Osteoporosis is a common senile bone metabolism disease， clinically characterized by decreased bone mass， destruction of bone microstructure， increased bone fragility， and easy fracture. It tends to occur in the elderly and postmenopausal women， seriously threatening the quality of life and physical and mental health of the elderly. At present， the treatment of osteoporosis is mainly based on oral western medicines， such as calcium， Vitamin D， and bisphosphonates. Still， there are drawbacks such as a long medication cycle and many adverse reactions. In recent years， due to the advantages of multi-component， multi-pathway， and multi-target， some traditional Chinese medicines and effective ingredients can regulate the osteogenic and osteoclastic differentiation process in both directions and are widely used in the prevention and treatment of osteoporosis. Hippophae rhamnoides is a commonly used herbal medicine， and its fruits are rich in flavonoids， polyphenols， fatty acids， vitamins， and trace elements， which have been proven to have a good anti-osteoporosis effect. Isorhamnetin is the main effective ingredient of Hippophae rhamnoides fruits， which has many pharmacological effects such as anti-inflammation， anti-oxidative stress， anti-aging， and anti-tumor. Studies have shown that isorhamnetin can participate in the regulation of bone metabolism and has a good anti-osteoporosis effect. However， the pharmacological effects and related mechanisms of isorhamnetin against osteoporosis have not been systematically summarized. Therefore， this paper reviewed the pharmacological effects and related mechanisms of isorhamnetin against osteoporosis by referring to relevant literature to provide more basis for the development and application of isorhamnetin.

This study investigated the effects of Rehmanniae Radix Praeparata on striatal neuronal apoptosis in rats with attention deficit hyperactivity disorder(ADHD) based on the B-cell lymphoma-2(Bcl-2)/Bcl-2-associated X protein(Bax)/caspase-3 signaling pathway. Twenty-four 3-week-old male spontaneously hypertensive rats(SHR) were randomly divided into a model group, a methylphenidate group(2 mg·kg~(-1)·d~(-1)), and a Rehmanniae Radix Praeparata group(2.4 mg·kg~(-1)·d~(-1)). Age-matched male Wistar Kyoto(WKY) rats were used as the normal control group, with 8 rats in each group. The rats were administered by gavage for 28 days. Body weight and food intake were recorded for each group. The open field test and elevated plus maze test were used to assess hyperactivity and impulsive behaviors. Nissl staining was used to detect changes in striatal neurons and Nissl bodies. Terminal deoxynucleotidyl transferase dUTP nick end labeling(TUNEL) fluorescence staining was used to detect striatal cell apoptosis. Western blot was employed to detect the expression levels of Bcl-2, Bax, and caspase-3 proteins in the striatum. The results showed that compared with the model group, Rehmanniae Radix Praeparata significantly reduced the total movement distance, average movement speed, and central area residence time in the open field test, and significantly reduced the ratio of open arm entries, open arm stay time, and head dipping in the elevated plus maze test. Furthermore, it increased the number of Nissl bodies in striatal neurons, significantly downregulated the apoptosis index, significantly increased Bcl-2 protein expression and the Bcl-2/Bax ratio, and reduced Bax and caspase-3 protein expression. In conclusion, Rehmanniae Radix Praeparata can reduce hyperactivity and impulsive behaviors in ADHD rats. Its mechanism may be related to the regulation of the Bcl-2/Bax/caspase-3 signaling pathway in the striatum, enhancing the anti-apoptotic capacity of striatal neurons.
Animals ; Male ; Apoptosis/drug effects* ; Rats ; Drugs, Chinese Herbal/administration & dosage* ; Caspase 3/genetics* ; Proto-Oncogene Proteins c-bcl-2/genetics* ; bcl-2-Associated X Protein/genetics* ; Rehmannia/chemistry* ; Attention Deficit Disorder with Hyperactivity/physiopathology* ; Signal Transduction/drug effects* ; Neurons/cytology* ; Rats, Inbred SHR ; Rats, Inbred WKY ; Humans ; Corpus Striatum/cytology* ; Plant Extracts

Osteoarthritis (OA) causes chronic pain that significantly impairs quality of life, with current treatments often proving insufficient and accompanied by adverse effects. Recent research has identified the dorsal root ganglion (DRG) and its resident macrophages as crucial mediators of chronic OA pain through neuroinflammation driven by macrophage polarization. We present a novel injectable thermo-sensitive hydrogel system, KAF@PLEL, designed to deliver an anti-inflammatory peptide (KAF) specifically to the DRG. This biodegradable hydrogel enables sustained KAF release, promoting the reprogramming of DRG macrophages from pro-inflammatory to anti-inflammatory phenotypes. Through comprehensive in vitro and in vivo studies, we evaluated the hydrogel's biocompatibility, effects on macrophage polarization, and therapeutic efficacy in chronic OA pain management. The system demonstrated significant capabilities in preserving macrophage mitochondrial function, suppressing neuroinflammation, alleviating chronic OA pain, reducing cartilage degradation, and improving motor function in OA rat models. The sustained-release properties of KAF@PLEL enabled prolonged therapeutic effects while minimizing systemic exposure and side effects. These findings suggest that KAF@PLEL represents a promising therapeutic approach for improving outcomes in OA patients through targeted, sustained treatment.

Gene regulation relies on the precise binding of transcription factors (TFs) at regulatory elements, but simultaneously detecting hundreds of TFs on chromatin is challenging. We developed cFOOT-seq, a cytosine deaminase-based TF footprinting assay, for high-resolution, quantitative genome-wide assessment of TF binding in both open and closed chromatin regions, even with small cell numbers. By utilizing the dsDNA deaminase SsdAtox, cFOOT-seq converts accessible cytosines to uracil while preserving genomic integrity, making it compatible with techniques like ATAC-seq for sensitive and cost-effective detection of TF occupancy at the single-molecule and single-cell level. Our approach enables the delineation of TF footprints, quantification of occupancy, and examination of chromatin influences on TF binding. Notably, cFOOT-seq, combined with FootTrack analysis, enables de novo prediction of TF binding sites and tracking of TF occupancy dynamics. We demonstrate its application in capturing cell type-specific TFs, analyzing TF dynamics during reprogramming, and revealing TF dependencies on chromatin remodelers. Overall, cFOOT-seq represents a robust approach for investigating the genome-wide dynamics of TF occupancy and elucidating the cis-regulatory architecture underlying gene regulation.
Transcription Factors/genetics* ; Humans ; Chromatin/genetics* ; Animals ; Binding Sites ; Mice ; DNA Footprinting/methods*

Objective This study aimed to explore the spatial heterogeneity and risk factors for dental caries in 12-year-old children in Shanxi province,China. Methods The data encompassed 3,721 participants from the two most recent oral health surveys conducted across 16 districts in Shanxi Province in 2015 and 2018.Eighteen specific variables were analyzed to examine the interplay between socioeconomic factors,medical resources and environmental conditions.The Geo-detector model was employed to assess the impacts and interactions of these ecological factors. Results Socioeconomic factors(Q=0.30,P<0.05)exhibited a more substantial impact compared to environmental(Q=0.19,P<0.05)and medical resource factors(Q=0.25,P<0.05).Notably,the urban population percentage(UPP)demonstrated the most significant explanatory power for the spatial heterogeneity in caries prevalence,as denoted by its highest q-value(q=0.51,P<0.05).Additionally,the spatial distribution's heterogeneity of caries was significantly affected by SO2 concentration(q=0.39,P<0.05)and water fluoride levels(q=0.27,P<0.05)among environmental factors. Conclusion The prevalence of caries exhibited spatial heterogeneity,escalating from North to South in Shanxi Province,China,influenced by socioeconomic factors,medical resources,and environmental conditions to varying extents.

Objective:To analyze the clinical efficacy of internal fixation and prosthesis revision in the treatment of periprosthesis fracture after total knee arthroplasty.Methods:A total of 35 patients (35 knees) with periprosthetic fractures after total knee arthroplasty were retrospectively analyzed from January 2008 to January 2022 in the Department of Orthopaedics, West China Hospital, Sichuan University, including 13 males and 22 females, aged 71.4±4.1 years (range, 62-81 years). Left knee 19 cases, right knee 16 cases. There were 20 cases of Rorabeck type II and 15 cases of Rorabeck type III. The initial replacement was performed using a fixed platform post-stabilized knee prosthesis, which was fixed with bone cement. Patients with Rorabeck type II were treated with internal fixation alone (internal fixation group) and patients with Rorabeck type III underwent revision with replacement prosthesis (revision group). The Hospital for Special Surgery (HSS) score, range of motion (ROM) of knee joint, alignment of lower extremity and incidence of postoperative complications were compared between the two groups.Results:All patients successfully completed the operation and were followed up for 5.2±3.6 years (range, 1-12 years). Intraoperative blood loss was 680±102 ml (range, 420-1100 ml). The operative time in the internal fixation group was 105±17 min, which was less than 140±21 min in the revision group, and the difference was statistically significant ( t=-5.450, P<0.001). There was no complication of nerve or blood vessel injury during the operation. Five cases in the internal fixation group had unsatisfactory lower extremity force lines (>3° deviation from normal) after surgery, and all lower extremity force lines in the revision group were satisfied, and the difference in the satisfaction rate of lower extremity force lines between the two groups was not statistically significant ( P=0.057). The fracture healing time, knee ROM and HSS scores at the last follow-up were 5.1±1.3 months, 86°±5° and 84±5 in the internal fixation group and 4.8±1.5 months, 83°±6° and 82±4 in the revision group. One case in the revision group was diagnosed postoperatively with periprosthetic infection with pathogen culture suggestive of Candida albicans, recurrent anterior knee sinus tracts and patellar ectasia, which progressed to osteomyelitis, and mid-thigh amputation was performed 1 year after revision. Conclusion:The stability of prosthesis is an important reference for the treatment of periprosthetic fractures after total knee arthroplasty. Strong internal fixation in patients with unloosened prosthesis and revision with replacement of prosthesis in patients with loose prosthesis can achieve good knee joint function.

ObjectiveTo explore the application effect of Jianpi Huoxue prescription combined with acupuncture in patients with chronic atrophic gastritis （CAG） of gastric blood stasis type. MethodA total of 86 patients with CAG admitted to Wuhan First Hospital from November 2021 to March 2023 were selected and randomly divided into two groups. The control group was treated with conventional Western medicine， while the observation group was treated with Jianpi Huoxue prescription combined with acupuncture. The clinical efficacy， traditional Chinese medicine （TCM） syndrome score， pathological score， negative conversion rate of Helicobacter pylori （Hp）， inflammatory indicators ［neutrophils/lymphocytes （NLR） and interleukin （IL）-1β］， changes in levels of gastric protease （PG） Ⅰ， PG Ⅰ/PG Ⅱ， and gastrin-17 （G-17）， and drug safety during treatment were observed after treatment in both groups. ResultAfter treatment， the total effective rate of the observation group ［95.35% （41/43）］ was significantly better than that of the control group ［79.07% （34/43）］， and the difference was statistically significant （χ²=5.108， P<0.05）. After treatment， the scores of the primary and secondary TCM syndromes in the observation group and the control group were significantly decreased （P<0.05）. After treatment， the scores of primary and secondary TCM syndromes in the observation group were significantly lower than those in the control group （P<0.05）. After treatment， the pathological scores of gastric mucosa atrophy， activity， chronic inflammation， intestinal metaplasia， and dysplasia were significantly lower in the observation group and control group （P<0.05）. After treatment， the pathological scores of gastric mucosa atrophy， activity， chronic inflammation， intestinal metaplasia， and dysplasia in the observation group were significantly lower than those in the control group （P<0.05）. After treatment， the Hp conversion rate in the observation group was significantly increased compared with the control group （P<0.05）. After treatment， the levels of inflammatory indicators NLR and IL-1β in the observation group and control group were significantly lower （P<0.05）， and the levels of inflammatory indicators NLR and IL-1β in the observation group were significantly lower than those in the control group （P<0.05）. After treatment， the levels of PGI and PGⅠ/PGⅡ in the observation group and control group were significantly higher （P<0.05）， and the levels of PGI and PGⅠ/PGⅡ in the observation group were significantly higher than those in the control group （P<0.05）. After treatment， the G-17 level of the observation group and the control group was different at different time points （P<0.05）， and the G-17 level of the observation group was higher at different time points than that of the control group （P<0.05）. The G-17 level of the observation group had an increasing trend compared with the control group （P<0.05）. There was no significant difference in the risk of adverse reactions between the two groups. ConclusionThe combination of Jianpi Huoxue prescription and acupuncture can effectively alleviate symptoms， increase Hp negative conversion rate， inhibit inflammation， and regulate PG and G-17 levels in CAG patients， thus controlling or even reversing gastric mucosal atrophy and reducing the probability of its progression to gastric cancer.

Objective To study the effect of reactive oxygen species(ROS)/p38 MAPK cascade reaction on the formation of kidney stones(KS)in rats and explore the mechanism.Methods Fifty SD rats were randomly divided into control group(normal feeding),N-acetylcysteine(NAC)group(intraperitoneally injected 200 mg/kg NAC),KS group(constructed calcium oxalate KS model),KS+NAC group(constructed calcium oxalate KS model,intraperitoneally injected 200 mg/kg NAC),KS+NAC+tunicamycin(TM)group(constructed calcium oxalate KS model,intraperitoneally injected 200 mg/kg NAC and 1 mg/kg TM),with 10 rats in each group.After 4 weeks of administration,24 hours urine volume and oxalic acid(Ox)of each group were measured,serum creatinine(Cr),urea nitrogen(BUN)and uric acid(UA)levels were detected by automatic biochemical analyzer.HE staining and Von Kossa staining were used to observe the histopathological changes and crystal deposition of the kidney.TUN EL staining was used to detect apoptosis of renal tissue cells.The activity of superoxide dismutase(SOD)and the content of malondialdehyde(MDA)in renal tissue were measured by the kit.DHE fluorescent probes detected the levels of reactive oxygen species(ROS)in kidney tissue.Immunohistochemical staining was used to detect the expressions of microtubule-associated protein 1 light chain 3 B(LC3B)and glucose regulatory protein 78(GRP78)in renal tissue,and the protein expression of LC3 Ⅱ/LC3 Ⅰ,Beclin1,GRP78,CCAAT/enhancer binding protein homologous protein(CHOP)in renal tissue was determined by Western blotting.Results Compared with the KS group,Ox in KS+NAC group decreased(P＜0.05),BUN,Cr and UA levels decreased(P＜0.05),renal tubule dilatation and calcium oxalate crystallization decreased,TUNEL positive cell rate decreased(P＜0.05),SOD activity increased and MDA content decreased(P＜0.05),ROS levels decreased(P＜0.05),LC3B and GRP78 positive staining levels decreased(P＜0.05),the relative protein expressions of p-p38 MAPK/p38 MAPK,LC3 Ⅱ/LC3 Ⅰ,Beclin1,GRP78 and CHOP were down-regulated(P＜0.05).Compared with the KS+NAC group,Ox in KS+NAC+TM group increased(P＜0.05),BUN,Cr and UA levels also increased(P＜0.05),renal tubule dilated significantly,calcium oxalate crystals increased,TUNEL positive cell rate increased(P＜0.05),SOD activity decreased and MDA content increased(P＜0.05),ROS levels increased(P＜0.05),LC3B and GRP78 positive staining levels increased(P＜0.05),the relative protein expressions of p-p38 MAPK/p38 MAPK,LC3 Ⅱ/LC3 Ⅰ,Beclin1,GRP78 and CHOP were also up-regulated(P＜0.05).Conclusion ROS/p38 MAPK cascade is involved in promoting KS formation in rats,which is related to the activation of endoplasmic reticulum stress-mediated autophagy pathway.

Background::Limited information exists regarding the impact of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection on psoriasis patients. The objective of this study was to identify clinical factors associated with the prognosis of psoriasis following SARS-CoV-2 infection.Methods::A retrospective, multicenter study was conducted between March and May 2023. Univariable and multivariable logistic regression analyses were employed to identify factors associated with coronavirus disease 2019 (COVID-19)-related psoriasis outcomes. The study included 2371 psoriasis patients from 12 clinical centers, with 2049 of them having been infected with SARS-CoV-2.Results::Among the infected groups, lower exacerbation rates were observed in individuals treated with biologics compared to those receiving traditional systemic or nonsystemic treatments (22.3% [236/1058] vs. 39.8% [92/231] vs. 37.5% [140/373], P <0.001). Psoriasis progression with lesions (adjusted odds ratio [OR] = 8.197, 95% confidence interval [95% CI] = 5.685–11.820, compared to no lesions), hypertension (adjusted OR = 1.582, 95% CI = 1.068–2.343), traditional systemic (adjusted OR = 1.887, 95% CI= 1.263–2.818), and nonsystemic treatment (adjusted OR= 1.602, 95% CI= 1.117–2.297) were found to be associated with exacerbation of psoriasis after SARS-CoV-2 infection, but not biologics (adjusted OR = 0.931, 95% CI = 0.680–1.274, compared to no treatment), according to multivariable logistic regression analysis. Conclusions::A reduced risk of psoriasis exacerbation after SARS-CoV-2 infection was observed with biologics compared to traditional systemic and nonsystemic treatments. Significant risk factors for exacerbation after infection were identified as existing psoriatic lesions and hypertension.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in tertiary hospitals in major regions of China in 2022.Methods Clinical isolates from 58 hospitals in China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2022 Clinical &Laboratory Standards Institute(CLSI)breakpoints.Results A total of 318 013 clinical isolates were collected from January 1,2022 to December 31,2022,of which 29.5％were gram-positive and 70.5％were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species(excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi)was 28.3％,76.7％and 77.9％,respectively.Overall,94.0％of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 90.8％of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis showed significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 94.2％in the isolates from children and 95.7％in the isolates from adults.The resistance rate to carbapenems was lower than 13.1％in most Enterobacterales species except for Klebsiella,21.7％-23.1％of which were resistant to carbapenems.Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.1％to 13.3％.The prevalence of meropenem-resistant strains decreased from 23.5％in 2019 to 18.0％in 2022 in Pseudomonas aeruginosa,and decreased from 79.0％in 2019 to 72.5％in 2022 in Acinetobacter baumannii.Conclusions The resistance of clinical isolates to the commonly used antimicrobial agents is still increasing in tertiary hospitals.However,the prevalence of important carbapenem-resistant organisms such as carbapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a downward trend in recent years.This finding suggests that the strategy of combining antimicrobial resistance surveillance with multidisciplinary concerted action works well in curbing the spread of resistant bacteria.