To summarize the clinical experience of treating idiopathic olfactory disorder from the perspective of heart and lungs. It is believed that the sense of olfaction is based on the nose， rooted in the heart， functioning through the lungs， and conveyed by pectoral qi. The key pathogenesis of idiopathic olfactory disorder lies in the accumulation of pathogenic factors in the heart and lungs， blood vessel obstruction， the failure of the lungs to disperse and descend， and the loss of control of pectoral qi. In treatment， internal and external therapies could be combined. The internal therapy can correct the imbalance of the zang-fu organs， using the self-prescribed Bilong Formula （鼻聋方） to dispel wind and diffuse the lung， invigorate blood and relieving stuffy orifices； the external therapy can clear nasal obstruction， supplemented by intradermal needle embedding at three acupoints， bilateral Yingxiang （LI 20）， bilateral Shangyingxiang （EX-HN 8） and Yintang （GV 29）， and integrated olfactory training for comprehensive treatment.

Objective: To present the plotting of trend analysis charts and the application of multi-rule trend analysis method for monitoring the quality of whole blood, washed red blood cells, and leukocyte-depleted suspended red blood cells. Methods: Samples of whole blood, washed red blood cells, and leukocyte-depleted suspended red blood cells were collected in accordance with relevant protocols and requirements. The results of blood quality testing were compiled. The trend line charts were plotted for the deviation rates of volume, hemoglobin (Hb) content, supernatant protein content, and leukocyte residual count. In addition, the trend line chart were plotted for hematocrit and post-storage hemolysis rate. Results: The trend analysis rules for the deviation rate of volume from the standard were: 1 categorized as out-of-control, (3 of 4) as warning, R as warning, 8 as alert, and 12 as alert. For Hb content deviation rate, the rules were: <0% categorized as out-of-control; <20% but ≥0% (for whole blood) or <10% but ≥0% (for washed red blood cells and leukocyte-depleted suspended red blood cells) as a warning. For supernatant protein content deviation rate, the rules were: ≥0.0% as out-of-control, and >-10% but <0.0% as a warning. For hematocrit, the rules were: 1 as out-of-control and (3 of 4) as warning. For leukocyte residual count deviation rate, the rules were: >0.0% as out-of-control, and >-10% but ≤0.0% as a warning. For post-storage hemolysis rate, the rule was: ≥0.8% out-of-control. Conclusion: The application of multi-rule trend analysis facilitates the timely identification of trend abnormalities and factors causing deviations in the collection and preparation processes of whole blood, washed red blood cells, and leukocyte-depleted suspended red blood cells, thereby providing reliable numerical evidence for their correction and adjustment.

BackgroundInvasive vagus nerve stimulation therapy has been approved for the adjunctive treatment of treatment-resistant depression， which may contribute to the anti-inflammatory properties of vagus nerve stimulation （VNS）， whereas the efficacy of non-invasive transcutaneous cervical vagus nerve stimulation （tcVNS） in treating major depressive disorder （MDD） and its impact on plasma inflammatory factors remain unclear. ObjectiveTo observe the effect of escitaloprom combined with tcVNS on the status of depression， anxiety and sleep quality as well as the plasma levels of interleukin-6 （IL-6） and interleukin-10 （IL-10） in MDD patients， in order to provide references for the recovery and treatment of MDD patients. MethodsFrom August 21， 2019 to April 17， 2024， 45 patients who met the diagnostic criteria for MDD in the Diagnostic and Statistical Manual of Mental Disorders， fifth edition （DSM-5） were recruited from the psychosomatic outpatient clinic of the First Affiliated Hospital of Air Force Military Medical University. Subjects were divided into study group （n=23） and control group （n=22） using random number table method. All patients were treated with escitalopram. On this basis， study group added a 30-minute tcVNS therapy once a day for 4 weeks. While control group was given corresponding sham stimulation， and the duration of each stimulation lasted 30 seconds. Before and after 4 weeks of treatment， Hamilton Depression Scale-17 item （HAMD-17） was used to assess depressive symptoms， and HAMD-17 anxiety/somatization subfactor and insomnia subfactor were used to assess patients' anxiety/somatization symptoms and sleep quality. Levels of plasma IL-6 and IL-10 were measured by enzyme-linked immunosorbent assay （ELISA）. ResultsThe generalized estimating equation model yielded a significant time effect for HAMD-17 total score， anxiety/somatization subfactor score and insomnia subfactor score in both groups （Wald χ²=315.226， 495.481， 82.420， P<0.01）. After 4 weeks of treatment， HAMD-17 total score and anxiety/somatization subfactor score of study group were lower than those of control group， with statistically significant differences （Wald χ²=4.967， 32.543， P<0.05 or 0.01）， while no statistically significant difference was found in the insomnia subfactor score between two groups （Wald χ²=0.819， P=0.366）. Significant time effects were reported on plasma IL-6 and IL-10 levels in both groups （Wald χ²=21.792， 5.242， P<0.05 or 0.01）. Compared with baseline data， a reduction in plasma IL-6 levels was detected in both groups （Wald χ²=22.015， 6.803， P<0.01）， and an increase in plasma IL-10 levels was reported in study group （Wald χ²=5.118， P=0.024） after 4 weeks of treatment. ConclusionEscitalopram combined with tcVNS therapy is effective in improving depressive symptoms， anxiety/somatization symptoms and sleep quality in patients with MDD. Additionally， it helps reduce plasma IL-6 levels and increase IL-10 levels. ［Funded by Shaanxi Provincial Key Research and Development Program-General Project （number， 2023-YBSF-185）， www.clinicaltrials.gov number， NCT04037111］

OBJECTIVE To explore comprehensive management and potential issues associated with long-term prescriptions medications of psychiatry， in order to provide a reference for the comprehensive management of long-term prescriptions of psychiatry in psychiatric hospitals and other medical institutions’ pharmacies. METHODS Starting from the applicable principles for long-term prescriptions of psychiatry， this study introduced the standardized assessment and precautions before issuing long-term prescriptions， the formulation and adjustment of the drug list， as well as the rational management of the long-term prescriptions. It also analyzed potential issues that may arise in the comprehensive management of long-term prescription medications and proposed corresponding countermeasures and suggestions. RESULTS & CONCLUSIONS Prior to initiating long-term prescriptions， a standardized assessment should be conducted on patients from the aspects of their psychiatric condition and long-term potential risk factors， pharmacological treatment plans and other non-pharmacological therapies， physical illnesses. Additionally， healthcare providers should fulfill their obligation to inform patients or their family members. The comprehensive management of long-term prescription medications should be jointly established and improved by multiple departments， and the formulation of drug catalogs should avoid including drugs with potential social harm or medication risks while complying with policy requirements. Furthermore， measures such as adding special identifiers to long-term prescriptions， providing patients with reminders about （No.YGLX202537） prescription expiration， or offering online consultations can also effectively enhance the rationality of medication use under long-term prescriptions. Currently， the implementation of long-term prescriptions in psychiatry remains challenged by inconsistencies in prescription duration， incomplete coverage of diagnostic categories， poor patient adherence， and the risk of deviation in clinical assessments. In this regard， measures such as collaborating with multiple departments to strengthen long-term prescription information management， providing matching pharmaceutical services， ensuring the quality and rationality of long-term prescription implementation， and using modern methods to screen high-risk patients can be taken to improve patient medication compliance and safety.

Objective:To provide preimplantation genetic testing (PGT) for a patient with Incontinentia pigmenti (IP) due to IKBKG gene variant but without family samples through construction of single nucleotide polymorphism (SNP)-based haplotype by Long-read sequencing (LRS) technology. Methods:A female IP patient with a heterozygous IKBKG c. 1167dup variant but without family genetic data who sought genetic counseling at Women and Children′s Hospital of Ningbo University in November 2021 was selected as the study subject. The IKBKG gene has a highly homologous pseudogene IKBKGP1. Genomic DNA was extracted from peripheral blood samples from the couple, and LRS was used to obtain informative SNP loci flanking the variant locus, enabling the construction of SNP haplotype with a long segment spanning from the non-homologous region of IKBKG to the variant site. Trophoblast cells were biopsied from blastocysts fertilized through intracytoplasmic sperm injection, and next-generation sequencing (NGS) was used to determine the SNP information of the embryos. Linkage analysis with the parental SNP haplotypes was conducted to detect the carrier status of the embryos and exclude chromosomal aneuploidies. Sanger sequencing was carried out to validate the result. A euploid embryo without the pathogenic variant was selected for transfer. Prenatal diagnosis was carried out by amniocentesis at mid-trimester to verify the result of PGT, and follow-up was conducted after the baby was born. This study has been approved by the Ethics Committee of the Women and Children′s Hospital of Ningbo University (Ethics No. EC2023-094). Results:In total seven blastocysts were tested, and PGT results indicated that two embryos were euploid and did not carry the pathogenic variant. One euploid embryo was transferred, which resulted in a singleton pregnancy. Amniocentesis at 24 weeks of gestation confirmed that the status of fetal IKBKG gene, and its chromosomal status was consistent with the PGT results. A healthy male infant was born at 38 + 6 weeks of gestation. Conclusion:For IP patients with de novo mutation or without family samples, PGT with LRS can directly construct the SNP-based haplotype while avoiding interference from pseudogenes, providing an effective strategy for PGT.

OBJECTIVE: To explore the effect mechanism of electroacupuncture (EA) for ameliorating diabetic peripheral neuropathy (DPN) based on the analysis of gut microbiota and metabolomics. METHODS: Thirty SPF-grade male SD rats were randomly divided into a normal group, a model group, and an EA group, with 10 rats in each one. Except in the normal group, the intraperitoneally injection with streptozotocin was used to induce diabetes mellitus model in the rest groups. In the EA group, acupuncture was delivered at bilateral "Zusanli" (ST36), "Sanyinjiao" (SP6), "Pishu" (BL20) and "Shenshu" (BL23), and electric stimulation was attached to "Zusanli" (ST36)-"Sanyinjiao" (SP6) and "Pishu" (BL20)-"Shenshu" (BL23), on the same side, with continuous wave and a frequency of 2 Hz, for 10 min in each intervention. The intervention measure of each group was delivered once every 2 days, 3 times a week, for 8 consecutive weeks. Body weight, random blood glucose (RBG), thermal withdrawal latency (TWL), and mechanical withdrawal threshold (MWT) before intervention, and in 4 and 8 weeks of intervention, separately, as well as sensory nerve conduction velocity (SCV) and motor nerve conduction velocity (MCV) of the sciatic nerve after intervention were measured. Metagenomic sequencing (MS) was used to analyze gut microbiota and screen for differential species. Liquid chromatography-mass spectrometry (LC-MS) was employed to detect the differential metabolites in plasma, and the metabolic pathway enrichment analysis was performed on the differential metabolites. Spearman correlation analysis was adopted to assess the relationship between gut microbiota and metabolomics. RESULTS: After 4 and 8 weeks of intervention, when compared with the model group, the EA group showed the increase in body weight, TWL, MWT (P<0.01), and the decrease in RBG (P<0.01). Compared with the normal group, SCV and MCV, as well as Chao1 index were dropped in the model group (P<0.01), and those were elevated in the EA group when compared with those in the model group (P<0.01). The dominant bacterial phyla of each group were Firmicutes (F) and Bacteroidota (B), the ratio of them (F/B) in the model group was lower than that of the normal group (P<0.05), and F/B in the EA group was higher when compared with that in the model group (P<0.05). In comparison with the normal group, the relative abundance increased in Prevotella, Segatella, Prevotella-hominis and Segatella-copri (P<0.05); and it decreased in Ligilactobacillus, Eubacterium, Pseudoflavonifractor, Ligilactobacillus-murinus (P<0.05) in the model group. Compared with the model group, the relevant abundance of the above mentioned gut bacteria was all ameliorated in the EA group (P<0.05, P<0.01). Among the three groups, 120 differential metabolites were identified and enriched in 28 key metabolic pathways, such as glycerophospholipid and linoleic acid, of which, glycerophospholipid was the most significantly affected pathway in EA intervention. Spearman correlation analysis showed that 6 phosphatidylcholine metabolites were significantly positively correlated with Pseudoflavonifractor and were negatively with Prevotella, Segatella, Prevotella-hominis, Segatella-copri; 5 phosphatidylethanolamine metabolites were significantly negatively correlated with Pseudoflavonifractor and positively correlated with Prevotella, Segatella, Prevotella-hominis, Segatella-copri. CONCLUSION EA may regulate metabolic pathways such as glycerophospholipid, modulate specific gut microbiota such as Pseudoflavonifractor, Prevotella, and Segatella, and the co-expressed differential metabolites like phosphatidylcholine and phosphatidylethanolamine, thereby reducing blood glucose and protecting nerve function, so as to relieve the symptoms of DPN of rats.
Animals ; Electroacupuncture ; Male ; Gastrointestinal Microbiome ; Diabetic Neuropathies/microbiology* ; Rats, Sprague-Dawley ; Rats ; Metabolomics ; Humans ; Acupuncture Points

Mevalonic aciduria is a rare early-onset cholesterol biosynthesis disorder，inherited in an autosomal recessive manner，which characterized with recurrent fever，hepatosplenomegaly，lymphadeno-pathy，vomiting，diarrhea and neurological damage symptoms. The symptoms of mevalonic aciduria could appear at any stage throughout the whole life cycle，and the youngest case has been diagnosed in the neonatal period. Lacking of specific clinical manifestations，it is easy to be confused with other diseases in real clinical settings. It is important that increasing awareness of this disease could effectively decrease misdiagnosis and delayed diagnosis. This paper introduces the advance of mevalonic aciduria from the aspects of genetic variants，clinical manifestations and neuroimaging changes，to help clinicians better identify and diagnose at an early stage.

OBJECTIVE: To provide preimplantation genetic testing (PGT) for a patient with Incontinentia pigmenti (IP) due to IKBKG gene variant but without family samples through construction of single nucleotide polymorphism (SNP)-based haplotype by Long-read sequencing (LRS) technology. METHODS: A female IP patient with a heterozygous IKBKG c.1167dup variant but without family genetic data who sought genetic counseling at Women and Children' Hospital of Ningbo University in November 2021 was selected as the study subject. The IKBKG gene has a highly homologous pseudogene IKBKGP1. Genomic DNA was extracted from peripheral blood samples from the couple, and LRS was used to obtain informative SNP loci flanking the variant locus, enabling the construction of SNP haplotype with a long segment spanning from the non-homologous region of IKBKG to the variant site. Trophoblast cells were biopsied from blastocysts fertilized through intracytoplasmic sperm injection, and next-generation sequencing (NGS) was used to determine the SNP information of the embryos. Linkage analysis with the parental SNP haplotypes was conducted to detect the carrier status of the embryos and exclude chromosomal aneuploidies. Sanger sequencing was carried out to validate the result. A euploid embryo without the pathogenic variant was selected for transfer. Prenatal diagnosis was carried out by amniocentesis at mid-trimester to verify the result of PGT tests, and follow-up was conducted after the baby was born. This study has been approved by the Ethics Committee of Women and Children's Hospital of Ningbo University (Ethics No. EC2023-094). RESULTS: A total of seven blastocysts were tested, and PGT results indicated that two embryos were euploid and did not carry the pathogenic variant. One euploid embryo was transferred, which resulted in a singleton pregnancy. Amniocentesis at 24 weeks of gestation confirmed that the status of fetal IKBKG gene, and its chromosomal status was consistent with the PGT results. A healthy male infant was born at 38+6 weeks of gestation. CONCLUSION For IP patients with de novo mutation or without family genetic samples, PGT with LRS can directly construct the SNP-based haplotype while avoiding interference from pseudogenes, providing an effective strategy for PGT.
Female ; Humans ; Male ; Pregnancy ; Genetic Testing/methods* ; Haplotypes/genetics* ; High-Throughput Nucleotide Sequencing/methods* ; I-kappa B Kinase/genetics* ; Incontinentia Pigmenti/diagnosis* ; Polymorphism, Single Nucleotide/genetics* ; Preimplantation Diagnosis/methods* ; Infant, Newborn

OBJECTIVE: To assess the value of Optical genome mapping (OGM) for the verification of chromosomal structural variations among patients undergoing assisting reproduction. METHODS: A retrospective analysis was carried out on the clinical data of 12 patients presented at the Reproductive Center of Ningbo University Women and Children's Hospital from October 2022 to October 2024. All patients had undergone OGM testing due to suspection of structural variants by chromosomal karyotyping or a suggestive medical history. This study was approved by the Medical Ethics Committee of the hospital (Ethics No.: EC2024-148). RESULTS: Among the 12 patients verified by OGM, one (8.3%) was in keeping with the result of chromosomal karyotyping. Revised karyotypes were confirmed in seven cases (58.3%), including four with complex chromosomal rearrangements. Structural variation was excluded in three cases (25.0%). Of note, OGM has identified a previously undetected cryptic balanced translocation, i.e., ogm[GRCh38] t(7;12)(q36.3;q24.23)(157511190_157523142;119205703_119198409). CONCLUSION OGM can serve as an auxiliary diagnostic technique to conventional karyotyping and enable validation of suspected structural variations in those with ambiguous karyotype results or a history of adverse pregnancies. This can provide more precise genetic diagnosis for patients undergoing assisted reproduction and selection of clinical intervention strategies.
Humans ; Female ; Adult ; Retrospective Studies ; Karyotyping ; Reproductive Techniques, Assisted ; Chromosome Mapping/methods* ; Chromosome Aberrations

OBJECTIVE: To investigate the genetic characteristics and clinical utility of Optical genome mapping (OGM) in resolving complex genomic rearrangements in families with recurrent pregnancy loss. METHODS: A recurrent miscarriage family which presented at both the People's Hospital of Qianxinan Buyi and Miao Autonomous Prefecture and the Affiliated Women and Children's Hospital of Ningbo University in September 2024 was selected as the study subject. Relevant clinical information was collected. Peripheral blood samples of the couple were collected for G banding karyotyping analysis, and copy number variation sequencing (CNV-seq) and OGM were used for verification. This study was approved by the Medical Ethics Committee of the Affiliated Women and Children's Hospital of Ningbo University (Ethics No.: EC2024-148). RESULTS: CNV-seq in an external hospital detected a 10.67 Mb deletion in the 16q12.1q21 region, a 142.4 kb deletion in the 5p15.2 region, and a 359.55 kb duplication in the 7p22.2 region. No abnormality was found in the chromosomal karyotype of the male partner, and the initial karyotyping of the female partner suggested 46,XX,?del(16)(q12.1q22). The CNV-seq verification of her indicated only variations in the 5p15.2 and 7p22.2 fragments, and no deletion of 16q was detected. As indicated by precise OGM analysis, multiple intrachromosomal and interchromosomal translocation variations had occurred between chromosomes 10 and 16 in the female partner, with complex balanced rearrangements (including 5 transchromosomal breakpoints). CONCLUSION The complex balanced rearrangements of the female partner's chromosomes had occurred during meiosis, the resultant unbalanced gametes may be the cause of repeated miscarriage in this family. OGM can delineate complex rearrangement breakpoints and directions that are difficult to reveal by conventional karyotyping analysis and provide a basis for accurate reproductive genetic counseling.
Humans ; Abortion, Habitual/etiology* ; Female ; Pregnancy ; Male ; DNA Copy Number Variations/genetics* ; Adult ; Karyotyping ; Pedigree ; Gene Rearrangement ; Chromosome Mapping