BACKGROUND:Marine traditional Chinese medicine offers a potentially effective and less adverse treatment for osteoporosis.OBJECTIVE:To explore the pharmacological regulations and procedures of traditional Chinese medicine in treating osteoporosis through data mining and network pharmacology techniques.METHODS:Data mining and network pharmacology methods were used to study the medication pattern and mechanism of marine Chinese medicine patented prescriptions approved by China National Intellectual Property Administration for the treatment of osteoporosis,and special attention was paid to the core Chinese medicine constituents of these prescriptions.The core constituents of the compound drug group composed of oyster-Dipsacus asper-epimedium were comprehensively identified and analyzed by using ultra-high-performance liquid chromatography tandem mass spectrometry.RESULTS AND CONCLUSION:(1)We collected 381 authorized compound patents for the treatment of osteoporosis from the database inception to April 1,2024.Among these,48 patent groups utilized marine traditional Chinese medicine.These prescriptions contained 183 Chinese herbal medicines,of which 13 marine traditional Chinese medicines were used 574 times in total,and the number of flavors used in a single patented formula ranged from 2 to 41.(2)Oyster was the most frequently used marine ingredient,while Dipsacus asper,epimedium,Rehmannia glutinosa,Eucommia ulmoides Oliv.were the most frequent non-marine components.Association rule analysis identified oyster,Dipsacus asper,and epimedium as the core drug group.Network pharmacology analysis revealed that the core targets of this group for the treatment of osteoporosis included ALB,AKT1,TP53,PPARG,and SRC.Sitosterol,liquiritigenin,japonine,luteolin,and kaempferol were identified as the core components within the marine traditional Chinese medicine prescriptions.(3)The GO and KEGFG enrichment analyses suggested a potential association between the mechanism of the core drug group and the rap1/mapk signaling pathway in the treatment of osteoporosis.(4)The molecular docking verified the beneficial interactions between core components and core targets.(5)The ultra-high-performance liquid chromatography tandem mass spectrometry analysis of the compound medicine confirmed the presence of luteolin,sitosterol,kaempferol,and other components,aligning with the drug components identified by network pharmacology.Quantitative analysis indicated that flavonoids,terpenes,and alkaloids constituted a significant proportion of the compound medicine's components.

BACKGROUND:Marine traditional Chinese medicine offers a potentially effective and less adverse treatment for osteoporosis.OBJECTIVE:To explore the pharmacological regulations and procedures of traditional Chinese medicine in treating osteoporosis through data mining and network pharmacology techniques.METHODS:Data mining and network pharmacology methods were used to study the medication pattern and mechanism of marine Chinese medicine patented prescriptions approved by China National Intellectual Property Administration for the treatment of osteoporosis,and special attention was paid to the core Chinese medicine constituents of these prescriptions.The core constituents of the compound drug group composed of oyster-Dipsacus asper-epimedium were comprehensively identified and analyzed by using ultra-high-performance liquid chromatography tandem mass spectrometry.RESULTS AND CONCLUSION:(1)We collected 381 authorized compound patents for the treatment of osteoporosis from the database inception to April 1,2024.Among these,48 patent groups utilized marine traditional Chinese medicine.These prescriptions contained 183 Chinese herbal medicines,of which 13 marine traditional Chinese medicines were used 574 times in total,and the number of flavors used in a single patented formula ranged from 2 to 41.(2)Oyster was the most frequently used marine ingredient,while Dipsacus asper,epimedium,Rehmannia glutinosa,Eucommia ulmoides Oliv.were the most frequent non-marine components.Association rule analysis identified oyster,Dipsacus asper,and epimedium as the core drug group.Network pharmacology analysis revealed that the core targets of this group for the treatment of osteoporosis included ALB,AKT1,TP53,PPARG,and SRC.Sitosterol,liquiritigenin,japonine,luteolin,and kaempferol were identified as the core components within the marine traditional Chinese medicine prescriptions.(3)The GO and KEGFG enrichment analyses suggested a potential association between the mechanism of the core drug group and the rap1/mapk signaling pathway in the treatment of osteoporosis.(4)The molecular docking verified the beneficial interactions between core components and core targets.(5)The ultra-high-performance liquid chromatography tandem mass spectrometry analysis of the compound medicine confirmed the presence of luteolin,sitosterol,kaempferol,and other components,aligning with the drug components identified by network pharmacology.Quantitative analysis indicated that flavonoids,terpenes,and alkaloids constituted a significant proportion of the compound medicine's components.

Objective:To evaluate the incidence of arrhythmias and electrocardiographic (ECG) characteristics in cancer patients treated with immune checkpoint inhibitors (ICIs).Methods:This was a cohort study conducted in the Fourth Hospital of Hebei Medical University. Cancer patients initiating ICIs treatments from November 2020 to September 2022 were included in this study. Baseline 12-leads ECG before ICIs initiation and post-treatment ECG were analyzed. An abnormal ECG was defined as the presence of any of the following changes: sinus arrhythmias, atrial fibrillation, atrial flutter, paroxysmal supraventricular tachycardia, ventricular tachycardia, premature contractions, conduction disorder, and ST-T changes.Results:A total of 87 patients were enrolled, aged 63 (57, 68) years, with 66 (75.9%) males. And 44.8% (39/87) of patients presented with at least one confirmed cardiovascular disease or cardiovascular risk factor at baseline. The incidence of abnormal ECG increased from 31.0% (27/87) at baseline to 65.5% (57/87) after receiving (5.0±2.7) cycles of ICIs treatment ( P<0.001). The incidence of sinus arrhythmias was significantly increased after ICIs treatment (23.0% (20/87) vs. 9.2% (8/87), P=0.023), of which only the incidence of sinus tachycardia was significantly increased (11.5% (10/87) vs. 2.3% (2/87), P=0.039). There was also a significantly increased incidence of ST-T changes after ICIs treatment (31.0% (27/87) vs. 17.2% (15/87), P=0.012), which mainly attributed to the T wave changes (29.9% (26/87) vs. 13.8% (12/87), P=0.001). The incidence of premature contractions was also significantly increased after ICIs treatment (9.2% (8/87) vs. 0, P=0.008). Additionally, compared with baseline, the P wave axis was significantly increased after ICIs treatment ((56.94±21.01)° vs. (52.00±22.69)°, P=0.043). After ICIs treatment, the heart rate was significantly increased ((79.07±15.37) beats/min vs. (75.64±13.37) beats/min, P=0.029). Sokolow-Lyon index ((2.21±0.81)mV vs. (2.33±0.75)mV, P=0.138), QTc interval ((431.44±36.04)ms vs. (428.00±30.05)ms, P=0.415) all showed signs of change after treatment, but did not reach the traditional significant level. Conclusions:The incidence of abnormal ECG is significantly increased after ICIs treatment, especially for sinus tachycardia, premature contractions and T wave changes; the P wave axis and heart rate is also significantly increased after treatment. It is important to perform regular ECG monitoring in patients receiving ICIs treatment.

Objective:To evaluate the efficacy and safety of antaitasvir phosphate 100 mg or 200 mg combined with yiqibuvir for 12 weeks in patients with various genotypes of chronic hepatitis C, without cirrhosis or compensated stage cirrhosis.Methods:Patients with chronic hepatitis C (without cirrhosis or compensated stage cirrhosis) were randomly assigned to the antaitasvir phosphate 100 mg+yiqibuvir 600 mg group (100 mg group) or the antaitasvir phosphate 200 mg+yiqibuvir 600 mg group (200 mg group) in a 1∶1 ratio. The drugs were continuously administered once a day for 12 weeks and observed for 24 weeks after drug withdrawal. The drug safety profile was assessed concurrently with the observation of the sustained virological response (SVR12) in the two patient groups 12 weeks following the drug cessation. The intention-to-treat concept was used to define as closely as possible a full analysis set, including all randomized cases who received the experimental drug at least once. The safety set was collected from all subjects who received the experimental drug at least once (regardless of whether they participated in the randomization group) in this study. All efficacy endpoints and safety profile data were summarized using descriptive statistics. The primary efficacy endpoint was SVR12. The primary analysis was performed on a full analysis set. The frequency and proportion of cases were calculated in the experimental drug group (antaitasvir phosphate capsules combined with yiqibuvir tablets) that achieved "HCV RNA

Objective:To investigate the current situation and influencing factors of humanistic care needs of family members of pregnant women in maternal intensive care unit, and to explore the relationship between humanistic care needs of family members of pregnant women in maternal intensive care unit, relocation stress level and perceived social support ability, so as to provide a basis for clinical nursing staff to implement targeted humanistic care for family members of pregnant women in maternal intensive care unit.Methods:From July to December 2022, 267 family members of pregnant women who were observed in the Maternal Intensive Care Unit of Maternity Hospital Affiliated to Nanjing Medical University/Nanjing Maternal and Child Health Hospital were selected as the research objects by the convenient sampling method. The general information questionnaire, Humanistic Care Needs Scale for Family Members of Pregnant Women in the Obstetric Intensive Care Unit, Family Relocation Stress Scale for Intensive Care Unit Patients and Perceived Social Support Scale were used to carry out a cross sectional investigation.Results:The scores of humanistic care needs, relocation stress scale and perceived social support scale were (175.32 ± 16.04), (35.12 ± 8.11), (57.30 ± 15.43) points, respectively. The length of maternal intensive care unit stay ( B=1.301, P<0.05), the family′s role changed for the first time ( B=2.328, P<0.05), the delivery mode doesn′t match the family′s expectations ( B=-2.407, P<0.05), maternal admission to maternal intensive care unit due to childbirth complications ( B=3.228, P<0.05), relocation stress level of intensive care unit patients′ family members ( B=0.891, P<0.05), and family members′ perceived social support ability ( B=0.461, P<0.05) were the influencing factors of humanistic care needs of maternal family members in maternal intensive care unit factors, which explained 83.2% of the total variation. Conclusions:The humanistic care needs of family members of pregnant women in maternal intensive care unit are at a high level. Medical staff should pay more attention to the family members of pregnant women who stay in maternal intensive care unit for a long time, undergo role change for the first time, have unexpected delivery mode and stay in maternal intensive care unit due to childbirth complications, so as to provide them with more comprehensive humanistic care and establish multiple support system, in order to improve the level of humanistic care for the family members of maternal intensive care unit.

Objective:To investigate whether astaxanthin (AST) down-regulates dynamin-related protein 1 (Drp1) through activating the silent mating type information regulation 2 homolog-1 (SIRT1) signaling pathway, thereby attenuating contrast-induced acute kidney injury.Methods:Forty adult male Sprague-Dawley rats weighing 160-180 g were randomly divided into five groups: sham surgery group (Sham group), contrast medium injury group (CM group), astaxanthin-intervention group (AST+CM group), SIRT1 inhibitor Ex527 intervention group (Ex527+CM group), and astaxanthin combined with Ex527 intervention group (AST+Ex527+CM group). After 72 hours of modeling, heart blood was removed and kidney tissues were collected for follow-up testing. Serum creatinine (Scr), blood urea nitrogen (BUN), and oxidative stress-related indexes total superoxide dismutase (T-SOD) and malondialdehyde (MDA) were measured by biochemistry; hematoxylin and eosin staining was performed to observe the pathological changes in the kidney; mitochondrial morphology and number were observed by transmission electron microscopy; reactive oxygen species (ROS) levels were detected by ROS staining in frozen sections; TUNEL staining was performed to detect apoptosis level. The expression levels of SIRT1, p53, peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), Drp1 and apoptosis-related proteins Bcl-2 and Bax were detected by Western blotting.Results:(1) Compared with the CM group, Scr and BUN level were significantly lower, T-SOD level was higher and MDA level was lower in the AST+CM group, while T-SOD level decreased and MDA level increased after the combination of Ex527 (all P<0.05). (2) ROS expression was lower in the AST+CM group compared to the CM group and higher after the combination of Ex527 (both P<0.05). (3) The number of apoptotic cells was significantly reduced in the AST+CM group compared to the CM group and increased after the combination of Ex527 (both P<0.05). (4) The protein expression levels of SIRT1, PGC-1α and Bcl-2 were increased and the protein expression levels of p53, Drp1 and Bax were decreased (all P<0.05) in the AST+CM group compared with the CM group, and the protein expression levels of SIRT1, PGC-1α and Bcl-2 were decreased and the protein expression levels of p53, Drp1 and Bax were increased when Ex527 was combined (all P<0.05). Conclusion:Astaxanthin can inhibit Drp1-mediated mitochondrial fission by activating the SIRT1 pathway, thereby reducing contrast-induced acute kidney injury in rats.

Objective To study the effect of ursolic acid (UA) intervention on hepatocyte apoptosis induced by TGF-β1 and its potential mechanism.Methods Primary hepatocytes were extracted from healthy SD rats by in situ perfusion,cultured for 12-24h,then randomly divided into the following groups:blank control group,UA control group (UA 25μmol/L),TGF-β1 group (TGF-β1 2.5ng/ml),UA intervention group (UA 25μmol/L and TGF-β1 2.5ng/ml),DPI intervention group (DPI 0.5μmol/L and TGF-β1 2.5ng/ml).Each group was treated with drugs for corresponding time and their proliferation and apoptosis were detected by flow cytometry,the expression of CD95 (Fas) mRNA was analyzed by RT-qPCR,the expression of protein CD95 and membrane translocation of NADPH oxidase (NOX) subunit p47Phox were analyzed by Western blotting,and the reactive oxygen species (ROS) generation in primary hepatocytes was analyzed with reactive oxygen detection kit.Results UA intervention at 30min before TGF-β1 stimulating hepatocytes markedly reduced hepatocyte apoptosis (63.97 ± 3.19 vs 80.53 ± 1.56,P＜0.01) and promoted hepatocyte proliferation (18.67 ± 1.60 vs 10.83 ± 2.03,P＜0.01).UA intervention notably down-regulated the expressions of CD95 mRNA and protein (1.28 ± 0.15 vs 2.40 ± 0.25,P＜0.01;1.05 ± 0.15 vs 1.37 ± 0.18,P＜0.05),restrained membrane translocation of p47phox (1.13 ± 0.12 vs 1.76 ± 0.22,P＜0.01),and decreased ROS level in primary hepatocytes induced by TGF-β1 (2.12 ± 0.45 vs 3.23 ± 0.53,P＜0.01).Conclusion The mechanism of UA inhibiting hepatocyte apoptosis induced by TGF-β1 is likely to be that UA intervention reduced hepatocyte apoptosis by inhibiting NOX activation and decrease generation of ROS so as to down-regulate expression of CD95 in hepatocytes.

Objective To investigate the serum level of calcium-binding protein A9(S100A9)in patients with rheumatoid arthritis and explore its potential clinical significance. Methods The serum level of S100A9 was measured by ELISA in 79 rheumatoid arthritis (RA) patients and 20 healthy controls (HC). The correlation of S100A9 level and relevant clinical parameters were analyzed. Results The serum level of S100A9 was significantly increase in RA patients than those in HC. The serum level of S100A9 was higher in high disease activity than that in moderate and low disease activity in the RA group. There was a positive correlation in serum S100A9 level and DAS28 score,Rheumatoid factor,tender joint count and swollen joint count. Conclusion The serum level of S100A9 increases in RA patients and correlates with RA activity.

Background:The TNM staging system is far from perfect in predicting the survival of individual cancer patients because only the gross anatomy is considered. The survival rates of the patients who have the same TNM stage disease vary across a wide spectrum. This study aimed to develop a nomogram that incorporates other clinicopatho-logic factors for predicting the overall survival (OS) of non-metastatic nasopharyngeal carcinoma (NPC) patients after curative treatments. Methods:We retrospectively collected the clinical data of 1520 NPC patients who were diagnosed histologically between November 2000 and September 2003. The clinical data of a separate cohort of 464 patients who received intensity-modulated radiation therapy (IMRT) between 2001 and 2010 were also retrieved to examine the extensibil-ity of the model. Cox regression analysis was used to identify the prognostic factors for building the nomogram. The predictive accuracy and discriminative ability were measured using the concordance index (c-index). Results:We identiifed and incorporated 12 independent clinical factors into the nomogram. The calibration curves showed that the prediction of OS was in good agreement with the actual observation in the internal validation set and IMRT cohort. The c-index of the nomogram was statistically higher than that of the 7th edition TNM staging sys-tem for predicting the survival in both the primary cohort (0.69 vs. 0.62) and the IMRT cohort (0.67 vs. 0.63). Conclusion:We developed and validated a novel nomogram that outperformed the TNM staging system in predict-ing the OS of non-metastatic NPC patients who underwent curative therapy.

Objective To observe the effects of ursolic acid (UA) on the activation of nicotinamide adenine dinucleotide phosphate oxidase (NOX) and the downstream signaling pathways in platelet derived growth factor (PDGF) activated rat hepatic stellate cell (HSC-T6).Methods Rat HSC-T6 cells were divided into blank control group (no treatment),UA control group (50 μmol/L UA),PDGF group (10 μg/L PDGF),UA intervention group (50 μmol/L UA + 10 μg/L PDGF),diphenyleneiodonium intervention(DPI) group (20 μmol/L DPI+ 10 μg/L PDGF),SB203580 (p38 mitogen-activated protein kirase(p38MAPK) inhibitor) intervention group (10 μmol/L SB203580 + 10 μg/LPDGF),LY294002 (phosphatidylinositop 3 kinase(PI3K) inhibitor) intervention group (10 μmol/L LY294002 + 10 μg/L PDGF) and rosup positive control group (5 μg/mL rosup).Except rosup positive control group,the expression of type Ⅰ collagen at mRNA level of each group was detected by fluorescence quantitavepolymerase chain reaction (RT-PCR).The expression of membrane protein p47phox (except rosup positive control group),PI3K(except rosup positive control group and SB203580 intervention group),p-protein kinase B (p-AKT,except rosup positive control group and SB203580 intervention group) and phosphorylated p38 mitogen-activated protein kinase (p-p38MAPK,except rosup positive control group and LY294002 intervention group) were tested by Western blot.Except SB203580 intervention group and LY294002 intervention group,the fluorescence intensity in the cells of each group was analyzed with active oxygen detection kit and fluorescence microplate reader.Single factor analysis of variance and LSD test were performed for comparison between groups.Results Type Ⅰ collagen at the mRNA level of PDGF group (3.74±0.32) was higher than that of blank control group (1.00±0.00) ; Type Ⅰ collagen at the mRNA level of UA group (0.21 ±0.02) was lower than that of blank control group,UA intervention group (1.02 ± 0.12),DPI intervention group (1.09±0.21),SB203580 intervention group (1.18± 0.27),and LY294002 intervention group (1.15 ± 0.26) were all lower than PDGF group,and the differences were statistically significant (t =15.667,-4.501,-15.553,-15.154,-14.642 and -14.813,all P＜0.05).p47phox at the protein expression level of PDGF group (1.98±0.53) was higher than that of blank control group (1.00±0.00) ; that of UA group (0.48±0.10) was lower than blank control group; those of UA intervention group (0.95 ± 0.26),DPI intervention group (0.99 ± 0.28),SB203580 intervention group (0.93±0.31),and LY294002 intervention group (1.07±0.19) were all lower than PDGF group (t=4.209,-2.234,4.424,-4.252,-4.510 and-3.909,all P＜0.05).The protein expression level of PI3K of PDGF group (2.27±0.46) was higher than that of blank control group (1.00±0.00); that of UA intervention group (0.14 ± 0.07) was lower than PDGF group and blank control group; that of UA group (0.14±0.07) was lower than blank control group; those of DPI intervention group (0.53±0.25) and LY294002 intervention group (0.35±0.14) were all lower than PDGFgroup (t 6.205,8.208,-2.003,4.202,-8.502 and-9.831,all P＜0.05).The protein expression level of p-Akt of PDGF group (2.54±0.49) was higher than that of blank control group (1.00± 0.00); those of UA intervention group (0.74± 0.20),DPI intervention group (0.94 ± 0.37) and LY294002 intervention group (1.17±0.41) were all lower than PDGF group; that of UA group (0.59± 0.15) was lower than blank control group (t=5.927,-6.928,-6.158,-5.273 and-1.578,all P＜ 0.05).The protein expression level of p-p38MAPK of PDGF group (1.98±0.35) was higher than that of blank control group (1.00±0.00); those of UA intervention group (0.68±0.28),DPI intervention group (0.63±0.27) and SB203580 intervention group (0.67 ± 0.29) was all lower than PDGF group; that of UAgroup (0.28±0.13) was lower than blank control group (t=4.897,-6.479,-6.727,-6.529 and-3.561,all P＜0.05).The level of active oxygen of PDGF group (105.57±7.51) was higher than that of blank control group (69.60±8.63) ; those of UA intervention group (64.56±9.11),DPI intervention group (65.75 ± 6.62) was lower than PDGF group,UA group (29.84 ±3.19) was lower than blank control group (t=6.368,-7.288,-7.071 and-7.255,all P＜0.05).Conclusion UA could inhibit membrane displacement of NOX subunit p47phox and reduce active oxygen production in PDGF induced rat HSC-T6 cells,and then block phosphorylation of PI3K Akt,p 38MAPK signal pathways and inhibited the expression of type Ⅰ collagen at mRNA level.