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.

The prevalence of Class III malocclusion varies among different countries and regions. The populations from Southeast Asian countries (Chinese and Malaysian) showed the highest prevalence rate of 15.8%, which can seriously affect oral function, facial appearance, and mental health. As anterior crossbite tends to worsen with growth, early orthodontic treatment can harness growth potential to normalize maxillofacial development or reduce skeletal malformation severity, thereby reducing the difficulty and shortening the treatment cycle of later-stage treatment. This is beneficial for the physical and mental growth of children. Therefore, early orthodontic treatment for Class III malocclusion is particularly important. Determining the optimal timing for early orthodontic treatment requires a comprehensive assessment of clinical manifestations, dental age, and skeletal age, and can lead to better results with less effort. Currently, standardized treatment guidelines for early orthodontic treatment of Class III malocclusion are lacking. This review provides a comprehensive summary of the etiology, clinical manifestations, classification, and early orthodontic techniques for Class III malocclusion, along with systematic discussions on selecting early treatment plans. The purpose of this expert consensus is to standardize clinical practices and improve the treatment outcomes of Class III malocclusion through early orthodontic treatment.
Humans ; Malocclusion, Angle Class III/classification* ; Orthodontics, Corrective/methods* ; Consensus ; Child

Reconstruction of low-dose CT image faced problems such as low resolution,blurred artifacts and strong noise.Deep learning reconstruction met the needs of reducing radiation dose and improving imaging quality,promoted reconstruction of CT image towards high efficiency,intelligence and integration of clinical diagnosis and treatment.The research progresses in deep learning low-dose CT imaging reconstruction were reviewed in this article.

Reconstruction of low-dose CT image faced problems such as low resolution,blurred artifacts and strong noise.Deep learning reconstruction met the needs of reducing radiation dose and improving imaging quality,promoted reconstruction of CT image towards high efficiency,intelligence and integration of clinical diagnosis and treatment.The research progresses in deep learning low-dose CT imaging reconstruction were reviewed in this article.

OBJECTIVE: To assess the value of using flat-sided culture tubes for preparing chromosomes through chorionic villi (CV) and amniotic fluid (AF) cell cultures during prenatal diagnosis. METHODS: From February to March 2020, 157 CV samples and 147 AF samples subjected to prenatal diagnosis at the Maternal and Child Health Care Hospital of Guangxi Zhuang Autonomous Region were selected as the study subjects. For each sample, one flat-sided tube and one flask culture were set up by following the standard protocols. The methods were evaluated by comparing the cell growth, experimental process, quality of chromosome preparation and costs. RESULTS: The success rates for the culturing of CV and AF samples by the flat-sided culture tube method were 97.45% (153/157) and 97.96% (144/147), respectively. By contrast, the success rates for the conventional flask method were 98.72% (155/157) for CV and 98.64% (145/147) for AF samples. No significant difference was found between the two methods (P > 0.05). The average harvest time required by the flat-sided culture tube method was 8.45 days for CV and 9.43 days for AF cultures, whilst the average harvest time for conventional flask method was 9.05 days and 9.54 days, respectively. The flat-sided culture tube method for CV had required significantly shorter average harvest time than the conventional method (P < 0.001). No statistical significant difference was found in the average harvest time for AF by the two methods (P > 0.05). The conventional culturing method had required three containers with two sample transfers. By contrast, the flat-sided culture tube method was carried out in one tube without any sample transfer. The average total amount of medium used was 3.91 mL for each flat-sided culture tube and 6.26 mL for each conventional flask. CONCLUSION The flat-sided culture tube method can provide a simple, cost-effective and error-reducing procedure for the CV and AF samples culture during prenatal diagnosis.
Child ; Female ; Pregnancy ; Humans ; China ; Prenatal Diagnosis ; Chorionic Villi Sampling ; Amniotic Fluid ; Cell Proliferation

Objective To investigate the correlation between atherogenic index of plasma (AIP) and the severity of hypertriglyceridemic acute pancreatitis (HTG-AP) and the value of AIP combined with Bedside Index for Severity in Acute Pancreatitis (BISAP) score in the early prediction of severe HTG-AP (sHTG-AP). Methods A retrospective analysis was performed for the clinical data of 170 patients with HTG-AP who were hospitalized in The General Hospital of Central Theater Command from January 2017 to December 2021, and according to related guidelines, they were divided into the sHTG-AP group with 28 patients and non-sHTG-AP group with 142 patients. Peripheral blood samples were collected from all patients within 24 hours after admission, and the two groups were compared in terms of sex, age, laboratory test results, AIP, BISAP score, and modified CT severity index (MCTSI) score. The chi-square test or the Fisher's exact test was used for comparison of categorical data between groups; the Mann-Whitney U test was used for comparison of continuous data between groups. The Spearman rank correlation test was used to investigate the correlation between each factor and the severity of HTG-AP, and the binary logistic regression analysis were used to investigate the independent risk factors for sHTG-AP. The receiver operating characteristic (ROC) curve was plotted to assess the predictive efficacy of each indicator. Results There were significant differences between the two groups in the medical history of diabetes, lymphocyte count, albumin, Ca 2+ , triglyceride, high-density lipoprotein cholesterol, AIP, BISAP score, MCTSI score, length of hospital stay, and hospital costs (all P < 0.05). The sHTG-AP group had a longer length of hospital stay, higher hospital costs, and a higher AIP value. AIP (odds ratio [ OR ]=1.244, 95% confidence interval [ CI ]: 1.062-1.458, P =0.007), BISAP score ( OR =5.525, 95% CI : 1.646-18.543, P =0.006), and MCTSI score ( OR =2.029, 95% CI : 1.245-3.305, P =0.004) were risk factors for sHTG-AP. AIP, BISAP score, and MCTSI score were positively correlated with the severity of HTG-AP ( r =0.291, 0.631, and 0.649, all P < 0.001), and AIP was positively correlated with BISAP score and MCTSI score ( r =0.190 and 0.215, both P < 0.05). AIP had an optimal cut-off value of 1.095 in predicting sHTG-AP, and AIP, BISAP score, and AIP combined with BISAP score had an area under the ROC curve of 0.759, 0.887, 0.925, respectively, a sensitivity of 0.821, 0.857, and 0.786, respectively, and a specificity of 0.627, 0.817, and 0.937, respectively (all P < 0.001). Conclusion AIP is a risk factor for sHTG-AP and is correlated with disease severity, and AIP combined with BISAP score has a relatively high value in the early prediction of sHTG-AP.

Objective:To evaluate the detection ability and efficiency of single nucleotide polymorphisms array (SNP-array) and next generation sequencing (NGS) in preimplantation genetic testing (PGT).Methods:Totally 188 couples who carried pathogenic gene mutation and requested preimplantation genetic testing for monogenic (PGT-M) treatment were retrospectively analyzed in the Reproductive Center of Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region during January 2020 and August 2022. After ovulation induction, insemination was conducted by intracytoplasmic sperm injection (ICSI) and cultured in vitro, 995 blastocysts were harvested and biopsied. After whole genome amplification (WGA) of the genetic material from embryonic cell samples, their carrying status of mutations and chromosome copy number variations (CNVs) were analyzed by SNP-array or NGS, respectively, and along with mutation direct detection by Sanger sequencing or Gap-PCR. The relationship between female age and the number of blastocysts was analyzed, as well as the proportion of embryos carrying mutations and pathogenic CNVs. The detection success rate and accuracy of different molecular diagnostic techniques used in PGT were compared. Amniocentesis prenatal diagnosis was performed in the second trimester after successful intrauterine transfer of embryos. Results:1) A total of 924 embryo samples were successfully performed genetic testing, with a total success rate of 92.9%, and 389 embryos (42.1%) can be transferred according to these results. 2) In detecting deletional α-thalassemia, the success rate of Gap-PCR [84.9% (465/548)] was lower than that of SNP-array [98.7% (81/82)] and NGS [92.5% (431/466)]. However, the success rate of direct mutation detection by Sanger sequencing [98.5% (440/447)] was not significantly different from that by SNP-array [95.6% (110/115)] and NGS [96.1% (319/332)]. There were 38 embryo samples with direct mutation detection results inconsistent with those based on SNP haplotyping. In addition, 4 embryo samples failed SNP haplotyping due to chromosomal recombination. 3) Compared with NGS, SNP-array had a lower success rate [83.7% (165/197)] in detecting CNVs, but it could find out more types of chromosomal abnormalities. 4) A total of 152 embryo transfers were performed, 107 patients got clinical pregnancies, 69 patients completed amniocentesis prenatal diagnosis, and 42 healthy infants were delivered.Conclusion:In considering the detection efficiency, SNP-array is suitable for analyzing embryos which carry multiple pathogenic genes, rare monogenic or deletion mutations, whereas NGS is suitable for detecting common types of mutations. Meanwhile, using Sanger sequencing and Gap-PCR to directly detect the mutations can improve the success rate and accuracy of PGT. Our findings would provide a basis for PGT technicians to select appropriate detection platforms based on the type of mutations and the situation of patients.

Objective:To evaluate the detection ability and efficiency of single nucleotide polymorphisms array (SNP-array) and next generation sequencing (NGS) in preimplantation genetic testing (PGT).Methods:Totally 188 couples who carried pathogenic gene mutation and requested preimplantation genetic testing for monogenic (PGT-M) treatment were retrospectively analyzed in the Reproductive Center of Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region during January 2020 and August 2022. After ovulation induction, insemination was conducted by intracytoplasmic sperm injection (ICSI) and cultured in vitro, 995 blastocysts were harvested and biopsied. After whole genome amplification (WGA) of the genetic material from embryonic cell samples, their carrying status of mutations and chromosome copy number variations (CNVs) were analyzed by SNP-array or NGS, respectively, and along with mutation direct detection by Sanger sequencing or Gap-PCR. The relationship between female age and the number of blastocysts was analyzed, as well as the proportion of embryos carrying mutations and pathogenic CNVs. The detection success rate and accuracy of different molecular diagnostic techniques used in PGT were compared. Amniocentesis prenatal diagnosis was performed in the second trimester after successful intrauterine transfer of embryos. Results:1) A total of 924 embryo samples were successfully performed genetic testing, with a total success rate of 92.9%, and 389 embryos (42.1%) can be transferred according to these results. 2) In detecting deletional α-thalassemia, the success rate of Gap-PCR [84.9% (465/548)] was lower than that of SNP-array [98.7% (81/82)] and NGS [92.5% (431/466)]. However, the success rate of direct mutation detection by Sanger sequencing [98.5% (440/447)] was not significantly different from that by SNP-array [95.6% (110/115)] and NGS [96.1% (319/332)]. There were 38 embryo samples with direct mutation detection results inconsistent with those based on SNP haplotyping. In addition, 4 embryo samples failed SNP haplotyping due to chromosomal recombination. 3) Compared with NGS, SNP-array had a lower success rate [83.7% (165/197)] in detecting CNVs, but it could find out more types of chromosomal abnormalities. 4) A total of 152 embryo transfers were performed, 107 patients got clinical pregnancies, 69 patients completed amniocentesis prenatal diagnosis, and 42 healthy infants were delivered.Conclusion:In considering the detection efficiency, SNP-array is suitable for analyzing embryos which carry multiple pathogenic genes, rare monogenic or deletion mutations, whereas NGS is suitable for detecting common types of mutations. Meanwhile, using Sanger sequencing and Gap-PCR to directly detect the mutations can improve the success rate and accuracy of PGT. Our findings would provide a basis for PGT technicians to select appropriate detection platforms based on the type of mutations and the situation of patients.

Bone regeneration remains a great clinical challenge. Low intensity near-infrared (NIR) light showed strong potential to promote tissue regeneration, offering a promising strategy for bone defect regeneration. However, the effect and underlying mechanism of NIR on bone regeneration remain unclear. We demonstrated that bone regeneration in the rat skull defect model was significantly accelerated with low-intensity NIR stimulation. In vitro studies showed that NIR stimulation could promote the osteoblast differentiation in bone mesenchymal stem cells (BMSCs) and MC3T3-E1 cells, which was associated with increased ubiquitination of the core circadian clock protein Cryptochrome 1 (CRY1) in the nucleus. We found that the reduction of CRY1 induced by NIR light activated the bone morphogenetic protein (BMP) signaling pathways, promoting SMAD1/5/9 phosphorylation and increasing the expression levels of Runx2 and Osterix. NIR light treatment may act through sodium voltage-gated channel Scn4a, which may be a potential responder of NIR light to accelerate bone regeneration. Together, these findings suggest that low-intensity NIR light may promote in situ bone regeneration in a CRY1-dependent manner, providing a novel, efficient and non-invasive strategy to promote bone regeneration for clinical bone defects.
Animals ; Rats ; Bone Morphogenetic Protein 2/metabolism* ; Bone Regeneration ; Cell Differentiation ; Circadian Clocks ; Cryptochromes/metabolism* ; Osteoblasts/metabolism* ; Osteogenesis ; Transcription Factors/metabolism*

More and more studies have found that red blood cell distribution width (RDW) can be used for acute pancreatitis (AP) classification, dynamic monitoring and evaluation of disease severity, mortality, prognosis and complication. Some inflammatory markers, such as procalcitonin (PCT), C-reactive protein (CRP), neutrophil-to-lymphocyte ratio (NLR) and pancreatitis scoring system are also associated with severity of AP, and can further improve the evaluation of AP severity when combined with RDW. This article reviewed the RDW and classification of AP, the dynamic changes of RDW and AP, RDW combined with inflammatory indices for prediction of severity of AP, and RDW combined with pancreatitis scoring system for prediction of severity of AP, so as to improve the understanding of predictive value of RDW in assessing the severity of AP.