ObjectiveTo investigate the mechanisms by which Huanglian Jiedutang （HLJDT） modulates microglial （MG） phenotypes through the sialic acid-binding Ig-like lectin 2 （SIGLEC2/CD22）/Src-homology-2-domain-containing protein tyrosine phosphatase-1 （SHP-1）/phosphorylated protein kinase B （p-Akt） signaling pathway， thereby promoting myelin repair and alleviating agitation-like behaviors in vascular dementia （VAD）. MethodsSixty C57BL/6J mice were randomly assigned to a sham （normal） group， model group， HLJDT low-， medium-， and high-dose groups （2.5， 5， and 10 g·kg^-1·d^-1）， and a risperidone group （2 mg·kg^-1·d^-1）， with 10 mice per group. VAD was induced by bilateral common carotid artery stenosis （BCAS）. From day 42， mice received drug interventions for 2 weeks. Agitation-like behaviors were assessed using the resident-intruder test. After behavioral testing， ventrolateral part of the ventromedial hypothalamus （VMHvl） tissues were collected. Western blot was used to measure protein levels of myelin oligodendrocyte glycoprotein （MOG）， myelin basic protein （MBP）， proteolipid protein （PLP）， inducible nitric oxide synthase （iNOS）， arginase-1 （Arg1）， CD86， CD206， and CD22， SHP-1， and p-Akt. Immunofluorescence was used to evaluate myelin-associated glycoprotein （MAG） intensity and the proportion of iNOS⁺/ionized calcium-binding adapter molecule 1 （Iba1）⁺ cells. ELISA was used to detect tumor necrosis factor-α （TNF-α）， interleukin （IL）-6， and IL-1β. ResultsCompared with the normal group， the model group exhibited markedly increased biting and aggressive behaviors and shortened attack latency （P<0.01）. MOG， MBP， and PLP protein levels and MAG fluorescence intensity were significantly reduced （P<0.05， P<0.01）. INOS and CD86 expression and TNF-α， IL-6， and IL-1β levels were significantly elevated （P<0.01）. CD22 and SHP-1 expression increased significantly （P<0.01）， whereas p-Akt expression decreased （P<0.01）. Compared with the model group， the medium- and high-dose HLJDT groups and the risperidone group showed markedly reduced biting and aggression （P<0.05， P<0.01） and prolonged attack latency （P<0.01）. MOG， MBP， and PLP levels and MAG fluorescence intensity were significantly increased （P<0.05， P<0.01）. INOS， CD86， TNF-α， IL-6， and IL-1β levels decreased significantly （P<0.05， P<0.01）. CD22 and SHP-1 expression decreased， while p-Akt expression increased significantly （P<0.05， P<0.01）. ConclusionHLJDT may modulate CD22/SHP-1/p-Akt signaling in the VMHvl， promote the shift of MG toward an anti-inflammatory and phagocytic phenotype， enhance myelin repair， and improve agitation-like behaviors in VAD mice.

Chronic mucocutaneous candidiasis (CMC) is an infectious phenotype characterized by recurrent or persistent infections caused by Candida species that affect the skin, nails, oral, and genital mucosae for a duration exceeding six months. Current research suggests that CMC is an immunodeficiency disease with a complex pathogenesis. Patients with CMC have various defects in nonspecific and/or specific immunity against Candida infection, resulting in the inability of patients to defend themselves against Candida infection. CMC can be stratified into primary CMC and secondary CMC based on etiology. Primary CMC is often associated with genetic mutations leading to immunodeficiencies in T helper cell 17 and interleukin-17, whereas secondary CMC is frequently linked to factors such as human immunodeficiency virus infection, diabetes mellitus, and immunosuppressive therapy. Primary CMC typically manifests as Candida infections, with distinct genetic mutations often correlating to varied concomitant symptoms. Secondary CMC may present with not only superficial mucosal Candida infections and manifestations of the underlying primary disease but also with invasive fungal infections. Diagnosing CMC requires an integration of medical history and clinical presentation, supplemented by the outcomes of auxiliary diagnostic procedures, including microscopic examination of fungal smear, fungal culture, immunological testing, and genetic sequencing and analysis. Furthermore, confirming primary CMC requires exclusion of the aforementioned secondary factors. At present, antifungal drugs such as triazoles, echinocandins, and polyenes are the main treatment for CMC. Moreover, immunotherapy with biologics such as Janus kinase (JAK) inhibitors provides more options for the clinical treatment of patients with CMC. Gene therapy also has potential clinical application value. In this review, we discuss the etiologies, pathogenesis, clinical manifestations, diagnosis, and treatments of CMC, aiming to provide a reference for the clinical diagnosis and treatment of CMC.

Objective: To assess the effect of 12-year-old children s pit and fissure sealants on the health of first permanent molars, so as to provide evidence for optimizing caries prevention strategies among children. Methods: In March 2025, a cluster random sampling method was used to conduct oral examinations on 965 students aged 12 from Chengdu s 2021 Comprehensive Intervention Program for Pediatric Oral Diseases. Data from the Comprehensive Intervention System for Children s Oral Diseases were referenced. Participants were divided into a sealed group ( n =755) and an unsealed group ( n =210) based on whether they had received sealants on their first permanent molars. Chi square test or analysis of variance were used to compare indicators such as caries incidence, new caries detection rate, and new caries mean (DMFT increment) between the two groups Results: The sealed group showed significantly lower caries incidence, new caries detection rate, and new caries mean (33.38%, 17.65%, 0.59±1.00) compared to the unsealed group (43.81%, 24.70%, 0.87±1.22)( χ 2/F =7.79, 18.26, 9.55, all P <0.05). However, no significant difference was found in the filled teeth ratio between the two groups (20.38% , 20.16%; χ 2=0.01, P =0.94). In girls, the sealed group exhibited significantly lower caries incidence, new caries detection rate, and new caries mean (36.78%, 20.99%, 0.69± 1.10 ) than the unsealed group (57.55%, 33.52%, 1.15±1.29) ( χ 2/F =14.42, 23.76, 10.92, all P <0.05), whereas no significant differences were observed between boys in the sealed (30.47%, 14.85%, 0.50±0.89) and unsealed groups (29.81%, 16.18%, 0.59± 1.08) ( χ 2/F =0.02, 0.41, 0.74, all P >0.05). Boys had significantly lower new caries detection rates and new caries means than girls in both groups ( χ 2/F =16.20, 6.94; 29.93, 11.84, all P <0.05). In urban areas, the sealed group had lower new caries detection rates and new caries means (19.37%, 0.68±1.04) than the unsealed group (24.66%, 0.90±1.20) ( χ 2/F =6.86, 3.94, both P <0.05). In suburban areas, all indicators for the sealed group (24.71%, 13.77%, 0.42±0.87) were significantly lower than those for the unsealed group (38.81%, 24.77%, 0.82±1.28) ( χ 2/F =5.28, 15.36, 6.00, all P <0.05). Indicators from specialized dental institutions (11.25%, 4.81%, 0.16±0.56) were significantly lower than those from county level or above general hospitals (33.33%, 19.11%, 0.38±1.00) and primary healthcare institutions (37.59%, 19.24%, 0.67±1.05) ( χ 2/F =20.99, 34.31, 21.08 , all P <0.01). Conclusions The 12-year-old children s pit and fissure sealants effectively reduce the caries incidence in first permanent molars, particularly showing significant effectiveness in girls and suburban children. Intervention strategies should be optimized according to gender.

ObjectiveTo investigate differential metabolites associated with browning in the post-harvest processing of Pinelliae Rhizoma， providing data support for elucidating the key metabolites and metabolic pathways involved in browning， and developing safe and efficient sulfur-free processing techniques. MethodsUltra-performance liquid chromatography-triple quadrupole/linear ion trap mass spectrometry（UPLC-QTRAP-MS/MS） was used to detect the metabolites of Pinelliae Rhizoma at different browning stages（0， 8， 16 h） for widely targeted metabolomics. Subsequently， Multivariate statistical analysis of metabolites was conducted using principal component analysis（PCA）， hierarchical cluster analysis（HCA）， orthogonal partial least squares-discriminant analysis（OPLS-DA）， and K-means cluster analysis. Differential metabolites at different browning stages were screened based on variable importance in the projection（VIP） value>1 and |log₂fold change（FC）|≥1， and metabolic pathway enrichment analysis was performed using Kyoto Encyclopedia of Genes and Genomes（KEGG）. ResultsA total of 1 416 metabolites were identified across the three browning stages of Pinelliae Rhizoma， predominantly comprising amino acids and their derivatives（239）， lipids（219）， alkaloids（156）， phenolic acids（121）， terpenoids（113）， and flavonoids（111）. A two-by-two comparison of the three browning phases， yielded 622 differential metabolites that were significantly enriched in the phenylpropanoid biosynthesis， flavone and flavonol biosynthesis， and purine metabolic pathway. Further analysis revealed that carbohydrates such as D-mannose and turanose， phenolic acids such as 1-O-caffeoyl-6-O-glucosyl-β-D-glucose， dicaffeoylshikimic acid， and flavonoids such as epigallocatechin gallate， vitexin-7-O-rutinoside， luteolin-7-O-（6″-malonyl）glucoside-5-O-arabinoside， catechin gallate， epicatechin gallate， isovitexin-7-O-glucoside-2″-O-rhamnoside， apigenin-7-O-rutinoside-4ʹ-O-sophoroside， 3，5，3ʹ，4ʹ，5ʹ-penta-hydroxyflavan-7-gallate may act as browning substrates and play important roles in the browning process. ConclusionCarbohydrates， phenolic acids， and flavonoids may serve as key substrates in the browning process of Pinelliae Rhizoma， involving pathways such as phenylpropanoid biosynthesis， flavone and flavonol biosynthesis， and purine metabolism， which can provide a theoretical basis for further exploration of the browning mechanism.

Objective To evaluate the impact of an integrated management mode of prenatal diagnosis-postnatal treatment for congenital heart disease (CHD) on perioperative and long-term outcomes of the arterial switch operation (ASO), and to analyze the efficacy of ASO in a single center. Methods This retrospective study analyzed the clinical data of 183 children who underwent ASO at Guangdong Provincial People’s Hospital from 2018 to 2024. The cohort included 106 (57.9%) patients of transposition of the great arteries with intact ventricular septum (TGA/IVS), 61 (33.3%) patients of transposition of the great arteries with ventricular septal defect (TGA/VSD), and 16 (8.7%) patients of Taussig-bing anomaly (TBA). Perioperative indicators were compared between 91 patients in the prenatal-postnatal integrated management group (an integrated group) and 92 patients in the traditional management group (a non-integrated group). Long-term survival and reoperation rates were analyzed using Kaplan-Meier curves. Results The overall perioperative mortality rate was 4.9% (9/183), showing a downward trend year by year. The primary cause of perioperative mortality was low cardiac output syndrome (LCOS), which occurred in 12 patients (6.6% incidence) with a mortality rate of 75.0%. The integrated group had a higher proportion of males (89.0% vs. 72.8%, P<0.05) and lower body weight [3.1 (2.7, 3.3) kg vs. 3.3 (3.0, 3.7) kg, P<0.05] compared to the non-integrated group. The age at surgery was significantly earlier in the integrated group [7 (3, 10) d vs. 14 (9, 48) d, P<0.05], and all children in the integrated group underwent ASO within the optimal surgical window (100.0% vs. 82.6%, P<0.05). Intraoperatively, cardiopulmonary bypass time [173 (150, 207) min vs. 186 (159, 237) min, P<0.05] and aortic cross-clamp time [100 (90, 117) min vs. 116 (97, 142) min, P<0.05] were significantly shorter in the integrated group. Although the integrated group had longer postoperative mechanical ventilation time [145 (98, 214) h vs. 116 (77, 147) h, P<0.05] and higher 48-hour maximum vasoactive inotropic score [15 (10, 21) points vs. 12 (8, 16) points, P<0.05], there was no statistically significant difference in the incidence of severe complications (LCOS, necrotizing enterocolitis, extracorporeal membrane oxygenation) or mortality rate (3.3% vs. 6.5%, P=0.51) between the two groups, despite earlier surgical intervention and a higher proportion of critically ill cases in the integrated group. The length of hospital stay in the emergency surgery group was significantly shorter than that in the elective surgery group [20 (15, 28) d vs. 25 (21, 30) d, P<0.05], suggesting that early surgery may be of potential benefit. A total of 163 patients were successfully followed up for a median of 4.7 years, with a 5-year survival rate of 95.1% and a freedom from reintervention survival rate of 95.1%. There were no late deaths, and the most common postoperative complication was pulmonary artery stenosis. Conclusion The integrated management model allowed critically ill children with lower body weights to safely undergo surgery, significantly optimizing the timing of surgery and shortening intraoperative times. The long-term risk of reoperation after ASO is primarily concentrated on pulmonary artery stenosis, necessitating long-term follow-up and monitoring.

ObjectiveThis paper aims to investigate the material basis of the anti-inflammatory efficacy and mechanism of action of Bushen Tongdu prescription （BSTDP）. MethodsThe chemical components of BSTDP and its blood-absorbed components in vivo were systematically identified by using ultra-performance liquid chromatography-linear ion trap-electrostatic field orbitrap high-resolution mass spectrometry （UPLC-LIT-Orbitrap-MS）. Network pharmacology was employed to screen blood-absorbed bioactive components and potential targets of this formula. A protein-protein interaction （PPI） network of core targets was constructed to conduct enrichment analysis. Molecular docking was further utilized to verify the binding affinity between key components and targets. The inflammatory model was established and verified in vivo by using a transgenic zebrafish Tg （mpx： GFP）. At three days post-fertilization （3 dpf）， larvae of zebrafish were randomly assigned to blank group， model group， positive drug dexamethasone acetate group （75 μmol·L^-1）， and BSTDP groups with low， medium， and high doses （500， 1 000， and 2 000 mg·L^-1）. The distribution and quantity of neutrophils in the yolk sac region were observed under a fluorescence microscope. The mRNA expression levels of key genes in the toll-like receptor 4 （TLR4）/myeloid differentiation factor 88 （MyD88）/nuclear factor kappa-B （NF-κB） signaling pathway and inflammatory factors including interleukin （IL）-1β， IL-6， and tumor necrosis factor-α （TNF-α） were detected by Real-time quantitative polymerase chain reaction （Real-time PCR）. ResultsA total of 120 chemical components were identified in BSTDP， among which 26 original components were confirmed by using serum pharmacochemical methods. A total of 227 common targets linking rheumatoid arthritis （RA） and the blood-absorbed components were screened by network pharmacology. It is suggested that pseudobrucine， vomicine， sinapine， rehmannioside， cinnamyl alcohol glycoside， and methylephedrine exert anti-inflammatory effects by acting on core targets including protein kinase B1 （Akt1）， signal transducer and activator of transcription 3 （STAT3）， tumor necrosis factor （TNF）， TLR4， mitogen-activated protein kinase 14 （MAPK14）， and phosphatidylinositol-4，5-bisphosphate 3-kinase catalytic subunit α （PIK3CA）， thereby modulating multiple signaling pathways such as TLR4 and NF-κB. In vivo verification in zebrafish demonstrates that the maximum tolerable concentration of Bushen Tongdu Formula is 2 000 mg·L^-1. Compared to those in the blank group， zebrafish in the model group showed a significantly higher number of neutrophils in the yolk sac region （P<0.01） and rising mRNA levels of TLR4， MyD88， NF-κB， TNF-α， IL-6， and IL-1β （P<0.01）. Compared to that in the model group， the number of neutrophils was significantly reduced in BSTDP groups with medium and high doses， as well as the dexamethasone acetate group （P<0.05， P<0.01）. There was no statistically significant difference in the low dose group. The mRNA expression levels of TLR4， MyD88， NF-κB， TNF-α， IL-6， and IL-1β were significantly down-regulated （P<0.05， P<0.01）. ConclusionThis paper identifies the material basis of the efficacy of BSTDP， demonstrating that the formula can exert an anti-inflammatory effect through the TLR4/MyD88/NF-κB signaling pathway. The results provide scientific experimental evidence for its further clinical application.

Puji Xiaoduyin， a specialized formula for the swollen-head epidemic， was recorded in the Catalogue of Ancient Classical Formula （the Second Batch）-Han Medicine， published in September 2023. It had been inherited and developed by medical experts of successive generations and passed down to this day. This paper sorted out the historical evolution of this formula using bibliometric methods. It also comprehensively analyzed key information on the formula name， historical origin， drug dosage， herb origin， processing methods， decocting methods， function， and clinical applications. Additionally， this paper analyzed the application of this formula in both modern and ancient times. Results showed that the formula was first recorded as "Puji Xiaodu Yinzi" in LI Dongyuan's Proven Formulas written by LI Gao from the Jin dynasty. The medicinal composition and dosage were： Scutellariae Radix and Coptidis Rhizoma （20.65 g each）， Ginseng Radix et Rhizoma 12.39 g， Scrophulariae Radix， Citri Reticulatae Pericarpium， and Glycyrrhizae Radix et Rhizoma （8.26 g each）， Forsythiae Fructus， Arctii Fructus， Isatidis Radix， and Lasiosphaera Calvatia （4.13 g each）， Bombyx Batryticatus and Cimicifugae Rhizoma （2.891 g each）， Bupleuri Radix and Platycodonis Radix （8.26 g each）. These medicines were grounded to fine powder. One dose， including 20.65 g of the powder， was mixed with 600 mL of water and decocted to 300 mL. After abandoning slag， the medicine should be taken warm frequently. In the formula， Bombyx Batryticatus is stir-fired. With the effect of dispersing wind and clearing heat， removing stagnation and dissipating mass， the formula is specialized in swollen-head epidemic， pestilence， red and swelling head， face， and neck， dry mouth and tongue， as well as other diseases resulting from toxic heat stagnated in the upper jiao. The formula is widely used in treating diseases involving the respiratory， dermal， ophthalmologic， otolaryngologic， and nervous systems. The formula is most frequently used for respiratory diseases， with a wide range of symptoms including parotitis/mumps （66 times）， followed by tonsillitis （28 times）. In conclusion， the broadly applied formula has accurate efficacy and great development value.

ObjectiveThis paper aims to investigate the material basis of the anti-inflammatory efficacy and mechanism of action of Bushen Tongdu prescription （BSTDP）. MethodsThe chemical components of BSTDP and its blood-absorbed components in vivo were systematically identified by using ultra-performance liquid chromatography-linear ion trap-electrostatic field orbitrap high-resolution mass spectrometry （UPLC-LIT-Orbitrap-MS）. Network pharmacology was employed to screen blood-absorbed bioactive components and potential targets of this formula. A protein-protein interaction （PPI） network of core targets was constructed to conduct enrichment analysis. Molecular docking was further utilized to verify the binding affinity between key components and targets. The inflammatory model was established and verified in vivo by using a transgenic zebrafish Tg （mpx： GFP）. At three days post-fertilization （3 dpf）， larvae of zebrafish were randomly assigned to blank group， model group， positive drug dexamethasone acetate group （75 μmol·L^-1）， and BSTDP groups with low， medium， and high doses （500， 1 000， and 2 000 mg·L^-1）. The distribution and quantity of neutrophils in the yolk sac region were observed under a fluorescence microscope. The mRNA expression levels of key genes in the toll-like receptor 4 （TLR4）/myeloid differentiation factor 88 （MyD88）/nuclear factor kappa-B （NF-κB） signaling pathway and inflammatory factors including interleukin （IL）-1β， IL-6， and tumor necrosis factor-α （TNF-α） were detected by Real-time quantitative polymerase chain reaction （Real-time PCR）. ResultsA total of 120 chemical components were identified in BSTDP， among which 26 original components were confirmed by using serum pharmacochemical methods. A total of 227 common targets linking rheumatoid arthritis （RA） and the blood-absorbed components were screened by network pharmacology. It is suggested that pseudobrucine， vomicine， sinapine， rehmannioside， cinnamyl alcohol glycoside， and methylephedrine exert anti-inflammatory effects by acting on core targets including protein kinase B1 （Akt1）， signal transducer and activator of transcription 3 （STAT3）， tumor necrosis factor （TNF）， TLR4， mitogen-activated protein kinase 14 （MAPK14）， and phosphatidylinositol-4，5-bisphosphate 3-kinase catalytic subunit α （PIK3CA）， thereby modulating multiple signaling pathways such as TLR4 and NF-κB. In vivo verification in zebrafish demonstrates that the maximum tolerable concentration of Bushen Tongdu Formula is 2 000 mg·L^-1. Compared to those in the blank group， zebrafish in the model group showed a significantly higher number of neutrophils in the yolk sac region （P<0.01） and rising mRNA levels of TLR4， MyD88， NF-κB， TNF-α， IL-6， and IL-1β （P<0.01）. Compared to that in the model group， the number of neutrophils was significantly reduced in BSTDP groups with medium and high doses， as well as the dexamethasone acetate group （P<0.05， P<0.01）. There was no statistically significant difference in the low dose group. The mRNA expression levels of TLR4， MyD88， NF-κB， TNF-α， IL-6， and IL-1β were significantly down-regulated （P<0.05， P<0.01）. ConclusionThis paper identifies the material basis of the efficacy of BSTDP， demonstrating that the formula can exert an anti-inflammatory effect through the TLR4/MyD88/NF-κB signaling pathway. The results provide scientific experimental evidence for its further clinical application.

Puji Xiaoduyin， a specialized formula for the swollen-head epidemic， was recorded in the Catalogue of Ancient Classical Formula （the Second Batch）-Han Medicine， published in September 2023. It had been inherited and developed by medical experts of successive generations and passed down to this day. This paper sorted out the historical evolution of this formula using bibliometric methods. It also comprehensively analyzed key information on the formula name， historical origin， drug dosage， herb origin， processing methods， decocting methods， function， and clinical applications. Additionally， this paper analyzed the application of this formula in both modern and ancient times. Results showed that the formula was first recorded as "Puji Xiaodu Yinzi" in LI Dongyuan's Proven Formulas written by LI Gao from the Jin dynasty. The medicinal composition and dosage were： Scutellariae Radix and Coptidis Rhizoma （20.65 g each）， Ginseng Radix et Rhizoma 12.39 g， Scrophulariae Radix， Citri Reticulatae Pericarpium， and Glycyrrhizae Radix et Rhizoma （8.26 g each）， Forsythiae Fructus， Arctii Fructus， Isatidis Radix， and Lasiosphaera Calvatia （4.13 g each）， Bombyx Batryticatus and Cimicifugae Rhizoma （2.891 g each）， Bupleuri Radix and Platycodonis Radix （8.26 g each）. These medicines were grounded to fine powder. One dose， including 20.65 g of the powder， was mixed with 600 mL of water and decocted to 300 mL. After abandoning slag， the medicine should be taken warm frequently. In the formula， Bombyx Batryticatus is stir-fired. With the effect of dispersing wind and clearing heat， removing stagnation and dissipating mass， the formula is specialized in swollen-head epidemic， pestilence， red and swelling head， face， and neck， dry mouth and tongue， as well as other diseases resulting from toxic heat stagnated in the upper jiao. The formula is widely used in treating diseases involving the respiratory， dermal， ophthalmologic， otolaryngologic， and nervous systems. The formula is most frequently used for respiratory diseases， with a wide range of symptoms including parotitis/mumps （66 times）， followed by tonsillitis （28 times）. In conclusion， the broadly applied formula has accurate efficacy and great development value.

OBJECTIVE: To explore the genetic etiology of 46 Chinese pedigrees affected with Hereditary multiple exostoses (HME) and provide genetic counseling and reproductive intervention. METHODS: Whole-exome sequencing and Sanger sequencing were carried out on 87 patients from the 46 pedigrees to analyze the variants of EXT1 and EXT2 genes. Pathogenicity of the variants was assessed based on the guidelines from the American College of Medical Genetics and Genomics and Association for Molecular Pathology (ACMG/AMP). Prenatal diagnosis and preimplantation genetic testing (PGT) were provided for couples with identified pathogenic mutations. This study was approved by the Medical Ethics Committee of the hospital (Ethics No.: LL-SC-SG-2014-010). RESULTS: In total 17 and 22 pathogenic variants were respectively identified in the EXT1 and EXT2 genes, among which 5 EXT1 and 12 EXT2 variants were unreported previously. Three patients with no family history were found to harbor de novo variants of the EXT1 gene. Twenty nine couples had opted for PGT or underwent prenatal diagnosis following natural conception, and 17 healthy babies were born. CONCLUSION This study has clarified the genetic etiology of 45 HME pedigrees and identified 17 novel variants, which has enriched the mutational spectrum of the EXT1 and EXT2 genes. Reproductive intervention through PGT and prenatal diagnosis have prevented the recurrence of HME in these families.
Humans ; Female ; Male ; Pedigree ; Exostoses, Multiple Hereditary/diagnosis* ; N-Acetylglucosaminyltransferases/genetics* ; Adult ; Exostosin 1 ; Asian People/genetics* ; Genetic Testing ; Exostosin 2 ; Mutation ; China ; Prenatal Diagnosis ; Pregnancy ; Genetic Counseling ; Preimplantation Diagnosis ; Exome Sequencing ; East Asian People