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.

Objective:To explore the effectiveness and application value of focused ultrasound ablation surgery (FUAS) combined with hysteroscopic surgery in treating solitary type Ⅱ submucosal uterine fibroids with maximum diameter >5 cm.Methods:Clinical data of 35 patients with a single type Ⅱ submucosal uterine fibroid with maximum diameter greater than 5 cm who underwent FUAS combined with hysteroscopic surgery at Qingdao Women and Children′s Hospital from June 2020 to December 2023 were collected. The clinical characteristics, treatments and treatment outcomes were retrospectively analyzed.Results:(1) Clinical characteristics: the mean age of the 35 patients was (36.7±6.6) years, with a median maximum diameter of fibroids of 56 mm (range: 51-80 mm). All patients presented with symptoms of menorrhagia, median menstrual bleeding score was 5 points (ranged from 3 to 5 points), and 34 cases (97.1%, 34/35) had concomitant anemia, the mean hemoglobin was (83.1±13.8) g/L of 35 patients. (2) Treatments: all 35 patients underwent FUAS treatment initially, with a lesion ablation rate ranging from 69.7% to 97.9% (median:90.7%), and no complications occurred. After FUAS treatment, the volume of fibroids decreased in all patients, with a volume reduction rate ranging from 30.57% to 87.22% (median:76.03%). Hysteroscopic surgery was performed 3-14 months (median: 5 months) after FUAS to remove the necrotic fibroid tissue, achieving a 100.0% (35/35) fibroid resection rate. Only 1 patient developed complications of hyperhyderation syndrome during hysteroscopic surgery, and no complications occurred in the remaining patients. (3) Evaluation of efficacy: after FUAS pretreatment, the maximum diameter of fibroids in the 35 patients decreased significantly ( Z=-5.171, P<0.001), as did the volume of fibroids ( Z=-5.159, P<0.001). The hemoglobin level increased significantly compared to the level before FUAS in all cases ( t=-8.657, P<0.001), and median menstrual bleeding score decreased to 2 points (range: 1-3 points), significantly lower than original level ( Z=-5.292, P<0.001). At the 3-month follow-up after hysteroscopic surgery, all patients were free of anemia symptoms, with menstrual bleeding scores totally decreased to 1 point, significantly lower than that before hysteroscopic surgery ( Z=-4.786, P<0.001); hemoglobin level [(118.7±5.6) g/L] significantly increased compared to that before hysteroscopic surgery ( t=-9.258, P<0.001). All patients underwent gynecological transvaginal ultrasound re-examination, which did not reveal any residual fibroids. Conclusion:FUAS combined with hysteroscopic surgery is effective in treating solitary type Ⅱ submucosal uterine fibroids with maximum diameter >5 cm, providing a new treatment option for patients.

Objective:To explore the effectiveness and application value of focused ultrasound ablation surgery (FUAS) combined with hysteroscopic surgery in treating solitary type Ⅱ submucosal uterine fibroids with maximum diameter >5 cm.Methods:Clinical data of 35 patients with a single type Ⅱ submucosal uterine fibroid with maximum diameter greater than 5 cm who underwent FUAS combined with hysteroscopic surgery at Qingdao Women and Children′s Hospital from June 2020 to December 2023 were collected. The clinical characteristics, treatments and treatment outcomes were retrospectively analyzed.Results:(1) Clinical characteristics: the mean age of the 35 patients was (36.7±6.6) years, with a median maximum diameter of fibroids of 56 mm (range: 51-80 mm). All patients presented with symptoms of menorrhagia, median menstrual bleeding score was 5 points (ranged from 3 to 5 points), and 34 cases (97.1%, 34/35) had concomitant anemia, the mean hemoglobin was (83.1±13.8) g/L of 35 patients. (2) Treatments: all 35 patients underwent FUAS treatment initially, with a lesion ablation rate ranging from 69.7% to 97.9% (median:90.7%), and no complications occurred. After FUAS treatment, the volume of fibroids decreased in all patients, with a volume reduction rate ranging from 30.57% to 87.22% (median:76.03%). Hysteroscopic surgery was performed 3-14 months (median: 5 months) after FUAS to remove the necrotic fibroid tissue, achieving a 100.0% (35/35) fibroid resection rate. Only 1 patient developed complications of hyperhyderation syndrome during hysteroscopic surgery, and no complications occurred in the remaining patients. (3) Evaluation of efficacy: after FUAS pretreatment, the maximum diameter of fibroids in the 35 patients decreased significantly ( Z=-5.171, P<0.001), as did the volume of fibroids ( Z=-5.159, P<0.001). The hemoglobin level increased significantly compared to the level before FUAS in all cases ( t=-8.657, P<0.001), and median menstrual bleeding score decreased to 2 points (range: 1-3 points), significantly lower than original level ( Z=-5.292, P<0.001). At the 3-month follow-up after hysteroscopic surgery, all patients were free of anemia symptoms, with menstrual bleeding scores totally decreased to 1 point, significantly lower than that before hysteroscopic surgery ( Z=-4.786, P<0.001); hemoglobin level [(118.7±5.6) g/L] significantly increased compared to that before hysteroscopic surgery ( t=-9.258, P<0.001). All patients underwent gynecological transvaginal ultrasound re-examination, which did not reveal any residual fibroids. Conclusion:FUAS combined with hysteroscopic surgery is effective in treating solitary type Ⅱ submucosal uterine fibroids with maximum diameter >5 cm, providing a new treatment option for patients.

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.

Objective:To explore the effectiveness and safety of focused ultrasound ablation surgery (FUAS) for abdominal wall endometriosis.Methods:From November 2019 to October 2022, a total of 34 patients with abdominal wall endometriosis who underwent FUAS were collected, and their clinical features, imaging features, intraoperative treatment and side effects after treatment were analyzed retrospectively, and the improvement of symptoms and re-intervention were followed up.Results:(1) Characteristics of clinical data: the average age of 34 patients with abdominal wall endometriosis was (32.8±3.8) years old. The largest diameter of the lesion was 48 mm, and the median lesion diameter was 24 mm. Thirty cases (88%, 30/34) had moderate to severe periodic pain in abdominal incision before FUAS. All patients were diagnosed by preoperative magnetic resonance imaging, including 19 cases (56%, 19/34) of superficial type, 8 cases (24%, 8/34) of intermediate type and 7 cases (21%, 7/34) of deep type. (2) FUAS treatment parameters: ablation was completed with average operation time of (64±18) minutes, average sonication time was (385±108) s, (103±11) W of average power, (38 819±16 309) J of average total energy, the average treatment area volume of (3.11±1.42) cm 3, and (377.79±106.34) s/h of average treatment intensity. (3) Efficiency: the pain of patients after FUAS was significantly relieved, and the pain scores of patients after 1 month, 3 months, 6 months and 1 year after FUAS were significantly decreased ( Z=-4.66, -5.13, -5.11 and -4.91, all P<0.01). One year after FUAS, the near relief and effective pain relief rate was 74% (25/34), and the clinical effective rate was 85% (29/34). Five patients recurred after one year, including 3 patients who underwent abdominal wall endometriosis lesion resection and 2 patients who received drug treatment. One month after FUAS, the size of the lesion did not change significantly compared with that before FUAS ( P>0.05), and the size of the lesion decreased significantly after FUAS at 3 months, 6 months and 1 year ( Z=-2.15, -2.67 and -3.41, all P<0.05). It has no difference in pain relief among different types ( P>0.05), but has significant difference in focus reduction among three types ( P<0.01). (4) Safety: there were 34 cases (100%, 34/34) of skin burning sensation, 19 cases (56%, 19/34) of pain in the treatment area and 2 cases (6%, 2/34) of hematuria. All patients got better after corresponding treatments. Conclusion:FUAS is safe and effective for the treatment of abdominal wall endometriosis, which has clinical application value.

Objective To establish a model of combined injury of thermal radiation and blast wave of gas explosion in closed pipeline,and investigate the characteristics of important organ injury induced by burn-blast combined injury in rats.Methods A total of 72 male SD rats(aged 8～10 weeks,weighing 200～10 g)were randomly divided into control group and mild and severe injured groups.After the model rats were inflicted with blast wave and thermal radiation,their physical parameters were detected and measured.The respiratory function of the survival rats was tested.In 24 h later,arterial blood gas analysis,blood biochemical tests,and detection for serum inflammatory factors and lung injury related protein levels were performed,and the pathological changes in the lung tissue and trachea were observed.Results The peak range of explosive blast wave overpressure was 209～493 kPa,and the temperature was 152～258 ℃.The mortality rate was 8.3％in the mild group and 53.1％in the severe group.Compared with the control group,longer inspiratory time(Ti)and relaxation time(Tr)and larger tidal volume(TV)(P＜0.05),while lower respiratory frequency(f)were observed in the 2 injured groups within 6 h after injury(P＜0.05).At 24 h after injury,the values of partial pressure of carbon dioxide(PaCO2),residual base value(BE)and bicarbonate(HCO3-)were increased significantly(P＜0.05),while partial pressure of oxygen(PaO2)was decreased(P＜0.05).The serum levels of alanine transaminase(ALT),aspartate aminotransferase(AST),alkaline phosphatase(ALP),total bilirubin(TBI)and total bile acid(TBA)were notably elevated(P＜0.05).So were the levels of IL-1 β,TNF-α and IL-6(P＜0.01).Various severities of hyperemia foci and inflammation in the tracheal mucosa were observed in the injured rats.The incidence of lung injury was high,and the pathological manifestations were dot-shaped hemorrhage to diffuse hemorrhage of the whole lobe,rupture of alveolar septum,thickening of septum,and infiltration of red blood cells and inflammatory cells.The levels of serum lung injury-related proteins were significantly increased(P＜0.05).Conclusion A rat model which can highly simulate mild to severe burn-blast combined injury is constructed,which can meet the needs for rat model in study of explosive burn-blast compound injury.The main characteristics of the injury are lung injury,respiratory dysfunction,liver damage and secondary infection.

Our earlier research has shown that mono-substituted N-phenyl-2, 2-dichloroacetamide exhibited much higher anti-cancer activity than the lead compound sodium dichloroacetate (DCA). In this paper, a variety of multi-substituted N-phenyl-2, 2-dichloroacetamides were synthesized and biologically evaluated. The results showed that 3, 5-disubstituted N-phenyl-2, 2-dichloroacetamide analogues had satisfactory potency. Among them, N-(3, 5-diiodophenyl)-2, 2-dichloroacetamide had an IC50 of 2.84 micromol x L(-1) against non-small cell lung cancer cell line A549 and could induce cancer cell apoptosis.