ObjectiveTo investigate the effects of Simiaowan on intestinal barrier function and adenosine triphosphate （ATP） binding cassette transporter G2 （ABCG2） expression in hyperuricemic （HUA） rats， and elucidate its therapeutic mechanisms. MethodsForty male Sprague Dawley （SD） rats were randomized into a normal group， a model group， low-dose （282.6 mg·kg^-1） and high-dose （565.2 mg·kg^-1） Simiaowan groups， and a Benzbromarone （4.7 mg·kg^-1） group. The HUA model was established via intraperitoneal injection of potassium oxonate （ip） combined with oral gavage of hypoxanthine （ig） for 14 days. Following modeling， treatments were administered for 14 days. Samples were collected and weighed 4 h after final dosing. Blood uric acid and hepatic function were analyzed. Histopathological changes were evaluated by hematoxylin-eosin （HE） staining， and Chiu's scoring was conducted. Enzyme-linked immunosorbent assay （ELISA） quantified tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， interleukin-1β （IL-1β）， lipopolysaccharide （LPS）， diamine oxidase （DAO）， and D-lactic acid （D-LA） levels. Real-time polymerase chain reaction （Real-time PCR）， Western blot， and immunohistochemistry assessed the expression of Claudin-1， Occludin， occludens-1 （ZO-1）， and ABCG2 mRNAs and proteins. 16S rDNA amplicon sequencing characterized ileal microbiota. ResultsCompared with the normal group， the model group exhibited epithelial shedding in the ileal villus， structural disruption， infiltration of extensive inflammatory cells， and significantly elevated Chiu's scores （P<0.01）. The DAO， TNF-α， IL-6， IL-1β， LPS， and D-LA levels in the ileum were markedly increased （P<0.01）， while mRNA and protein expressions of Claudin 1， Occludin， ZO-1， and ABCG2， as well as positive staining area and proportion， were significantly reduced （P<0.01）. Compared with the model group， the Simiaowan groups at all doses showed improved epithelial damage in the ileal villus， significantly lowered Chiu's scores （P<0.01）， significantly reduced DAO， TNF-α， IL-6， IL-1β， LPS， and D-LA levels in the ileum （P<0.01）， and upregulated mRNA and protein expressions of Claudin 1， Occludin， ZO-1， and ABCG2， as well as positive staining area and proportion （P<0.01）. The 16S rDNA results showed that in the model group， the α-diversity index of the ileal microbiota was increased， and species diversity and richness were enhanced， with microbiota dysfunction observed. The community structure of the gut microbiota was significantly different from that of the normal microbiota. The abundance of probiotics was decreased， and the abundance of pathogenic bacteria was increased， with butyrate-producing bacteria showing a low abundance. In contrast， Simiaowan at all doses reduced species diversity and richness， regulated microbiota dysfunction， and promoted the shift of the structure of the gut microbiota community towards a normal one. This increased the abundance of beneficial bacteria， decreased the abundance of harmful bacteria， and restored the abundance of butyrate-producing bacteria. ConclusionSimiaowan enhances ileal uric acid excretion and further alleviates HUA by modulating the gut microbiota composition to improve the intestinal barrier and upregulate the expression of the urate transporter ABCG2 in HUA rats.

ObjectiveTo investigate the epidemiological and clinical characteristics of human bocavirus (HBoV) in hospitalized children with acute lower respiratory tract infection (ALRTI) at a single-center children’s hospital in Shanghai, thereby providing evidence for the diagnosis, treatment, and prevention of HBoV infection. MethodsA retrospective study was conducted on 19 537 hospitalized children with ALRTI at Shanghai Children’s Hospital from January 2021 to December 2023. Multiplex polymerase chain reaction (PCR) combined with capillary electrophoresis was used to detect HBoV and 12 other common respiratory viruses /atypical pathogens. The positive detection rate, demographic characteristics (sex, age), temporal distribution (year, season) of HBoV, as well as the clinical characteristics of severe and non-severe pneumonia were analyzed. ResultsThe overall HBoV-positive rate was 2.57% (503/19 537), with 59.44% (299/503) being single infections and 40.56% (204/503) being co-infections. The positive detection rate was significantly higher in boys than that in girls (2.78% vs 2.33%, χ²=3.88, P=0.049). The highest infection rate was observed in toddlers, followed by infants (χ²=379.57, P<0.001). The positive rate peaked in 2021 and reached its lowest point in 2023 (χ²=45.49, P<0.001), with epidemics mainly prevalent in summer and autumn. The main clinical symptoms were cough (90.06%, 453/503), fever (75.94%, 382/503), and wheezing (39.96%, 201/503). Children with severe pneumonia showed a higher incidence of wheezing compared with the non-severe group (P<0.001), while underlying diseases and co-infections had no significant association with disease severity (P>0.05). ConclusionHBoV was an important pathogen of ALRTI in children, predominantly affecting infants and toddlers, with higher susceptibility in boys and seasonal peaks in autumn and summer. The main clinical manifestations included cough, fever, and wheezing, with wheezing being more prevalent in children with severe pneumonia.

ObjectiveTo investigate the mechanism by which Simiao Wan improve intestinal uric acid excretion in hyperuricemic （HUA） rats by inhibiting ferroptosis via the solute carrier family 7 member 11/glutathione peroxidase 4 （SLC7A11/GPX4） signaling pathway. MethodsForty-eight male SD rats were randomly assigned to a normal group， a model group， a low-dose Simiao Wan group （282.6 mg·kg^-1）， a high-dose Simiao Wan group （565.2 mg·kg^-1）， an etoricoxib group （5.4 mg·kg^-1）， and a ferroptosis inhibitor （Fer-1） group （2 mg·kg^-1）. Except for the normal group， rats in all other groups were intraperitoneally injected with potassium oxonate （100 mg·kg^-1） combined with intragastric administration of hypoxanthine （500 mg·kg^-1） to establish the HUA rat model. After 21 days， rats in each administration group received the corresponding dose of drug by gavage， rats in the Fer-1 group received intraperitoneal injection of Fer-1， and rats in the normal and model groups were given an equal volume of normal saline by gavage. After sampling， serum levels of uric acid （SUA）， creatinine （Cr）， and blood urea nitrogen （BUN） were measured using biochemical assays. The content of ferrous ion （Fe²⁺）， reduced glutathione （GSH）， and malondialdehyde （MDA）， as well as superoxide dismutase （SOD） activity in ileal tissues were determined. Hematoxylin and eosin （HE） staining was performed to observe the histopathological changes in the ileum， and transmission electron microscopy was used to observe mitochondrial alterations in the ileal tissue. Immunohistochemistry （IHC） and Western blot were used to detect the protein expression levels of GPX4， ferritin heavy chain 1 （FTH1）， acyl-CoA synthetase long-chain family member 4 （ACSL4）， SLC7A11， and ATP-binding cassette transporter G2 （ABCG2） in ileal tissue. Real-time quantitative polymerase chain reaction （Real-time PCR） was used to determine the mRNA expression of GPX4， FTH1， ACSL4， SLC7A11， and ABCG2 in the ileal tissue. ResultsCompared with the normal group， the model group exhibited significantly elevated serum UA， Cr， and BUN levels （P<0.01）， significantly increased content of MDA and Fe²⁺ in ileal tissue， and significantly decreased GSH content and SOD activity （P<0.01）. HE staining showed extensive shedding of the ileal villous epithelium， disrupted and disorganized villous structure， and incomplete local tissue architecture. Transmission electron microscopy revealed reduced mitochondrial volume， decreased or even vanished cristae， indicating ultrastructural features characteristic of ferroptosis. Molecular and immunohistochemical results demonstrated that the protein and mRNA expression levels of GPX4， FTH1， SLC7A11， and ABCG2 were significantly downregulated， whereas those of ACSL4 were significantly upregulated （P<0.05， P<0.01）. Compared with the model group， after intervention with Simiao Wan， the serum UA， Cr， and BUN levels significantly decreased in all dose groups （P<0.05，P<0.01）， the MDA and Fe²⁺ content in ileal tissues were significantly reduced （P<0.01）， and the GSH content and SOD activity significantly increased （P<0.01）. HE staining showed that the shedding of ileal villous epithelium was markedly alleviated， the villous structure became relatively intact and regularly arranged， and local tissue damage was obviously improved. Transmission electron microscopy showed attenuated mitochondrial damage， improvement in mitochondrial shrinkage， and partial restoration of mitochondrial cristae. Molecular and immunohistochemical results showed that Simiao Wan upregulated GPX4， FTH1， SLC7A11， and ABCG2， and downregulated ACSL4 in a dose-dependent manner. In the high‑dose group， all indices improved significantly （P<0.05，P<0.01）， whereas in the low‑dose group， only improving trends were observed for FTH1， SLC7A11 mRNA， and ABCG2 protein. ConclusionSimiao Wan may inhibit ferroptosis of ileal epithelial cells by regulating the SLC7A11/GPX4 signaling pathway， and upregulate the expression of the uric acid transporter ABCG2， thereby promoting intestinal uric acid excretion and improving HUA.

Objective: To examine the relationship between self-management behaviors and time perspective among patients with comorbid diabetes, so as to provide the evidence for improving self-management behaviors among patients with comorbid diabetes. Methods: The patients with comorbid diabetes who were registered in the chronic disease health management system of Minhang District, Shanghai Municipality in 2021, followed up regularly, and lived in Meilong Town were recruited. Demographic information and family history of diabetes were collected through questionnaire surveys. Time perspective and self-management behaviors were assessed using the Zimbardo Time Perspective Inventory and Diabetes Self-Management Behavior Scale, respectively. The relationship between self-management behaviors and time perspective was analyzed using a multivariable ordinal logistic regression model. Results: A total of 907 patients with comorbid diabetes were enrolled, including 472 males (52.04%) and 435 females (47.96%). There were 652 cases aged 65 years and above, accounting for 71.89%. In terms of the types of time perspective, 280 patients were future-oriented (30.87%), 236 were balanced (26.02%), 162 were sensation-seeking (17.86%), 123 were fatalistic (13.56%), and 106 were negative (11.69%). In terms of the self-management behaviors, 46 patients were good (5.07%), 643 were moderate (70.89%), and 218 were poor (24.04%). Multivariable ordinal logistic regression analysis showed that after adjusting for age, gender, educational level, marital status, occupation status, monthly income, and family history of diabetes, the patients with comorbid diabetes who had a future-oriented time perspective had better self-management behaviors (OR=1.874, 95%CI: 1.204-2.915). Conclusion The self-management behaviors among patients with comorbid diabetes are moderate to poor, and patients with a future-oriented time perspective can better engage in self-management behaviors.

BACKGROUND:Spinal cord injury is a neurological disorder caused by traumatic or non-traumatic events,often leading to severe functional impairment below the injured segment.In recent years,neural stem cell transplantation has been considered to have significant therapeutic potential in regulating the inflammatory response after spinal cord injury,inhibiting excessive proliferation of glial scars,and promoting nerve regeneration. OBJECTIVE:To review and discuss the potential mechanism of action of acupuncture and neural stem cell transplantation therapy in inhibiting spinal cord injury-induced secondary injury,and to delve into the scientific basis for its treatment of spinal cord injury. METHODS:PubMed,Elsevier,WanFang,and CNKI databases were searched using"spinal cord injury,acupuncture,neural stem cells,SDF-1α/CXCR4 axis"as Chinese and English search terms.Totally 96 articles were finally included.The research findings of acupuncture combined with neural stem cells in the treatment of spinal cord injury were summarized and analyzed,and the mechanism of this combination therapy in the treatment of secondary injury after spinal cord injury was summarized. RESULTS AND CONCLUSION:(1)The stromal-derived factor 1α(SDF-1α)/chemokine receptor 4(CXCR4)axis plays a crucial role in neural stem cell transplantation for spinal cord injury.This signaling mechanism not only affects neural stem cell migration,proliferation,and differentiation,but is also a key factor in determining the efficiency of stem cell homing to the injury site.Therefore,the regulation of targeting this axis is of great significance in enhancing the therapeutic effect of spinal cord injury.(2)Acupuncture,as a traditional Chinese medicine therapy,shows unique advantages in the regulation of secondary injury in spinal cord injury.It can effectively reduce secondary injury after spinal cord injury by regulating inflammatory response,inhibiting apoptosis,improving microcirculation,reducing glial scar formation,and counteracting oxidative stress.(3)Acupuncture was also able to influence the expression and function of the SDF-1α/CXCR4 axis,thereby enhancing the homing and survival ability of neural stem cells and promoting nerve regeneration and functional recovery.(4)The therapy combining acupuncture and stem cell transplantation is an innovative treatment strategy for spinal cord injury and suitable for repairing neural circuits.It combines the wisdom of traditional Chinese medicine with the advantages of modern biotechnology,providing a new treatment option for spinal cord injury patients.However,this combination therapy is still in the research and exploration stage,and its long-term efficacy and safety need to be further verified.(5)Taken together,acupuncture and neural stem cell transplantation for the treatment of spinal cord injury has great potential for clinical application,but in-depth research and optimization of treatment options are still needed.In the future,we look forward to further revealing the efficacy mechanism and optimal indications of this therapy through more clinical trials and mechanism studies,so as to bring better hope of recovery and more efficient therapeutic effects to spinal cord injury patients.

BACKGROUND:Rev-erbα is involved in the regulation of inflammation,but pharmacological activation of Rev-erbα increases the risk for cardiovascular diseases.To reduce the relevant risk,an exploration on SR9009,a Rev-erbα agonist,combined with other drugs to relieve inflammation in skeletal myoblasts was conducted,laying the theoretical foundation for the treatment of inflammation-associated skeletal muscle atrophy. OBJECTIVE:To investigate the relationship of SR9009,indolepropionic acid and nuclear factor-κB signaling pathways in lipopolysaccharide-induced C2C12 myoblasts. METHODS:(1)C2C12 myoblasts were induced to differentiate in the presence of lipopolysaccharide(1 μg/mL).RNA-seq and KEGG pathway analysis were used to study signaling pathways.(2)C2C12 myoblast viability was assessed using the cell counting kit-8 assay to determine optimal concentrations of indolepropionic acid.Subsequently,cells were categorized into control group,lipopolysaccharide(1 μg/mL)group,SR9009(10 μmol/L)+lipopolysaccharide group,indolepropionic acid(80μmol/L)+lipopolysaccharide group,and SR9009+indolepropionic acid+lipopolysaccharide group.ELISA was employed to measure protein expression levels of interleukin-6 in the cultured supernatant.Real-time quantitative PCR were employed to measure mRNA expression levels of interleukin-6,tumor necrosis factor α,TLR4 and CD14.Western blot assay were employed to measure protein expression levels of NF-κB p65 and p-NF-κB p65.(3)After Rev-erbα was knocked down by siRNA,knockdown efficiency was assessed by RT-qPCR.And mRNA levels of interleukin-6 and tumor necrosis factor α were also measured. RESULTS AND CONCLUSION:Compared with the blank control group,lipopolysaccharide time-dependently inhibited myofibroblast fusion to form myotubes,the mRNA expression levels of interleukin-6 and tumor necrosis factor α were elevated,and the level of interleukin-6 in the cell supernatant was significantly increased.The results of KEGG pathway showed that the nuclear factor-κB signaling pathway was activated by lipopolysaccharide.Indolepropionic acid exhibited significant suppression of C2C12 myoblasts viability when its concentration exceeded 80 μmol/L.Indolepropionic acid and SR9009 inhibited the activation of NF-κB signaling pathway,thereby played an anti-inflammatory role,and suppressed the mRNA expression levels of interleukin-6,tumor necrosis factor α,TLR4 and CD14.Compared with the lipopolysaccharide group,the ratio of p-NF-κB p65/NF-κB p65 protein expression were downregulated.SR9009 combined with indolepropionic acid notably reduced lipopolysaccharide-induced inflammation,further downregulated the mRNA expression levels of interleukin-6,tumor necrosis factor α,TLR4 and CD14.The ratio of p-NF-κB p65/NF-κB p65 protein expression was significantly lower than that in the SR9009+lipopolysaccharide group or indolepropionic acid+lipopolysaccharide group.Rev-erbα increases time-dependently with lipopolysaccharide induction.The knockdown efficiency of Rev-erbα by siRNA reached over 58%,and lipopolysaccharide was added after Rev-erbα was successfully knocked down.Compared with the lipopolysaccharide group,the mRNA expression levels of interleukin-6 and tumor necrosis factor α were significantly up-regulated.These results conclude that Rev-erbα may act as a promising pharmacological target to reduce inflammation.SR9009 targeted activation of Rev-erbα combined with indolepropionic acid significantly inhibits the nuclear factor-κB signaling pathway and attenuates the inflammatory response of C2C12 myofibroblasts.Moreover,the combined anti-inflammatory effect is superior to that of the intervention alone.

Background/Aims: Liver transplantation is the most effective treatment for the sickest patients with acute-on-chronic liver failure (ACLF). However, the influence of donor age on liver transplantation, especially in ACLF patients, is still unclear. Methods: In this study, we used the data of the Scientific Registry of Transplant Recipients. We included patients with ACLF who received liver transplantation from January 1, 2007, to December 31, 2017, and the total number was 13,857. We allocated the ACLF recipients by age intogroup I (donor age ≤17 years, n=647); group II (donor age 18–59 years, n=11,423); and group III (donor age ≥60 years, n=1,787). Overall survival (OS), graft survival, and mortality were com-pared among the three age groups and the four ACLF grades. Cox regression was also analyzed. Results: The 1-, 3-, and 5-year OS rates were 89.6%, 85.5%, and 82.0% in group I; 89.4%, 83.4%, and 78.2% in group II; and 86.8%, 78.4%, and 71.4% in group III, respectively (p<0.001).When we analyzed the different effects of donor age on OS with different ACLF grades, in groupsII and III, we observed statistical differences. Finally, the cubic spline curve told us that the relative death rate changed linearly with increasing donor age. Conclusions Donor age is related to OS and graft survival of ACLF patients after transplanta-tion, and poorer results were associated with elderly donors. In addition, different donor ages have different effects on recipients with different ACLF grades.

Objective: To investigate the trajectories of fasting blood glucose fluctuations and their influencing factors among patients with comorbidity of type 2 diabetes mellitus (T2DM), so as to provide the basis for strengthening blood glucose management in this population. Methods: In October 2023, data of patients diagnosed with comorbid T2DM from January to October 2021, including demographic information, lifestyle, health status and fasting blood glucose were collected through the chronic disease health management system of Minhang District, Shanghai Municipality. Fasting blood glucose fluctuation trajectories were analyzed by group-based trajectory model established based on fasting blood glucose values from January 2021 to October 2023. Influencing factors of fasting blood glucose fluctuation trajectories among patients with comorbidity of T2DM were analyzed using a multinomial logistic regression model. Results: A total of 907 patients with comorbidity of T2DM were enrolled, including 472 males (52.04%) and 435 females (47.96%). There were 652 cases aged ≥65 years, accounting for 71.89%. The group-based trajectory model analysis identified three trajectory groups: a low-level stable group (492 cases, 54.24%), a medium-level stable group (287 cases, 31.64%), and a high-level decreasing group (128 cases, 14.11%). Multinomial logistic regression analysis showed that, compared with the low-level stable group, patients with comorbidity of T2DM who had an education level of junior high school or below (OR=1.420, 95%CI: 1.011-1.995) or college degree or above (OR=2.109, 95%CI: 1.249-3.560), as well as those who engaged in regular exercise (OR=1.387, 95%CI: 1.017-1.893), were more likely to be in the medium-level stable group. Patients with comorbidity of T2DM who were overweight or obese (OR=1.675, 95%CI: 1.116-2.513) or had dyslipidemia (OR=3.195, 95%CI: 1.642-6.216) were more likely to be in the high-level decreasing group. Conclusions From January 2021 to October 2023, the fasting blood glucose levels of patients with comorbidity of T2DM exhibited three fluctuating trajectories: low-level stability, medium-level stability, and high-level decline. Compared with the low-level stable group, the medium-level stable group was mainly influenced by educational level and regular exercise. The high-level decline group was primarily affected by overweight/obesity and dyslipidemia.

OBJECTIVE: To observe the effects of moxibustion at "Shenque" (CV8) on urodynamics and the expression of brain-derived neurotrophic factor (BDNF) and immediate early gene (c-fos) in pontine micturition center (PMC), periaqueductal gray (PAG), medial prefrontal cortex (mPFC) of neurogenic bladder (NB) rats after spinal cord injury. METHODS: Twenty-four SPF female SD rats were randomly divided into a sham-operation group (6 rats) and a modeling group (18 rats). In the modeling group, T₉ complete spinal cord transection method was used to establish a neurogenic detrusor overactivity model, and the 12 rats with successful modeling were randomized into a model group and a moxibustion group, with 6 rats in each group. The rats in the moxibustion group were treated with ginger/salt-insulated moxibustion at "Shenque" (CV8), and 4 consecutive moxa cones were delivered in one intervention. Moxibustion was operated once daily and for 14 days. After intervention completion, the urodynamic indexes of rats in each group were detected. Fluorescence quantitative PCR was used to detect the mRNA expression of BDNF and c-fos in PMC, PAG and mPFC in rats. Western blot was used to detect the protein expression of BDNF and c-fos in PMC, PAG and mPFC. RESULTS: The rats in the sham-operation group did not show phasic detrusor contraction during bladder filling. Compared with the model group, the frequency and amplitude of the phasic detrusor contraction were reduced 5 min before urine leakage in the rats of the moxibustion group (P<0.05), and the duration of the first phasic detrusor contraction during bladder filling was prolonged (P<0.05). Compared with the sham-operation group, the mRNA and protein expression of BDNF and c-fos in PMC, PAG and mPFC increased in the model group (P<0.05). Compared with the model group, the mRNA and protein expression of BDNF and c-fos in PMC, PAG and mPFC decreased in the moxibustion group (P<0.05). CONCLUSION Moxibustion at "Shenque" (CV8) can improve the phasic contraction during bladder filling in NB rats after spinal cord injury, possibly by down-regulating the mRNA and protein expression of BDNF and c-fos in PMC, PAG, and mPFC.
Animals ; Moxibustion ; Female ; Rats ; Brain-Derived Neurotrophic Factor/metabolism* ; Rats, Sprague-Dawley ; Acupuncture Points ; Spinal Cord Injuries/metabolism* ; Urinary Bladder, Neurogenic/etiology* ; Proto-Oncogene Proteins c-fos/metabolism* ; Humans ; Urinary Bladder/physiopathology* ; Brain/metabolism* ; Urination

After being treated with acupuncture, some patients with idiopathic tinnitus may experience a short-term aggravation of tinnitus symptoms on the original basis. These symptoms can be gradually relieved and the overall condition fluctuates towards recovery. This phenomenon has brought some difficulties to patients and clinicians. Based on the academic view of TCM, "destroying pathogens and re-building balance", and in association with the existing understanding of acupuncture in modern medicine for tinnitus, this paper briefly discusses the mechanism and influencing factors of symptom fluctuation in patients with idiopathic tinnitus after acupuncture treatment in terms of both TCM and modern medicine, and proposes the future direction in the research of symptom fluctuation, so as to promote the recognition of clinicians and patients on symptom fluctuation and make rational use of its positive effects. Besides, it is hoped that more researchers will pay attention to symptom fluctuation and advance the exploration of it in academic field.
Humans ; Tinnitus/physiopathology* ; Acupuncture Therapy ; Male ; Female