BACKGROUND:Psoralen has a strong anti-osteoporotic activity and may have a restorative effect on chemotherapy-induced osteoporosis. OBJECTIVE:To explore the restorative effect of psoralen on the osteogenic differentiation of bone marrow mesenchymal stem cells in mice inhibited by cyclophosphamide and its mechanism. METHODS:C57BL/6 mouse bone marrow mesenchymal stem cells were isolated and cultured.Effect of psoralen on viability of bone marrow mesenchymal stem cells was detected by MTT assay.Osteogenic induction combined with alkaline phosphatase staining was used to determine the optimal dose of psoralen to restore the osteogenic differentiation of bone marrow mesenchymal stem cells inhibited by cyclophosphamide.The mRNA expression levels of Runx2,alkaline phosphatase,Osteocalcin,osteoprotegerin,and Wnt/β-catenin signaling pathway-related genes Wnt1,Wnt4,Wnt10b,β-catenin,and c-MYC were measured by RT-qPCR at different time points under the intervention with psoralen.The protein expression of osteogenic specific transcription factor Runx2 and Wnt/β-catenin signaling pathway related genes Active β-catenin,DKK1,c-MYC,and Cyclin D1 was determined by western blot assay at different time points under the intervention with psoralen. RESULTS AND CONCLUSION:(1)There was no significant effect of different concentrations of psoralen on the viability of bone marrow mesenchymal stem cells.The best recovery of the inhibition of osteogenic differentiation of bone marrow mesenchymal stem cells caused by cyclophosphamide was under the intervention of psoralen at a concentration of 200 μmol/L.(2)Psoralen reversed the reduction in osteogenic differentiation marker genes Runx2,alkaline phosphatase,Osteocalcin and osteoprotegerin mRNA expression and Runx2 protein expression in bone marrow mesenchymal stem cells caused by cyclophosphamide conditioned medium.(3)Psoralen reversed the decrease in Wnt/β-catenin pathway-related genes Wnt4,β-catenin,c-MYC mRNA and Active β-catenin,c-MYC,and Cyclin D1 protein expression and the increase in DKK1 protein expression in bone marrow mesenchymal stem cells caused by cyclophosphamide conditioned medium.(4)The results showed that cyclophosphamide inhibited osteogenic differentiation of bone marrow mesenchymal stem cells in mice,and psoralen had a restorative effect on it.The best intervention effect was achieved at a concentration of 200 μmol/L psoralen,and this protective effect might be related to the activation of Wnt4/β-catenin signaling pathway by psoralen.

Objective: To find a viable alternative to reduce the number of doses required for the patients with post-traumatic stress disorder (PTSD), and to improve efficacy and patient compliance. Methods: In this study, we used ginger oil, a phytochemical with potential therapeutic properties, to prepare ginger oil patches. High-performance liquid chromatography (HPLC) was used to quantify the main active component of ginger oil, 6-gingerol. Transdermal absorption experiments were conducted to optimize the various pressure-sensitive adhesives and permeation enhancers, including their type and concentration. Subsequently, the ginger oil patches were optimized and subjected to content determination and property evaluations. A PTSD mouse model was established using the foot-shock method. The therapeutic effect of ginger oil patches on PTSD was assessed through pathological sections, behavioral tests, and the evaluation of biomarkers such as tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), brain-derived neurotrophic factor (BDNF), and melatonin (MT). Results: The results demonstrated that ginger oil patches exerted therapeutic effects against PTSD by inhibiting inflammatory responses and modulating MT and BDNF levels. Pharmacokinetic experiments revealed that ginger oil patches maintained a stable blood drug concentration for at least one day, addressing the rapid metabolism drawback of 6-gingerol and enhancing its therapeutic efficacy. Conclusions Ginger oil can be prepared as a transdermal drug patch that meets these requirements, and the bioavailability of the prepared patch is better than that of oral administration. It can improve PTSD with good patient compliance and ease of administration. Therefore, it is a promising therapeutic formulation for the treatment of PTSD.

OBJECTIVE To evaluate the antioxidant activity compounds extracted from the pine needle of Cedrus deodara. METHODS Using vitamin C （VC） and gallic acid as positive control， HPLC method was employed to determine the changes of the DPPH peak area after antioxidant compounds from pine needle of C. deodara were treated with 1， 1-diphenyl-2-picrylhydrazyl radical （DPPH）. Then， the antioxidant activities of 3 active parts and 8 monomer compositions from pine needle of C. deodara were evaluated by calculating the inhibition rate of DPPH free radicals and the half inhibitory concentration （IC50）. HPLC conditions were using Agilent Eclipse Plus-C18 column （250 mm × 4.6 mm， 5 μm） with acetonitrile-water （62∶38， V/V） as the mobile phase. The detection wavelength was 517 nm； the flow rate was 1.0 mL/min； the column temperature was 25 ℃ ； the injection volume was 20 μL. RESULTS The order of DPPH free radical inhibition activity of active parts from pine needle of C. deodara was total flavonoids＞total polyphenols＞total lignans， with IC50 of 76.10， 100.50 and 115.40 μg/mL， respectively. Compared with positive control， except for kaempferol-3-O-β-D-glucoside， the sequence of seven monomer compounds for DPPH free radical inhibition activity was dihydromyricetin＞hypericin＞protocatechuic acid＞gallic acid＞ferulic acid＞myricetin＞ kaempferol-3-O-（6″-O-E-feruloyl）-β-D-glucopyranoside＞VC＞isohamnin， with IC50 of 16.50， 19.40， 23.73， 27.24， 32.10， 32.20， 47.60， 93.20 and 297.20 μg/mL， respectively. CONCLUSIONS HPLC-DPPH method is established to evaluate the antioxidant activity of pine needle of C. deodara. The pine needle of C. deodara has strong antioxidant activity， among which the effective compounds of total flavonoids， total polyphenols， monomer dihydromyricetin and hypericin are natural antioxidants with development prospects.

Background::With an increasing proportion of multiparas, proper interpregnancy intervals (IPIs) are urgently needed. However, the association between IPIs and adverse perinatal outcomes has always been debated. This study aimed to explore the association between IPIs and adverse outcomes in different fertility policy periods and for different previous gestational ages.Methods::We used individual data from China’s National Maternal Near Miss Surveillance System between 2014 and 2019. Multivariable Poisson models with restricted cubic splines were used. Each adverse outcome was analyzed separately in the overall model and stratified models. The stratified models included different categories of fertility policy periods (2014–2015, 2016–2017, and 2018–2019) and infant gestational age in previous pregnancy (<28 weeks, 28–36 weeks, and ≥37 weeks).Results::There were 781,731 pregnancies enrolled in this study. A short IPI (≤6 months) was associated with an increased risk of preterm birth (OR [95% CI]: 1.63 [1.55, 1.71] for vaginal delivery [VD] and 1.10 [1.03, 1.19] for cesarean section [CS]), low Apgar scores and small for gestational age (SGA), and a decreased risk of diabetes mellitus in pregnancy, preeclampsia or eclampsia, and gestational hypertension. A long IPI (≥60 months) was associated with an increased risk of preterm birth (OR [95% CI]: 1.18 [1.11, 1.26] for VD and 1.39 [1.32, 1.47] for CS), placenta previa, postpartum hemorrhage, diabetes mellitus in pregnancy, preeclampsia or eclampsia, and gestational hypertension. Fertility policy changes had little effect on the association of IPIs and adverse maternal and neonatal outcomes. The estimated risk of preterm birth, low Apgar scores, SGA, diabetes mellitus in pregnancy, and gestational hypertension was more profound among women with previous term births than among those with preterm births or pregnancy loss.Conclusion::For pregnant women with shorter or longer IPIs, more targeted health care measures during pregnancy should be formulated according to infant gestational age in previous pregnancy.

Objective This study aims to analyze the application value of the Kirkpatrick Evaluation Model in the evalu-ation of hospital service training.Methods A total of 100 hospital front desk service personnel participating in service training from July 2021 to July 2023 at Qingyuan People's Hospital were selected as the research subjects.They were randomly divided into a study group and a control group,with 50 participants in each group.The study group implemented training based on the Kirkpatrick Evaluation Model,while the control group received conventional training.The learning level,behavior level,reaction level,and result level(including service satisfaction,complaint rate,and occurrence of service incidents)of the two groups were compared,as well as the evaluation effects.Results The study group showed significantly higher scores in theoretical knowl-edge,skill operations,thinking patterns,and humanistic care compared to the control group.The training satisfaction was signifi-cantly higher in the study group.The scores for interpersonal communication,question answering,and front desk material man-agement were significantly higher in the study group.The service satisfaction and training effectiveness were significantly higher,while the complaint rate and occurrence of service incidents were significantly lower in the study group compared to the control group(P<0.05).Conclusion Implementing training for hospital front desk service personnel based on the Kirkpatrick Evalua-tion Model can improve their theoretical knowledge and service level,enhance patient satisfaction,and reduce the complaint rate and occurrence of service incidents.

Objective To analyze the effect of service supervision group on the improvement of medical experience of nursing quality.Methods 108 nurses who participated in the supervision and management of Qingyuan People's Hospital from June 2023 to December 2023 were selected as the observation objects.All nurses established a service supervision group to carry out management,and analyzed the score of training quality,excellent knowledge mastery rate,patient complaint rate and patient satisfaction with medical treatment after management.Results The score of training quality and the excellent and good rate of knowledge mastery of nurses were higher than those before management.Among the 385 patients treated during the period,the complaint rate of patients was lower,and the satisfaction of patients with medical treatment was increased,the difference was sta-tistically significant(P＜0.05).Conclusion The effect of service supervision group on the improvement of medical experience of nursing quality is accurate and worthy of promotion.

AIM:To explore the mechanism by which Qingshen granules(QSG)intervene in the microRNA-4516(miR-4516)targeted regulation of the SIAH3/PINK1 axis,enhancing mitophagy and inhibiting renal fibrosis.METHODS:Male SD rats were randomly divided into three groups:control,model,and QSG groups.The QSG aqueous solution was administered via gavage once daily,4 mL each time,for 8 consecutive weeks.Blood creatinine levels were measured in each group.Hematoxylin-eosin(HE)and Masson staining were utilized to assess the degree of renal patholog-ical damage.Western blot analysis was performed to determine the expression levels of β-actin,PINK1,Parkin,SIAH3,VDAC1,Mfn1,Mfn2,OPA1,LC3B,and P62 proteins in renal tissue.RT-qPCR was used to detect the mRNA expres-sion level of SIAH3 in rat kidney tissue,and transmission electron microscopy was employed to observe mitochondrial dam-age in renal tissue.QSG-containing serum and transforming growth factor-β1(TGF-β1)were used to induce an HK-2 cell fibrosis model.The cells were divided into the following groups:normal cell(NC)group,model cell(MC)group,MC+miR-4516 mimics group,MC+miR-4516 NC+QSG group,MC+miR-4516 mimics+QSG group,and MC+QSG group.Cell activity in each group was detected using the CCK-8 method,and Western blot analysis was performed to determine E-cad-herin and α-SMA protein expression levels.The regulation of SIAH3 by miR-4516 was verified using a dual luciferase re-porter assay.RT-qPCR was used to detect the mRNA expression of miR-4516,SIAH3 mRNA,and PINK1.RESULTS:The results indicated that QSG intervention reduced fibrosis in rat renal tissue and HK-2 cells,decreased SIAH3 mRNA expression,increased PINK1 expression,and activated mitophagy in renal tissue.In vitro results confirmed that QSG can elevate miR-4516 expression,inhibit SIAH3 mRNA expression,promote PINK1 expression in HK-2 cells,and reduce the expression of the fibrosis marker protein α-SMA.CONCLUSION:In summary,this study preliminarily clarified the mechanism by which QSG intervention targets miR-4516 to regulate the SIAH3/PINK1 axis,thereby enhancing mitophagy and inhibiting renal fibrosis.

Objective:To explore the application of union physio-psycho-social assessment questionnaire (UPPSAQ-70) in screening anxiety and depression in outpatients from general hospital.Methods:A total of 510 outpatients from Peking Union Medical College Hospital from June 2020 to November 2021 were recruited.They were assessed with UPPSAQ-70, self-rating anxiety scale (SAS) and self-rating depression scale (SDS). The internal consistency of the UPPSAQ-70 was tested by Cronbach′s α coefficient.The convergent validity of the UPPSAQ-70 was evaluated by examining correlations with the SAS and SDS.Clinical diagnosis, being considering as the " gold standard" , was used to test criterion validity.Result:The UPPSAQ-70 showed good item characteristics and reliability (Cronbach α=0.947). The UPPSAQ-70 total score showed significant correlations with SAS( r=0.843, P<0.01) and SDS ( r=0.852, P<0.01). The area under the curve (AUC) of the UPPSAQ-70 was 0.875 ( P<0.01), the cut-off value was 65 points with the sensitivity 83.2% and the specificity 75.5%.The AUC of the SAS and SDS was 0.848 and 0.808 respectively(both P<0.001). For the SAS(standard score of 50 as the cut-off value), the sensitivity was 47.3%, and specificity was 92.5%.For the SDS(standard score of 53 as the cut-off value), the sensitivity was 62.9%, and specificity was 86.8%. Conclusion:UPPSAQ-70 has high sensitivity and is more suitable for screening of anxiety and depression in general hospital outpatients.

Objective:To evaluate the safety and efficacy of trimodality treatment (TMT) which is complete transurethral resection of bladder tumor with concurrent radiotherapy and chemotherapy for invasive bladder cancer.Methods:From Mar. 2016 to Oct.2021, patients who were indicated of radical cystectomy (RC) but refused were enrolled to TMT treatment prospectively. Inclusive criteria were: ① the patients refused radical surgery; ② male or female, no older than 80 years; ③ no matter the tumor size, the bladder tumor be completely resected by transurethral surgery, and the hydronephrosis be improved after resecting the tumor; ④ the postoperative pathology of urothelial carcinoma; ⑤ recurrent T 1 and high-grade non-muscle invasive bladder cancer (NMIBC) or T 2-4a muscle invasive bladder cancer (MIBC); ⑥ no definitive metastasis in preoperative chest, abdominal CT or MRI; ⑦ hemoglobin ≥100 g/L, white blood cell count ≥4×10 9/L, platelet count ≥100×10 9/L, and normal liver and renal function. The exclusion criteria were: ① tumor invading bladder neck or anterior or posterior urethra; ② bladder contracture or severe urethral stricture; ③ regional lymph node metastasis or distant metastasis by imaging examination; ④ no improvement of hydronephrosis after resection; ⑤ definitive contraindications of radiotherapy or chemotherapy; ⑥ uncontrolled hypertension, diabetes, coronary heart disease or other severe diseases. After cTURBT, paclitaxel (50 mg/m 2 on Day 1 of each week) combined with cisplatin(20 mg/m 2 on day 1-2 of each week)was administered with concurrent radiotherapy (2 Gy/fraction/day) for 4 weeks. If cystoscopy and/or radiographic detected no recurrence or metastasis, the patients were treated with concurrent chemoradiotherapy for 2 and a half weeks (total dose of 64 Gy). The side effects of radiotherapy and chemotherapy during TMT were observed, the quality of life(QOL)was evaluated by FACT-P scale, and the bladder recurrence, distant metastasis and survival were assessed with imaging and cystoscopy. From March 2016 to October 2021, 79 patients with RC were enrolled, including 67 males and 12 females, aged 44-86 years. The pathology of RC was urothelial carcinoma of the bladder. There was no definitive lymph node or distant metastasis in preoperative imaging. The progress and survival after TMT and RC treatment were followed up and the survival rates were calculated by Kaplan-Meier method. Results:Of the 30 patients who underwent TMT, including 25 males and 5 females, aged 32-76 years, there were 7 cases of cT 1 (23.3%), 19 cases (63.3%) of cT 2, 2 cases of cT 3 (6.7%)and 2 cases of cT 4(6.7%), respectively. A total of 132 adverse events of all grades of chemoradiotherapy occurred, of which only 4 were grade Ⅳ, with no bowel leakage or death due to complications. The mean scores of negative questions in FACT-P were 3.22±0.67, 1.30±0.63 and 0.87±0.69 before TMT treatment, 6 and 12 months after TMT treatment, respectively. The quality of life was significantly improved( F=129.081, P<0.001), and the rate of bladder preservation was 86.7%(26/30). Two cases underwent salvage RC(6.7%)and 2 cases died of bladder recurrence(6.7%). There were 8, 4 and 2 patients survived 4, 5 and 6 years, respectively. Seven cases (23.3%) had bladder recurrence, 3 cases (10.0%) underwent distant metastasis and 6 patients (20.0%)died after TMT because of the progression. The 1, 2 and 5 year overall survival rates by TMT treatment were 88.89%, 82.96% and 62.77%, respectively. Median follow-up was 19.5(6.8-44.5) months in the TMT group and 35.5(18.8-53.3) months in the RC group ( z=-1.998, P=0.046). Progression-free survival in the TMT and RC group were 66.7% and 80.0%( χ2=1.047, P=0.306), and the overall survival rates were 80.0% and 80.0% ( χ2=0.482, P=0.488) respectively. The difference was not statistically significant. Conclusions:The TMT is a safe and effective alternative for RC, which can improve the quality of life and control the tumor sufficiently.

Objective:To analyze the efficacy and safety of radium-223 in the treatment of metastatic castration resistant prostate cancer (mCRPC).Methods:The clinical data of 22 patients with mCRPC treated with radium-223 in the Chongqing University Cancer Hospital from January 2021 to January 2022 were analyzed retrospectively. The average age was (70.7±1.3)years old. There were 7 cases with ECOG score of 1 and 15 cases with ECOG score of 2. There were 7 cases with grade 2 and 15 cases with grade 3 bone metastasis. For mCRPC, 1 case (4.6%) received first-line treatment, 4 cases (18.2%) received second-line treatment, 10 cases (45.5%) received third-line treatment, 4 cases (18.2%) received fourth-line treatment, and 3 cases (13.6%) received fifth-line treatment. The median time from the diagnosis of mCRPC to the start of radium-223 treatment was 29 (20, 34) months. Radium-223 (55kbq/kg) was injected intravenously every 4 weeks for up to 6 cycles. Before treatment, the median alkaline phosphatase (ALP) was 147.0 (101.8, 212.5)U/L, the median prostate specific antigen (PSA) was 44.7(20.2, 99.1)ng/ml, and 6 patients (27.3%) were complicated with grade 1-2 anemia. The median hemoglobin was 115.0 (103.8, 122.5) g/L, the average neutrophil was (3.0 ± 0.3)×10 9/L, and the average platelet was (169.8 ± 17.0)×10 9/L. The overall survival (OS), radiographic progression-free survival time (rPFS), time to PSA progression, PSA response rate, pain response rate, and time to pain progression were analyzed. Stratified analysis was carried out according to the number of treatment lines experienced before radium-223 treatment. At the same time, the main adverse reactions during radium-223 treatment were analyzed. Results:The mean number of treatment courses with radium-223 was 2.7(ranging 1 to 6), with 4 patients completing 6 courses, 12 (54.6%) completing ≥ 3 courses, and 10 (45.5%) completing < 3 courses. Thirteen patients (59.1%) were treated with radium-223 alone and 9 (40.9%) in combination with other treatments (1 of docetaxel chemotherapy, 2 of enzalutamide, 3 of olaparib, and 3 of estramustine phosphate). None of the patients in this group were treated with bisphosphonates. Ten patients (45.5%) in this group died, all due to disease progression. The median overall survival time of the 22 cases was 11.0 (2.2, 19.8) months. Three patients (13.6%), 7 patients (31.8%), 3 patients (13.6%), and 1 patient (4.5%) showed radiographic progression at 2, 3, 4, and 10 months after treatment, respectively, while the remaining 8 patients (36.4%) did not show radiographic progression during the follow-up period, and the median radiographic progression free time for the 22 patients was 4.0 (3.1, 4.9) months. There were four cases (18.2%) showed PSA response, of which three cases (13.6%) showed PSA rising again later, and one case (4.5%) showed continuous PSA decline. The median time to PSA progression for the 22 patients was 3.6 (2.2, 5.1) months. Fifteen patients (68.2%) experienced pain response at 1 month of treatment, of whom 5 (22.7%) experienced increased pain later and 10 (45.5%) experienced sustained pain relief. The median time to pain progression was 5.5 (3.5, 7.6) months in 22 patients. No patients received radiotherapy or surgery for pain, and no patients experienced fracture. In this group, 7 patients (31.8%) had a post-treatment ALP decrease ≥30% from baseline. Major adverse events during radium-223 treatment were all grade 1 to 2 events, no grade ≥3 adverse events, and no treatment discontinuers due to adverse events.Conclusions:Radium-223 resulted in high pain response rates and prolonged OS, rPFS and time to PSA progression in patients with mCRPC. Adverse effects were low during treatment. The conclusions need to be validated by further expansion of the sample size and extended follow-up.