Objective To explore the difference of efficacy and safety between denosumab and zoledronic acid in the treatment of patients with postmenopausal osteoporosis (PMOP), and to optimize the medication regimen for PMOP patients. Methods A total of 123 PMOP patients with high risk of fracture at the Second Affiliated Hospital of Naval Medical University from September 2021 to March 2024 were selected and randomly divided into two groups: the denosumab group (n=63) and the zoledronic acid group (n=60). Both groups underwent one-year treatment and follow-up, bone metabolism indexes, lumbar vertebrae, femoral neck, and total hip bone mineral density (BMD) were monitored, and any adverse reactions were documented. Results After treatment, the lumbar vertebrae and total hip BMD of patients in the denosumab group and the zoledronic acid group were significantly improved (P＜0.05); the femoral neck BMD of patients in the zoledronic acid group was also significantly improved (P＜0.05). The improvement of lumbar vertebrae BMD in the denosumab group was significantly better than that in the zoledronic acid group, while the improvement of femoral neck and total hip BMD in the zoledronic acid group was significantly better than that in the denosumab group (P＜0.05). Bone metabolism indicators were significantly improved in both groups (P＜0.05), and no significant liver and kidney dysfunction were observed. A total of 7 patients in the zoledronic acid group had mild adverse reactions and 5 patients in the denosumab group had mild adverse reactions. Conclusions Denosumab significantly increased lumbar vertebrae BMD and improved bone metabolism markers in PMOP patients, thus reducing risk of fracture and demonstrating good safety.

AIM: To investigate the effects of insulin-like growth factor 1(IGF-1)on the secretion of transforming growth factor β2(TGF-β2), matrix metalloproteinase 2(MMP-2)and hypoxia-inducible factor 1α(HIF-1α)in human scleral fibroblasts(HSF)and their mechanism.METHODS: The cells were cultured with IGF-1 and PI3K/AKT pathway inhibitor LY294002, respectively. CCK-8 method was used to detect cell viability and determine the optimal concentration and time of drug action. Cell migration activity was observed by cell scratch method. To determine the effects of IGF-1 on HSF cells and the regulatory role of PI3K/AKT pathway, HSF cells were divided into control group(without drugs), IGF-1(80 μg/L)group, IGF-1+LY294002(80 μg/L+5 mmol/L)group, and LY294002(5 mmol/L)group, and were cultured for 24 h; the protein expression levels of TGF-β2, MMP-2, HIF-1α, PI3K and AKT were detected by Western blot; the fluorescence expression of TGF-β2, MMP-2 and HIF-1α was detected by cellular immunofluorescence.RESULTS: The results of CCK-8 showed that the cell viability of the 80 μg/L IGF-1 group cultured with different concentrations of IGF-1 was the highest(all P<0.05), and the cell viability of the 80 μg/L IGF-1 group at 24 h was the highest under different culture times. Therefore, the concentration of IGF-1 was selected as 80 μg/L for 24 h. The viability of cells cultured with different concentrations of LY294002 gradually decreased from 6 h(all P<0.05). According to the IC50 value, therefore, the concentration of LY294002 was selected as 5 mmol/L for 24 h. The cell scratch results showed that compared with the control group, the cell mobility of 40 μg/L and 80 μg/L IGF-1 groups was increased(all P<0.05). Compared with the control group, cell mobility in the 2.5 and 5 mmol/L LY294002 groups was decreased(all P<0.05). Western blot results showed that compared with the control group, the protein expressions of TGF-β2, MMP-2, HIF-1α, PI3K and AKT in the IGF-1 group were increased, while those in the LY294002 group were decreased(all P<0.05). Compared with the IGF-1 group, the expression levels of TGF-β2, MMP-2, HIF-1α, PI3K and AKT in the IGF-1+LY294002 group were decreased(all P<0.05). The results of cell immunofluorescence showed that compared with the control group, the fluorescence expressions of TGF-β2, MMP-2 and HIF-1α in the IGF-1 group were increased, while those in the LY294002 group were decreased(all P<0.05). Compared with the IGF-1 group, the fluorescence expressions of TGF-β2, MMP-2 and HIF-1α in the IGF-1+LY294002 group were significantly decreased(all P<0.05).CONCLUSION: IGF-1 promoted the proliferation and migration of human HSF. IGF-1 may up-regulate the expression of TGF-β2, MMP-2 and HIF-1α in HSF through the PI3K/AKT signaling pathway, and participate in the occurrence and development of myopia.

The innate immune system can be boosted in response to subsequent triggers by pre-exposure to microbes or microbial products, known as “trained immunity”. Compared to classical immune memory, innate trained immunity has several different features. Firstly, the molecules involved in trained immunity differ from those involved in classical immune memory. Innate trained immunity mainly involves innate immune cells (e.g., myeloid immune cells, natural killer cells, innate lymphoid cells) and their effector molecules (e.g., pattern recognition receptor (PRR), various cytokines), as well as some kinds of non-immune cells (e.g., microglial cells). Secondly, the increased responsiveness to secondary stimuli during innate trained immunity is not specific to a particular pathogen, but influences epigenetic reprogramming in the cell through signaling pathways, leading to the sustained changes in genes transcriptional process, which ultimately affects cellular physiology without permanent genetic changes (e.g., mutations or recombination). Finally, innate trained immunity relies on an altered functional state of innate immune cells that could persist for weeks to months after initial stimulus removal. An appropriate inducer could induce trained immunity in innate lymphocytes, such as exogenous stimulants (including vaccines) and endogenous stimulants, which was firstly discovered in bone marrow derived immune cells. However, mature bone marrow derived immune cells are short-lived cells, that may not be able to transmit memory phenotypes to their offspring and provide long-term protection. Therefore, trained immunity is more likely to be relied on long-lived cells, such as epithelial stem cells, mesenchymal stromal cells and non-immune cells such as fibroblasts. Epigenetic reprogramming is one of the key molecular mechanisms that induces trained immunity, including DNA modifications, non-coding RNAs, histone modifications and chromatin remodeling. In addition to epigenetic reprogramming, different cellular metabolic pathways are involved in the regulation of innate trained immunity, including aerobic glycolysis, glutamine catabolism, cholesterol metabolism and fatty acid synthesis, through a series of intracellular cascade responses triggered by the recognition of PRR specific ligands. In the view of evolutionary, trained immunity is beneficial in enhancing protection against secondary infections with an induction in the evolutionary protective process against infections. Therefore, innate trained immunity plays an important role in therapy against diseases such as tumors and infections, which has signature therapeutic effects in these diseases. In organ transplantation, trained immunity has been associated with acute rejection, which prolongs the survival of allografts. However, trained immunity is not always protective but pathological in some cases, and dysregulated trained immunity contributes to the development of inflammatory and autoimmune diseases. Trained immunity provides a novel form of immune memory, but when inappropriately activated, may lead to an attack on tissues, causing autoinflammation. In autoimmune diseases such as rheumatoid arthritis and atherosclerosis, trained immunity may lead to enhance inflammation and tissue lesion in diseased regions. In Alzheimer’s disease and Parkinson’s disease, trained immunity may lead to over-activation of microglial cells, triggering neuroinflammation even nerve injury. This paper summarizes the basis and mechanisms of innate trained immunity, including the different cell types involved, the impacts on diseases and the effects as a therapeutic strategy to provide novel ideas for different diseases.

ObjectiveTo explore the effect of different drying conditions on the appearance and intrinsic quality indicators of Pinelliae Rhizoma for screening suitable drying conditions， so as to provide reference for its standardized production and quality evaluation. MethodsDifferent dried samples of Pinelliae Rhizoma were prepared by lime-assisted sweating method and intermittent drying method. Visual analysis was employed to measure the color brightness values（L^*） of the surface， cross-section and powder of the samples， texture analyzer was used to determine the hardness of the samples under different drying conditions. The total starch content was calculated by measuring the contents of amylose and amylopectin in the samples with ultraviolet-visible spectroscopy. High performance liquid chromatography（HPLC） was used to determine the contents of seven nucleoside components（uracil， hypoxanthine， uridine， inosine， guanosine， β-thymidine and adenosine） in the samples. Pearson correlation analysis was conducted to explore the correlation between the external characteristics and intrinsic indicators of the different dried samples. Principal component analysis（PCA） was used to comprehensively rank the data of various indicators， and partial least squares-discriminant analysis（PLS-DA） was used to screen differential components with variable importance in the projection（VIP） value>1. Furthermore， the difference between the optimal drying condition for Pinelliae Rhizoma and the traditional sun-drying method was explored by independent samples t-test. ResultsWith the increase of temperature， the color of the intermittently dried samples gradually deepened， while their hardness gradually decreased. Concurrently， the contents of extract， total starch， uridine and adenosine exhibited an upward trend， whereas the contents of uracil， hypoxanthine and inosine displayed a downward trajectory. Compared with the intermittent drying group， the content of extract in the samples subjected to lime-assisted sweating increased. With the increase of lime dose， the hardness and the total content of nucleoside components in the samples showed a downward trend， while the total starch content showed an upward trend. Correlation analysis showed that the comprehensive score of L^* was negatively correlated with the contents of uracil， hypoxanthine and inosine， and positively correlated with the contents of uridine， guanosine and adenosine. Hardness was negatively correlated with adenosine content， and positively correlated with the contents of inosine， uracil and hypoxanthine. Through comprehensive consideration and comprehensive score of principal components， the method of 5% lime-mixed sweating for 6 days emerged as the top-ranking approach. Except for the extract， the results of independent samples t-test showed that there was no significant difference between the 5% lime-mixed sweating for 6 days and the traditional sun-drying in terms of other content indicators. ConclusionThe whiteness and firmness of Pinelliae Rhizoma exhibit significant correlations with its chemical composition， while uridine， uracil， guanosine， adenosine and inosine are the key constituents responsible for the quality difference of Pinelliae Rhizoma under different drying conditions. The lime-assisted sweating method optimized in this study can be proposed as a viable alternative to the traditional sun-drying method. This method not only ensures the quality of the medicinal material but also effectively reduces the drying time and prevents mold contamination， which provides a valuable reference for the standardization of drying conditions and the establishment of quality evaluation criteria for Pinelliae Rhizoma.

Objective To construct large medical model named by "Huaxi HongYi"and explore its application effectiveness in assisting medical record generation. Methods By the way of a full-chain medical large model construction paradigm of "data annotation - model training - scenario incubation", through strategies such as multimodal data fusion, domain adaptation training, and localization of hardware adaptation, "Huaxi HongYi" with 72 billion parameters was constructed. Combined with technologies such as speech recognition, knowledge graphs, and reinforcement learning, an application system for assisting in the generation of medical records was developed. Results Taking the assisted generation of discharge records as an example, in the pilot department, after using the application system, the average completion times of writing a medical records shortened (21 min vs. 5 min) with efficiency increased by 3.2 time, the accuracy rate of the model output reached 92.4%. Conclusion It is feasible for medical institutions to build independently controllable medical large models and incubate various applications based on these models, providing a reference pathway for artificial intelligence development in similar institutions.

Objective To evaluate the current situation of disease control in middle-aged and elderly patients with chronic obstructive pulmonary disease (COPD) and analyze the relationship with disease cognition. Methods Among the 360 middle-aged and elderly COPD patients diagnosed and treated in our hospital from January 2022 to June 2024 were retrospectively selected as research subjects, and the COPD Assessment Test Questionnaire (CAT), COPD Patient Knowledge Questionnaire (BCKQ) and the hampion Health Belief Model Scale were used to evaluate disease control, disease cognition and health beliefs in COPD patients. The Pearson chi-square test was used to analyze the relationship between disease control level and disease cognition and health beliefs in older patients with COPD. Results A total of 360 middle-aged and elderly COPD patients, 112 were in the complete control group, 189 were in the partial control group, and 59 were in the uncontrolled group, the disease control rate was 83.61%. The differences in disease cognitive scores, severity cognition, susceptibility cognition, disorder cognition, benefit cognition, health motivation, self-efficacy score and total health belief scores in middle-aged and elderly COPD patients with different disease control conditions are statistically significant. The scores of the complete control group were higher than those of partial control group and uncontrolled group, and the scores of partial control group were higher than those of the uncontrolled group (P <0.05). The disease control level of middle-aged and elderly patients with COPD is positively correlated with disease cognitive level and health belief in all dimensions. The higher the disease control level, the higher the disease cognitive level and health belief in the patient . Conclusions Middle-aged and elderly COPD patients still have insufficient awareness of the disease, and the level of disease control needs to be improved. There is a significant correlation between disease cognition, health beliefs and the level of disease control, and the improved cognitive level may help to improve the disease management and control effect. For middle-aged and elderly COPD patients, the community can provide health education courses, personalized health guidance and self-management training to enhance their awareness of diseases, so as to improve the long-term management of COPD and the quality of life of patients.

Objective　To investigate the effects of capsaicin on gut microbiota and antimicrobial peptide expression of Anopheles stephensi, providing experimental references for the application of capsaicin in mosquito-borne disease prevention and control. Methods Anopheles stephensi were continuously fed with sugary water containing capsaicin or DMSO for the capsaicin-treated group and the control, respectively. The DNA of the female mosquito's midguts and gut bacteria was extracted. Bacterial 16S rDNA high-throughput sequencing and real-time fluorescence quantitative PCR were used to analyze and compare the bacteria diversity, gut flora composition, relative abundance, and total bacterial load in female mosquitoes’ midgut between the control and capsaicin treatment groups. Total RNA was extracted from the midguts of the two groups of Anopheles mosquitoes, and the transcriptional levels of important antimicrobial peptides were detected and compared by reverse transcription and real-time fluorescence quantitative PCR. Results A total of 10 phyla, 11 classes, 28 orders, 43 families, and 62 genera were identified in the two groups. The capsaicin-treated group had fewer taxa, with significantly reduced bacterial diversity, and different community composition and relative abundance of the flora compared to the control group. At the phylum level, Bacteroidota, Proteobacteria, and Firmicutes predominated in both two groups. At the order level, Flavobacteriales, Acetobacterales, Pseudomonadales, and Lactobacillales were the dominant bacteria, with reduced relative abundance of Pseudomonadales and Acetobacterales and increased relative abundance of Flavobacteriales and Lactobacillales in the capsaicin-treated group. At the genus level, Elizabethkingia was predominantly abundant in both samples, with higher relative abundance of Elizabethkingia, Leuconostoc, and Gluconobacter in the capsaicin-treated group, while Asaia and Acinetobacter had significantly lower relative abundance compared to the control group. In addition to these changes, the total bacterial load was increased and the transcriptional levels of attacin C, cecropin A, and defensin were significantly decreased by capsaicin treatment. Conclusions Capsaicin treatment significantly affects the composition of the gut flora in Anopheles stephensi and increases the total bacterial load while inhibiting the expression of antimicrobial peptides. Based on the analysis, it indicates that capsaicin might affect the fecundity and vector competence of Anopheles by changing the energy metabolism and immune-related bacteria.

OBJECTIVE: To observe the effect of acupuncture at "four pharyngeal points" on simple vocal tics with liver hyperactivity disturbed wind in children. METHODS: Sixty children with simple vocal tics of liver hyperactivity disturbed wind were randomly divided into an observation group (30 cases, 1 case dropped out) and a control group (30 cases). The control group was given Changma Xifeng tablets orally, 3 times a day, while the observation group was treated with acupuncture at "four pharyngeal points" on the basis of the treatment in the control group, 15-20 min a time, once daily for 7 days, with a 3-day break. Both groups were treated for 3 months. The TCM syndrome score and Yale global tic severity scale (YGTSS) score of the two groups were observed before treatment and after 1, 2, 3 months of treatment, the disappearance time of simple vocal tics was recorded, and the therapeutic efficacy was evaluated after treatment. RESULTS: After 1, 2, 3 months of treatment, the TCM syndrome scores and YGTSS scores of the two groups were decreased compared with those before treatment (P<0.01, P<0.05), and the scores of the observation group were lower than those in the control group (P<0.05, P<0.01). The disappearance time of simple vocal tics in the observation group was earlier than that in the control group (P<0.05). The effective rate of the observation group was 93.1% (27/29), which was higher than 73.3% (22/30) in the control group (P<0.05). CONCLUSION Acupuncture at "four pharyngeal points" could improve symptoms in children with simple vocal tics of liver hyperactivity disturbed wind, and shorten the disappearance time of simple vocal tics.
Humans ; Male ; Acupuncture Points ; Female ; Child ; Acupuncture Therapy ; Drugs, Chinese Herbal/administration & dosage* ; Child, Preschool ; Liver/drug effects* ; Tics/drug therapy* ; Treatment Outcome

BACKGROUND: Poly adenosine-diphosphate-ribose polymerase (PARP) inhibitors (PARPi) have been approved to act as first-line maintenance (FL-M) therapy and as platinum-sensitive recurrent maintenance (PSR-M) therapy for ovarian cancer in China for >5 years. Herein, we have analyzed the clinical-application characteristics of olaparib and niraparib in ovarian cancer-maintenance therapy in a real-world setting to strengthen our understanding and promote their rational usage. METHODS: A retrospective chart review identified patients with newly diagnosed or platinum-sensitive recurrent ovarian cancer, who received olaparib or niraparib as maintenance therapy at Sichuan Cancer Hospital between August 1, 2018, and December 31, 2021. Patient medical records were reviewed. We grouped and analyzed patients based on the type of PARPi they used (the olaparib group and the niraparib group) and the line of PARPi maintenance therapy (the FL-M setting and the PSR-M setting). The primary endpoint was the 24-month progression-free survival (PFS) rate. RESULTS: In total, 131 patients (olaparib: n = 67, 51.1%; niraparib: n = 64, 48.9%) were enrolled. Breast cancer susceptibility genes ( BRCA ) mutations ( BRCA m) were significantly less common in the niraparib group than in the olaparib group [9.4% (6/64) vs . 62.7% (42/67), P <0.001], especially in the FL-M setting [10.4% (5/48) vs . 91.4% (32/35), P <0.001]. The 24-month progression-free survival (PFS) rates in the FL-M and PSR-M settings were 60.4% and 45.7%, respectively. In patients with BRCA m, the 24-month PFS rates in the FL-M and PSR-M settings were 62.2% and 72.7%, respectively. CONCLUSIONS Olaparib and niraparib were effective in patients with ovarian cancer without any new safety signals except for skin pigmentation. In patients with BRCA m, the 24-month PFS of the PARPi used in the PSR-M setting was even higher than that used in the FL-M setting.
Humans ; Female ; Ovarian Neoplasms/drug therapy* ; Piperazines/therapeutic use* ; Middle Aged ; Retrospective Studies ; Phthalazines/therapeutic use* ; Piperidines/therapeutic use* ; Indazoles/therapeutic use* ; Poly(ADP-ribose) Polymerase Inhibitors/therapeutic use* ; Adult ; Aged ; China ; Neoplasm Recurrence, Local/drug therapy* ; Progression-Free Survival