To summarise the clinical experience of treating insomnia with the method of resolving depression， regulating the middle， and tranquilising mind. It is believed that the key to the pathogenesis of insomnia lies in qi depression， disharmony of qi pivot， and disharmony of qi and blood， and the core treatment is to resolve depression， regulating the middle， and tranquilising mind. The self-prescribed Jieyu Anmian Formula （解郁安眠方） could be used as the basic treatment， then modified according to the performance of the patient and syndromes. For syndrome of liver depression restricting spleen， the treatment should soothe liver and invigorate spleen， resolve depression and regulate the middle； for syndrome of liver depression and phlegm coagulation， the treatment should resolve depression and phlegm， support the earth and free the wood； for syndrome of liver depression transforming into fire， the treatment should soothe liver and clear fire， resolve depression and dysphoria； for syndrome of qi stagnation and blood stasis， the treatment should activate blood and regulate the middle， resolve depression and tranquilise mind.

Objective:To observe the effects of Yiyuan moxibustion on bladder function and antioxidant level of spinal cord tissues in rats with urinary retention after spinal cord injury (SCI); To explore the mechanism of inhibition of ferroptosis in spinal cord neurons after SCI by Yiyuan moxibustion.Methods:Wistar female rats were divided into sham-operation group, model group, and Yiyuan moxibustion group according to random number table method, with 12 rats in each group. The modified Allen′s vertical percussion method was used to construct the model of urinary retention after SCI in T10 segment. The rats in the Yiyuan moxibustion group were moxibued at the Zhongji acupoint, Guanyuan acupoint, and Shenque acupoint for 20 min per day, and the intervention was continued for 2 weeks. Urodynamic test was used to observe the degree of urinary retention in rats; HE staining was used to observe the morphological changes of the injured spinal cord tissues; transmission electron microscopy was used to observe the mitochondrial ultrastructure of the spinal cord tissues; ferric ion kit was used to detect the ferric ion content of the spinal cord tissues; ELISA was used to detect the GSH and MDA contents of the spinal cord tissues of the rats; Western blot was used to measure the relative expressions of glutathione peroxidase 4 (GPX4) and solute carrier family 7 member 11 (SLC7A11) proteins in rat spinal cord tissue.Results:Compared with the model group, the basal and leakage point pressures of the bladder, and bladder compliance were significantly reduced in the Yiyuan moxibustion group ( P<0.05); the spinal cord tissue structure was restored and mitochondrial morphology improved; the levels of iron ions and MDA in spinal cord tissue decreased ( P<0.05), while the level of GSH increased ( P<0.05), and the relative expressions of GPX4 and SLC7A11 proteins increased ( P<0.05). Conclusion:Yiyuan moxibustion can improve bladder function in rats with urinary retention after SCI, and the mechanism may involve the initiation of antioxidant defense and reduction of lipid peroxidation in spinal cord neuronal cells, thus preventing the occurrence of ferroptosis and achieving the protection of neuronal cells.

BACKGROUND: Chronic kidney disease (CKD)-associated anemia (CKD-anemia) is associated with poor survival, and hemoglobin targets are often not achieved with current therapies. Phase 3 trials have demonstrated the treatment efficacy of roxadustat for CKD-anemia. This phase 4 study aims to evaluate the long-term (52-week) safety and effectiveness of roxadustat in a broad real-world patient population with CKD-anemia with and without dialysis in China. METHODS: This Phase 4 multicenter, open-label, prospective study, conducted from 24 November 2020 to 11 November 2022, evaluated the long-term safety and effectiveness of roxadustat for CKD-anemia in China. Patients aged ≥18 years with CKD-anemia with or without dialysis were included. The initial oral dose was 70-120 mg (weight-based followed by dose adjustment) over 52 weeks. The primary endpoint was safety based on adverse events (AEs). The secondary endpoints were hemoglobin changes from baseline and the proportion of patients who achieved mean hemoglobin ≥100 g/L. Effectiveness evaluable populations 1 (EE1) and EE2 included roxadustat-naïve and previously roxadustat-treated patients, respectively. The safety analysis set (SAF) included all patients who received ≥1 occasion. RESULTS: The EE1, EE2, and SAF populations included 1804, 193, and 2021 patients, respectively. In the SAF, the mean age was 50 ± 14 years, and 1087 patients (53.8%) were male. Mean baseline hemoglobin was 96.9 ± 14.0 g/L in EE1 and 100.3 ± 12.9 g/L in EE2. In EE1, the mean (95% confidence interval) hemoglobin changes from baseline over weeks 24-36 and 36-52 were 14.2 (13.5-14.9) g/L and 14.3 (13.5-15.0) g/L, respectively. Over weeks 24-36 and 36-52, 83.3% and 86.1% of patients in EE1 and 82.7% and 84.7% in EE2 achieved mean hemoglobin ≥100 g/L, respectively. In the SAF, 1643 (81.3%) patients experienced treatment-emergent AEs (TEAEs). Overall, 219 (10.8%) patients experienced drug-related TEAEs. Thirty-eight (1.9%) patients died of TEAEs (unrelated to the study drug). Vascular access thrombosis was uncommon. CONCLUSIONS: Roxadustat (52 weeks) increased hemoglobin and maintained the treatment target in Chinese patients with CKD-anemia with acceptable safety, supporting its use in real-world settings. REGISTRATION Chinese Clinical Trial Registry ( www.chictr.org.cn ) ChiCTR2100046322; CDE ( www.chinadrugtrials.org.cn ) CTR20201568.
Humans ; Male ; Female ; Anemia/etiology* ; Middle Aged ; Renal Insufficiency, Chronic/complications* ; Glycine/adverse effects* ; Isoquinolines/adverse effects* ; Aged ; Prospective Studies ; Adult ; Hemoglobins/metabolism* ; Treatment Outcome ; China ; Registries ; East Asian People

Objective:This study aims to investigate the relationship between high-risk human papillomavirus (HR-HPV) infection and the composition of vaginal microecology. It will analyze the efficacy of integrated traditional Chinese and Western medicine intervention in treating HR-HPV infection, as well as the effects of this combined approach on vaginal microecology. Additionally, the study seeks to identify new methods to inhibit the malignant progression of cervical intraepithelial lesions.Methods:A prospective study was conducted involving 100 patients with HR-HPV infection who visited the Department of Gynecology, The Second Affiliated Hospital of Shaanxi University of Chinese Medicine from April to June 2023. The participants were randomly divided into a control group and an observation group, with 50 patients in each group using a random number table method. The control group received interferon treatment, while the observation group was treated with a combination of interferon and Yanfukang Lotion. High-throughput DNA sequencing of vaginal secretions was conducted to compare the differences in pre- and post-treatment vaginal microecological composition and the rate of HR-HPV clearance between the two groups. Results:In the observation group, both the diversity index and the abundance of vaginal microecology showed significant improvements compared with the control group, particularly in the abundance of dominant Lactobacillus species. These differences were statistically significant ( R = 0.124, 0.304, 0.030, all P < 0.05). The rates of HR-HPV clearance and overall effective rate (clearance + effective) in the observation group were 44% (22/50) and 68% (34/50), respectively, which were significantly higher than those in the control group [20% (10/50), 32% (16/50), χ2 = 12.98, both P < 0.05). There was no statistically significant difference in the incidence of adverse reactions between the two groups (χ2 = 1.76, P > 0.05). Conclusion:The combination of interferon and Yanfukang Lotion effectively treats HR-HPV infection by regulating the composition of vaginal microecology. This approach shows considerable efficacy and good safety, indicating its potential for further clinical application.

Objective To explore the value of dual-phase enhanced CT radiomics in predicting post-acute pancreatitis diabetes mellitus(PPDM-A).Methods A total of 145 patients with acute pancreatitis(AP)were retrospectively collected,including 62 patients in PPDM-A group and 83 patients in non-PPDM-A group.The patients were randomly divided into training set and test set at a ratio of 7︰3,the pancreatic parenchyma in arterial phase and venous phase was delineated and the radiomics features were extracted.Vari-ance threshold method,univariate selection method and least absolute shrinkage and selection operator(LASSO)were used to screen radiomics features.The prediction performance of the model was evaluated by the area under the curve(AUC).The DeLong test was used to compare the prediction efficiency between the models,and the calibration curve and decision curve were used to evaluate the prediction efficiency of the model.Results The AUC of arterial phase model,venous phase model,combined arterial venous phase model,clinical model and radiomics combined clinical model in the training set were 0.845,0.792,0.829,0.656 and 0.862,respec-tively.The DeLong test results showed that only the difference between the radiomics combined clinical model and the clinical model in the training set and the test set was statistically significant(P<0.05).The decision curve showed that the radiomics combined clinical model had high clinical practicability in a certain range,and the calibration curve showed that the radiomics combined clinical model had the best fitting degree with the actual observation value.Conclusion Based on the dual-phase enhanced CT radiomics combined clinical model,PPDM-A can be predicted more accurately,and it can provide a certain reference value for the clinical development of per-sonalized treatment programs.

Objective:To investigate the effect of tofacitinib,a pan-Janus kinase(JAK)inhibitor,on transforming growth factor-beta 1(TGF-β1)-induced fibroblast to myofibroblast transition(FMT)and to explore its mechanism.To provide a theoretical basis for the clinical treatment of connective tissue disease-related interstitial lung disease(CTD-ILD).Methods:(1)Human fetal lung fibroblast 1(HFL-1)were cultured in vitro,and 6 groups were established:DMSO blank control group,TGF-β1 in-duction group,and TGF-β1 with different concentrations of tofacitinib(0.5,1.0,2.0,5.0 μmol/L)drug intervention experimental groups.CCK-8 was used to measure the cell viability,and wound-healing assay was performed to measure cell migration ability.After 48 h of combined treatment,quantitative real-time PCR(RT-PCR)and Western blotting were used to detect the gene and protein expression levels of α-smooth muscle actin(α-SMA),fibronectin(FN),and collagen type Ⅰ(COL1).(2)RT-PCR and enzyme-linked immunosorbnent assay(ELISA)were used to detect the interleukin-6(IL-6)gene and protein expression changes,respectively.(3)DMSO carrier controls,1.0 μmol/L and 5.0 μmol/L tofacitinib were added to the cell culture media of different groups for pre-incubation for 30 min,and then TGF-β1 was added to treat for 1 h,6 h and 24 h.The phosphorylation levels of Smad2/3 and signal transducer and activator of transcription 3(STAT3)protein were detected by Western blotting.Results:(1)Tofacitinib inhibited the viability and migration ability of HFL-1 cells after TGF-β1 induction.(2)The expression of α-SMA,COL1A1 and FN1 genes of HFL-1 in the TGF-β1-induced groups was signifi-cantly up-regulated compared with the blank control group(P＜0.05).Compared with the TGF-β1 in-duction group,α-SMA expression in the 5.0 μmol/L tofacitinib intervention group was significantly inhi-bited(P＜0.05).Compared with the TGF-β1-induced group,FN1 gene was significantly inhibited in each intervention group at a concentration of 0.5-5.0 μmol/L(P＜0.05).Compared with the TGF-β1-induced group,the COL1A1 gene expression in each intervention group did not change significantly.(3)Western blotting results showed that the protein levels of α-SMA and FN1 in the TGF-β1-induced group were significantly higher than those in the control group(P＜0.05),and there was no significant difference in the expression of COL1A1.Compared with the TGF-β1-induced group,the α-SMA protein level in the intervention groups with different concentrations decreased.And the differences between the TGF-β1-induced group and 2.0 μmol/L or 5.0 μmol/L intervention groups were statistically significant(P＜0.05).Compared with the TGF-β1-induced group,the FN1 protein levels in the intervention groups with different concentrations showed a downward trend,but the difference was not statistically sig-nificant.There was no difference in COL1A1 protein expression between the intervention groups com-pared with the TGF-β1-induced group.(4)After TGF-β1 acted on HFL-1 cells for 48 h,the gene ex-pression of the IL-6 was up-regulated and IL-6 in culture supernatant was increased,the intervention with tofacitinib partly inhibited the TGF-β1-induced IL-6 gene expression and IL-6 in culture supernatant.TGF-β1 induced the increase of Smad2/3 protein phosphorylation in HFL-1 cells for 1 h and 6 h,STAT3 protein phosphorylation increased at 1 h,6 h and 24 h,the pre-intervention with tofacitinib inhibited the TGF-β1-induced Smad2/3 phosphorylation at 6 h and inhibited TGF-β1-induced STAT3 phosphorylation at 1 h,6 h and 24 h.Conclusion:Tofacitinib can inhibit the transformation of HFL-1 cells into myofi-broblasts induced by TGF-β1,and the mechanism may be through inhibiting the classic Smad2/3 path-way as well as the phosphorylation of STAT3 induced by TGF-β1,thereby protecting the disease progres-sion of pulmonary fibrosis.

Objective:This study aims to investigate the relationship between high-risk human papillomavirus (HR-HPV) infection and the composition of vaginal microecology. It will analyze the efficacy of integrated traditional Chinese and Western medicine intervention in treating HR-HPV infection, as well as the effects of this combined approach on vaginal microecology. Additionally, the study seeks to identify new methods to inhibit the malignant progression of cervical intraepithelial lesions.Methods:A prospective study was conducted involving 100 patients with HR-HPV infection who visited the Department of Gynecology, The Second Affiliated Hospital of Shaanxi University of Chinese Medicine from April to June 2023. The participants were randomly divided into a control group and an observation group, with 50 patients in each group using a random number table method. The control group received interferon treatment, while the observation group was treated with a combination of interferon and Yanfukang Lotion. High-throughput DNA sequencing of vaginal secretions was conducted to compare the differences in pre- and post-treatment vaginal microecological composition and the rate of HR-HPV clearance between the two groups. Results:In the observation group, both the diversity index and the abundance of vaginal microecology showed significant improvements compared with the control group, particularly in the abundance of dominant Lactobacillus species. These differences were statistically significant ( R = 0.124, 0.304, 0.030, all P < 0.05). The rates of HR-HPV clearance and overall effective rate (clearance + effective) in the observation group were 44% (22/50) and 68% (34/50), respectively, which were significantly higher than those in the control group [20% (10/50), 32% (16/50), χ2 = 12.98, both P < 0.05). There was no statistically significant difference in the incidence of adverse reactions between the two groups (χ2 = 1.76, P > 0.05). Conclusion:The combination of interferon and Yanfukang Lotion effectively treats HR-HPV infection by regulating the composition of vaginal microecology. This approach shows considerable efficacy and good safety, indicating its potential for further clinical application.

Objective:To investigate the effect and possible mechanism of the X-ray radiation-induced abscopal effects (X-RIAEs) on the ovarian reserve of mice.Methods:Totally sixteen female C57BL/6J mice aged 6-8 weeks with regular estrous cycle were randomly divided into the sham group ( n=8) and irradiation group ( n=8). After anesthesia, the mice in the irradiation group were irradiated with 8 Gy X-ray on the local area of the chest every day for 3 d, while the mice in the sham group were not irradiated. After irradiation 21 d, the estrous cycle, serum hormones, serum pro-inflammatory factors, and ovarian morphological changes were detected. Ribonucleic acid sequencing (RNA-seq) was used to detect the expression of transcriptional levels in mouse ovarian tissues. The differentially expressed genes (DEGs) were screened and analyzed by gene ontology-biological process (GO_BP). Real-time quantitative polymerase chain reaction (RT-qPCR) verified the sequencing results. The expression and localization of spermatogenesis- and oogenesis-specific basic helix-loop-helix-containing protein 1 (SOHLH1) and neutrophil elastase (NE) in ovarian tissues were detected by immunohistochemistry (IHC). Results:Compared with mice in the sham group, the irradiation group had a disordered estrous cycle, reduced primordial follicles[10.50 (1.25, 12.75) vs. 60.00 (30.00, 90.25), P<0.001] and growing follicles [(4.50 (2.50, 9.00) vs. 18.50 (18.00, 20.75), P<0.001], significantly increased atretic follicles [56.00 (45.25, 98.75) vs. 12.50 (5.25, 20.25), P<0.001]. The levels of serum estradiol [(70.28±5.27) pmol/L] and anti-Müllerian hormone [(104.00±6.98) μg/L] in the irradiation group were significantly lower than those in the sham group [(97.58±7.25) pmol/L, P=0.016; (129.70±8.39) μg/L, P=0.046], but the follicle-stimulating hormone (FSH) level in the irradiation group was not significantly different from that in the sham group ( P>0.05). Compared with the sham group, the serum levels of TNF-α [(488.30±36.20) μg/L vs. (31.61±12.89) μg/L, P<0.001] and IL-1β [(62.37±2.50) μg/L vs. (52.75±2.06) μg/L, P=0.018] in the irradiation group were significantly increased, and the serum level of interleukin (IL)-6 in the irradiation group was also increased compared with the sham group, but the difference was not statistically significant ( P>0.05). The results of GO_BP analysis showed that the down-regulated DGEs were mainly involved in the process of follicular development, and the up-regulated DGEs were involved in the inflammation process. The results of RT-qPCR were consistent with those of sequencing. The immunohistochemistry results showed that the positive expression area of SOHLH1 in the irradiation group [(23.18±4.00)%] was significantly lower than that of the sham group [(65.90±6.28)%, P=0.005], while the positive expression area of NE [(30.73±4.00)%] was significantly higher than that of the sham group [(14.47±2.22)%, P=0.024]. Conclusion:X-RIAEs can induce an inflammatory reaction in ovarian tissue and inhibit the growth and development of ovarian follicles in mice, which leads to a decrease in ovarian reserve.

Objective:To investigate the effect and possible mechanism of the X-ray radiation-induced abscopal effects (X-RIAEs) on the ovarian reserve of mice.Methods:Totally sixteen female C57BL/6J mice aged 6-8 weeks with regular estrous cycle were randomly divided into the sham group ( n=8) and irradiation group ( n=8). After anesthesia, the mice in the irradiation group were irradiated with 8 Gy X-ray on the local area of the chest every day for 3 d, while the mice in the sham group were not irradiated. After irradiation 21 d, the estrous cycle, serum hormones, serum pro-inflammatory factors, and ovarian morphological changes were detected. Ribonucleic acid sequencing (RNA-seq) was used to detect the expression of transcriptional levels in mouse ovarian tissues. The differentially expressed genes (DEGs) were screened and analyzed by gene ontology-biological process (GO_BP). Real-time quantitative polymerase chain reaction (RT-qPCR) verified the sequencing results. The expression and localization of spermatogenesis- and oogenesis-specific basic helix-loop-helix-containing protein 1 (SOHLH1) and neutrophil elastase (NE) in ovarian tissues were detected by immunohistochemistry (IHC). Results:Compared with mice in the sham group, the irradiation group had a disordered estrous cycle, reduced primordial follicles[10.50 (1.25, 12.75) vs. 60.00 (30.00, 90.25), P<0.001] and growing follicles [(4.50 (2.50, 9.00) vs. 18.50 (18.00, 20.75), P<0.001], significantly increased atretic follicles [56.00 (45.25, 98.75) vs. 12.50 (5.25, 20.25), P<0.001]. The levels of serum estradiol [(70.28±5.27) pmol/L] and anti-Müllerian hormone [(104.00±6.98) μg/L] in the irradiation group were significantly lower than those in the sham group [(97.58±7.25) pmol/L, P=0.016; (129.70±8.39) μg/L, P=0.046], but the follicle-stimulating hormone (FSH) level in the irradiation group was not significantly different from that in the sham group ( P>0.05). Compared with the sham group, the serum levels of TNF-α [(488.30±36.20) μg/L vs. (31.61±12.89) μg/L, P<0.001] and IL-1β [(62.37±2.50) μg/L vs. (52.75±2.06) μg/L, P=0.018] in the irradiation group were significantly increased, and the serum level of interleukin (IL)-6 in the irradiation group was also increased compared with the sham group, but the difference was not statistically significant ( P>0.05). The results of GO_BP analysis showed that the down-regulated DGEs were mainly involved in the process of follicular development, and the up-regulated DGEs were involved in the inflammation process. The results of RT-qPCR were consistent with those of sequencing. The immunohistochemistry results showed that the positive expression area of SOHLH1 in the irradiation group [(23.18±4.00)%] was significantly lower than that of the sham group [(65.90±6.28)%, P=0.005], while the positive expression area of NE [(30.73±4.00)%] was significantly higher than that of the sham group [(14.47±2.22)%, P=0.024]. Conclusion:X-RIAEs can induce an inflammatory reaction in ovarian tissue and inhibit the growth and development of ovarian follicles in mice, which leads to a decrease in ovarian reserve.

Objective:To explore the therapeutic efficacy and toxicity of oral Etoposide chemotherapy in children with disseminated medulloblastoma (MB) after the standard treatment plan.Methods:The clinical data of 86 children with disseminated MB admitted in the Department of Pediatrics, Beijing Shijitan Hospital of Capital Medical University from January 2016 to May 2020 were analyzed retrospectively.The median age of children was 8.8 (3.0-16.7) years old.Among them, 33 children treated with maintenance chemotherapy via oral Etoposide were included in the chemotherapy group, and 53 children without oral maintenance chemotherapy were included in the non-chemotherapy group.The gender distribution, surgical resection range, pathological type, molecular classification, postoperative mutism, M-stage and survival[progression-free survival (PFS) and overall survival (OS)] of the 2 groups were compared.The main adverse events of oral Etoposide chemotherapy were recorded. Chi- square test is used for data comparison, Kaplan-Meier method was used to plot the survival curve of disseminated MB patients, followed by the Log- rank test. Results:There were no significant differences in gender, surgical resection range, pathological type, molecular typing, postoperative mutism and M-stage between the 2 groups (all P>0.05). Of 86 patients, the median PFS and OS were 3.0 (0.2-6.3) years, and 3.6 (0.5-6.3) years, respectively.Twenty five cases (29.1%) relapsed, 13 cases (15.1%) died.The 3-year[(65.8±6.8)% vs.(82.0±7.3)%] and 5-year PFS[(56.8±7.7)% vs.(82.0±7.3)%] in non-chemotherapy group were significantly lower than those of chemotherapy group ( P=0.037). The 3-year[(81.6±5.6)% vs.100.0%] and 5-year OS[(71.2±7.7)% vs.(92.3±7.4)%] in non-chemotherapy group were significantly lower than those of chemotherapy group ( P=0.025). Among the children with the SHH subtype, the PFS of children with oral Etoposide maintenance chemotherapy after a regular treatment was significantly higher than that without oral maintenance chemotherapy (100.0% vs.57.1%)( P=0.021). The major adverse events of oral Etoposide were myelosuppression and gastrointestinal symptoms, which were mostly relieved after a symptomatic treatment.Treatment-related deaths were not reported. Conclusions:The prognosis of disseminated MB in children is relatively poor.Oral Etoposide for maintenance therapy after a standard treatment is beneficial in reducing relapse and improving the 5-year survival, which is well tolerated.