Accurate timing of myelination is crucial for the proper functioning of the central nervous system. Here, we identified a de novo heterozygous mutation in TMEM63A (c.1894G>A; p. Ala632Thr) in a 7-year-old boy exhibiting hypomyelination. A Ca²⁺ influx assay suggested that this is a loss-of-function mutation. To explore how TMEM63A deficiency causes hypomyelination, we generated Tmem63a knockout mice. Genetic deletion of TMEM63A resulted in hypomyelination at postnatal day 14 (P14) arising from impaired differentiation of oligodendrocyte precursor cells (OPCs). Notably, the myelin dysplasia was transient, returning to normal levels by P28. Primary cultures of Tmem63a^-/- OPCs presented delayed differentiation. Lentivirus-based expression of TMEM63A but not TMEM63A_A632T rescued the differentiation of Tmem63a^-/- OPCs in vitro and myelination in Tmem63a^-/- mice. These data thus support the conclusion that the mutation in TMEM63A is the pathogenesis of the hypomyelination in the patient. Our study further demonstrated that TMEM63A-mediated Ca²⁺ influx plays critical roles in the early development of myelin and oligodendrocyte differentiation.
Animals ; Cell Differentiation/physiology* ; Oligodendroglia/metabolism* ; Mice, Knockout ; Mice ; Male ; Myelin Sheath/metabolism* ; Humans ; Child ; Cells, Cultured ; Oligodendrocyte Precursor Cells/metabolism*

Objective:To investigate the clinical, epidemic and laboratory characteristics of brucellosis in Hainan, and to summarize the experience of diagnosis and treatment.Methods:The epidemiological characteristics, clinical manifestations, laboratory results, treatment and prognosis of 27 inpatients with brucellosis admitted to the Second Affiliated Hospital of Hainan Medical University from January 2019 to December 2023 were retrospectively analyzed.Results:In 27 cases, the male to female ratio was 2.38 ∶ 1.00 (19 ∶ 8). Occupational distribution was dominated by farmers and herdsmen, with a total of 21 cases (77.8%). Twenty-one patients (77.8%) had a clear history of contact with cattle, sheep, and related products, and there was a phenomenon of family clustering. Eighteen patients (66.7%) developed symptoms from March to July. The clinical manifestations of the patients were lack of specificity, mainly fever (24 cases, 88.9%), dizziness and headache (13 cases, 48.1%), and low back pain (11 cases, 40.7%). Some patients also had symptoms and signs such as fatigue (8 cases), muscle pain (6 cases), chest tightness (4 cases), and splenomegaly (6 cases). Complications commonly included pulmonary infection (13 cases, 48.1%) and spinal involvement (11 cases, 40.7%). The positive rates of Brucella blood culture, tube agglutination test, Rose Bengal plate agglutination test, and cerebrospinal fluid or joint cavity effusion culture were 76.9% (20/26), 100.0% (21/21), 100.0% (11/11), and 3/4, respectively. The combination therapy of doxycycline and rifampicin showed good therapeutic effects, and 22 patients were cured. Conclusions:Hainan is not an epidemic area of brucellosis, and the clinical manifestations of the disease are not specific. The epidemic and clinical characteristics of the disease should be paid attention to in order to improve the level of diagnosis and treatment and control effectiveness.

Objective:To study the epidemiological and clinical characteristics of patients infected with Streptococcus suis in Hainan Province. Methods:Clinical data of patients diagnosed with human infection with Streptococcus suis at the Second Affiliated Hospital of Hainan Medical University from January 2017 to December 2023 were collected, and their epidemiological characteristics, clinical manifestations, auxiliary examination results, treatment and prognosis were retrospectively analyzed. Results:A total of 29 patients infected with Streptococcus suis were included, with 26 males (89.66%) and 3 females (10.34%). The age of the patients was (54.52 ± 10.89) years old, with the highest number of patients aged 51 to 60 years, accounting for 41.38% (12 cases). Farmers were the main occupation (72.41%, 21/29). Forty-four point eighty-three percent (13/29) of the patients had a history of direct or indirect contact with dead or sick pigs. The number of cases from January to December was 0, 0, 2, 2, 4, 8, 2, 3, 2, 2, 3, and 1, respectively. June was the peak period of incidence (27.59%, 8/29). The main clinical manifestations were fever (100.00%, 29/29), altered state of consciousness (51.72%, 15/29), headache (48.28%, 14/29), and hearing impairment (44.83%, 13/29). In clinical classification, common type, meningitis type, and mixed type accounted for 20.69% (6/29), 75.86% (22/29), and 3.45% (1/29), respectively. In the pathogen examination, all 29 patients underwent blood culture, and 18 patients (62.07%, 18/29) had positive blood culture; 26 patients underwent cerebrospinal fluid culture, and 8 cases (30.77%) tested positive for cerebrospinal fluid culture. Eighty-nine point sixty-six percent (26/29) of the patients were treated with ceftriaxone sodium; 55.17% (16/29) of the patients were treated with combined treatment of ceftriaxone sodium and glucocorticoids, including 11 cases treated with dexamethasone and 5 cases treated with methylprednisolone. After treatment, 7 patients were cured and discharged, and 22 patients showed improvement in their condition and discharged from hospital. At discharge, both blood and/or cerebrospinal fluid cultures turned negative. Telephone follow-up was conducted 6 months after discharge, and 20 patients had no sequelae, 9 patients still had hearing impairment, including one who also developed walking difficulties. Conclusions:The patients infected with Streptococcus suis in Hainan Province are mainly middle-aged, elderly, male and farmers, with June being the peak period of the disease. The main clinical manifestations are fever, altered state of consciousness, headache, and hearing impairment. After follow-up, there are still patients with residual hearing impairment. In clinical practice, patients with fever and hearing impairment should be considered as this disease as early as possible.

Leptospirosis is a global natural zoonotic infectious disease.Research shows that short-chain fatty acids,metabolites of gut microbiota,are involved in host immune regulation and affect disease progression.This experiment was conducted to investigate the role of short-chain fatty acids in leptospirosis.The results showed that supplementation of short-chain fatty acid butyric acid could significantly improve the survival rate of leptospirosis in hamsters.In vitro experiments showed that butyric acid treatment inhibited the expression of Cat and Gsr genes in macrophages after infection with Leptospira,but enhanced the expression of NOX1 and NOX4 genes.At the same time,butyric acid treatment enhanced macrophage ROS levels after leptospirosis infection,and high levels of ROS enhanced the bactericidal function of macrophages.In vivo experiments al-so confirmed that butyric acid protects hamsters against acute leptospirosis by regulating ROS production.Collectively,the short-chain fatty acid butyric acid,a metabolite of gut microbiota,en-hances the bactericidal function of macrophages by regulating ROS expression,thereby protecting the host against leptospirosis.

Objective:To investigate the clinical, epidemic and laboratory characteristics of brucellosis in Hainan, and to summarize the experience of diagnosis and treatment.Methods:The epidemiological characteristics, clinical manifestations, laboratory results, treatment and prognosis of 27 inpatients with brucellosis admitted to the Second Affiliated Hospital of Hainan Medical University from January 2019 to December 2023 were retrospectively analyzed.Results:In 27 cases, the male to female ratio was 2.38 ∶ 1.00 (19 ∶ 8). Occupational distribution was dominated by farmers and herdsmen, with a total of 21 cases (77.8%). Twenty-one patients (77.8%) had a clear history of contact with cattle, sheep, and related products, and there was a phenomenon of family clustering. Eighteen patients (66.7%) developed symptoms from March to July. The clinical manifestations of the patients were lack of specificity, mainly fever (24 cases, 88.9%), dizziness and headache (13 cases, 48.1%), and low back pain (11 cases, 40.7%). Some patients also had symptoms and signs such as fatigue (8 cases), muscle pain (6 cases), chest tightness (4 cases), and splenomegaly (6 cases). Complications commonly included pulmonary infection (13 cases, 48.1%) and spinal involvement (11 cases, 40.7%). The positive rates of Brucella blood culture, tube agglutination test, Rose Bengal plate agglutination test, and cerebrospinal fluid or joint cavity effusion culture were 76.9% (20/26), 100.0% (21/21), 100.0% (11/11), and 3/4, respectively. The combination therapy of doxycycline and rifampicin showed good therapeutic effects, and 22 patients were cured. Conclusions:Hainan is not an epidemic area of brucellosis, and the clinical manifestations of the disease are not specific. The epidemic and clinical characteristics of the disease should be paid attention to in order to improve the level of diagnosis and treatment and control effectiveness.

Objective:To study the epidemiological and clinical characteristics of patients infected with Streptococcus suis in Hainan Province. Methods:Clinical data of patients diagnosed with human infection with Streptococcus suis at the Second Affiliated Hospital of Hainan Medical University from January 2017 to December 2023 were collected, and their epidemiological characteristics, clinical manifestations, auxiliary examination results, treatment and prognosis were retrospectively analyzed. Results:A total of 29 patients infected with Streptococcus suis were included, with 26 males (89.66%) and 3 females (10.34%). The age of the patients was (54.52 ± 10.89) years old, with the highest number of patients aged 51 to 60 years, accounting for 41.38% (12 cases). Farmers were the main occupation (72.41%, 21/29). Forty-four point eighty-three percent (13/29) of the patients had a history of direct or indirect contact with dead or sick pigs. The number of cases from January to December was 0, 0, 2, 2, 4, 8, 2, 3, 2, 2, 3, and 1, respectively. June was the peak period of incidence (27.59%, 8/29). The main clinical manifestations were fever (100.00%, 29/29), altered state of consciousness (51.72%, 15/29), headache (48.28%, 14/29), and hearing impairment (44.83%, 13/29). In clinical classification, common type, meningitis type, and mixed type accounted for 20.69% (6/29), 75.86% (22/29), and 3.45% (1/29), respectively. In the pathogen examination, all 29 patients underwent blood culture, and 18 patients (62.07%, 18/29) had positive blood culture; 26 patients underwent cerebrospinal fluid culture, and 8 cases (30.77%) tested positive for cerebrospinal fluid culture. Eighty-nine point sixty-six percent (26/29) of the patients were treated with ceftriaxone sodium; 55.17% (16/29) of the patients were treated with combined treatment of ceftriaxone sodium and glucocorticoids, including 11 cases treated with dexamethasone and 5 cases treated with methylprednisolone. After treatment, 7 patients were cured and discharged, and 22 patients showed improvement in their condition and discharged from hospital. At discharge, both blood and/or cerebrospinal fluid cultures turned negative. Telephone follow-up was conducted 6 months after discharge, and 20 patients had no sequelae, 9 patients still had hearing impairment, including one who also developed walking difficulties. Conclusions:The patients infected with Streptococcus suis in Hainan Province are mainly middle-aged, elderly, male and farmers, with June being the peak period of the disease. The main clinical manifestations are fever, altered state of consciousness, headache, and hearing impairment. After follow-up, there are still patients with residual hearing impairment. In clinical practice, patients with fever and hearing impairment should be considered as this disease as early as possible.

Medication during pregnancy is widespread, but there are few reports on its fetal safety. Recent studies suggest that medication during pregnancy can affect fetal morphological and functional development through multiple pathways, multiple organs, and multiple targets. Its mechanisms involve direct ways such as oxidative stress, epigenetic modification, and metabolic activation, and it may also be indirectly caused by placental dysfunction. Further studies have found that medication during pregnancy may also indirectly lead to multi-organ developmental programming, functional homeostasis changes, and susceptibility to related diseases in offspring by inducing fetal intrauterine exposure to too high or too low levels of maternal-derived glucocorticoids. The organ developmental toxicity and programming alterations caused by medication during pregnancy may also have gender differences and multi-generational genetic effects mediated by abnormal epigenetic modification. Combined with the latest research results of our laboratory, this paper reviews the latest research progress on the developmental toxicity and functional programming alterations of multiple organs in offspring induced by medication during pregnancy, which can provide a theoretical and experimental basis for rational medication during pregnancy and effective prevention and treatment of drug-related multiple fetal-originated diseases.

Ginsenoside Rc,a dammarane-type tetracyclic triterpenoid saponin primarily derived from Panax ginseng,has garnered significant attention due to its diverse pharmacological properties.This review outlined the sources,putative biosynthetic pathways,extraction,and quantification techniques,as well as the pharmacokinetic properties of ginsenoside Rc.Furthermore,this study explored the pharmaco-logical effects of ginsenoside Rc against metabolic syndrome(MetS)across various phenotypes including obesity,diabetes,atherosclerosis,non-alcoholic fatty liver disease,and osteoarthritis.It also highlighted the impact of ginsenoside Rc on multiple associated signaling molecules.In conclusion,the anti-MetS effect of ginsenoside Rc is characterized by its influence on multiple organs,multiple targets,and multiple ways.Although clinical investigations regarding the effects of ginsenoside Rc on MetS are limited,its proven safety and tolerability suggest its potential as an effective treatment option.

OBJECTIVE To evaluate the impact of mastoid obliteration withsingle-pedicle muscle flap covered by bone pate on vestibular stimulation. METHODS A retrospective study was performed on 59 patients who were treated for chronic otitis media with or without cholesteatoma by two techniques: canal wall down tympano-mastoidectomy(CWD) and subsequent mastoid obliteration(MO). The postoperative vestibular functions of all the patients in both groups were assessed by vestibular function tests and questionnaires. Finally, the data of examination a nd symptoms were a nalyzed. RESULTS After a minimum follow up period of 12 months, the rate of ear dry was 84％(22/26) for MO group and 55％(18/33) for CWD group(χ2=4.72, P <0.05). The dry ear time were 5.46±1.39 weeks for MO group and 8.67±2.3 weeks for CWD group(t =6.2529, P <0.05). When compared latent period of Caloric testing in the MO group (10.3±2.57)s and CWD group (12.7±3.33)s, significant differencewas found(t =3.1639, P <0.05). The postoperative caloric vestibular tests revealed an average nystagmus count of 52.96±20.82 beats per minute in the MO group and 69.94±18.98 beats in the CWD group(t =3.2688, P <0.05). By analyzing the questionnaire, 30％(10/33) of the patients who received CWD treatment reported vertigo by caloric stimuli such as wind, water compared with MO group(0)(χ2=7.45, P <0.05). The rate of suction cleaning induced vertigo was 48％(16/33) in CWD group and 23％(6/26) in MO group(χ2=3.17, P =0.075). CONCLUSION Our technique of mastoid obliteration with single-pedicle muscle flap covered by bone pate results in small cavities with complete epithelialization of all surfaces. Furthermore, obliteration of mastoid cavities provides protection to the labyrinthine organ and reduces postoperative vertigo to caloric stimulation.

Objective: To investigate the effect of pseudodeficiency alleles on the newborn screening of glycogen storage disease type Ⅱ(GSDⅡ) by using afluorometric enzymatic assay to determine acid α-glucosidase (GAA) activity in dried blood spot (DBS). Methods: A total of 30 507 newborns′ DBSs, obtained from Newborn Screening Center of Xinhua Hospital Shanghai Jiao Tong University School of Medicine from May to December 2017, were screened for GSD Ⅱ by fluorometric enzymatic assay of GAA activity. The suspected positive DBSs after the first and second screening were directly analyzed by Sanger sequencing of GAA to confirm the diagnosis. Retrospective analysis of 3 172 controls without GSDⅡand 36 GSD Ⅱ patients were conducted to investigate the carrier status of pseudodeficiency alleles. Statistical analysis of frequency of pseudodeficiency alleles were carried out by Chi-square test or Fisher exact probability test. Results: GAA activity of 30 507 newborns showed a positively skewed distribution.Twenty-nine cases of newborns, suspected to be GSDⅡwere confirmed to be normal with genetic analysis of the original DBSs. Among the 29 suspected positive cases, 24 cases were homozygous for pseudodeficiency alleles c.[1726A/A; 2065A/A], and the other 5 cases were c.[1726G/A; 2065G/A] heterozygote. The frequency of c.1726G>Ahomozygote in 3 172 non-GSD Ⅱcontrols was 2.08% (66/3 172), and c.1726G>A homozygote occurred in allelic conjunction with c.2065G>Ahomozygote. Frequency of c.[1726A; 2065A] haplotype in 3 172 controls was 3.2%(206/6 344). Frequency of c.[1726A/A; 2065A/A] homozygote in 36 GSDⅡpatients (16.67%, 6/36) was significantly higher than that in non-GSD Ⅱcontrols(2.08%, 66/3 172) (χ²=34.517, P<0.001). Conclusions Pseudodeficiency alleles show a high frequency in Chinese, which leads to a high false positive rate in the newborns screening of GSDⅡ.The afterword genetic analysis of the original DBS after the GAA activity screening could reduce the effect of pseudodeficiency alleles on the newborns screening of GSDⅡ.