ObjectiveTo investigate the effects of Yueju Wan on the 5-hydroxytryptamine （5-HT） signaling pathway in rats with functional dyspepsia （FD） and to explore its therapeutic mechanism in the treatment of FD. MethodsSixty Sprague-Dawley （SD） rats were randomly divided into a normal group， model group， mosapride group （1.575 mg·kg^-1）， and Yueju Wan low-， medium-， and high-dose groups （0.735， 1.47， and 2.94 g·kg^-1， respectively）. The FD rat model was established using GUO's tail-clamping stimulation combined with irregular feeding. After 14 days of modeling， rats were administered the corresponding drugs by gavage for 28 days. After treatment， gastric emptying rate and small intestinal propulsion rate were measured. Serum levels of 5-HT， tryptophan hydroxylase （TPH）， and substance P （SP） were detected by enzyme-linked immunosorbent assay （ELISA）， and acetylcholine （ACh） levels were determined by chemical methods. Histopathological changes in the gastric antrum were observed using hematoxylin-eosin （HE） staining. Real-time quantitative polymerase chain reaction （Real-time PCR） and Western blot were used to assess the mRNA and protein expression levels of 5-hydroxytryptamine 4 receptor （5-HT4R）， SP， and acetylcholinesterase （AChE） in colon tissue， as well as 5-hydroxytryptamine 3 receptor （5-HT3R）， SP， and AChE in hypothalamic tissue. Immunohistochemistry （IHC） was used to examine the expression of 5-HT and 5-HT4R in the colon and 5-HT and 5-HT3R in the hypothalamus. ResultsCompared with the normal group， the gastric emptying rate and small intestinal propulsion rate in the model group were significantly decreased （P<0.01）. Serum levels of 5-HT， SP， ACh， and TPH were significantly reduced （P<0.01）. Histopathological examination revealed irregular arrangement of glands in the gastric antrum， slight mucosal atrophy， and mild inflammatory cell infiltration. The mRNA and protein expression levels of 5-HT4R， SP， and AChE in colon tissue， as well as 5-HT3R， SP， and AChE in hypothalamic tissue， were significantly decreased （P<0.01）， and 5-HT protein expression in both the colon and hypothalamus was also significantly reduced （P<0.01）. Compared with the model group， all Yueju Wan groups showed significantly increased gastric emptying rate and small intestinal propulsion rate （P<0.01）. The glands in the gastric antrum were more regularly arranged， with no inflammatory cell infiltration observed. Serum levels of 5-HT， SP， ACh， and TPH were significantly increased （P<0.01）. The mRNA and protein expression levels of 5-HT4R， SP， and AChE in colon tissue and 5-HT3R， SP， and AChE in hypothalamic tissue were significantly upregulated （P<0.05， P<0.01）， and 5-HT protein expression in both the colon and hypothalamus was significantly increased （P<0.01）. ConclusionYueju Wan has preventive and therapeutic effects on FD， and its mechanism may be related to regulation of the 5-HT signaling pathway， promotion of brain-gut peptide secretion， and enhancement of gastric motility.

OBJECTIVE: To investigate the safety and effectiveness of using the Taylor spatial frame (TSF) based on the Ilizarov tension-stress principle for treatment of post-burn foot and ankle deformities in adults. METHODS: A clinical data of 6 patients with post-burn foot and ankle deformities treated between April 2019 and November 2023 was retrospectively analyzed. There was 1 male and 5 females with an average age of 28.7 years (range, 20-49 years). There were 3 cases of simple ankle equinus, 2 cases of ankle equinus, midfoot rocker-bottom foot, and forefoot pronation, and 1 case of calcaneus foot and forefoot pronation. Preoperative American Orthopedic Foot and Ankle Society (AOFAS) score was 45.3±18.2, 12-Item Short-Form Health Survey (SF-12)-Physical Component Summary (PCS) score was 34.3±7.3 and Mental Component Summary (MCS) score was 50.4±8.8. Imaging examination showed tibial-calcaneal angle of (79.8±31.5)°, calcaneus-first metatarsal angle of (154.5±45.3)°, talus-first metatarsal angle of (-19.3±35.0)°. Except for 1 case with severe deformity that could not be measured, the remaining 5 cases had talus-second metatarsal angle of (40.6±16.4)°. The deformities were fixed with TSF after soft tissue release and osteotomy. Then, the residual deformities were gradually corrected according to software-calculated prescriptions. TSF was removed after maximum deformity correction and osteotomy healing. External fixation time, brace wearing time after removing the TSF, and pin tract infection occurrence were recorded. Infection severity was evaluated based on Checketts-Otterburns grading. Joint function was evaluated using AOFAS score and SF-12 PCS and MCS scores. Patient satisfaction was assessed using Likert score. Imaging follow-up measured relevant indicators to evaluate the degree of deformity correction. Deformity recurrence was observed during follow-up. RESULTS: The external fixation time was 103-268 days (mean, 193.5 days). The mild pin tract infections occurred during external fixation in all patients, which healed after pin tract care and oral antibiotics. No serious complication such as osteomyelitis, fractures, neurovascular injury, or skin necrosis occurred. After external fixation removal, 3 cases did not wear braces, while the remaining 3 cases wore braces continuously for 6 weeks, 8 weeks, and 3 years, respectively. All patients were followed up 13.9-70.0 months, with an average of 41.7 months. During follow-up, none of the 6 patients had recurrence of foot deformity. At 1 year after operation, the AOFAS score was 70.0±18.1, SF-12-PCS and MCS scores were 48.9±4.5 and 58.8±6.4, respectively, all showing significant improvement compared to preoperative values ( P<0.05). Imaging follow-up showed that all osteotomies healed, and all distraction cases achieved bony union at 6 months after stopping stretching. At 1 year after operation, tibial-calcaneal angle was (117.5±12.8)° and talus-first metatarsal angle was (-3.3±19.3)°, both showing significant improvement compared to preoperative values ( P<0.05). Calcaneus-first metatarsal angle was (132.0±14.4)°, which also improved compared to preoperative values but without significant difference ( P>0.05). Except for 1 case with severe deformity that could not be measured, the remaining 5 cases had talus-second metatarsal angle of (18.0±6.4)°. And there was no significant difference ( P>0.05) between pre-and post-operative data of 4 patients with complete data. At 1 year after operation, 1 patient was satisfied with effectiveness and 5 patients were very satisfied. CONCLUSION The TSF, by applying the Ilizarov tension-stress principle for gradual distraction and multi-planar adjustment, combined with soft tissue release and osteotomy, can effectively correct foot and ankle deformities after burns, especially equinus deformity with contracture of the posterior soft tissues of the lower leg. There are still limitations in treating cases with tight, adherent scars on the dorsum of the foot that require long-distance distraction. If necessary, a multidisciplinary approach combined with microsurgical techniques can be utilized.
Humans ; Adult ; Male ; Female ; Middle Aged ; Retrospective Studies ; External Fixators ; Young Adult ; Burns/complications* ; Foot Deformities, Acquired/etiology* ; Treatment Outcome ; Ilizarov Technique/instrumentation*

Objective:To analyze the clinical data of seven patients with a clinical diagnosis of likely sporadic Creutzfeldt-Jakob disease (sCJD) in order to improve the understanding and diagnosis of sporadic Creutzfeldt-Jakob disease.Methods:The clinical data of 7 sCJD patients admitted to the Department of Neurology of Our Hospital from 2021 to 2023 were retrospectively analyzed.Results:All seven patients had a subacute onset of disease, and the main clinical features included rapidly progressive dementia (RPD), cerebellar symptoms, pyramidal signs, myoclonus and akinetic mutism. Magnetic resonance diffusion-weighted imaging (DWI) reveals widespread asymmetrical lace-like high signal distributed along the cortex and a basal curved ball-and-stick sign. Electroencephalography (EEG) shows diffuse spiking and spiking slow waves, and periodic triphasic waves in advanced stages of the disease. Cerebrospinal fluid 14-3-3 protein testing was performed in 6 of the 7 patients, and 4 were positive. Four patients died within six months of onset of illness.Conclusions:The disease is prevalent in middle-aged and elderly patients, with a non-significant male-to-female ratio, and is dominated by the presence of Rapidly Progressive Dementia (RPD), especially the presence of cortical high signals in the DWI sequences and diffuse sharp and slow wave issuance in the electroencephalograph (EEG), which need to be alerted to the occurrence of Creutzfeldt-Jakob Disease. Dynamic review of MRI, EEG, cerebrospinal fluid 14-3-3 protein, prion protein gene (PRNP) sequence analysis and cerebrospinal fluid prion real-time vibration-induced protein amplification (RT-QuIC) monitoring whenever possible to avoid misdiagnosis, under-diagnosis, and under-recognition.

ObjectiveTo investigate the effect of Danggui Shaoyaosan on ferroptosis in the rat model of non-alcoholic fatty liver disease （NAFLD） and explore the underlying mechanism based on the nuclear factor E₂-related factor 2 （Nrf2）/solute carrier family 7 member 11 （SLC7A11）/glutathione peroxidase 4 （GPX4） signaling pathway. MethodsThe sixty SD rats were randomly grouped as follows： control， model， Yishanfu （0.144 g·kg^-1）， and low-， medium-， and high-dose （2.44， 4.88， and 9.76 g·kg^-1， respectively） Danggui Shaoyaosan. A high-fat diet was used to establish the rat model of NAFLD. After 12 weeks of modeling， rats were treated with corresponding agents for 4 weeks. Then， the body weight and liver weight were measured， and the liver index was calculated. At the same time， serum and liver samples were collected. The levels or activities of total cholesterol （TC）， triglycerides （TG）， alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， and Fe²⁺ in the serum and TC， TG， free fatty acids （FFA）， malondialdehyde （MDA）， superoxide dismutase （SOD）， glutathione peroxidase （GPX）， and Fe²⁺ in the liver were measured. Hematoxylin-eosin staining and oil red O staining were employed to observe the pathological changes in the liver. Immunofluorescence was used to assess the reactive oxygen species （ROS） content in the liver. Mitochondrial morphology was observed by transmission electron microscopy. The protein levels of Nrf2， SLC7A11， GPX4， transferrin receptor 1 （TFR1）， and divalent metal transporter 1 （DMT1） in the liver were determined by Western blot. ResultsCompared with the control group， the model group showed increases in the body weight， liver weight， liver index， levels or activities of TC， TG， ALT， AST， and Fe²⁺ in the serum， levels of TC， TG， FFA， MDA， Fe²⁺， and ROS in the liver， and protein levels of TFR1 and DMT1 in the liver （P<0.01）， and decreases in the activities of SOD， GPX and the protein levels of Nrf2， SLC7A11， and GPX4 in the liver （P<0.05， P<0.01）. Meanwhile， the liver tissue in the model group presented steatosis， iron deposition， mitochondrial shrinkage， and blurred or swollen mitochondrial cristae. Compared with the model group， all doses of Danggui Shaoyaosan reduced the body weight， liver weight， liver index， levels or activities of TC， TG， ALT， AST， and Fe²⁺ in the serum， levels of TC， TG， FFA， MDA， Fe²⁺， and ROS in the liver， and protein levels of TFR1 and DMT1 in the liver （P<0.01）， while increasing the activities of SOD and GPX and the protein levels of Nrf2， SLC7A11， and GPX4 in the liver （P<0.01）. Furthermore， Danggui Shaoyaosan alleviated steatosis， iron deposition， and mitochondrial damage in the liver. ConclusionDanggui Shaoyaosan may inhibit lipid peroxidation and ferroptosis by activating the Nrf2/SLC7A11/GPX4 signaling pathway to treat NAFLD.

Objective:To analyze the clinical data of seven patients with a clinical diagnosis of likely sporadic Creutzfeldt-Jakob disease (sCJD) in order to improve the understanding and diagnosis of sporadic Creutzfeldt-Jakob disease.Methods:The clinical data of 7 sCJD patients admitted to the Department of Neurology of Our Hospital from 2021 to 2023 were retrospectively analyzed.Results:All seven patients had a subacute onset of disease, and the main clinical features included rapidly progressive dementia (RPD), cerebellar symptoms, pyramidal signs, myoclonus and akinetic mutism. Magnetic resonance diffusion-weighted imaging (DWI) reveals widespread asymmetrical lace-like high signal distributed along the cortex and a basal curved ball-and-stick sign. Electroencephalography (EEG) shows diffuse spiking and spiking slow waves, and periodic triphasic waves in advanced stages of the disease. Cerebrospinal fluid 14-3-3 protein testing was performed in 6 of the 7 patients, and 4 were positive. Four patients died within six months of onset of illness.Conclusions:The disease is prevalent in middle-aged and elderly patients, with a non-significant male-to-female ratio, and is dominated by the presence of Rapidly Progressive Dementia (RPD), especially the presence of cortical high signals in the DWI sequences and diffuse sharp and slow wave issuance in the electroencephalograph (EEG), which need to be alerted to the occurrence of Creutzfeldt-Jakob Disease. Dynamic review of MRI, EEG, cerebrospinal fluid 14-3-3 protein, prion protein gene (PRNP) sequence analysis and cerebrospinal fluid prion real-time vibration-induced protein amplification (RT-QuIC) monitoring whenever possible to avoid misdiagnosis, under-diagnosis, and under-recognition.

Objective:To investigate the value of neutrophil-lymphocyte ratio(NLR),platelet-lymphocyte ratio(PLR),lymphocyte-monocyte ratio(LMR)and prognostic nutrition index(PNI)in predicting the curative effect and prognosis of patients with advanced hepatocellular carcinoma(HCC)treated with combined therapy of immune checkpoint inhibitors(ICI)and antiangiogenic drugs.Methods:The general clinical data,NLR,PLR,LMR and PNI of patients before treatment,clinical efficacy and prognosis of 85 advanced HCC patients admitted and treated with combined therapy of ICI and antiangiogenic drugs between January 2020 and December 2023 in the First Affiliated Hospital of Dali University were collected.The optimal cut-off values of NLR、PLR、LMR and PNI were obtained using receiver operating characteristic(ROC)curve,and used to divide the patients into the high and low groups.Kaplan-Meier method was used for survival analysis;Cox proportional risk model was used for the univariate and multivariate analysis of the effects of these values on the patient's OS.Results:The therapeutic effective rates in the low NLR,low PLR,high LMR and high PNI groups were respectively higher than those of the high NLR,high PLR,low LMR and low PNI groups(all P<0.05).The patient's OS rates in the low NLR,low PLR groups were respectively significantly higher than those in the high NLR,high PLR groups(all P<0.05).The patient's OS rates in the high LMR,high PNI groups were respectively significantly higher than those in the low LMR,low PUI groups(all P<0.05).NLR≥1.94,male and HBV infection were independent risk factors for the prognosis of advanced HCC patients(all P<0.05).Conclusion:NLR≥1.94,male,HBV positive are risk factors influencing the efficacy and prognosis of patients.NLR≥1.94 has certain clinical value in evaluating the efficacy and prognosis of combined immunotherapy and targeted therapy for advanced HCC patients.

Objective To investigate the therapeutic effect of isoorientin on ulcerative colitis(UC)mice induced by dextran sulfate sodium(DSS)and its mechanism.Methods Forty-eight C57BL/6J mice were randomly divided into control group,model group,mesalazine group(600 mg·kg-1),isoorientin low dose group(25 mg·kg-1),isoorientin high dose group(50 mg·kg-1)and isoorientin control group(50 mg·kg-1),with eight mice in each group.Mice were free to drink 2%DSS solution to replicate UC model.After three weeks of experiment,each drug administration group was given corresponding drug by intragastric administration for four weeks.After the last administration,the body weight was weighed,blood was taken from eyeballs,and colon tissue was dissected.The pathological changes of colon were observed by hematoxylin-eosin(HE)and alcian blue-periodic acid-Schiff(AB-PAS)staining.The ultrastructure of colon tissue was observed by transmission electron microscope.Serum levels of interleukin(IL)-6,IL-8,IL-10,IL-1β,tumor necrosis factor α(TNF-α),lipopolysaccharide(LPS)and myeloperoxidase(MPO)were detected by enzyme-linked immunosorbent assay(ELISA).The expression of galectin-3(Gal-3)protein in colon tissue of mice was detected by immunohistochemistry analysis.The expression of MUC2 and the co-localization of NOD-like receptor heat protein domain associated protein 3(NLRP3)and apoptosis-associated speck-like protein(ASC)were detected by immunofluorescence assay.The protein expression of Gal-3,NLRP3,ASC,Caspase-1,IL-1β,IL-18,Occludin,and zonula occludens protein-1(ZO-1)in colon tissue of mice were detected by Western Blot.Results Compared with the control group,the body weight and colon length in the model group were shortened significantly,while the index of colonic weight of mice were increased significantly(P＜0.01).The intestinal mucosal structure of mice was disordered,the microvilli were sparse,the crypt structure was infiltrated by a large number of inflammatory cells,mitochondria were significantly swollen,and goblet cells were obviously decreased.Serum levels of IL-6,IL-8,IL-1β,TNF-α,LPS,and MPO were significantly increased,while IL-10 level was significantly decreased(P＜0.01).The positive expression of MUC2 protein in colon tissue was decreased and the co-localization of NLRP3 and ASC was enhanced.The protein expression of Gal-3,NLRP3,ASC,Caspase-1,IL-1β,and IL-18 in colon tissue were significantly increased,and the protein expression of Occludin and ZO-1 were significantly decreased(P＜0.01).Compared with the model group,the body weight and colon length of mice in isoorientin low-and high-dose groups were significantly increased,the index of colonic weight of mice was apparently decreased(P＜0.05,P＜0.01).The structure of intestinal mucosa,microvilli and mitochondria recovered obviously,inflammatory infiltration was alleviated,and goblet cells were increased obviously.Serum levels of IL-6,IL-8,IL-1β,TNF-α,LPS,and MPO were significantly decreased,while IL-10 level was significantly increased(P＜0.05,P＜0.01).The positive expression of MUC2 protein in colon tissue was increased and the co-localization of NLRP3 and ASC was reduced.The protein expression of Gal-3,NLRP3,ASC,Caspase-1,IL-1β,and IL-18 in colon tissue were significantly decreased,and the protein expression of Occludin and ZO-1 were significantly increased(P＜0.05,P＜0.01).Conclusion Isoorientin has a great therapeutic effect on DSS-induced UC mice.Its mechanism may be related to the protection of intestinal mucosal barrier by Gal-3/NLRP3/IL-1β signaling pathway.

OBJECTIVE: This study aimed to explore the association between humidity exposure and the risk of cardiovascular disease (CVD), utilizing follow-up data and relative humidity (RH) metric assessments. METHODS: We extracted the baseline data from the China Hypertension Survey (CHS) of 24,510 enrolled participants aged ≥ 35 years without a history of CVD between 2012 and 2015 and followed them up from 2018 to 2019. The National Meteorological Information Center (NMIC) of the China Meteorological Administration (CMA) provided the quality-controlled relative humidity (RH) datasets. Cox proportional hazards models were used to estimate hazard ratios ( HRs) for CVD in relation to RH. RESULTS: During the follow-up period (2018-2019), 973 patients with CVD were identified. The HR of CVD risk was 1.17 (95% CI: 1.04-1.31) per 10% increase in summer mean RH. Compared with participants in the 3 ^rd quintile group, those in the 1 ^st and 5 ^th quintiles of RH had a higher risk of CVD. For summer mean RH, the HRs (95% CIs) for the 1 ^st and 5 ^th quintiles were 1.34 (1.04-1.71) and 1.44 (1.14-1.83), respectively. The relationship ("U" shape) between summer mean RH and the risk of CVD was nonlinear. Stratified analyses indicated that the risk of CVD was substantially influenced by the summer mean RH in female, older individuals, and those in southern China. CONCLUSION Unsuitable (too high or low) humidity environments affect the risk of CVD. Our study highlights those future policies for adapting to climate change should consider the humidity-CVD relationship.
Humans ; Humidity/adverse effects* ; Cardiovascular Diseases/etiology* ; Female ; Male ; Middle Aged ; Prospective Studies ; China/epidemiology* ; Adult ; Aged ; Risk Factors ; Proportional Hazards Models ; Seasons

Objective To establish a nomogram model for efficiently predicting overall survival(OS)and cancer-specific survival(CSS)in patients with CRCHBM.Method 2239 patients from 2010 to 2019 were retrospectively analyzed from the Surveillance,Epidemiology,and End Results Program(SEER)databases and Wuhan Union Hospital Cancer Center.SEER is randomly assigned to the training and internal validation cohorts,and the Wuhan database serves as the external validation.Cox regression analyses were used to determine the independent clinicopathological prognosis factors affecting OS and CSS,and a nomogram was constructed to predict OS and CSS.The clinical utility of columnar plots was assessed using calibration curves,area under the curve(AUC),and decision curve analysis(DCA).Result OS column line graphs were constructed based on nine independent predictors:age,tumor location,degree of differentiation,tumor size,TNM stage,chemotherapy,primary focus surgery,number of lymph nodes sampled,and serum carcinoembryonic antigen(CEA)level.The C-index of the nomogram to predict the 1-,3-,and 5-year OS were 0.764,0.790,and 0.805 in the training group,0.754,0.760,and 0.801 in the internal validation group,and 0.822,0.874,and 0.906 in the external validation group.CSS column line graphs were constructed based on 3 independent predictors of TNM staging,radiotherapy and chemotherapy.The 1-,3-,and 5-year CSS AUROC values of the training group were 0.791,0.757,and 0.782,respectively.0.682,0.709,0.625 in the internal validation group and 0.759,0.702,0.755 in the external validation group,respectively.The results of receiver operating characteristic curve(ROC),ROC and DCA showed that the use of our model was more effective in predicting OS and CSS than other single clinicopathological features.Conclusion In summary,the nomogram based on significant clinicopathological features can be conveniently used to predict OS and CSS individually in patients with CRCHBM.

Objectives:To investigate the association between social determinants of health(SDOH)and incident stroke and analyze the main risk factors for stroke among resident with different SDOH levels. Methods:From 2012 to 2015,30 036 residents(≥35 years old)from 30 districts in 14 provincial-level administrative divisions in China were enrolled this study based on stratified multi-stage-random-sampling method.The prevalence of cardiovascular diseases and related risk factors were investigated,and stroke events were followed up in 2018 to 2019.Principal component analysis was performed to establish SDOH scores based on 9 indicators related to socioeconomic and healthcare resources,participants were divided into low SDOH group(n=8 343)when it was≥-2.01 to<-1.14,middle SDOH group(n=7 257)when it was≥-1.14 to<0.10,and high SDOH group(n=8 457)when it was≥0.10 to≤5.79.Multivariate Cox regression was applied to estimate the association of SDOH levels with incident stroke.The random survival forest method was used to analyze the major risk factors in different SDOH levels. Results:A total of 24 057 participants were finally included,669(2.8%)participants developed stroke during a mean of(4.7±0.8)years follow-up.The incidence densities of stroke in the low,medium,and high SDOH groups were 468.39,628.85,and 700.39/100 000 person-years,respectively(Pdifference<0.05,Ptrend=0.01).Compared with individuals with low SDOH level group,fully HR for incident stroke among those with medium and high were 1.91(95%CI:1.54-2.36)and 1.59(95%CI:1.30-1.95),respectively(Ptrend<0.001).Advanced age is the primary risk factor for stroke in the population,especially in districts with high SDOH level.In districts with medium SDOH level,diabetes is an important risk factor for stroke.High blood pressure and alcohol consumption are important modifiable risk factors in low SDOH level districts. Conclusions:Present study shows that higher levels of SDOH are associated with increased risk of stroke.The main risk factors for stroke differ among participants with different SDOH level districts.Targeted interventions should be implemented to improve the prevention and treatment of stroke in populations with different levels of SDOH.