ObjectiveTo explore the effects of Jingui Shenqiwan （JSW） and Liuwei Dihuangwan （LDW） on the reproductive ability and brain function of normal mice and compare the actions of the two medications. MethodsSeven groups of female and male mice were divided at a ratio of 2∶1. Except for the control group， the other six groups were as follows： a group of both males and females receiving JSW （3.0 g·kg^-1）， a group of both males and females receiving LDW （4.5 g·kg^-1）， a group of males receiving water and females receiving JSW， a group of males receiving water while females receiving LDW， a group of females receiving water while males receiving JSW， and a group of females receiving water while males receiving LDW. Each group was administered the drug for 14 days and then caged together at a 2∶1 （female∶male） ratio to detect the number of pregnant mice and calculate the pregnancy rate. Pregnant mice continued receiving the drug until they naturally gave birth， which was followed by the observation of newborn mice， calculation of their average number， and the measurement of the offspring's preference for sugar water and neonatal recognition index. At the end of the experiment， the weights of the thymus and spleen were measured to calculate the organ coefficients， and mRNA or protein expression was analyzed in the brain and testes or ovaries. A 1% sucrose solution was used to examine the euphoria of their brain reward systems， while novel object recognition test （NOR） was applied to assess their memory capabilities. mRNA expression was detected using real-time quantitative polymerase chain reaction （Real-time PCR） assay， and protein expression was analyzed with Western blot. ResultsCompared with the control group， oral administration of JSW to both male and female mice for 14 days significantly increased the pregnancy rate of female mice on day 2 after being caged together （P<0.05）， while LDW showed a trend but no statistical significance. Additionally， compared with the control group， JSW could upregulate the gene expression of gonadotropin-releasing hormone （GnRH） in the thalamus， as well as reproductive stem cell factor （SCF） and tyrosine kinase receptor （c-Kit） in the testes and reproductive stem cell marker mouse vasa homologue （MVH） in the ovaries， upregulate the expression of proteins influencing neuronal functional activity， such as brain-derived neurotrophic factor （BDNF）， in hippocampal neurons （P<0.05）， and enhance sucrose preference in male mice （P<0.05）. Compared with the control group， JSW significantly increased sucrose preference and novel object recognition index in offspring mice （P<0.05）， which was related to the upregulation of hippocampal dopamine D1 receptor （D1R） and N-methyl-D-aspartate receptor （Nmdar） gene expression. Compared with the control group， both JSW and LDW could upregulate the protein expression of glucocorticoid receptor （GR）， BDNF， and tyrosine kinase receptor B （TrkB） in the hippocampus of offspring mice （P<0.05）. ConclusionJSW significantly enhances the reproductive ability of normal mice， which is not only related to the release of gonadotropin but also associated with its regulation of brain function. Additionally， JSW has a certain regulatory effect on the brain function of the offspring mice.

The gut microbiota is regarded as the "eighth organ" of the human body and plays a critical regulatory role in the occurrence and progression of various diseases. Ulcerative colitis （UC） is a chronic inflammatory bowel disease with a complex etiology and a tendency toward recurrent episodes. In recent years， studies have shown that gut microbiota dysbiosis plays a key role in its pathological processes. Meanwhile， an increasing number of studies have demonstrated that imbalances in the gut microbiota and abnormalities in its metabolites are closely associated with the development of atrial fibrillation （AF）. Although UC and AF belong to diseases of the digestive system and cardiovascular system， respectively， both exhibit systemic inflammatory characteristics and are often accompanied by gut microbiota dysregulation and abnormal metabolic products. However， systematic investigations into the mechanisms by which gut microbiota-derived metabolites act in these two diseases remain limited. Based on this， the present study adopts literature review and theoretical analysis methods， taking the "gut microbiota-gut-heart" axis as the entry point， to systematically summarize the signaling networks of three key classes of metabolites， i.e.， short-chain fatty acids （SCFAs）， bile acids （BAs）， and trimethylamine N-oxide （TMAO）， in the comorbidity mechanism of UC and AF. The findings indicate that these metabolites may activate key inflammatory pathways， such as NF-κB and NLRP3， thereby synergistically mediating intestinal barrier dysfunction and systemic inflammation and constructing a potential comorbidity network. On this basis， potential intervention strategies for the treatment of UC-AF comorbidity， including probiotic intervention and fecal microbiota transplantation， are further discussed. This study aims to provide new theoretical evidence and research perspectives for prevention and treatment strategies of cross-system diseases.

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

BACKGROUND:Needle-knife release of the ligamentum flavum can effectively improve symptoms in patients with lumbar degeneration,and ultrasound guidance can increase the precision of needle-knife release;however,the specific effects of needle-knife release of the ligamentum flavum on the degenerated intervertebral discs and the possible mechanisms remain to be clarified. OBJECTIVE:To investigate the effect of ultrasound-guided needle-knife release of the ligamentum flavum. METHODS:Twenty-four New Zealand rabbits were randomized into control(n=6)and model(n=18)groups.A rabbit model of lumbar disc degeneration model was established in the model group by cutting the supraspinous and interspinous ligaments of the L5/6 and L6/7 segments to maintain a standing posture and apply axial load to the lumbar spine.After successful modeling,the model rabbits were subdivided into a control group,a model group,an ultrasonic needle-knife group,and a sham needle-knife group according to a random number table method,with six animals in each group.The ultrasonic needle-knife group underwent ultrasound-guided needle-knife release of the right yellow ligament of L7/S1,once every week,for a total of four times.The needle-knife approach in the sham needle-knife group was the same as that in the ultrasound needle-knife group,but the ligamentum flavum was not released.At 30 days after the intervention,MRI was used to observe the changes in the signal intensity of the nucleus pulposus within the L7/S1 segment.Hematoxylin-eosin staining was used to observe the morphological changes of the L7/S1 segment.Immunohistochemical staining was used to detect the expression of type I and II collagen in the nucleus pulposus of the L7/S1 segment.RT-PCR and western blot were used to detect the expression of integrin α5 and β1,p38,and nuclear factor κB in the L7/S1 segment. RESULTS AND CONCLUSION:MRI findings indicated that the nucleus pulposus of the intervertebral disc of rabbits in the model group was gray-black in color,and the gray value of the nucleus pulposus was significantly lower than that of the control group(P<0.01).The brightness of the nucleus pulposus of the intervertebral disc of the rabbits in the ultrasonic needle-knife group was elevated compared with that of the model group,and the gray value of the nucleus pulposus was higher than that of the model group(P<0.01).Results from hematoxylin-eosin staining showed that in the model group,the shape of the nucleus pulposus was irregular,the number of nucleus pulposus cells was reduced,the extracellular matrix was compressed,the fibrous ring was ruptured,the structure and boundary of the end plate were unclear,and the chondrocytes were arranged disorderly.Compared with the model group,the ultrasonic needle-knife group showed an increase in the number of the nucleus pulposus,an improvement in the rupture of the fibrous ring,and more regular arrangement of cartilage endplate cells.Results from immunohistochemical staining showed an increase in positive expression of type I collagen(P<0.01)and a decrease in positive expression of type II collagen in the nucleus pulposus of the model group compared with the control group as well as a decrease in positive expression of type I collagen and an increase in positive expression of type II collagen in the nucleus pulposus of the ultrasonic needle-knife group compared with the model group(P<0.01).RT-PCR and western blot assays showed that the mRNA and protein expression of integrin α5,integrin β1,p38,and nuclear factor κB in the intervertebral discs of rabbits in the model group were increased compared with that in the control group(P<0.01);the mRNA and protein expression of integrin α5,integrin β1,p38,and nuclear factor κB in the intervertebral discs of rabbits in the ultrasonic needle-knife group was decreased compared with that in the model group(P<0.01).To conclude,ultrasound-guided needle-knife release of the ligamentum flavum can improve the degree of lumbar disc degeneration in rabbits,which may be related to the inhibition of p38 and nuclear factor-κB expression by modulating integrin α5 and β1 expression.

ObjectiveTo explore the effect of Shenge Bushen Capsules （SBC） on sexual development in normal 3-week-old mice. MethodsThe experiment consisted of two parts. In the first part， mice were divided into four groups： The control group and the low， medium， and high-dose SBC groups （234.7， 469.4， 938.7 mg·kg^-1， respectively）. In the second part， mice were divided into four groups： Control group， Pseudostellariae Radix polysaccharide （PRP） group， total flavonoids group， and SBC group， all receiving a dose of 469.4 mg·kg^-1. After 7 days of administration， the vaginal opening of female mice and the descent of testes and scrotum in male mice， as well as the ovarian and testicular organ indices， were observed. After 4 weeks of administration， female and male mice were housed together for 2 days， and the pregnancy rate of females was monitored. After delivery， the pregnant female mice continued receiving the treatment for 4 weeks， and the sexual development of their offspring， including vaginal opening， testicular descent， and organ indices of ovaries and testes， was observed. Serum sex hormones were measured by enzyme-linked immunosorbent assay （ELISA）， and the expression of gonadotropin-releasing hormone （GnRH） and growth hormone （GH） proteins in the hypothalamus was assessed by Western blot. ResultsCompared with the control group， there was no significant effect on the vaginal opening of female mice or the descent of testes in male mice after 7 days of SBC administration. After 4 weeks of administration， the pregnancy rate in the low-dose group was significantly reduced （P<0.05）， but no significant effects were observed in the other groups. The three doses of SBC did not significantly affect the ovarian or testicular organ indices， and there was no significant upregulation in the expression of GnRH or GH in the hypothalamus. The primary component of SBC， Pseudostellariae Radix polysaccharide， significantly reduced the vaginal opening in female mice after 7 days of administration （P<0.05）. After 4 weeks， the serum estradiol levels of non-pregnant female mice were decreased （P<0.05）， but there was no significant effect on the expression of GnRH or GH proteins in the hypothalamus of either male or female mice. Additionally， there were no significant effects on precocious puberty indicators， such as vaginal opening and testicular descent， in the offspring mice. ConclusionSBC does not significantly promote precocious puberty in young mice， and it does not have any noticeable effects on the pregnancy rate of adult mice or the sexual development of their offspring.

Based on the holistic view of "spleen-vessels-heart-spirit" system， this article explores the pathogenesis and progression of atrial fibrillation. It is proposed that the onset of atrial fibrillation is due to failure of the spleen to transport and disharmony of blood vessels； phlegm and blood stasis obstructing the collaterals and damage to the heart structure are the basis of its pathogenesis； the unclear mind and disorder of body and spirit are the causes of its progression. Based on the characteristics of pathological changes in different stages of the disease， it is proposed that early treatment should focus on restoring the middle jiao， clearing and promoting blood vessels， using modified Yigong Powder （异功散）； during the progression of the disease， treatment should remove blood stasis and phlegm， nourish heart and protect the pulse， using self-prescribed modified Mengshi Tongmai Decoction （礞石通脉汤）； meanwhile， calming mind and stabilizing palpitations， and regulating spirit should be sequentially incorporated， with self-prescribed Jiazao Ningmai Decoction （甲枣宁脉汤） or Shenying Dingji Decoction （参英定悸汤） and modified as appropriate. Clinical treatment should focus on the whole disease course of atrial fibrillation， implementing stage-based treatments to enable early intervention and holistic regulation.

ObjectiveTo observe the clinical efficacy of acupuncture combined with bloodletting and cupping in the treatment of chronic spontaneous urticaria（CSU） and to explore its potential mechanisms of action. MethodsSeventy CSU patients were randomly divided into loratadine group and acupuncture + bloodletting group， with 35 patients in each group. The loratadine group received oral loratadine tablets， 10 mg once daily in the evening. The acupuncture + bloodletting group received acupuncture at Zhongwan （CV 12）， Guanyuan （CV 4）， Tianshu （ST 25）， Zusanli （ST 36）， Sanyinjiao （SP 6）， Xuehai （SP 10）， Quchi （LI 11）， Hegu （LI 4）， Taichong （LR 3）， Baihui （GV 20）， and Shenting （GV 24）， once daily，along with bloodletting and cupping at Dazhui （GV 14） and Geshu （BL 17）， every other day. Both groups were treated for 4 weeks. The 7-day urticaria activity score（UAS7） was assessed before and after the treatment， and levels of serum immunoglobulin E （IgE）， interleukin-4 （IL-4）， interleukin-5 （IL-5）， eosinophil cationic protein （ECP）， plasma tissue factor （TF）， activated factor Ⅶ （FⅦa）， prothrombin fragment 1+2 （F1+2）， D-dimer （D-D） and complement component 5a （C5a） were detected. ResultsA total of 65 patients were included in the final analysis， 32 in the loratadine group and 33 in the acupuncture + bloodletting group. Before treatment， there was no significant difference in UAS7 score， serum IgE， IL-4， IL-5， ECP levels， or plasma TF， FⅦa， F1+2， D-D， C5a levels between groups （P＞ 0.05）. After treatment， both groups showed significant reductions in UAS7 score， serum IgE， IL-4， IL-5， and plasma TF， FⅦa， F1+2， D-D， and C5a levels compared to those before treatment （P＜0.01）. However， after treatment， there was no significant difference in UAS7 score and serum ECP， IgE， IL-4， IL-5 levels between groups （P＞0.05）. The acupuncture + bloodletting group showed lower plasma TF， FⅦa， F1+2， D-D and C5a levels compared to the loratadine group （P＜0.05 or P＜0.01）. ConclusionAcupuncture combined with bloodletting and cupping can effectively improve the skin symptoms of CSU patients and reduce the levels of inflammatory factors. The potential mechanism of action may involve the regulation of the coagulation-complement-mast cell activation axis， thereby inhibiting mast cell degranulation.

To summarise the clinical experience of treating insomnia with the method of resolving depression， regulating the middle， and tranquilising mind. It is believed that the key to the pathogenesis of insomnia lies in qi depression， disharmony of qi pivot， and disharmony of qi and blood， and the core treatment is to resolve depression， regulating the middle， and tranquilising mind. The self-prescribed Jieyu Anmian Formula （解郁安眠方） could be used as the basic treatment， then modified according to the performance of the patient and syndromes. For syndrome of liver depression restricting spleen， the treatment should soothe liver and invigorate spleen， resolve depression and regulate the middle； for syndrome of liver depression and phlegm coagulation， the treatment should resolve depression and phlegm， support the earth and free the wood； for syndrome of liver depression transforming into fire， the treatment should soothe liver and clear fire， resolve depression and dysphoria； for syndrome of qi stagnation and blood stasis， the treatment should activate blood and regulate the middle， resolve depression and tranquilise mind.

BACKGROUND: Without timely and effective rehabilitation, hearing loss may profoundly affect human life quality. China has a large population of hearing-impaired individuals, which imposes a heavy health burden on society. Moreover, this population is projected to increase rapidly owing to China's aging society. METHODS: We used data from a population-representative epidemiological investigation of hearing loss and ear diseases in four Chinese provinces. We estimated the national prevalence using multiple linear regression of the age-group proportions and prevalence in 31 provinces with clustering analysis. We used years lived with disability (YLDs) to analyze the disease burden and forecasted the prevalence of hearing loss by 2060 in China. RESULTS: An estimated 115 million people had moderate-to-complete hearing loss in 2015 across the 31 provinces of China (8.4% of 1.37 billion people). Of these, 85.7% were older than age 50 years (99 million people) and 2.4% were younger than 20 years old (2.8 million people). Of all YLDs attributable to hearing loss, 68.9% were attributable to moderate-to-complete cases. By 2060, a projected 242 million people in China will have moderate-to-complete hearing loss, a 110.0% increase from 2015. CONCLUSIONS The hearing loss prevalence in China is high. Population aging and socioeconomic factors substantially affect the prevalence and severity of hearing loss and the disease burden. The prevalence and severity of hearing loss are unevenly distributed across different provinces. Future public health policies should take these trends and regional variations into account.
Humans ; China/epidemiology* ; Hearing Loss/epidemiology* ; Prevalence ; Middle Aged ; Male ; Female ; Adult ; Aged ; Adolescent ; Young Adult ; Child ; Child, Preschool ; Infant ; Aged, 80 and over ; Cost of Illness

BACKGROUND: Whether adherence to a healthy lifestyle is associated with a lower risk of developing pneumonia and a better long-term prognosis remains unclear. This study aimed to investigate associations of individual and combined lifestyle factors (LFs) with the incidence risk and long-term prognosis of pneumonia hospitalization. METHODS: Using data from the China Kadoorie Biobank study, we used the multistate models to investigate the role of five high-risk LFs, including smoking, excessive alcohol drinking, unhealthy dietary habits, physical inactivity, and unhealthy body shape, alone or in combination in the transitions from a generally healthy state at baseline to pneumonia hospitalization or cardiovascular disease (CVD, regarded as a reference outcome), and subsequently to mortality. RESULTS: Most of the five high-risk LFs were associated with increased risks of transitions from baseline to pneumonia and from pneumonia to death, but with different risk estimates. The greater the number of high-risk LFs, the higher the risk of developing pneumonia and long-term mortality risk after pneumonia, with the strength of associations comparable to that of LFs and CVD. Compared to participants with 0-1 high-risk LF, the adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for transitions from baseline to pneumonia and from pneumonia to death in those with five high-risk LFs were 1.43 (1.28-1.60) and 1.98 (1.61-2.42), respectively. Correspondingly, the respective HRs (95% CIs) for transitions from baseline to CVD and from CVD to death were 2.00 (1.89-2.11) and 1.44 (1.30-1.59), respectively. The risk estimates changed slightly when further adjusting for the presence of major chronic diseases. CONCLUSION In this Chinese population, unhealthy LFs were associated with an increased incidence and long-term mortality risk of pneumonia.
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Cardiovascular Diseases/etiology* ; China/epidemiology* ; Life Style ; Pneumonia/etiology* ; Prognosis ; Risk Factors ; Smoking