distance and the change of tongue muscle thickness of semi quantitative description of ultrasound between two groups were compared.Results:The intra group correlation coefficient(ICC),movement time,movement distance and movement speed of grade description of muscle abnormalities of cases group were respectively 0.90,(1.743±0.235)s,(6.323±0.823)mm and(3.826±0.778)mm/s,which intra reliabilities were high correlation(ICC=0.90,0.82,0.87,0.85,P＜0.01),which inter reliabilities of these indicators were high correlation(ICC=0.86,0.85,0.88,0.87,P＜0.01),respectively.The positive results of ultrasound test highly correlated with the results of VFSS examination(r=0.91,P＜0.01).The movement distance,the average movement speed and the changes of the thickness of tongue muscle in patients of cases group were significantly smaller than those of healthy control group,but the movement time was larger than that of healthy control group(t=9.03,30.49,-7.02,22.69,P＜0.05),respectively.The results of the ultrasound on the muscles of all patients in cases group existed abnormality.Conclusion:Ultrasound technique can quantitatively assess dysphagia after stroke.Compared with VFSS technique,ultrasonography can measure and determine the related data of the movement of swallowing muscle,and dynamically record movement parameters of geniohyoid muscle and the changes of the thickness of tongue muscle.At the same time,it can detect the grade of muscle abnormalities of patients with dysphagia,which will contribute to further explore the potential pathological mechanism about muscle,and promote the healthy management for patients with dysphagia.

OBJECTIVE: To explore the genetic basis for a patient with early-onset retinitis pigmentosa (RP). METHODS: A patient who had presented at the West China Hospital of Sichuan University on March 10, 2020 was selected as the study subject. The patient and his parents were subjected to whole exome sequencing (WES). Candidate variants were verified by Sanger sequencing and in silico analysis. RESULTS: The patient has featured substantial loss of binocular vision field. Funduscopy revealed characteristic bone spicule-type pigment deposits, as well as attenuated retinal arterioles and pale-appearing optic discs. WES revealed that he has harbored compound missense variants of a RP-associated CRB1 gene, including c.2969T>C (p.Leu990Ser) and c.1816T>C (p.Cys606Arg), which were respectively inherited from his father and mother. Homozygous c.1816T>C (p.Cys606Arg) variant has been identified among RP patients, whilst the c.2969T>C (p.Leu990Ser) variant was unreported previously. Both variants were predicted as likely pathogenic based on the guidelines from the American College of Medical Genetics and Genomics (ACMG). CONCLUSION The novel compound heterozygous variants of the CRB1 gene probably underlay the early-onset RP in this patient. Above finding has enriched the mutational spectrum of the CRB1 gene.
Male ; Female ; Humans ; China ; Genomics ; Homozygote ; Mothers ; Retinitis Pigmentosa/genetics* ; Eye Proteins/genetics* ; Membrane Proteins/genetics* ; Nerve Tissue Proteins/genetics*

OBJECTIVE: To identify the pathogenic variants from a patient with suspected congenital contractural arachnodactyly, and to explore the possible molecular genetic pathogenesis, so as to provide evidence for clinical diagnosis. METHODS: Whole exome sequencing was performed for the patient. The splicing site variation of candidate pathogenic genes was verified by Sanger sequencing, and the new transcript sequence was determined by RT-PCR and TA-cloning sequencing. RESULTS: The patient carried a heterozygous c.533-1G>C variant of FBN2 gene, which was not reported. The sequencing of mRNA showed that the variant leaded to the disappearance of the canonical splice acceptor site of FBN2 gene and the activation of a cryptic splice acceptor site at c.533-71, resulting in the insertion of 70 bp sequence in the new transcript. It was speculated that the polypeptide encoded by the new transcript changed from valine (Val) to serine (Ser) at amino acid 179, and prematurely terminated after 26 aminoacids. According to the guidelines of American College of Medical Genetics and Genomics, the variant of FBN2 gene c. 533-1G>C was determined as pathogenic (PVS1+PM2+PP3 ). CONCLUSION A novel splicing variant of FBN2 gene (c.533-1G>C) was identified, which can lead to congenital contractural arachnodactyly.
Arachnodactyly/genetics* ; Contracture/genetics* ; Fibrillin-2/genetics* ; Humans ; Mutation ; RNA Splice Sites ; Whole Exome Sequencing

Objective:To investigate the efficacy of treatment of Sanders Ⅱ & Ⅲ calcaneal fractures with an absorbable stick plus Kirschner wire through the tarsal sinus incision.Methods:From July 2017 to May 2020, 37 patients with 42 Sanders Ⅱ & Ⅲ calcaneal fractures were treated with an absorbable stick plus Kirschner wire through the tarsal sinus incision at The Third Ward of Department of Traumatic Orthopeadics, The Sixth Hospital of Ningbo. There were 25 males and 12 females, with an age of (48.2±5.6) years (from 20 to 69 years). The fractures were at the left side in 12 cases, at the right side in 20 and at bilateral sides in 5. By Sanders classification, 20 fractures were type Ⅱ and 22 ones type Ⅲ. Fracture union time and complications were recorded. Their B?hler and Gissane angles were compared between preoperation, postoperation and the last follow-up. The range of motion of the subtalar joint was evaluated by the Morrey method at 6 months postoperation. The functional recovery was evaluated by the American Society of Foot and Ankle Surgery (AOFAS) ankle-hindfoot score at 12 months postoperation.Results:The 37 patients were followed up for (15.2±2.7) months (from 13 to 18 months). There were no such complications as incision skin necrosis, Kirschner wire deformation, loss of fracture reduction or Kirschner wire infection. The anatomical morphology of the calcaneus was restored satisfactorily in the 37 patients. At preoperation, postoperation and the last follow-up, the B?hler angles were 13.3°±1.6°, 32.5°±5.5° and 32.7°±5.4° and the Gissane angles 78.3°±6.7°, 127.2°±6.7° and 128.0°±6.4°, respectively, showing significant differences between the preoperative and postoperative values ( P<0.05) but no significant differences between postoperation and the last follow-up ( P>0.05). The range of motion of the subtalar joint at 6 months postoperation was slightly limited in 25 cases and moderately limited in 12 cases, giving a rate of moderate and above limitation of 32.4% (12/37). By the AOFAS ankle-hindfoot score at 12 months postoperation, 12 cases were excellent, 21 ones good and 4 ones fair, giving a good to excellent rate of 89.2% (33/37). Conclusion:Treatment with an absorbable stick plus Kirschner wire through the tarsal sinus incision may lead to fine clinical efficacy for Sanders Ⅱ & Ⅲ calcaneal fractures.

Objective:To compare the efficacy and safety of robot-assisted laparoscopic and laparoscopic partial nephrectomy (RAPN and LPN) for patients with completely endophytic renal tumor.Methods:A total of 73 patients with completely endophytic renal tumor receiving RAPN (n=29) or LPN (n=44) in our center between January 2015 and June 2021 were retrospectively collected. There were 21 males and 8 females in RAPN group. The average age was 48.6±13.7 years old, average tumor size was 2.9±0.9 cm with 13 left tumors and 16 right tumors, average R. E.N.A.L. score was 9.2±1.0, and average preoperative eGFR was 82.6±10.7 ml/(min·1.73 m 2). There were 27 males and 17 females in LPN group. The average age was 50.1±12.3 years old, average tumor size was 2.9±0.9 cm with 24 left tumors and 20 right tumors, average R. E.N.A.L. score was 9.1±1.3, and average preoperative eGFR was 81.7±9.6 ml/(min·1.73 m 2). There was no significant difference in above variables between two groups. The operative time, warm ischemia time, blood loss, postoperative complication, postoperative hospital stay and postoperative 3 months renal function of two groups were compared. Results:All 73 patients successfully underwent RAPN or LPN and no patient converted to radical nephrectomy or open surgery. There was no significant difference in operation time [140(80, 160) min vs. 150 (90, 180) min, P=0.264], intraoperative estimated blood loss[150 (100, 200)vs. 180 (120, 200) ml, P=0.576]and postoperative hospital stay (7.0±2.7 vs. 7.4±2.1 days, P=0.480) between two groups. Compared with LPN group, RAPN group had obvious less warm ischemia time (23.1±3.3 vs. 27.6±4.7 min, P<0.001). No obvious complication occurred in RAPN group and one case with postoperative hemorrhage occurred in LPN group. No positive margin occurred in either group. There was no difference in renal function 3 months after operation between the two groups [73.2±6.3 vs.70.5±7.6ml/(min·1.73 m 2), P=0.117]. The median follow-up period was 22.6 months with no tumor recurrence or metastasis. Conclusions:For experienced surgeons, both RAPN and LPN are safe and feasible for patients with completely endophytic renal tumor. Compared with LPN, RAPN has advantages of perioperative curative effect, which could reduce the operating difficulty and shorten the warm ischemia time.

Objective:To investigate and evaluate the efficacy of HeartCon left ventricular assist device (LVAD) in the treatment of adult patients with end-stage heart failure (ESHF).Methods:A prospective and observational study was conducted. Patients with ESHF who underwent LVAD implantation in the department of cardiac surgery of Teda International Cardiovascular Hospital from September 2020 to August 2021 were selected. The left ventricular end-diastolic diameter (LVEDD), left ventricular ejection fraction (LVEF), New York Heart Association (NYHA) classification, N-terminal pro-B type natriuretic peptide (NT-proBNP), and six minute walk distance (6MWD) before operation and 90 days after operation were compared. The incidence of equipment failures and major adverse events within 90 days after operation were recorded.Results:A total of 20 patients with ESHF were included, with 15 males and 5 females. Patients' age ranged from 20 to 67 years old, with an average of (50.2±13.6) years old. The range of body weight was 49.8-106.1 kg, with an average of (67.9±15.5) kg, and the body surface area (BSA) was from 1.49 to 2.32 m 2, with an average of (17.6±0.22) m 2. The operation process of all the patients were successful. The length of hospital stay ranged from 33 to 90 days, and the average was 56.0 (42.8, 75.0) days. Complications within 90 days after operation as follows, 2 cases with pericardial tamponade (10%), 1 case with cerebral hemorrhage (5%), 1 case with mediastinum infection (5%), 3 cases with acute renal injury (AKI, 15%), 5 cases with gastrointestinal bleeding (25%). There were no mechanical failure of LVAD and hemolysis events, right ventricular failure (RVF), cerebral infarction and death occurred. Compared with preoperative, the LVEDD significantly decreased (mm: 67.50±13.98 vs. 77.40±9.73), LVEF significantly increased (%: 34.80±9.76 vs. 22.70±5.62), NT-proBNP significantly decreased (ng/L: 2 028.65±1 752.05 vs. 4 796.45±4 355.40), 6MWD significantly increased (m: 385.20±144.12 vs. 85.81±63.50) at 90 days after operation, and the differences were statistically significant (all P < 0.05). 18 cases (90%) of the 20 patients reached NYHA classification Ⅰ and 2 cases (10%) reached NYHA classification Ⅱ, which were significantly improved compared with those before surgery (all patients' NYHA classification were Ⅳ before surgery). Conclusion:HeartCon LVAD can effectively improve the life quality of patients with ESHF, which has been proved safe and effective in clinical trials, but its long-term effects and complications need further observation and study.