Background:To compare the efficacy and safety of monthly administrations of gonadotropin releasing hormone (GnRH) agonists LY01005 and Zoladex ? in Chinese patients with premenopausal breast cancer. Methods:From October 2020 to November 2021, 188 premenopausal breast cancer patients were enrolled in 34 hospitals and randomized 1:1 to receive either LY01005 or Zoladex ? every 28 days for a total of three injections. All patients concomitantly received oral tamoxifen (TAM). The primary efficacy endpoint was cumulative probability of maintaining menopausal level [oestradiol (E2) ≤30 pg/ml] from day 29 to day 85. The second efficacy endpoint included changes in E2, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) compared with the baseline. Pharmacokinetics (PK), pharmacodynamics (PD), and safety were analyzed. The study also evaluated the pharmacokinetic and pharmacodynamic characteristics of LY01005. Results:A total of 188 patients were randomised and 187 patients received either LY01005 or Zoladex ?. Cumulative probabilities of maintaining menopausal level (E2≤30 pg/ml) from day 29 to day 85 were 93.1% for LY01005 and 86.3% for Zoladex ?. The between-group difference was 6.8% (95% CI: -2.3%, 15.9%) and primary efficacy in the LY01005 group was not inferior to that in the Zoladex ? group. Changes in E2, LH, and FSH levels compared with the baseline were equivalent between the two groups (E2: 89.34% to 90.23% vs. 82.11% to 85.02%; LH: 88.89% to 95.52% vs. 89.70% to 97.02%; FSH: 75.36% to 80.85% vs.73.07% to 80.24%, respectively). After three consecutive doses of LY01005, the LH and FSH levels of the subjects showed a transient increase after the first dose, reached a peak on the second day and then started to decrease. The LH and FSH reached a lower level and remained at or below that level until the 85th day. Both treatments were well-tolerated. Conclusion:LY01005 is as effective as Zoladex ? in suppressing E2 to menopausal levels in Chinese patients with premenopausal breast cancer, with a similar safety profile.

AIM:To study the protective effect of transient receptor potential vanilic acid subtype 1(TRPV1)agonist capsaicin(CAP)on traumatic blood loss shock rats,and to further explore its possible mechanism by network pharmacology.METHODS:Forty-five SD rats were divided into 5 groups by random number table method:normal group,shock group,lactated Ringer's solution(LR)group,CAP pretreatment(single administration before shock)group,CAP pre-final administration(twice administration before and after shock)group,with 9 rats in each group for survival observation.Then 32 SD rats were divided into 4 groups according to the results of survival experiment:normal group,shock group,LR group,CAP pre-final administration group,with 8 rats in each group for blood pressure,hemodynamics,arterial blood gas,vascular reactivi-ty and hepaticand renal blood flow.At the same time,the potential mechanism of CAP in the treat-ment of traumatic hemorrhagic shock was investi-gated by network pharmacology.Furthermore,ap-ply the dataset to validate and analyse the diagnos-tic value of the hub genes.RESULTS:Rats in shock group died within hours of the completion of the shock model,and the mean survival time was 1.25(0.42,6.21)h.LR resuscitation could improve the survival of rats to some extent.The survival rate and survival time of rats in the CAP pretreatment group were slightly increased as compared with the LR group,while twice administration of CAP be-fore and after shock(CAP pre-final administration)resulted in better outcomes than LR resuscitation alone.Further results indicated that CAP pre-final administration significantly reduced the blood lac-tic acid level,improved the vasoconstrictive and di-astolic reactivity,and increased the liver and kidney blood flow of shock rats as compared with LR group.The improvement of hemodynamics and blood gas indexes in CAP group was slightly higher than LR group,but there was no statistical signifi-cance.A total of 37 genes related to CAP anti-trau-matic hemorrhage shock were obtained by net-work pharmacology.KEGG enrichment analysis showed that the Ca ion signaling pathway and Ras signaling pathway were significantly enriched.Vali-dation of the dataset showed that the expression levels of CXCR4,NF-kB1,GFPA and NTF3 hub gene were significantly different in the normal and shock groups,and that CXCR4 has a high diagnostic value for traumatic haemorrhagic shock.CONCLUSIONS:CAP,the TRPV1 agonist,significantly improved vas-cular function,increased organ blood flow,and cor-rected the lactic acidosis in rats with traumatic hemorrhagic shock,thus markedly improved the survival outcomes.The mechanism may be related to Ca ion signal pathway and Ras signal pathway.CXCR4,NF-kB1,GFPA and NTF3 may be having an important role in it.

AIM:To study the protective effect of transient receptor potential vanilic acid subtype 1(TRPV1)agonist capsaicin(CAP)on traumatic blood loss shock rats,and to further explore its possible mechanism by network pharmacology.METHODS:Forty-five SD rats were divided into 5 groups by random number table method:normal group,shock group,lactated Ringer's solution(LR)group,CAP pretreatment(single administration before shock)group,CAP pre-final administration(twice administration before and after shock)group,with 9 rats in each group for survival observation.Then 32 SD rats were divided into 4 groups according to the results of survival experiment:normal group,shock group,LR group,CAP pre-final administration group,with 8 rats in each group for blood pressure,hemodynamics,arterial blood gas,vascular reactivi-ty and hepaticand renal blood flow.At the same time,the potential mechanism of CAP in the treat-ment of traumatic hemorrhagic shock was investi-gated by network pharmacology.Furthermore,ap-ply the dataset to validate and analyse the diagnos-tic value of the hub genes.RESULTS:Rats in shock group died within hours of the completion of the shock model,and the mean survival time was 1.25(0.42,6.21)h.LR resuscitation could improve the survival of rats to some extent.The survival rate and survival time of rats in the CAP pretreatment group were slightly increased as compared with the LR group,while twice administration of CAP be-fore and after shock(CAP pre-final administration)resulted in better outcomes than LR resuscitation alone.Further results indicated that CAP pre-final administration significantly reduced the blood lac-tic acid level,improved the vasoconstrictive and di-astolic reactivity,and increased the liver and kidney blood flow of shock rats as compared with LR group.The improvement of hemodynamics and blood gas indexes in CAP group was slightly higher than LR group,but there was no statistical signifi-cance.A total of 37 genes related to CAP anti-trau-matic hemorrhage shock were obtained by net-work pharmacology.KEGG enrichment analysis showed that the Ca ion signaling pathway and Ras signaling pathway were significantly enriched.Vali-dation of the dataset showed that the expression levels of CXCR4,NF-kB1,GFPA and NTF3 hub gene were significantly different in the normal and shock groups,and that CXCR4 has a high diagnostic value for traumatic haemorrhagic shock.CONCLUSIONS:CAP,the TRPV1 agonist,significantly improved vas-cular function,increased organ blood flow,and cor-rected the lactic acidosis in rats with traumatic hemorrhagic shock,thus markedly improved the survival outcomes.The mechanism may be related to Ca ion signal pathway and Ras signal pathway.CXCR4,NF-kB1,GFPA and NTF3 may be having an important role in it.

Background:To compare the efficacy and safety of monthly administrations of gonadotropin releasing hormone (GnRH) agonists LY01005 and Zoladex ? in Chinese patients with premenopausal breast cancer. Methods:From October 2020 to November 2021, 188 premenopausal breast cancer patients were enrolled in 34 hospitals and randomized 1:1 to receive either LY01005 or Zoladex ? every 28 days for a total of three injections. All patients concomitantly received oral tamoxifen (TAM). The primary efficacy endpoint was cumulative probability of maintaining menopausal level [oestradiol (E2) ≤30 pg/ml] from day 29 to day 85. The second efficacy endpoint included changes in E2, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) compared with the baseline. Pharmacokinetics (PK), pharmacodynamics (PD), and safety were analyzed. The study also evaluated the pharmacokinetic and pharmacodynamic characteristics of LY01005. Results:A total of 188 patients were randomised and 187 patients received either LY01005 or Zoladex ?. Cumulative probabilities of maintaining menopausal level (E2≤30 pg/ml) from day 29 to day 85 were 93.1% for LY01005 and 86.3% for Zoladex ?. The between-group difference was 6.8% (95% CI: -2.3%, 15.9%) and primary efficacy in the LY01005 group was not inferior to that in the Zoladex ? group. Changes in E2, LH, and FSH levels compared with the baseline were equivalent between the two groups (E2: 89.34% to 90.23% vs. 82.11% to 85.02%; LH: 88.89% to 95.52% vs. 89.70% to 97.02%; FSH: 75.36% to 80.85% vs.73.07% to 80.24%, respectively). After three consecutive doses of LY01005, the LH and FSH levels of the subjects showed a transient increase after the first dose, reached a peak on the second day and then started to decrease. The LH and FSH reached a lower level and remained at or below that level until the 85th day. Both treatments were well-tolerated. Conclusion:LY01005 is as effective as Zoladex ? in suppressing E2 to menopausal levels in Chinese patients with premenopausal breast cancer, with a similar safety profile.

AIM: To investigate the relationship between vascular smooth muscle cell (VSMC) injury, organelle stress response and autophagic cell death (autophagy) and ferroptosis induced by the chemical hypoxia inducer cobalt chloride (CoCl2) through the bioinformatics analysis and in vitro cell experimentation. METHODS: The dataset GSE119226 of VSMC treated with cobalt chloride was acquired from the gene expression database (GEO). The R language was used to investigate the relationship between CoCl2 treatment and organelle stress response (Golgi stress, endoplasmic reticulum stress) and two forms of cell death (ferroptosis and autophagic cell death). With primary cultured rat VSMC (rVSMC) and CoCl2-induced anoxia model, the changes in cell viability were detected by CCK-8 method, and reactive oxygen species (ROS) levels were measured using DCFH-DA method. The expression levels of HIF-1α (a key molecule in hypoxia), Golgi stress markers GM130 and p115, endoplasmic reticulum stress markers GRP78 and CHOP, autophagy markers LC3-II / LC3-I and Beclin1, and ferroptosis markers GPx4 and xCT were detected by Western blot. The effect of inducing or inhibiting organelle stress and cell death on the CoCl2-induced cell damage was also observed. RESULTS: Differentially expressed genes analysis of GSE119226 dataset showed that CoCl2 treatment of VSMCs had significant effects on organelle function and stress response, autophagy and ferroptosis-related genes, in which endoplasmic reticulum stress, protein processing in endoplasmic reticulum, regulation of Golgi to plasma membrane protein transport, autophagy / autophagic cell death, and ferroptosis pathways were remarkably enriched. The results of in vitro experiment showed that compared with normal rVSMC, cell viability was significantly decreased after CoCl2 treatment, as well as HIF-1α protein expression and ROS levels in rVSMCs were increased. In rVSMC treated with Co-Cl2, the expression levels of Golgi structural proteins GM130 and p115 (reflecting the occurrence of Golgi stress) were decreased, while the markers GRP78 and CHOP (reflecting the occurrence of endoplasmic reticulum stress) were increased. At the same time, CoCl2 treatment also reduced the expression of autophagy markers LC3-II/LC3-I and Beclin1 (indicating the decrease levels of autophagy), while the expression of ferroptosis markers GPx4 and xCT were decreased (indicating the occurrence of ferroptosis). Compared with CoCl2 treatment group, induced Golgi stress, endoplasmic reticulum stress, or ferroptosis could further reduce cell viability, while inhibition of these processes could improve cell viability. On the other hand, increasing the level of autophagy can improve the cell viability. CONCLUSION: Hypoxia induced by cobalt chloride can lead to VSMC injury. Golgi stress, endoplasmic reticulum stress, ferroptosis, and the reduction of autophagy level play an important role in it. Inhibition of organelle stress response and ferroptosis, or increase of autophagy level can improve VSMC injury caused by cobalt chloride.

OBJECTIVE To evaluate the efficacy of intranasal branches neurotomy of vidian nerve in the treatment of persistent moderate to severe allergic rhinitis. METHODS Cases diagnosed as persistent moderate-severe allergic rhinitis in our department were collected. those treated with branches neurotomy of vidian nerve were selected as the treatment group,and those treated with conservative medicine were selected as the control group. The visual analogue scale(VAS),rhinoconjunctivitis quality of life questionnaire(RQLQ),Nitric oxide in nose(nNO) and medication score evaluation of two groups of cases were evaluated respectively short-term(<1 year),medium-term(1 to 3 years) and long-term prognosis of outcome(3 to 5 years). RESULTS The short-term,mid-term and long-term postoperative VAS(2.26±0.75,2.30±0.63,2.49±0.57),RQLQ(0.55±0.11,0.55±0.11,1.00±0.12),nNO[(464.62±75.84)ppb,(378.63±110.21)ppb,(368.23±104.25)ppb]and medication scores (2.50±1.03,2.54±0.99,2.95±0.93) were significantly lower than those before operation[6.76±0.58,3.35±0.40,(696.64±132.69)ppb,5.17±1.50)]. The VAS,RQLQ,nNO and medication scores of the control group were lower than those of the control group at the corresponding time points(all P<0.05). One patient developed blindness in the right eye after interventional treatment due to epistaxis 21 days after operation,but no serious complications directly related to intranasal branches neurotomy of vidian nerve occurred. CONCLUSION The branches neurotomy of vidian nerve have a positive outcome in short,medium and long-term for persistent moderate to severe allergic rhinitis,the operation is safe and effective.

Animals ; Ctenophora ; Nervous System ; Neurons

Humans ; Neuroinflammatory Diseases ; COVID-19/complications* ; Brain

Objective:To investigate the effects of endocrine drugs on tumor markers and endometrium after breast cancer surgery.Methods:Eighty-eight patients with endocrine therapy for breast cancer admitted to the Heping Hospital Affiliated to Changzhi Medical College from November 2018 to March 2022 were selected, 44 patients taken orally tamoxifen citrate tablets were enrolled in the study group, 44 patients taken orally anastrozole tablets were enrolled in the control group, the patients in the two groups were treated for 12 months. The tumor markers, endometrial thickness were compared between the two groups before treatment and 12 months after treatment. The drug safety was compared too.Results:After treatment, the serum levels of carcinoembryonic antigen (CEA), carbohydrate antigen 125 (CA125) and glycochain antigen 15-3 (CA15-3) in both groups were decreased, and the level of tumor markers in the study group were lower than those in the control group: (3.01 ± 0.23) μg/L vs.(3.89 ± 1.15) μg/L, (4.22 ± 1.21) kU/L vs. (7.38 ± 2.19) kU/L, (16.76 ± 2.19) kU/L vs. (19.87 ± 2.21) kU/L, there were statistical differences ( P<0.05). The endometrial thickness in the study group at 6 months and 12 months after treatment were higher than those in the control group: (7.23 ± 0.22) mm vs. (6.21 ± 0.19)mm, (7.98 ± 0.24) mm vs. (6.47 ± 0.22) mm, there were statistical differences ( P<0.05). At 12 months after treatment, the scores of functional dimension, emotional dimension, social/family dimension and physical dimension in functional assessment of cancer therapy (FACT-G) scale in the study group were significantly higher than those in the control group ( P<0.05). There was no statistically significant difference in adverse reactions between the two groups ( P>0.05). Conclusions:Tamoxifen citrate tablets can effectively inhibit the levels of serum tumor markers and improve the quality of life of patients, and anastrozole tablets can significantly reduce the endometrial thickness of breast cancer patients.

Objective:To explore the effect of hyperbaric oxygen (HBO) therapy on the healing of the skin flap, the vascular endothelial growth factor (VEGF) and hypoxia inducing factor-1α (HIF-1α) after modified radical mastectomy.Methods:A total of 132 patients with breast cancer admitted in the Department of Breast Surgery of Heping Hospital Affiliated to Changzhi Medical College from January 2017 to June 2019 were selected as the research subjects and randomly divided into control group ( n=66) and observation group ( n=66). The control group was given the modified radical mastectomy, while the observation group was additionally given hyperbaric oxygen therapy. The postoperative healing condition of incision flap, including healing time, drainage volume, and pain score, was compared between two groups. And the serum VEGF and HIF-1α levels of patients in the two groups were compared before and after the treatment. Besides, postoperative complications were also observed. Results:The healing time of the skin flap in the observation group with HBO [(10.43±0.96) d] was significantly shorter than that in the control group [(13.81±1.15) d]. The drainage volume of the observation group was (274.01±13.10) ml, and the visual analogue scale (VAS) were (4.02±0.34) and (2.84±0.30) on the first and the third day after the operation respectively. The healing condition and VAS scores of the observation group were both better than those in the control group, and all the differences were statistically significant ( P<0.05). Serum VEGF and HIF-1α levels in the observation group were (809.67±40.22) pg/ml and (243.71±22.84) pg/ml respectively, which were significantly improved compared with those before the treatment and those of the control group, and all the differences were statistically significant ( P<0.05). The incidence of postoperative complications in the observation group (3.03%) was lower than that of the control group (10.61%). Conclusion:The hyperbaric oxygen therapy has a significant clinical effect on the patient after the modified radical mastectomy. It can accelerate skin flap healing, relieve patients’ pain, and promote prognosis by reducing HIF-1α level and increasing VEGF content.