Pathological vascular remodeling is a hallmark of various vascular diseases. Previous research has established the significance of andrographolide in maintaining gastric vascular homeostasis and its pivotal role in modulating endothelial barrier dysfunction, which leads to pathological vascular remodeling. Potassium dehydroandrographolide succinate (PDA), a derivative of andrographolide, has been clinically utilized in the treatment of inflammatory diseases precipitated by viral infections. This study investigates the potential of PDA in regulating pathological vascular remodeling. The effect of PDA on vascular remodeling was assessed through the complete ligation of the carotid artery in C57BL/6 mice. Experimental approaches, including rat aortic primary smooth muscle cell culture, flow cytometry, bromodeoxyuridine (BrdU) incorporation assay, Boyden chamber cell migration assay, spheroid sprouting assay, and Matrigel-based tube formation assay, were employed to evaluate the influence of PDA on the proliferation and motility of smooth muscle cells (SMCs). Molecular docking simulations and co-immunoprecipitation assays were conducted to examine protein interactions. The results revealed that PDA exacerbates vascular injury-induced pathological remodeling, as evidenced by enhanced neointima formation. PDA treatment significantly increased the proliferation and migration of SMCs. Further mechanistic studies disclosed that PDA upregulated myeloid differentiation factor 88 (MyD88) expression in SMCs and interacted with T-cadherin (CDH13). This interaction augmented proliferation, migration, and extracellular matrix deposition, culminating in pathological vascular remodeling. Our findings underscore the critical role of PDA in the regulation of pathological vascular remodeling, mediated through the MyD88/CDH13 signaling pathway.
Mice ; Rats ; Animals ; Myeloid Differentiation Factor 88/metabolism* ; Vascular Remodeling ; Cell Proliferation ; Vascular System Injuries/pathology* ; Carotid Artery Injuries/pathology* ; Molecular Docking Simulation ; Muscle, Smooth, Vascular ; Cell Movement ; Mice, Inbred C57BL ; Signal Transduction ; Succinates/pharmacology* ; Potassium/pharmacology* ; Cells, Cultured ; Diterpenes ; Cadherins

ObjectiveThe mechanisms underlying therapeutic efficacies of Detumescence Analgesic Plaster was analyzed based on "effect-target" associations. MethodBased on CNKI and PubMed databases， the chemical components of Artemisia seed， bastard speedwell， and menthol in Detumescence Analgesic Plaster were collected. The capacity of transdermal absorption was predicted based on the Encyclopedia of Traditional Chinese Medicine （ETCM 2.0）. Golden Triangle of compounds with Accepted used for candidate target prediction based on the Integrative Pharmacology-based Research Platform of Traditional Chinese Medicine （TCMIP v2.0）according to the similarity of chemical structures. At the same time， the SoFDA data platform was employed to collect the symptoms related to the efficacy of Detumescence Analgesic Plaster and its related genes information. In addition， based on the interaction between the above-mentioned candidate targets and their efficacy-related genes， the "effect-target" interaction network of Detumescence Analgesic Plaster was constructed. The key targets by topological features calculation， and functional mining was carried out to explain the efficacy mechanism of Detumescence Analgesic Plaster. ResultA total of 165 candidate targets were obtained based on ETCM 2.0 and TCMIP v2.0 databases， and symptoms related to the efficacy of clearing heat， detumescence， and relieving pain， as well as 1 744 related genes were collected based on the SoFDA database. Network construction and analysis showed that the core effect targets of Detumescence Analgesic Plaster were mainly involved in regulating the "immune-inflammation" balance of the body and maintaining the homeostasis of material and energy metabolism， blood circulation， and nervous system functions， and they were closely related to the efficacy of this prescription in clearing heat， reducing detumescence， and relieving pain. Among them， the heat clearing group of Detumescence Analgesic Plaster had the functions of heat clearing， detoxifying， antibacteria， and anti-inflammation. The biological function of its key effect target group was related to correcting the imbalance of "immune-inflammation" induced by pathogens. The detumescence group of Detumescence Analgesic Plaster had the functions of reducing water and swelling and resolving hard lumps， and the biological function of its core effect target group was related to improving microcirculation disturbance. The pain relieving group of Detumescence Analgesic Plaster had the functions of removing stasis， promoting blood circulation， and relieving pain， and its core effect target group was related to correcting the nervous system and the disorder of material and energy metabolism. ConclusionThe heat clearing， swelling reducing， and pain relieving effects of Detumescence Analgesic Plaster may be closely related to its act on related candidate targets， so as to correct the imbalance of "nerve-immunity-vascular-axis"， regulate neuronal excitability and inflammatory response， and intervene in material and energy metabolism. The relevant research results lay a theoretical foundation for clarifying the advantages of Detumescence Analgesic Plaster and assisting its clinical precise positioning.

Objective:To evaluate the efficacy and safety of domestic recombinant human chorionic gonadotropin (r-hCG) for injection in Chinese women undergoing assisted reproductive technology (ART) of controlled ovarian hyperstimulation (COH).Methods:In a multicenter, randomized, double-blind, positive, parallel controlled clinical trial, the infertile women with normal ovarian reserve who received COH in seven reproductive medical centers from July 2017 to October 2018 were randomly divided into two groups: experimental group (domestic r-hCG, n=112) and control group (imported r-hCG, n=116). Interactive web response system was used to randomize. The total number of oocytes obtained, cleavage cells, two pronuclei fertilization, mid-division oocytes rate, positive serum hCG rate, early embryo loss rate, clinical pregnancy rate, sustained pregnancy rate and the incidence of adverse reactions were compared between the two groups during the cycle of COH. Results:During the initiation cycle of ovulation induction therapy, the total number of oocytes obtained in experimental group and control group were (12.1±5.6) and (12.0±6.7) respectively, with no statistically significant difference ( P>0.05). There were no significant differences in the rate of mid-division oocytes, the number of cleavage cells, the number of double pronuclear fertilization, the positive rate of serum hCG during the transplantation cycle, the loss rate of early embryo, the clinical pregnancy rate, and the sustained pregnancy rate between the two groups (all P>0.05), and the 90% confidence interval ( CI) of the difference between the two groups fell within the preset equivalence threshold (-3, +3). The difference in immunogenicity assessment between the two groups was not statistically significant ( P>0.05). The incidence of ovarian hyperstimulation syndrome (OHSS) and other adverse reactions in treatment period were not significantly different between the two groups (all P>0.05), which were known adverse reaction occurred in the imported r-hCG. Conclusion:In the COH cycle of Chinese infertile women with normal ovarian reserve, the effectiveness and safety of domestic r-hCG are equivalent to imported r-hCG.

Objective:To summarize the management of unicornuate uterus with ectopic ovary during in vitro fertilization and embryo transfer (IVF-ET). Methods:The clinical data of 2 rare cases of uniangular uterus with ectopic ovary undergoing IVF-ET were retrospectively analyzed and the related literatures were reviewed.Results:Two patients were diagnosed as unicornuate uterus with unilateral ovary missing by vaginal ultrasound, subsequent abdominal ultrasound and magnetic resonance imaging (MRI) results indicated follicular structure in the peritoneal area, suggesting ectopic ovary. Case 1 showed flank pain as well as discrepancy between serum estradiol level and follicle numbers during ovarian hyperstimulation. The patient received trans-abdominal combined with trans-vaginal oocyte retrieval and successfully delivered a healthy baby at 36 weeks by transferring frozen blastocyst embryo. Case 2 was diagnosed as unicornuate uterus with lateral ectopic ovary by abdominal ultrasound before IVF treatment. We performed synchronized monitoring of bilateral ovarian follicular development and oocytes retrieval by transabdominal and transvaginal ultrasound, and then the two blastocysts were cryopreserved. However, the patient experienced spontaneous abortion following single frozen-thawed blastocyst transfer.Conclusion:Ectopic ovaries present no obvious clinical manifestation and is easy to be ignored in diagnosis. For patients with unicornuate uterus treated by assisted reproductive technology, if vaginal ultrasound fails to detect ovary, we should further perform abdominal ultrasound or MRI to screen for ectopic ovary. If diagnosed with ectopic ovary, the patients should simultaneously be monitored the follicullar development of bilateral ovaries during the process of ovarian hyperstimulation and adopt both transabdominal and transvaginal ultrasound-guided follicular aspiration to maximize the numbers of oocyte and pregnancy chance.

Objective:To evaluate the efficacy and safety of domestic recombinant human chorionic gonadotropin (r-hCG) for injection in Chinese women undergoing assisted reproductive technology (ART) of controlled ovarian hyperstimulation (COH).Methods:In a multicenter, randomized, double-blind, positive, parallel controlled clinical trial, the infertile women with normal ovarian reserve who received COH in seven reproductive medical centers from July 2017 to October 2018 were randomly divided into two groups: experimental group (domestic r-hCG, n=112) and control group (imported r-hCG, n=116). Interactive web response system was used to randomize. The total number of oocytes obtained, cleavage cells, two pronuclei fertilization, mid-division oocytes rate, positive serum hCG rate, early embryo loss rate, clinical pregnancy rate, sustained pregnancy rate and the incidence of adverse reactions were compared between the two groups during the cycle of COH. Results:During the initiation cycle of ovulation induction therapy, the total number of oocytes obtained in experimental group and control group were (12.1±5.6) and (12.0±6.7) respectively, with no statistically significant difference ( P>0.05). There were no significant differences in the rate of mid-division oocytes, the number of cleavage cells, the number of double pronuclear fertilization, the positive rate of serum hCG during the transplantation cycle, the loss rate of early embryo, the clinical pregnancy rate, and the sustained pregnancy rate between the two groups (all P>0.05), and the 90% confidence interval ( CI) of the difference between the two groups fell within the preset equivalence threshold (-3, +3). The difference in immunogenicity assessment between the two groups was not statistically significant ( P>0.05). The incidence of ovarian hyperstimulation syndrome (OHSS) and other adverse reactions in treatment period were not significantly different between the two groups (all P>0.05), which were known adverse reaction occurred in the imported r-hCG. Conclusion:In the COH cycle of Chinese infertile women with normal ovarian reserve, the effectiveness and safety of domestic r-hCG are equivalent to imported r-hCG.

Objective:To summarize the management of unicornuate uterus with ectopic ovary during in vitro fertilization and embryo transfer (IVF-ET). Methods:The clinical data of 2 rare cases of uniangular uterus with ectopic ovary undergoing IVF-ET were retrospectively analyzed and the related literatures were reviewed.Results:Two patients were diagnosed as unicornuate uterus with unilateral ovary missing by vaginal ultrasound, subsequent abdominal ultrasound and magnetic resonance imaging (MRI) results indicated follicular structure in the peritoneal area, suggesting ectopic ovary. Case 1 showed flank pain as well as discrepancy between serum estradiol level and follicle numbers during ovarian hyperstimulation. The patient received trans-abdominal combined with trans-vaginal oocyte retrieval and successfully delivered a healthy baby at 36 weeks by transferring frozen blastocyst embryo. Case 2 was diagnosed as unicornuate uterus with lateral ectopic ovary by abdominal ultrasound before IVF treatment. We performed synchronized monitoring of bilateral ovarian follicular development and oocytes retrieval by transabdominal and transvaginal ultrasound, and then the two blastocysts were cryopreserved. However, the patient experienced spontaneous abortion following single frozen-thawed blastocyst transfer.Conclusion:Ectopic ovaries present no obvious clinical manifestation and is easy to be ignored in diagnosis. For patients with unicornuate uterus treated by assisted reproductive technology, if vaginal ultrasound fails to detect ovary, we should further perform abdominal ultrasound or MRI to screen for ectopic ovary. If diagnosed with ectopic ovary, the patients should simultaneously be monitored the follicullar development of bilateral ovaries during the process of ovarian hyperstimulation and adopt both transabdominal and transvaginal ultrasound-guided follicular aspiration to maximize the numbers of oocyte and pregnancy chance.

Objective To explore the genetic etiology of a child with autism,mental retardation and epilepsy.Methods Conventional G-banding chromosomal analysis was carried out.Chromosomal variation was also detected by single nucleotide polymorphism microarray (SNP array).Pathogenic mutations were screened by high-throughput sequencing and validated by Sanger sequencing.Pathologic significance of the candidate mutations was analyzed through search of database and literature review.Results No karyotypic abnormality was found with the child and his parents,while SNP array has detected a 460 kb deletion in the 14q11.2 region in the child.High-throughput and Sanger sequencing revealed a novel mutation of the NALCN gene in the child,in addition with a hemizygous mutation of the COL4A5 gene in the child and his mother.Conclusion The 14q11.2 microdeletion and NALCN mutation may contribute to the autism,mental retardation and epilepsy in this child.

OBJECTIVE: The aim of this study was to investigate voluntary wheel running behavior in the unilateral 6-hydroxydopamine (6-OHDA) rat model. METHODS: Male Sprague-Dawley rats were assigned to 2 groups : 6-OHDA group (n=17) and control group (n=8). The unilateral 6-OHDA rat model was induced by injection of 6-OHDA into unilateral medial forebrain bundle using a stereotaxic instrument. Voluntary wheel running activity was assessed per day in successfully lesioned rats (n=10) and control rats. Each behavioral test lasted an hour. The following parameters were investigated during behavioral tests : the number of running bouts, the distance moved in the wheel, average peak speed in running bouts and average duration from the running start to the peak speed. RESULTS: The number of running bouts and the distance moved in the wheel were significantly decreased in successfully lesioned rats compared with control rats. In addition, average peak speed in running bouts was decreased, and average duration from the running start to the peak speed was increased in lesioned animals, which might indicate motor deficits in these rats. These behavioral changes were still observed 42 days after lesion. CONCLUSION: Voluntary wheel running behavior is impaired in the unilateral 6-OHDA rat model and may represent a useful tool to quantify motor deficits in this model.
Animals ; Humans ; Male ; Medial Forebrain Bundle ; Models, Animal* ; Oxidopamine* ; Parkinson Disease* ; Rats ; Rats, Sprague-Dawley ; Running*

Objective To investigate the clinical characteristics and surgical treatment of primary bone non-Hodgkin′s lymphoma.Methods Recalling a case of primary bone non -Hodgkin′s lymphoma patient data in Affiliated Maojian Hospital of Hubei University of Medicine .This patient was hospitalized because of pain in the right upper arm.By improving the relevant examination and diagnosis of right humeral bone tumors ,We had successfully completed a bone tumor resection and graft as well as dual plate fixation .Results Pathological diag-nosis after surgery showed the primary non -Hodgkin′s lymphoma of bone ,9 months follow-up after surgery ,the treatment effecincy was good .There were no tumor recurrence and distant metastasis .Conclusion Primary non-Hodgkin′s lymphoma of bone is uncommon in clinical practice .If there is primary bone tumor with no obvious sys-temic symptoms in elderly patients , we should considered it as a possible diagnosis of primary bone non -Hodgkin′s lymphoma,in order to reduce the possibility of misdiagnosis and mistreatment .Short-term effects of surgical treatment of this disease is excellent .

Objective To evaluate the characteristics and treatment of ovary torsion after controlled ovarian hyperstimulation.Methods Between Jan.2008 and Dec.2011,5 cases with ovary torsion who underwent ovarian hyperstimulation were retrospectively studied.Results Five cases presented intermittent lower abdominal from I to 38 days after oocyte retrieval.Enlargement of ovary and decreased or absent venous and/or arterial flow were demonstrated by Doppler sonography.Two torsions at left side,two torsions at right side,and one on bilateral side were observed.Three cases give up embryo transplantation,2 cases were pregnant after surgical treatment.One case with partial torsion was successfully treated with simple conservative treatment.Two cases with complete torsion were performed adnexectomy by laparotomy.One case with complete torsion with early pregnancy was managed by laparoscopic adnexectomy.One case with chemical pregnancy was managed by laparoscopic detorsion for left side and excision for right side.Postoperative pathology of ovary tissue all confirmed haemorrhage and necrosis.Conclusions Ovary torsion might occur after controlled ovarian hyperstimulation.The early management on ovary torsion will be benefit for preserving ovarian function.