This study aims to investigate the potential effect of the water extract of fresh Rehmanniae Radix on hypercholesterolemia in mice that was induced by a high-fat and high-cholesterol diet and explore its possible mechanism from bile acid reabsorption. Male C57BL/6 mice were randomly assigned into the following groups: control, model, low-and high-dose(4 and 8 g·kg~(-1), respectively) fresh Rehmanniae Radix, and positive drug(simvastatin, 0.05 g·kg~(-1)). Other groups except the control group were fed with a high-fat and high-cholesterol diet for 6 consecutive weeks to induce hypercholesterolemia. From the 6th week, mice were administrated with corresponding drugs daily via gavage for additional 6 weeks, while continuing to be fed with a high-fat and high-cholesterol diet. Serum levels of total cholesterol(TC), triglycerides(TG), low density lipoprotein-cholesterol(LDL-c), high density lipoprotein-cholesterol(HDL-c), and total bile acid(TBA), as well as liver TC and TG levels and fecal TBA level, were determined by commercial assay kits. Hematoxylin-eosin(HE) staining, oil red O staining, and transmission electron microscopy were performed to observe the pathological changes in the liver. Three livers samples were randomly selected from each of the control, model, and high-dose fresh Rehmanniae Radix groups for high-throughput transcriptome sequencing. Differentially expressed genes were mined and KEGG pathway enrichment analysis was performed to predict the key pathways and target genes of the water extract of fresh Rehmanniae Radix in the treatment of hypercholesterolemia. RT-qPCR was employed to measure the mRNA levels of cholesterol 7α-hydroxylase(CYP7A1) and cholesterol 27α-hydroxylase(CYP27A1) in the liver. Western blot was employed to determine the protein levels of CYP7A1 and CYP27A1 in the liver as well as farnesoid X receptor(FXR), apical sodium-dependent bile acid transporter(ASBT), and ileum bile acid-binding protein(I-BABP) in the ileum. The results showed that the water extract of fresh Rehmanniae Radix significantly lowered the levels of TC and TG in the serum and liver, as well as the level of LDL-c in the serum. Conversely, it elevated the level of HDL-c in the serum and TBA in feces. No significant difference was observed in the level of TBA in the serum among groups. HE staining, oil red O staining, and transmission electron microscopy showed that the water extract reduced the accumulation of lipid droplets in the liver. Further mechanism studies revealed that the water extract of fresh Rehmanniae Radix significantly down-regulated the protein levels of FXR and bile acid reabsorption-related proteins ASBT and I-BABP. Additionally, it enhanced CYP7A1 and CYP27A1, the key enzymes involved in bile acid synthesis. Therefore, it is hypothesized that the water extract of fresh Rehmanniae Radix may exert an anti-hypercholesterolemic effect by regulating FXR/ASBT/I-BABP signaling, inhibiting bile acid reabsorption, and increasing bile acid excretion, thus facilitating the conversion of cholesterol to bile acids.
Animals ; Male ; Bile Acids and Salts/metabolism* ; Mice, Inbred C57BL ; Mice ; Diet, High-Fat/adverse effects* ; Cholesterol/metabolism* ; Drugs, Chinese Herbal/administration & dosage* ; Hypercholesterolemia/genetics* ; Receptors, Cytoplasmic and Nuclear/genetics* ; Rehmannia/chemistry* ; Liver/drug effects* ; Humans ; Cholesterol 7-alpha-Hydroxylase/genetics* ; Plant Extracts

PURPOSE: The rate of complications among patients undergoing surgery has increased due to infection with SARS-CoV-2 and other variants of concern. However, Omicron has shown decreased pathogenicity, raising questions about the risk of postoperative complications among patients who are infected with this variant. This study aimed to investigate complications and related factors among patients with recent Omicron infection prior to undergoing orthopedic surgery. METHODS: A historical control study was conducted. Data were collected from all patients who underwent surgery during 2 distinct periods: (1) between Dec 12, 2022 and Jan 31, 2023 (COVID-19 positive group), (2) between Dec 12, 2021 and Jan 31, 2022 (COVID-19 negative control group). The patients were at least 18 years old. Patients who received conservative treatment after admission or had high-risk diseases or special circumstances (use of anticoagulants before surgery) were excluded from the study. The study outcomes were the total complication rate and related factors. Binary logistic regression analysis was used to identify related factors, and odds ratio (OR) and 95% confidence interval (CI) were calculated to assess the impact of COVID-19 infection on complications. RESULTS: In the analysis, a total of 847 patients who underwent surgery were included, with 275 of these patients testing positive for COVID-19 and 572 testing negative. The COVID-19-positive group had a significantly higher rate of total complications (11.27%) than the control group (4.90%, p < 0.001). After adjusting for relevant factors, the OR was 3.08 (95% CI: 1.45-6.53). Patients who were diagnosed with COVID-19 at 3-4 weeks (OR = 0.20 (95% CI: 0.06-0.59), p = 0.005), 5-6 weeks (OR = 0.16 (95% CI: 0.04-0.59), p = 0.010), or ≥7 weeks (OR = 0.26 (95% CI: 0.06-1.02), p = 0.069) prior to surgery had a lower risk of complications than those who were diagnosed at 0-2 weeks prior to surgery. Seven factors (age, indications for surgery, time of operation, time of COVID-19 diagnosis prior to surgery, C-reactive protein levels, alanine transaminase levels, and aspartate aminotransferase levels) were found to be associated with complications; thus, these factors were used to create a nomogram. CONCLUSION Omicron continues to be a significant factor in the incidence of postoperative complications among patients undergoing orthopedic surgery. By identifying the factors associated with these complications, we can determine the optimal surgical timing, provide more accurate prognostic information, and offer appropriate consultation for orthopedic surgery patients who have been infected with Omicron.
Humans ; COVID-19/complications* ; Male ; Female ; Middle Aged ; Postoperative Complications/epidemiology* ; SARS-CoV-2 ; Orthopedic Procedures/adverse effects* ; Aged ; Nomograms ; Adult ; Retrospective Studies ; Risk Factors

OBJECTIVE: To evaluate the clinical efficacy and safety of Yangxue Qingnao Pills (YXQNP) combined with amlodipine in treating patients with grade 1 hypertension. METHODS: This is a multicenter, randomized, double-blind, and placebo-controlled study. Adult patients with grade 1 hypertension of blood deficiency and Gan (Liver)-yang hyperactivity syndrome were randomly divided into the treatment or the control groups at a 1:1 ratio. The treatment group received YXQNP and amlodipine besylate, while the control group received YXQNP's placebo and amlodipine besylate. The treatment duration lasted for 180 days. Outcomes assessed included changes in blood pressure, Chinese medicine (CM) syndrome scores, symptoms and target organ functions before and after treatment in both groups. Additionally, adverse events, such as nausea, vomiting, rash, itching, and diarrhea, were recorded in both groups. RESULTS: A total of 662 subjects were enrolled, of whom 608 (91.8%) completed the trial (306 in the treatment and 302 in the control groups). After 180 days of treatment, the standard deviations and coefficients of variation of systolic and diastolic blood pressure levels were lower in the treatment group compared with the control group. The improvement rates of dizziness, headache, insomnia, and waist soreness were significantly higher in the treatment group compared with the control group (P<0.05). After 30 days of treatment, the overall therapeutic effects on CM clinical syndromes were significantly increased in the treatment group as compared with the control group (P<0.05). After 180 days of treatment, brachial-ankle pulse wave velocity, ankle brachial index and albumin-to-creatinine ratio were improved in both groups, with no statistically significant differences (P>0.05). No serious treatment-related adverse events occurred during the study period. CONCLUSIONS Combination therapy of YXQNP with amlodipine significantly improved symptoms such as dizziness and headache, reduced blood pressure variability, and showed a trend toward lowering urinary microalbumin in hypertensive patients. These findings suggest that this regimen has good clinical efficacy and safety. (Registration No. ChiCTR1900022470).
Humans ; Amlodipine/adverse effects* ; Drugs, Chinese Herbal/adverse effects* ; Male ; Female ; Hypertension/complications* ; Middle Aged ; Treatment Outcome ; Drug Therapy, Combination ; Adult ; Blood Pressure/drug effects* ; Double-Blind Method ; Aged ; Antihypertensive Agents/adverse effects*

OBJECTIVE: To explore the therapeutic effects and underlying mechanisms of Dendrobium officinale (Tiepi Shihu) extract (DOE) on insomnia. METHODS: Forty-two male Sprague-Dawley rats were randomly divided into 6 groups (n=7 per group): normal control, model control, melatonin (MT, 40 mg/kg), and 3-dose DOE (0.25, 0.50, and 1.00 g/kg) groups. Rats were raised in a strong-light (10,000 LUX) and -noise (>80 db) environment (12 h/d) for 16 weeks to induce insomnia, and from week 10 to week 16, MT and DOE were correspondingly administered to rats. The behavior tests including sodium pentobarbital-induced sleep experiment, sucrose preference test, and autonomous activity test were used to evaluate changes in sleep and emotions of rats. The metabolic-related indicators such as blood pressure, blood viscosity, blood glucose, and uric acid in rats were measured. The pathological changes in the cornu ammonis 1 (CA1) region of rat brain were evaluated using hematoxylin and eosin staining and Nissl staining. Additionally, the sleep-related factors gamma-aminobutyric acid (GABA), glutamate (GA), 5-hydroxytryptamine (5-HT), and interleukin-6 (IL-6) were measured using enzyme linked immunosorbent assay. Finally, we screened potential sleep-improving receptors of DOE using polymerase chain reaction (PCR) array and validated the results with quantitative PCR and immunohistochemistry. RESULTS: DOE significantly improved rats' sleep and mood, increased the sodium pentobarbital-induced sleep time and sucrose preference index, and reduced autonomic activity times (P<0.05 or P<0.01). DOE also had a good effect on metabolic abnormalities, significantly reducing triglyceride, blood glucose, blood pressure, and blood viscosity indicators (P<0.05 or P<0.01). DOE significantly increased the GABA content in hippocampus and reduced the GA/GABA ratio and IL-6 level (P<0.05 or P<0.01). In addition, DOE improved the pathological changes such as the disorder of cell arrangement in the hippocampus and the decrease of Nissel bodies. Seven differential genes were screened by PCR array, and the GABA_A receptors (Gabra5, Gabra6, Gabrq) were selected for verification. The results showed that DOE could up-regulate their expressions (P<0.05 or P<0.01). CONCLUSION DOE demonstrated remarkable potential for improving insomnia, which may be through regulating GABA_A receptors expressions and GA/GABA ratio.
Animals ; Dendrobium/chemistry* ; Rats, Sprague-Dawley ; Male ; Sleep Initiation and Maintenance Disorders/blood* ; Plant Extracts/therapeutic use* ; Receptors, GABA-A/metabolism* ; Noise/adverse effects* ; Light/adverse effects* ; gamma-Aminobutyric Acid/metabolism* ; Sleep/drug effects* ; Rats ; Receptors, GABA/metabolism*

The persistent high prevalence and poor survival outcomes of lung cancer underscore the urgent need for innovative therapeutic modalities. Here, we present a novel multifunctional delivery platform for the synergistic treatment of lung malignancies, combining in situ-triggerable photodynamic therapy (PDT) with radiotherapy. The new platform CLL was developed by loading a new reactive oxygen species (ROS)-triggerable photosensitizer, luminol-conjugated chlorin e6 (Ce6), into liposomes. CLL can be activated through the bioluminescence resonance energy transfer effect under oxidative stress, thereby producing singlet oxygen for targeted tumor treatment without external irradiation. In vitro studies showed significant cytotoxic effects of CLL in both 4T1 and A549 tumor cells. Furthermore, a PDT-radiopharmaceutical combination nanotherapy CLL-¹⁷⁷Lu was engineered by incorporating the radionuclide ¹⁷⁷Lu into CLL. CLL-¹⁷⁷Lu demonstrated synergistic antitumor effects in 4T1 and A549 tumor cells, as well as in mouse models of 4T1 breast cancer lung metastasis or A549 tumor xenografts. Mechanistically, CLL-¹⁷⁷Lu can induce singlet oxygen/ROS generation, enhance tumor cell apoptosis, and promote M1 macrophage-mediated immunotherapy. Preliminary assessments showed a favorable profile for CLL-¹⁷⁷Lu, highlighting its potential as a promising nanotherapy for cancer treatment. Additionally, CLL can serve as a versatile platform for delivering a range of therapies to achieve synergistic antitumor effects.

BACKGROUND:Pyroptosis participate in the degradation of the extracellular matrix of chondrocytes,synovial inflammation and pain,and plays an important role in the prevention and treatment of osteoarthritis.In addition,exercise can inhibit the occurrence of pyroptosis to regulate the progression of osteoarthritis,which has become a research hot spot in the prevention and treatment of osteoarthritis. OBJECTIVE:To summarize the regulatory role of pyroptosis in osteoarthritis and the mechanism of exercise-mediated pyroptosis in osteoarthritis. METHODS:PubMed and CNKI databases were searched during 1992 to 2024 with the keywords"pyroptosis,osteoarthritis,chondrocyte pyroptosis,synovial cell pyroptosis,exercise"in English and Chinese,respectively.Finally,71 relevant articles were selected according to the inclusion and exclusion criteria. RESULTS AND CONCLUSION:(1)Osteoarthritis is a chronic degenerative joint disease characterized by the breakdown of cartilage extracellular matrix,synovial inflammation,and subchondral bone remodeling.This condition often leads to organic lesions,bone pain,and functional impairment.(2)Pyroptosis,a distinct programmed cell death mechanism,involves cell lysis and the release of inflammatory cytokines,triggering a robust inflammatory response,and is closely related to the development of osteoarthritis.Pyroptosis can result in the release of numerous inflammatory factors,thereby activate the nuclear factor kappa-B transcription and increase pyroptosis protein production,and in turn exacerbate the occurrence and development of osteoarthritis.Therefore,pyroptosis can be a new direction for the prevention and treatment of osteoarthritis.(3)Exercise has been shown to down-regulate the pyroptosis protein signaling pathway and inhibit the expression of related inflammatory factors,thereby playing a pivotal role in osteoarthritis prevention and treatment.Aerobic and anaerobic exercises can delay the pathological process of osteoarthritis by inhibiting the occurrence of pyroptosis.Moderate-intensity aerobic exercise is most effective in improving osteoarthritis by inhibiting pyroptosis signaling pathways,while anaerobic exercise can have beneficial effects on osteoarthritis by improving muscle mass.

BACKGROUND:Intestinal flora is a diverse and dynamic microbial community located in the human gastrointestinal tract,which plays a crucial role in maintaining human immunity and health.In recent years,the concept of"gut-lung axis"has been proposed,suggesting that intestinal flora is closely related to the lung,and exercise can regulate respiratory diseases by maintaining the balance of intestinal flora.OBJECTIVE:To review the relationship between intestinal flora and different respiratory diseases such as pneumonia,lung cancer,asthma and chronic pulmonary obstruction,and the influence of different exercise modes on intestinal flora and respiratory diseases,providing new ideas for an in-depth exploration of the mechanisms by which exercise regulates the role of intestinal flora in respiratory diseases.METHODS:CNKI and PubMed databases were searched for relevant literature published from 1944 to 2024,using the search terms of"intestinal flora,gut bacteria,respiratory illness,pneumonia,lung cancer,asthma,chronic obstructive pulmonary diseases,aerobic exercise,resistance training"in Chinese and English,respectively.Totally 101 documents were included according to inclusion and exclusion criteria.RESULTS AND CONCLUSION:(1)Intestinal flora plays an important role in the regulation of respiratory diseases such as pneumonia,lung cancer,asthma and chronic pulmonary obstruction diseases.(2)Different exercise modes are closely related to intestinal flora.Aerobic exercise can play a beneficial role in the regulation of intestinal flora by improving insulin sensitivity,increasing microbial diversity and inhibiting systemic chronic inflammation.Resistance exercise can decrease the permeability of intestinal mucosa and promote the production of short-chain fatty acids.Aerobic exercise combined with resistance exercise can also increase the diversity of intestinal flora and affect the composition of intestinal flora.(3)Exercise can improve respiratory diseases by regulating inflammatory response and reducing oxidative stress damage as well as improving cardiopulmonary function and exercise performance.(4)Exercise plays a key role in the prevention and treatment of respiratory diseases by regulating intestinal flora,inhibiting inflammatory response,regulating oxidative stress,improving intestinal barrier permeability and maintaining intestinal flora homeostasis.

Objective:To summarize the best available evidence for donor and recipient site flap management in head and neck cancer patients undergoing free flap reconstruction.Method:Following the 6S evidence hierarchy model, a comprehensive search was conducted in databases and websites including UpToDate, BMJ Best Practice, Guidelines International Network, National Institute for Health and Care Excellence, National Comprehensive Cancer Network, Joanna Briggs Institute Evidence-Based Healthcare Database, Cochrane Library, PubMed, Embase, Web of Science, China Biology Medicine disc, China National Knowledge Infrastructure, and Wanfang Data. The search period covered all publications up to May 1, 2024.Results:A total of 14 articles were included, comprising two clinical decisions, two guidelines, two systematic reviews, five expert consensuses, two randomized controlled trials, and one prospective cohort study.A total of 28 pieces of evidence were summarized from six aspects: establishing multidisciplinary collaboration, standardized assessment, prehabilitation training, donor site management strategies, recipient site management strategies, and risk identification and management.Conclusions:This study provides a comprehensive summary of evidence regarding donor and recipient site flap management in patients with head and neck cancer undergoing free flap reconstruction, offering an evidence-based foundation for guiding clinical nursing practice.

Uterine arteriovenous fistula (UAVF), a relatively rare vascular anomaly, may lead to life-threatening hemorrhage and poses diagnostic and management challenges for primary hospitals during initial encounters. This article reports four cases of UAVF treated with Drospirenone and ethinyl estradiol tablets at Department of Gynaecology, Zhuji Maternal and Child Health Hospital between 2023 and 2024. Combined with literature review, we systematically analyzed the etiological mechanisms, clinical characteristics, and diagnostic-therapeutic strategies of this condition, with particular focus on evaluating the efficacy and safety of conservative pharmacological management. By summarizing case features and individualized treatment protocols, this study aims to provide clinical references for early identification, accurate diagnosis, and rational intervention of UAVF, thereby reducing risks of massive hemorrhage and long-term complications while improving patient prognosis.

Objective:To summarize the best available evidence for donor and recipient site flap management in head and neck cancer patients undergoing free flap reconstruction.Method:Following the 6S evidence hierarchy model, a comprehensive search was conducted in databases and websites including UpToDate, BMJ Best Practice, Guidelines International Network, National Institute for Health and Care Excellence, National Comprehensive Cancer Network, Joanna Briggs Institute Evidence-Based Healthcare Database, Cochrane Library, PubMed, Embase, Web of Science, China Biology Medicine disc, China National Knowledge Infrastructure, and Wanfang Data. The search period covered all publications up to May 1, 2024.Results:A total of 14 articles were included, comprising two clinical decisions, two guidelines, two systematic reviews, five expert consensuses, two randomized controlled trials, and one prospective cohort study.A total of 28 pieces of evidence were summarized from six aspects: establishing multidisciplinary collaboration, standardized assessment, prehabilitation training, donor site management strategies, recipient site management strategies, and risk identification and management.Conclusions:This study provides a comprehensive summary of evidence regarding donor and recipient site flap management in patients with head and neck cancer undergoing free flap reconstruction, offering an evidence-based foundation for guiding clinical nursing practice.