ObjectiveTo investigate the relationship between the vasodilation and hydrogen sulfide （H₂S） mechanism of total flavonoids of chrysanthemum （TFCC） and the large conductance Ca²⁺- activated K⁺ （BK_Ca） channels on vascular smooth muscle cells （VSMCs） of the middle cerebral artery in rats. In addition， this study will also investigate the effect of TFCC on the expression of BK_Ca channel alpha protein in rat middle cerebral artery VSMCs. MethodsThe primary method employed was acute digestion to isolate VSMCs from the middle cerebral artery of rats； whole-cell patch-clamp techniques were used to measure BK_Ca channel currents； primary tissue adherence culture was utilized to cultivate VSMCs from the middle cerebral artery of rats； Western blot were employed to determine protein expression levels. ResultsIn whole-cell patch-clamp experiments， both the H₂S donor NaHS （100 μmol/L） and endogenous H₂S enhanced BK_Ca channel currents. TFCC （30， 90， and 270 mg/L） also activatedBK_Ca channels and exhibited a certain concentration-dependent effect. Even after blocking endogenous H₂S production， TFCC （270 mg/L） still activated BK_Ca channels in VSMCs of the middle cerebral artery in rats. In Western blot experiments， the α-subunit of BK_Ca channel proteins was expressed in all groups of cells， but TFCC （30， 90， and 270 mg/L） and inhibitor IBTX group did not affect the expression of channel protein content.Conclusion TFCC can promote the opening of BK_Ca channels by promoting the generation of endogenous H₂S， or directly activate BK_Ca channels， thereby playing a role in relaxing cerebral blood vessels. However， TFCC had no significant effect on the expression of BK_Ca channel proteins.

Ischemic stroke (IS) is a globally life-threatening disease. Presently, few therapeutic medicines are available for treating IS, and rt-PA is the only drug approved by the US Food and Drug Administration (FDA) in the US. In fact, many agents showing excellent neuroprotection but no blood flow-improving activity in animals have not achieved ideal clinical efficacy, while thrombolytic drugs only improving blood flow without neuroprotection have limited their wider application. To address these challenges and meet the huge unmet clinical need, we have designed and identified a novel compound AAPB with dual effects of neuroprotection and cerebral blood flow improvement. AAPB significantly reduced cerebral infarction and neural function deficit in tMCAO rats, pMCAO rats, and IS rhesus monkeys, as well as displayed exceptional safety profiles and excellent pharmacokinetic properties in rats and dogs. AAPB has now entered phase I of clinical trials fighting IS in China.

Objective:To investigate the relationship between the single nucleotide polymorphisms (SNP) rs174575 and rs2845574 in the fatty acid desaturase 2 ( FADS2) gene and gestational diabetes mellitus (GDM). Methods:A total of 1 514 pregnant women who visited West China Second University Hospital, Sichuan University, between January 1, 2013, and December 31, 2021, were enrolled in this study. Among them, 583 were diagnosed with gestational diabetes mellitus (GDM group), and 931 had normal pregnancies (control group). The SNPs rs174575 and rs2845574 in the FADS2 gene were analyzed using Sanger DNA sequencing. Plasma levels, insulin (INS), apolipoprotein A1 (apoA1) and apolipoprotein B (apoB) levels were measured using enzymatic methods, chemiluminescence and immunoturbidimetry. This study was approved by Medical Ethics Committee of the West China Second University Hospital, Sichuan University (Ethics No. 2020-036). Results:① The main type of genotype at the rs174575 C/G and rs2845574 C/T polymorphic sites were CC in both GDM and control groups. No statistically significant differences were observed between the GDM and control groups regarding the genotype frequencies or allele frequencies of rs174575 and rs2845574 sites ( P>0.05). ② Among the GDM group, individuals with the GG genotype at the rs174575 site had lower plasma HDL-C levels compared to those with the CC genotype ( P<0.05), and had higher atherogenic indices (AI) than CC and CG genotype ( P<0.05; P<0.05). Individuals with the TT genotype at the rs2845574 site had higher AI than CT genotype ( P<0.05). Among the control group, individuals with the GG genotype had lower diastolic blood pressure (DBP) compared to those with the CC genotype ( P<0.05). ③ Additional subgroup analysis demonstrated that the rs174575 polymorphism was associated with AI levels in obesity subgroup of GDM, TG levels in non-obese subgroup of control and DBP levels in obese subgroup of control ( P<0.05; P<0.05; P<0.05). Conclusion:The FADS2 rs174575 and rs2845574 polymorphisms in GDM patients were associated wit HDL-C and AI levels, and the FADS2 rs174575 polymorphisms was also associated with DBP levels in normal pregnant women. The AI and DBP levels have BMI-dependent effect.

Objective:This study aimed to explore the impact of a single Scutellaria baicalensis decoction on the intestinal flora and barrier function in sepsis rats subjected to an endotoxin "second strike."Methods:Twenty-eight healthy adult male SPF-grade SD rats were utilized to develop an acute lung injury model of sepsis induced by an endotoxin "second strike." The rats were randomLy allocated into four groups: sham operation, model, normal dose Scutellaria baicalensis, and high dose Scutellaria baicalensis, with seven rats in each group. Six hours prior to model induction, the normal dose group received 2 mL of Scutellaria baicalensis decoction at 1 g/kg, while the high dose group received 4 g/kg. Both the sham operation and model groups were administered an equivalent volume of normal saline once daily for three consecutive days. Post-experiment, intestinal tissue, blood, and stool samples were collected. HE staining was used to observe intestinal histopathological changes, ELISA to detect serum D-lactic acid and Fn levels, Western blot to measure intestinal tissue NF-κB, and 16S rRNA gene sequencing to analyze intestinal flora. Correlations between intestinal flora and D-lactic acid, Fn, and NF-κB were examined.Results:Compared to the sham operation group, the model group exhibited inflammatory cell infiltration and tissue structure damage in the intestinal tissue, significantly increased NF-κB expression, markedly decreased serum Fn, and elevated D-lactic acid levels. The abundance of Firmicutes and Lactobacillus in the intestine significantly decreased, while Bacteroidota increased ( P<0.05). In contrast, the normal and high dose groups showed significantly reduced serum Fn and D-lactic acid levels, decreased intestinal NF-κB expression, and increased Firmicutes and Lactobacillus abundance ( P<0.05). Bacteroidota levels decreased, and intestinal tissue inflammatory pathology was notably alleviated. No significant differences were observed in Fn, D-lactic acid, and NF-κB expressions between the normal and high dose groups, nor in the abundance of Firmicutes, Bacteroidota, and Lactobacillus. Firmicutes abundance and the Firmicutes/Bacteroidota ratio positively correlated with Fn ( P<0.01) but negatively with D-lactic acid and NF-κB ( P<0.01). Bacteroidota abundance negatively correlated with Fn ( P<0.01) and positively with D-lactic acid and NF-κB ( P<0.01). Conclusions:Alterations in intestinal flora and mucosal barrier damage are implicated in the lung injury of sepsis rats induced by an endotoxin "second strike." Scutellaria baicalensis decoction exerts a protective effect on intestinal function in these rats, potentially by optimizing the abundance of beneficial intestinal flora, preserving the intestinal mucosal barrier, mitigating inflammatory responses, and safeguarding endothelial cell function.

OBJECTIVE: To assess the association between the single nucleotide polymorphisms (SNP) rs174575 and rs2845574 of the fatty acid desaturase 2 (FADS2) gene and gestational diabetes mellitus (GDM). METHODS: A total of 1 514 pregnant women who visited West China Second University Hospital of Sichuan University between January 1, 2013 and December 31, 2021 were enrolled in this study. Among them, 583 were diagnosed with gestational diabetes mellitus (GDM group), and 931 had normal pregnancies (control group). The SNPs rs174575 and rs2845574 of the FADS2 gene were analyzed using Sanger DNA sequencing. Plasma levels of insulin (INS), apolipoprotein A1 (apoA1) and apolipoprotein B (apoB) were measured using enzymatic methods, chemiluminescence and immunoturbidimetry. This study was approved by the Medical Ethics Committee of the West China Second University Hospital of Sichuan University (Ethics No.: 2020-036). RESULTS: The main genotype at the rs174575 C/G and rs2845574 C/T loci were CC in both GDM and control groups. No significant difference was found between the GDM and control groups regarding the genotypic or allelic frequencies of rs174575 and rs2845574 sites (P > 0.05). Among the GDM group, individuals with the GG genotype at the rs174575 site had lower plasma HDL-C levels compared to those with the CC genotype (P < 0.05), and had higher atherogenic indices (AI) compared with the CC and CG genotype (P < 0.05; P < 0.05). Individuals with the TT genotype at the rs2845574 site had higher AI compared with the CT genotype (P < 0.05). Among the control group, individuals with the GG genotype had lower diastolic blood pressure (DBP) compared to those with the CC genotype (P < 0.05). Additional subgroup analysis demonstrated that the rs174575 polymorphism was associated with AI levels in obesity subgroup of GDM, TG levels in non-obese subgroup of control and DBP levels in the obese subgroup of control (P < 0.05; P < 0.05; P < 0.05). CONCLUSION The FADS2 rs174575 and rs2845574 polymorphisms in GDM patients are associated wit HDL-C and AI levels, and the FADS2 rs174575 polymorphisms was also associated with DBP levels in normal pregnant women. The AI and DBP levels have a BMI-dependent effect.
Humans ; Female ; Pregnancy ; Fatty Acid Desaturases/genetics* ; Polymorphism, Single Nucleotide ; Adult ; Diabetes, Gestational/blood* ; Blood Pressure/genetics* ; Lipids/blood* ; Genotype ; Genetic Predisposition to Disease

Objective:To investigate the relationship between the single nucleotide polymorphisms (SNP) rs174575 and rs2845574 in the fatty acid desaturase 2 ( FADS2) gene and gestational diabetes mellitus (GDM). Methods:A total of 1 514 pregnant women who visited West China Second University Hospital, Sichuan University, between January 1, 2013, and December 31, 2021, were enrolled in this study. Among them, 583 were diagnosed with gestational diabetes mellitus (GDM group), and 931 had normal pregnancies (control group). The SNPs rs174575 and rs2845574 in the FADS2 gene were analyzed using Sanger DNA sequencing. Plasma levels, insulin (INS), apolipoprotein A1 (apoA1) and apolipoprotein B (apoB) levels were measured using enzymatic methods, chemiluminescence and immunoturbidimetry. This study was approved by Medical Ethics Committee of the West China Second University Hospital, Sichuan University (Ethics No. 2020-036). Results:① The main type of genotype at the rs174575 C/G and rs2845574 C/T polymorphic sites were CC in both GDM and control groups. No statistically significant differences were observed between the GDM and control groups regarding the genotype frequencies or allele frequencies of rs174575 and rs2845574 sites ( P>0.05). ② Among the GDM group, individuals with the GG genotype at the rs174575 site had lower plasma HDL-C levels compared to those with the CC genotype ( P<0.05), and had higher atherogenic indices (AI) than CC and CG genotype ( P<0.05; P<0.05). Individuals with the TT genotype at the rs2845574 site had higher AI than CT genotype ( P<0.05). Among the control group, individuals with the GG genotype had lower diastolic blood pressure (DBP) compared to those with the CC genotype ( P<0.05). ③ Additional subgroup analysis demonstrated that the rs174575 polymorphism was associated with AI levels in obesity subgroup of GDM, TG levels in non-obese subgroup of control and DBP levels in obese subgroup of control ( P<0.05; P<0.05; P<0.05). Conclusion:The FADS2 rs174575 and rs2845574 polymorphisms in GDM patients were associated wit HDL-C and AI levels, and the FADS2 rs174575 polymorphisms was also associated with DBP levels in normal pregnant women. The AI and DBP levels have BMI-dependent effect.

Background: and Purpose X-linked Charcot-Marie-Tooth disease type 1 (CMTX1) is characterized by peripheral neuropathy with or without episodic neurological dysfunction. We performed clinical, neuropathological, and genetic investigations of a series of patients with mutations of the gap-junction beta-1 gene (GJB1) to extend the phenotypic and genetic description of CMTX1. Methods: Detailed clinical evaluations, sural nerve biopsy, and genetic analysis were applied to patients with CMTX1. Results: We collected 27 patients with CMTX1 with GJB1 mutations from 14 unrelated families. The age at onset (AAO) was 20.9±12.2 years (mean±standard deviation; range, 2–45 years). Walking difficulties, weakness in the legs, and pes cavus were common initial symptoms. Compared with female patients, males tended to have a younger AAO (males vs. females=15.4±9.6 vs. 32.0±8.8 years, p=0.002), a longer disease course (16.8±16.1 vs. 5.5±3.8 years, p=0.034), and more-severe electrophysiological results. Besides peripheral neuropathy, six of the patients had special episodic central nervous system (CNS) evidence from symptoms, signs, and/or reversible white-matter lesions. Neuropathology revealed the loss of large myelinated fibers, increased number of regenerated axon clusters with abnormally thin myelin sheaths, and excessively folded myelin. Genetic analysis identified 14 GJB1 variants, 6 of which were novel. Conclusions These findings expand the phenotypic and genetic spectrum of CMTX1. Although CMTX1 was found to have high phenotypic and CNS involvement variabilities, detailed neurological examinations and nerve conduction studies will provide critical clues for accurate diagnoses. Further exploration of the underlying mechanisms of connexin 32 involvement in neuropathy or CNS dysfunction is warranted to develop promising therapies.

Shoulder pain ranks the third in musculoskeletal pain,with relatively high incidence in the population.Early diagnosis of shoulder diseases is crucial.Deep learning(DL)in shoulder joint imaging was conducive to clinical diagnosis,treatment and prognosis evaluation of shoulder diseases.The research progresses of DL in shoulder joint imaging were reviewed in this article.

Objective:To retrospectively summarize the clinical characteristics and treatment of 49 patients with hyperthyroid cardiopath and to explore the diagnosis and treatment methods of hyperthyroid cardiopathy.Methods:A total of 49 patients with hyperthyroid cardiopath(HC group) who were successfully treated and followed up in the Department of Endocrinology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, from January 2016 to December 2021 were collected, and 85 cases of Graves′ disease without heart disease were collected as the control group(GD group). The medical history, laboratory tests, and echocardiographic parameters of the two groups were compared. Differences in thyroid and cardiac indicators before and after treatment in the HC group were summarized, along with the dosage of β-receptor blockers used in treating different types of conditions(atrial fibrillation and heart failure.Results:Patients in the HC group were older and had a longer duration of hyperthyroidism than those in the GD group( P<0.001, P=0.002). There were no significant differences in thyroid hormone levels between the two groups except for reverse triiodothyronine(rT 3). Age and rT 3 were independent risk factors of hyperthyroid cardiopathy. rT 3 level was linearly positively correlated with brain natriuretic peptide, systolic pulmonary artery pressure, left artrium diamete (LAD) and left ventricular end-systolic diameter(LVDs; r=0.352, P<0.001; r=0.392, P=0.019; r=0.202, P=0.029; r=0.242, P=0.028). In patients of HC group, free triiodothyronine(FT 3) level returned to normal range after 2.87(1.63, 5.53) months of treatment with radioiodine(41/49) or antithyroid drugs(8/49), while brain natriuretic peptide, LAD, LVDs, and systolic pulmonary artery pressure declined after 5.00(1.25, 8.00) months of treatment. Non-selective β-receptor blockers were used for both hyperthyroid heart failure and atrial fibrillation, and there was no statistically significant difference in dosage[(86.52±47.83)mg vs(88.67±47.19)mg, P>0.05]. Conclusions:rT 3 may be a biomarker of hyperthyroid cardiopath and indicate the severity of hyperthyroidism. β-receptor blockers are crucial in treating patients with hyperthyroidism who develop atrial fibrillation and heart failure.

Objective:To analyze the short-term clinical efficacy and safety of arsenic trioxide (ATO) combined with a modified N7 induction regimen in the treatment of children with high-risk neuroblastoma (NB).Methods:This study was a prospective, single-arm, multicenter phase Ⅱ clinical study. Sixty-seven high-risk NB children from eight units of Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Wuhan Children′s Hospital of Tongji Medical College of Huazhong University of Science and Technology, First Affiliated Hospital of Guangxi Medical University, Hainan General Hospital, Affiliated Hospital of Guangdong Medical University, Kunming Children′s Hospital, Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology, and Guangdong Provincial Agricultural Reclamation Center Hospital were enrolled from January 2019 to August 2023 and were treated with ATO combined with a modified N7 induction regimen. The efficacy and adverse effects at the end of induction chemotherapy were assessed and analyzed, and the differences in the clinical characteristics were further compared between the treatment-responsive and treatment-unresponsive groups by using the Fisher′s exact test.Results:Among 67 high-risk NB children, there were 40 males (60%) and 27 females (40%), with the age of disease onset of 3.5 (2.6, 4.8) years. Primary NB sites were mostly in retroperitoneum (including adrenal gland) (56/67, 84%) and the common metastases sites at initial diagnosis were distant lymph node in 25 cases (37%),bone in 48 cases (72%),bone marrow in 56 cases (84%) and intracalvarium in 3 cases (4%). MYCN gene amplification were detected in 28 cases (42%). At the end of induction, 33 cases (49%) achieved complete remission, 29 cases (43%) achieved partial remission, 1 case (1%) with stable disease, and 4 cases (6%) were assessed as progressive disease (PD). The objective remission rate was 93% (62/67) and the disease control rate was 94% (63/67). The percentage of central system metastases at the initial diagnosis was higher in the treatment-unresponsive group than in the treatment-responsive group (2/5 vs. 2% (1/62), P=0.013), whereas the difference in MYCN gene amplification was not statistically significant between two groups (3/5 vs.40% (25/62), P=0.786). Grade Ⅲ or higher adverse reactions during the induction chemotherapy period were myelosuppression occurred in 60 cases (90%), gastrointestinal symptoms occurred in 33 cases (49%), infections occurred in 20 cases (30%), hepatotoxicity occurred in 4 cases (6%), and cardiovascular toxicity occurred in 1 case (2%). There were no chemotherapy-related deaths. Conclusion:ATO combined with N7-modified induction regimen had a superiority in efficacy and safety, which deserved further promotion in clinical practice.