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.

ObjectiveTo systematically explore the underlying mechanisms of Huashi Baidu prescription （HBP） against myocardial injury through a multidimensional network analysis of "transcriptome-putative target-phenotype gene". MethodPutative targets of compounds in HBP were predicted using the Encyclopedia of Traditional Chinese Medicine （ETCM 2.0，http：//www.tcmip.cn/ETCM2/front/） and the Integrative Pharmacology-based Research Platform of Traditional Chinese Medicine （TCMIP v2.0，http：//www.tcmip.cn/TCMIP/index.php/Home/Login/login.html）. Clinical predominant symptom phenotypes for HBP against coronavirus disease 2019 （COVID-19） were collected from CNKI and PubMed databases， while clinical side effects of doxorubicin were gathered from the CTD database. Phenotype-related genes were collected from the HPO database and SoFDA data platform （http：//www.tcmip.cn/Syndrome/front/#/）. An interaction network of "transcriptome-putative target-phenotype gene" was constructed. Key nodes were identified through topological feature calculations， and functional enrichment analysis was conducted to explain the underlying mechanism. Pharmacodynamic evaluation and mechanism verification were performed using a doxorubicin-induced myocardial injury mouse model. Sixty-five SPF-grade C57BL/6J male mice were randomly divided into a control group， a doxorubicin model group， and low-， medium-， and high-dose HBP groups （HBP-L/M/H）， with 13 mice per group. Histopathological severity was assessed using hematoxylin-eosin （HE） and Masson staining. Fibrosis markers were measured by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）， and protein expression was detected by Western blot. ResultA total of 1 044 putative targets for HBP were obtained from ETCM 2.0 and TCMIP v2.0. From the CTD， HPO， and SoFDA databases， 1 223 potential effect-related targets were identified. Cardiac transcriptome sequencing （RNA-seq） yielded 214 genes related to doxorubicin-induced myocardial injury and 58 genes associated with the effects of HBP， using criteria of P-value<0.05 and FC > 1.5/< 0.667. Analysis of the multidimensional molecular network revealed that the mechanisms of HBP on myocardial injury were mainly related to immune-inflammation imbalance， cellular metabolism， myocardial cell function and fibrosis， angiogenesis， contraction and platelet activation， DNA synthesis， metabolism and repair， as well as cell death and oxidative stress. HBP improved cardiovascular abnormalities such as reduced ejection fraction， myocardial fibrosis， myocarditis， hypertriglyceridemia， and arterial/venous thrombosis. Animal experiments demonstrated that HBP reduced the abnormal high expression of Nod-like receptor heat protein domain Protein 3 （NLRP3）， Caspase-1， apoptosis-associated speck-like protein （ASC）， and Gasdermin D （GSDMD） in myocardial tissue induced by doxorubicin （P<0.05）， and improved the elevated mRNA levels of fibrosis markers transforming growth factor-β₁ （TGF-β₁）， Smad3， and α-smooth muscle actin （α-SMA） （P<0.05）. ConclusionHBP can improve myocardial injury through multiple components， targets， and effects， with the inhibition of the NLRP3 inflammasome activation pathway being a key pharmacodynamic mechanism. This study is expected to provide new insights for the development of targeted therapeutic drugs.

ObjectiveTo systematically explore the roles and contributions of the sovereign drug Gypsum Fibrosum contained in Baihu Guizhitang （BHGZT） against rheumatoid arthritis （RA） with heat syndrome from property-efficacy association by an approach integrating transcriptomics with gene regulatory network analysis. MethodA total of 20 male Lewis rats were randomly assigned into 4 groups： a control group （n=5）， a group of adjuvant-induced arthritis rat model with heat syndrome （AIA-H， n=5）， an AIA-H + BHGZT group （BHGZT， 21.4 g·kg^-1， n=5）， and an AIA-H + BHGZT without Gypsum Fibrosum group （BHGZT-GYP， 10.7 g·kg^-1， n=5）. We combined the gene expression profiling based on AIA-H rat model and "disease-gene-drug effective target" network analysis to predict the major function of Gypsum Fibrosum contained in BHGZT against RA with heat syndrome. Furthermore， in vivo experiments with the AIA-H rat model were performed to validate the therapeutic effects on the severity of arthritis based on the representative images of arthritis， limb diameter， infrared thermography， pain thresholds， and joint injury， as well as at the level of immunity-inflammation imbalance. Oil Red O staining was employed for the differentiation of 3T3-L1 pre-adipocytes in the AIA-H rats treated by BHGZT， BHGZT-GYP， and GYP. ResultGene expression profiling and network analysis demonstrated that Gypsum Fibrosum mainly regulated the energy metabolism disorders and the immunity-inflammation imbalance during the development and progression of RA. In vivo experiments showed that both BHGZT and BHGZT-GYP reduced the disease severity of AIA-H rats （P<0.01） by relieving joint redness and distortion， decreasing arthritis score and limb diameter， elevating pain thresholds， alleviating joint erosion， joint inflammation， and bone destruction （P<0.05）. Notably， BHGZT outperformed BHGZT-GYP （P<0.05）. Both BHGZT and BHGZT-GYP inhibited the pathological changes and decreased the indexes of thymus and spleen （P<0.05）， and down-regulated the expression of inflammatory cytokines including Toll-like receptor 4 （TLR4）， tumor necrosis factor-alpha （TNF-α）， interleukin-6 （IL-6）， IL-12， IL-1β， and IL-18 （P<0.05）. In addition， BHGZT and GYP significantly inhibited the adipogenic differentiation of 3T3-L1 cells， with the performance superior to that of BHGZT-GYP. ConclusionThe sovereign drug Gypsum Fibrosum contained in BHGZT played a crucial role in reversing energy metabolism disorders and immunity-inflammation imbalance， which may be associated with its cold property and function of clearing heat and purging fire.

Objective:To improve clinicians' understanding of Multisystem Inflammatory Syndrome in Children (MIS-C) and to reduce missed and misdiagnosis.Methods:The clinical data of a patient with Multisystem inflammatory syndrome in children admitted to Maternal and Child Health Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology in January 2023 were analyzed retrospectively, together with literature review.Results:A 10-year-old male patient was admitted to hospital with a fever for 5 days. This patient had a history of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection 1 month prior to admission; after admission, he continued to have recurring high fevers, accompanied by abdominal pain and Kawasaki disease like manifestations, shock, multiple organ function impairment, and a significant increase in inflammatory indicators. Finally, the patient was diagnosed with MIS-C, treated with intravenous immunoglobulin, glucocorticoids and aspirin, and discharged with clinical improvement.Conclusion:MIS-C was a novel syndrome with Kawasaki-like manifestations.Currently, the overall prognosis for MIS-C is good, but its pathogenesis is unclear and the therapeutic consensus remains limited. More studies are needed to clarify the best diagnosis and treatment methods and true prognosis.

Allografts ; COVID-19 ; China/epidemiology* ; Disease Outbreaks ; Humans ; Kidney Transplantation/adverse effects* ; SARS-CoV-2

Objective:To summarize the medium-term outcomes of single kidney transplantation from senile deceased donors aged above 65 years.Methods:Forty-three kidney recipients from donors aged above 65(old-aged donor group, OAD) and 43 kidney recipients of the same age and gender from donors aged 18 to 49 years(standard-criteria donor group, SCD) were retrospectively reviewed.The survival outcomes of patients and grafts, renal functions, the incidence of delayed graft function(DGF)and other complications were recorded within the 3-year follow-up post-transplantation.Results:The 3-year patient survival rates were 95.3% both in OAD and SCD and the 3-year death-censored graft survival rates 92.7% and 97.6% respectively.The serum levels of creatinine were significantly higher in OAD than that in SCD( P<0.05). And lower estimated glomerular filtration rate(eGFR)was found in OAD as compared with SCD( P<0.05). No significant difference existed in the incidence of DGF(OAD 20.9% and SCD 18.6%, P>0.05), acute rejection (OAD 4.7% and SCD 2.3%, P>0.05)or proteinuria(OAD 27.9%and SCD 14.0%, P>0.05). Conclusions:Single kidney transplantation from old-aged deceased donors may achieve excellent medium-term survival outcomes of patients and grafts.It can expand the donor pool though kidney functions were not as good as those of SCD.

Objective:To investigate the clinical efficacy of a new method of hymenoplasty using local vaginal mucosa.Methods:A total of 18 patients with wide vaginal opening or deep laceration of hymen, admitted by Guangdong Wemen and Children Hospital from January 2018 to March 2020 were enrolled. The edge of the hymen was trimmed horizontally for a new incision, while the edge of the crack was also trimmed horizontally separating the vaginal mucosa into the vagina, about 2 cm deep, forming a wavy line-like cutting edge. The submucosa of the vaginal mucosa was stretched and sutured to form the outer edge of the new hymen. The vaginal mucosa was intermittently sutured from the inside to the outside with a 6-0 absorbale thread. The marginal base narrowed the external vaginal opening while the hymen was formed. Photos were taken for patients before operation and 1 month after operation. Satisfaction was monitored during postoperative follow-up.Results:One month after the operation, the incision healing rate of the 18 patients was 94.44%(17/18). The finger examination only accommodated one finger wide, and there was slight pain. During the 6-12 months follow-up by phone or WeChat, 10 cases indicated that they had sex for the first time and all their hymen were ruptured again with bleeding. The remaining 3 cases had no sex and the other three were lost to follow-up. The satisfaction survey showed excellent outcomes in 10 patients and good outcomes in 2 patients. The total satisfaction rate was 92.31%(12/13).Conclusions:This study demonstrates that hymen reformation using local vaginal mucosa can achieved satisfactory outcomes in patients with wide vaginal opening or deep laceration of hymen.

Objective:To investigate the clinical efficacy of a new method of hymenoplasty using local vaginal mucosa.Methods:A total of 18 patients with wide vaginal opening or deep laceration of hymen, admitted by Guangdong Wemen and Children Hospital from January 2018 to March 2020 were enrolled. The edge of the hymen was trimmed horizontally for a new incision, while the edge of the crack was also trimmed horizontally separating the vaginal mucosa into the vagina, about 2 cm deep, forming a wavy line-like cutting edge. The submucosa of the vaginal mucosa was stretched and sutured to form the outer edge of the new hymen. The vaginal mucosa was intermittently sutured from the inside to the outside with a 6-0 absorbale thread. The marginal base narrowed the external vaginal opening while the hymen was formed. Photos were taken for patients before operation and 1 month after operation. Satisfaction was monitored during postoperative follow-up.Results:One month after the operation, the incision healing rate of the 18 patients was 94.44%(17/18). The finger examination only accommodated one finger wide, and there was slight pain. During the 6-12 months follow-up by phone or WeChat, 10 cases indicated that they had sex for the first time and all their hymen were ruptured again with bleeding. The remaining 3 cases had no sex and the other three were lost to follow-up. The satisfaction survey showed excellent outcomes in 10 patients and good outcomes in 2 patients. The total satisfaction rate was 92.31%(12/13).Conclusions:This study demonstrates that hymen reformation using local vaginal mucosa can achieved satisfactory outcomes in patients with wide vaginal opening or deep laceration of hymen.