Objective:To investigate the alterations in gut microbiota diversity and inflammatory cytokine levels among patients with varying severities of insomnia, and to explore their interrelationships, in order to provide a theoretical basis for understanding the pathophysiology of insomnia.Methods:A total of 42 patients with chronic insomnia who visited the First Hospital of Hebei Medical University between March and December 2023 were enrolled in the insomnia group, and 22 age-and sex-matched healthy volunteers were recruited from the same hospital as the control group. General demographic data were collected, and Mini-International Neuropsychiatric Interview (MINI) was used to screen for comorbid psychiatric disorders. The Self-Rating Depression Scale (SDS) and the Self-Rating Anxiety Scale (SAS) were employed to evaluate individual′s depressive and anxiety symptoms. Sleep quality and insomnia severity were assessed using the Pittsburgh Sleep Quality Index (PSQI) and the Insomnia Severity Index (ISI), Participants′ gastrointestinal function and symptoms over the past week were evaluated using the Gastrointestinal Symptom Rating Scale (GSRS). Fecal and blood samples were collected from all participants. Gut microbiota diversity was analyzed using 16S rRNA sequencing. Differential taxa were identified using linear discriminant analysis effect size (LEfSe) and random forest analysis. Serum levels of inflammatory cytokines were measured by enzyme-linked immunosorbent assay (ELISA). Spearman correlation analysis was used to explore the relationships between insomnia symptoms, microbial diversity indices, key microbial taxa, and inflammatory markers. Multiple linear regression analysis was conducted to identify factors associated with insomnia severity.Results:Compared to the control group, both the mild insomnia group and the moderate-to-severe insomnia group showed significantly higher GSRS scores ( Z=-3.51, -2.72, both P<0.05). The Chao1 index was significantly lower in the mild and moderate-to-severe insomnia groups than in controls ( Z=-3.53, -3.87, both P<0.05). Similarly, the Observed species index was lower in both the mild and moderate-to-severe groups ( Z=-3.33, -3.74, both P<0.05). The Shannon index was significantly reduced in the moderate-to-severe group compared to both the mild group and controls ( Z=-2.81, -2.23, both P<0.05). The Simpson index in the moderate-to-severe group also tended to be lower than in the mild group ( Z=-1.95, P=0.051). Beta diversity differed significantly among the mild insomnia group, the moderate-to-severe insomnia group ( P<0.05), and the control group ( F=2.96, 3.12, both P<0.05). Random forest analysis identified Ruminococcus_D and Klebsiella as key microbial genera distinguishing between mild and moderate-to-severe insomnia. Inflammatory cytokine levels were significantly elevated in both insomnia groups compared to controls ( P<0.05). PSQI scores were negatively correlated with the Shannon index, the Observed species index, and the relative abundance of Ruminococcus_D ( r=-0.34, -0.30, and -0.25, respectively; all P<0.05). Multiple linear regression revealed that serum IL-1β (β=0.339, 95% CI=0.014-0.716, P=0.042) and Ruminococcus_D (β=-0.309, 95% CI=-194.591--8.318, P=0.034) were independent predictors of insomnia severity. Conclusion:Elevated inflammatory cytokine levels and reduced gut microbial richness may be closely associated with increased insomnia severity. Additionally, Ruminococcus_D and IL-1β may be important factors contributing to the severity of insomnia in affected individuals.

Dysphagia is a common complication of stroke. Combining the principles of traditional Chinese medicine with modern research findings， it is proposed that "latent pathogen in the cerebral collaterals" constitutes the core pathogenesis of post-stroke dysphagia （PSD）. In clinical practice， treatment is tailored according to the location of PSD. During the oral stage， when the pathogen invades the face and mouth， resulting in excessive salivation， acupoints are primarily selected from the foot shaoyin （少阴） kidney channel， in combination with ren mai （任脉） ， du mai （督脉）， chong mai （冲脉） and the spleen channel， to replenish essence and fill the marrow， dispel dampness and unblock the channels. In the pharyngeal stage， as the pathogen obstructs the throat， disrupting normal swallowing， the therapy emphasizes dredging the shaoyang （少阳） channel and warming and tonifying the jueyin （厥阴） channel， by taking acupoints mainly from the hand and foot shaoyang channels， along with the jueyin channels， so as to soothe the liver and promote bile secretion， regulate and harmonize qi and blood. During the esophageal stage， where the pathogen damages the esophagus， impeding food passage， the treatment emphasizes activating the yangming （阳明） channels and regulating taiyin （太阴） channels； acupoints are mainly selected from the foot yangming stomach channel， along with the taiyin channels， aiming to warm yang， unblock the channels and dispel stasis.

Objective : To investigate the effects of acarbose and pioglitazone on the levels of sex hormones in adult female rats ，and to explore their regulatory effects on the hypothalamic-pituitary-ovarian axis ( HPOA) and its mechanism． Methods : Adult female SD rats aged 2 months were randomly divided into 0．9% sodium chloride so- lution control group (NS) ，acarbose low (AL) ，medium (AM) and high (AH) dose groups and pioglitazone low (PL) ，medium (PM) and high (PH) dose groups．AL，AM and AH groups were given 20，40 and 60 mg / (kg · d) acarbose，and PL，PM and PH groups were given 5，10 and 15 mg / (kg · d) pioglitazone，respectively．Af- ter 28 days of intervention，serum gonadotropin (FSH，LH) and ovarian secreted hormone ( E2，P，T) were de- tected by ELISA，and the effects of acarbose and pioglitazone on HPOA were investigated by organ index analysis and histopathological observation of pituitary gland and ovary． Results : Compared with the NS group，the serum FSH in the PL，PM and PH groups decreased ( all P＜0. 01) ，the serum LH in the PL，PM and PH groups de- creased (P＜0. 05，P＜0. 01，P ＜0. 01) ，and the organ indices in the PM and PH groups decreased ( all P < 0. 01) ．HE staining of the adenohypophysis in the PL，PM and PH groups showed an increase in eosinophils，a de- crease in basophils，and an expansion and increase in the number of blood sinuses．In the PM and PH groups，HE staining of the ovaries showed that there were no significant differences in follicles at all levels，but the development was poor，the number of primordial follicles decreased，and the number of corpus luteum increased．Compared with the NS group，the serum P in the AM and AH groups decreased ( all P ＜0. 01) ，and serum E2 in AM and AH groups decreasd (all P＜0. 05) ． Conclusion Pioglitazone affects HPOA by regulating pituitary function directly． However，the effect of acarbose on HPOA may be mediated through the gut-brain axis，and has no direct correlation with the ovarian structure．

Currently,there are practical and technical difficulties in the construction of clinical ques-tions in the development of clinical practice guidelines.Clinicians or guideline developers seldom construct clin-ical questions based the actual case scenario,leading to some information loss between structured and actual clinical connotation.To overcome this challenge,we proposed a case-guided questions construction approach,and carried out case research and verification in the formulation of the guideline.We found that this method could more efficiently and scientifically assist the formulation of clinical questions,and provide reference for clinicians or guideline developers.

Objective:To investigate the alterations in gut microbiota diversity and inflammatory cytokine levels among patients with varying severities of insomnia, and to explore their interrelationships, in order to provide a theoretical basis for understanding the pathophysiology of insomnia.Methods:A total of 42 patients with chronic insomnia who visited the First Hospital of Hebei Medical University between March and December 2023 were enrolled in the insomnia group, and 22 age-and sex-matched healthy volunteers were recruited from the same hospital as the control group. General demographic data were collected, and Mini-International Neuropsychiatric Interview (MINI) was used to screen for comorbid psychiatric disorders. The Self-Rating Depression Scale (SDS) and the Self-Rating Anxiety Scale (SAS) were employed to evaluate individual′s depressive and anxiety symptoms. Sleep quality and insomnia severity were assessed using the Pittsburgh Sleep Quality Index (PSQI) and the Insomnia Severity Index (ISI), Participants′ gastrointestinal function and symptoms over the past week were evaluated using the Gastrointestinal Symptom Rating Scale (GSRS). Fecal and blood samples were collected from all participants. Gut microbiota diversity was analyzed using 16S rRNA sequencing. Differential taxa were identified using linear discriminant analysis effect size (LEfSe) and random forest analysis. Serum levels of inflammatory cytokines were measured by enzyme-linked immunosorbent assay (ELISA). Spearman correlation analysis was used to explore the relationships between insomnia symptoms, microbial diversity indices, key microbial taxa, and inflammatory markers. Multiple linear regression analysis was conducted to identify factors associated with insomnia severity.Results:Compared to the control group, both the mild insomnia group and the moderate-to-severe insomnia group showed significantly higher GSRS scores ( Z=-3.51, -2.72, both P<0.05). The Chao1 index was significantly lower in the mild and moderate-to-severe insomnia groups than in controls ( Z=-3.53, -3.87, both P<0.05). Similarly, the Observed species index was lower in both the mild and moderate-to-severe groups ( Z=-3.33, -3.74, both P<0.05). The Shannon index was significantly reduced in the moderate-to-severe group compared to both the mild group and controls ( Z=-2.81, -2.23, both P<0.05). The Simpson index in the moderate-to-severe group also tended to be lower than in the mild group ( Z=-1.95, P=0.051). Beta diversity differed significantly among the mild insomnia group, the moderate-to-severe insomnia group ( P<0.05), and the control group ( F=2.96, 3.12, both P<0.05). Random forest analysis identified Ruminococcus_D and Klebsiella as key microbial genera distinguishing between mild and moderate-to-severe insomnia. Inflammatory cytokine levels were significantly elevated in both insomnia groups compared to controls ( P<0.05). PSQI scores were negatively correlated with the Shannon index, the Observed species index, and the relative abundance of Ruminococcus_D ( r=-0.34, -0.30, and -0.25, respectively; all P<0.05). Multiple linear regression revealed that serum IL-1β (β=0.339, 95% CI=0.014-0.716, P=0.042) and Ruminococcus_D (β=-0.309, 95% CI=-194.591--8.318, P=0.034) were independent predictors of insomnia severity. Conclusion:Elevated inflammatory cytokine levels and reduced gut microbial richness may be closely associated with increased insomnia severity. Additionally, Ruminococcus_D and IL-1β may be important factors contributing to the severity of insomnia in affected individuals.

Diabetic osteoporosis （DOP） is a kind of bone complication caused by diabetes， which is characterized by the decrease of bone mineral density， the change of bone microstructure and the increase of bone fragility. The process of DOP is closely related to high glucose， insulin resistance， oxidative stress and other mechanisms. The Wnt/β-catenin signaling pathway plays an important role in mediating insulin resistance and bone metabolic balance in diabetes. Regulation of Wnt signal transduction promotes the expression of glycogen synthase kinase-3β（GSK-3β）phosphorylation and improves glucose and lipid metabolism. The Wnt/β-catenin signaling pathway is also an important way regulating osteocyte-driven bone remodeling， which not only plays an important regulatory role in the balance between osteoblasts and osteoclasts and improve bone metabolic homeostasis， but also promotes the expression of osteopontin， osteocalcin and type Ⅰ collagen， and improves bone proliferation and osteogenic differentiation by regulating the Wnt pathway. In recent years， the research of traditional Chinese medicine （TCM） in the prevention and treatment of DOP has gradually increased， and the exploration of TCM to interfere with the Wnt pathway to improve DOP has made some progress. This paper collects and summarizes the studies on the Wnt signaling pathway in glucose metabolism， bone metabolism and DOP worldwide in the past decade， as well as the related literature on the intervention of DOP by TCM compounds （classical and other compounds）， single Chinese medicine and TCM monomers based on the Wnt pathway， in order to provide a reference and direction for the development of new drugs for clinical prevention and treatment of DOP.

ObjectiveTo evaluate the clinical effect of Jiechang Buxu pills on chronic relapsing ulcerative colitis （syndrome of spleen-kidney Yang deficiency） and the repair effect on mucosal barrier injury. MethodA total of 108 patients were randomly assigned into observation （54 cases） and control （54 cases） groups. Both groups were treated with mesalazine enteric-coated tablets， 0.5 g/time， 3 times/d. In addition， the observation group received Jiechang Buxu pills， 10 g/time， 3 times/d， and the control group received simulant of Jiechang Buxu pills， 10 g/time， 3 times/d. Both groups were treated for 3 consecutive months. During monthly follow-up， clinical response， clinical remission rate， C-reactive protein （CRP） compliance rate， fecal calprotectin （FC） compliance rate， and endoscopic mucosal healing rate were compared. The early recurrence rate was recorded after 3 months of follow-up. The modified Mayo score， mucosal histological score， colonoscopic mucosal score， inflammatory bowel disease questionnaire （IBDQ） score， and syndrome score of spleen-kidney Yang deficiency were compared before and after treatment. The levels of hypoxia-inducible factor-1α （HIF-1α）， diamine oxidase （DAO）， D-lactic acid （D-LA）， interleukin（IL）-1β， IL-6， IL-17A， IL-22， tumor necrosis factor-α （TNF-α）， T helper 17 （Th17）， and regulatory T cells （Treg）， and Th17/Treg ratio were measured and calculated before and after treatment. ResultThe clinical response rate， clinical remission rate， and CRP compliance rate in the observation group were higher than those in the control group （P<0.05， P<0.01） 1， 2 and 3 months after treatment. The FC compliance rate in the observation group was higher than that in the control group （P<0.05） 2 and 3 months after treatment. After treatment， the observation group had higher endoscopic mucosal healing rate （P<0.01） and lower early recurrence rate （P<0.05） than the control group. In addition， the observation group had lower Mayo score， mucosal histological score， colonoscopic mucosal score， and syndrome score of spleen-kidney Yang deficiency （P<0.01）， higher IBDQ score （P<0.01）， lower levels of HIF-1α， DAO， D-LA， IL-1β， IL-6， IL-17A， TNF-α， Th17， and Th17/Treg and higher levels of IL-22 and Treg （P<0.01） than the control group. ConclusionJiechang Buxu pills combined with mesalazine enteric-coated tablets can improve the clinical response rate， clinical remission rate， CRP compliance rate， FC compliance rate， and endoscopic mucosal healing rate， reduce the early recurrence rate and disease activity， promote histological remission， and improve the quality of life in the patients with chronic relapsing ulcerative colitis （syndrome of spleen-kidney Yang deficiency）. The therapy may exert the therapeutic effect by inhibiting inflammation， inducing intestinal mucosal immune tolerance， and protecting the function of intestinal mucosal barrier.

Objective To explore the value of plaque-to-aorta CT value ratio(standardized CT value)in differentiating coronary lipid and fibrous plaques,and to preliminarily analyze the stability of the cutoff.Methods Patients who underwent coronary computed tomography angiography(CCTA)and intravascular ultrasound(IVUS)within 1 week were included.The plaque CT value was obtained by measuring the all,four and two short-axis planes,respectively.The CT value of the ascending aorta was measured and standardized(plaque-to-aorta CT value ratio).The receiver operating characteristic(ROC)curves of the standardized and the traditional CT values were drawn.Results A total of 60 patients with 74 plaques were included,35 lipid and 39 fibrous plaques were diagnosed by IVUS.The aorta CT value was significantly correlated with the plaque(r=0.420,P<0.01);the cutoffs for the CT value of all,four and two plaque slices were 55 HU,48 HU and 52 HU,respectively,and all there of the cutoffs of standardized CT value were 0.149;the sensitivity,specificity,positive predictive value(PPV)and negative predictive value(NPV)of four-slice traditional and standardized CT values to differentiate lipid and fibrous plaques were 69%,87%,83%,76%and 91%,82%,82%,91%,respectively.Conclusion Compared with traditional CT value,the standardized CT value can greatly improve the sensitivity and NPV in differentiating coronary lipid and fibrous plaques,while maintaining modest to high specificity and PPV.Furthermore,the cutoff is stable.

Currently, there are practical and technical difficulties in the construction of clinical questions in the development of clinical practice guidelines. Clinicians or guideline developers seldom construct clinical questions based the actual case scenario, leading to some information loss between structured and actual clinical connotation. To overcome this challenge, we proposed a case-guided questions construction approach, and carried out case research and verification in the formulation of the guideline. We found that this method could more efficiently and scientifically assist the formulation of clinical questions, and provide reference for clinicians or guideline developers.