Objective To evaluate the role of aquaporin 1(AQPI)expression in the cartiopulmonary bypass(CPB)-induced lung injury in dogs.Methods Twenty-four healthy dogs,weighing 15-20 kg,were randomly divided into 4 group(n =6 each):control group(group C),acetazolamide Ⅰ group(group A Ⅰ),acetazolamide Ⅱ group(group A Ⅱ),and acetazolarnide Ⅲ group(group AⅢ).Lung injury was produced by CPB.The traditional priming solution was infused in group C.Priming solutions containing acetaaolamide 20,40 and 60 mg/kgwere infused in groups A Ⅰ,A Ⅱ and A Ⅲ respectively.Blood samples were collected from the femoral artery before mechanical ventilation,at the end of CPB and at 1 h after end of CPB(T1-3)for arterial blood gas analysis.Respiration index(RI)and oxygenation index(OI)were calculated.The lung specimens were oblained for determination of AQPI mRNA and protein expression(by RT-PCR and Western blot)and for microscopic examination.The pathological changes of the lung were scored.Results Compared with group C,P(A-a)O2,RI and the pathological score were significantly increased at T2.3,OI was significantly decreased at T2.3,and AQP1 protein expression was down-regulated at T2.3 in groups A Ⅰ,A Ⅱ and AⅢ,and AQP1 mRNA expression was down-regulated at T2.3 in groups AⅡ and AⅢ(P＜0.05).Compared with group A Ⅰ,P(A-a)O2,RI and the pathological score were significantly increased at T2.3,OI was significantly decreased at T2.3,and AQP1 protein expression was down-regulated at T2.3 in groups A Ⅱ and AⅢ,and AQP1 mRNA expression was down-regulated at T2.3 ingroup A Ⅲ(P ＜ 0.05).Compared with group A Ⅱ,RI and the pathological score were significantly increased at T2.3,and AQP1 protein expression was down-regulated at T2.3 in group A Ⅲ(P ＜ 0.05).Conclutsion Down-regulation of AQPI expression is involved in the CPB-induced lung injury in dogs.

Objective To investigate the effect of lung ischemic preconditioning (IP) on the expression of aquaporin-1 (AQP1) during lung ischemia-reperfusion (I/R) induced by cardiopulmonary bypass (CPB) in dogs.Methods Twelve adult mongrel dogs,weighing 15-20 kg,were randomly divided into 2 groups (n =6 each):lung I/R (group I/R) and ischemic preconditioning group (group IP).The left pulmonary artery was occluded at 10 min of off-pump CPB and mechanical ventilation was stopped in the left lung,60 min later occlusion was released,and mechanical ventilation was recovered to establish the model of left lung ischemia-reperfusion injury induced by CPB.In group IP,lung ischemic preconditioning was induced by 2 cycles of 5 min ischemia followed by 5 min reperfusion before occlusion of the left pulmonary artery.Before CPB (T1),immediately after occlusion of the left pulmonary artery (T2),at the end of CPB (T3),and at 2 h after the end of CPB (T4),pulmonary specimens were collected for determination of wet to dry lung weight ratio (W/D ratio) and expression of AQP1 and for examination of the pathological changes of lungs which were scored.Respiration index (RI),oxygenation index (OI),and alveolar-arterial oxygen tension difference (P(A-a)O2) were calculated at T1,T3 and T4,and the left pulmonary alveolar fluid clearance (AFC) was calculated at T4.Results Compared with group I/R,P(A-a) O2 and RI were significantly decreased,OI was increased,W/D ratio and pathological scores were decreased,the expression of AQP1 was up-regulated,and the AFC was increased at T3 and T4 in group IP.The pathological changes of the lung were significantly attenuated in group IP as compared with group I/R.Conclusion The mechanism by which lung ischemic preconditioning mitigates lung I/R injury induced by CPB is related to upregulation of the expression of AQP1 in dog lung tissues.

Objective To evaluate the effects of modified ultrafiltration on the expression of aquaporin 1 (AQP1) in cardiopulmonary bypass (CPB)-induced lung injury in dogs.Methods Eighteen healthy adult dogs of either sex,weighing 15-20 kg,were randomly divided into 3 groups (n =6 each):control group (group C),group CPB and modified ultrafiltration group (group MUF).The dogs were anesthetized with intraperitoneal 2.5％pentobarbital 25 mg/kg.Thoracotomy was performed in all the three groups and in addition lung injury was produced by CPB in CPB and MUF groups.In group MUF,modified ultrafiltration was performed at 10-15 min after termination of CPB.Arterial blood samples were collected before mechanical ventilation (T1),at end of CPB (T2),and at 1 h after termination of CPB (T3) to calculate respiration index (RI) and oxygenation index (OI).The lungs were removed for microscopic examination of pathologic changes in lung tissues under light microscope and for detection of AQP1 mRNA expression by real-time PCR.Results RI and OI were significantly higher and AQP1 mRNA expression was lower at T2 and T3 than at T1 in CPB and MUF groups (P ＜ 0.05).Compared with group C,RI was significantly increased and AQP1 mRNA expression was down-regulated at T2,3 in CPB and MUF groups,and OI at T2.3 in CPB group and at T2 in MUF group was decreased (P ＜ 0.05).Compared with group CBP,RI was significantly decreased,OI was increased and AQP1 mRNA expression was up-regulated at T3 in group MUF (P ＜ 0.05).Conclusion Modified ultrafiltration can reduce CPB-induced lung injury in dogs and upregulation of AQP1 may be involved in the mechanism.

Objective To evaluate the role of PI3K∕Akt signaling pathway in dexmedetomidine-in-duced reduction of lung ischemia-reperfusion ( I∕R ) injury in rats undergoing cardiopulmonary bypass (CPB). Methods Twenty-four healthy adult male Sprague-Dawley rats, weighing 350-450 g, were di-vided into 3 groups (n＝8 each) using a random number table method: group I∕R, dexmedetomidine group ( group D) and dexmedetomidine plus wortmannin group (group D+W). Rats were anesthetized with pento-barbital sodium. Lung I∕R was induced by clamping the left hilum of lung for 60 min starting from 10 min of CPB, followed by 120-min reperfusion. Dexmedetomidine was injected via the tail vein in a dose of 3 μg∕kg at 10 min before clamping the left hilum of lung, followed by a continuous infusion of 1. 5 μg·kg-1·h-1 until the end of CPB in group D. Dexmedetomidine was injected via the tail vein in a dose of 3 μg∕kg at 10 min before clamping the left hilum of lung, followed by a continuous infusion of 1. 5 μg·kg-1·h-1until the end of CPB, and wortmannin was simultaneously injected via the tail vein in a dose of 15 μg∕kg, fol-lowed by a continuous infusion of 2. 0 μg·kg-1·min-1until the end of CPB in group D+W. Arterial blood samples were collected immediately before CPB ( T1), immediately after opening the left hilum of lung (T2) and at 1. 5 h after the end of CPB (T3), and oxygenation index (OI) and respiratory index (RI) were calculated. The rats were sacrificed at T3, and the left lung was removed for examination of the patho-logical changes which were scored and for determination of apoptosis rate ( by flow cytometry) and Akt, Bad, activated caspase-3, phosphorylated Akt ( p-Akt) and phosphorylated Bad ( p-Bad) in lung tissues ( by Western blot). Results Compared with the baseline at T1, OI was significantly decreased and RI was increased at T2and T3in the three groups (P＜0. 05). OI was significantly decreased and RI was increased at T3than at T2in the three groups ( P＜0. 05). Compared with group I∕R, OI was significantly increased and RI was decreased at T3, the pathological damage score and apoptosis rate were decreased, ratios of p-Akt∕Akt and p-Bad∕Bad were increased, and the expression of activated caspase-3 was down-regulated in group D, and OI was significantly decreased and RI was increased at T2in group D+W ( P＜0. 05). Com-pared with group D, OI was significantly decreased and RI was increased at T3, the pathological damage score and apoptosis rate were increased, ratios of p-Akt∕Akt and p-Bad∕Bad were decreased, and the ex-pression of activated caspase-3 was up-regulated in group D+W ( P＜0. 05). Conclusion Dexmedetomi-dine can reduce dexmedetomidine-induced reduction of lung I∕R injury through activating PI3K∕Akt signa-ling pathway and inhibiting cell apoptosis in rats undergoing CPB.

Objective:To investigate the influence of clinical administration of dobutamine on blood perfusion in free flap repair of diabetic foot wounds.Methods:A prospective self‐controlled study was conducted. From January to November 2022, 20 patients with diabetic foot who met the inclusion criteria were hospitalized in the Department of Burns and Plastic Surgery of Affiliated Hospital of Zunyi Medical University, including 9 males and 11 females, aged from 44 to 75 years, with the foot wounds area ranging from 5 cm×4 cm to 20 cm×10 cm, which were repaired by free anterolateral thigh flaps. Heart rate (HR) and mean arterial pressure (MAP) were recorded before anesthesia induction, 10 minutes after vascular recanalization, when the target blood pressure (i.e., MAP being 6-10 mmHg (1 mmHg=0.133 kPa) higher than that before anesthesia induction) was reached after infusion of dobutamine, and 10 minutes after tracheal catheter removal. Additionally, indocyanine green, a contrast agent, was injected intravenously at 10 minutes after vascular recanalization and when the target blood pressure was reached after infusion of dobutamine to assess flap blood perfusion using infrared imager, and the area ratio of flaps with hyperperfusion and hypoperfusion was calculated. Other recorded variables included flap harvesting area, surgical duration, total fluid infusion amount, infusion dose and total usage of dobutamine, intraoperative adverse events, postoperative flap complications, and follow‐up outcomes. Data were statistically analyzed with paired sample t test, analysis of variance for repeated measurement, Bonferroni method, and generalized estimating equation. Results:Compared with those before anesthesia induction, HR and MAP of patients were significantly decreased at 10 minutes after vascular recanalization ( P<0.05), while HR and MAP of patients were significantly increased when the target blood pressure was reached after infusion of dobutamine ( P<0.05). Compared with those at 10 minutes after vascular recanalization, HR and MAP of patients were significantly increased when the target blood pressure was reached after infusion of dobutamine and at 10 minutes after tracheal catheter removal ( P<0.05). Compared with those when the target blood pressure was reached after infusion of dobutamine, HR and MAP of patients were significantly decreased at 10 minutes after tracheal catheter removal ( P<0.05). The area ratio of flaps with hyperperfusion of patients was 0.63±0.11 when the target blood pressure was reached after infusion of dobutamine, which was significantly higher than 0.31±0.09 at 10 minutes after vascular recanalization ( t=-9.92, P<0.05). The area ratio of flaps with hypoperfusion of patients was 0.12±0.05 when the target blood pressure was reached after infusion of dobutamine, which was significantly lower than 0.45±0.10 at 10 minutes after vascular recanalization ( t=17.05, P<0.05). The flap harvesting area of patients was (174±35) cm2, the surgical duration was (372±52) min, the total fluid infusion amount was (2 485±361) mL, the infusion dose of dobutamine was 3-13 μg·kg?1·min?1, and the total usage of dobutamine was 5.7 (2.1, 9.7) mg. Two patients showed a significant increase in MAP during the infusion of dobutamine compared with that at 10 minutes after vascular recanalization, but before reaching 6 mmHg higher than that before anesthesia induction, their HR had reached the maximum (over 130 beats/min). The HR gradually returned to around 90 beats/min after the infusion of dobutamine was stopped. On post operation day 2, one patient had partial necrosis at the distal part of the flap, which was repaired by transplantation of thin split-thickness skin graft from the opposite thigh. During the follow‐up of 3 to 6 months after operation, all the flaps survived well, with soft texture and well-formed shape, and no adverse cardiovascular events of patients were reported. Conclusions:The administration of dobutamine in free flap repair of diabetic foot wounds can significantly improve the MAP of patients, expand the area of hyperperfusion, reduce the area of hypoperfusion, and enhance the flap viability, with promising short‐term follow‐up results, which is suitable for promotion in clinical applications.

Objective To evaluate the effects of pretreatment with exogenous insulin-like growth factor-1 (IGF-1) on lung injury in rats undergoing cardiopulmonary bypass (CPB).Methods Seventy-two SPF healthy male Sprague-Dawley rats,weighing 350-500 g,were divided into 4 groups (n =18 each) using a random number table:sham operation group (group S),CPB group,CPB plus left lung ischemia-reperfusion group (group LI) and IGF-1 group.The chest was only opened,and the rats underwent no CPB in group S.Only the CPB model was established in group CPB.The model of left lung ischemia-reperfusion injury was established based on the CPB model in group LI.The model of CPB and left lung ischemia-reperfusion injury was established,and IGF-1 30 μg/kg was intravenously injected at 10 min before clamping the hilum of lung and immediately after opening the hilum of lung in group IGF-1.Six rats were selected before operation (T1),10 min after opening the left hilum (T2) and at the end of operation (T3),and blood samples were collected from the femoral artery for blood gas analysis.The oxygenation index (OI) and respiratory index (RI) were calculated.Serum was obtained from blood,and the concentrations of interleukin-6 (IL-6),IL-1β and tumor necrosis factor-alpha (TNF-α) in serum were measured using enzyme-linked immunosorbent assay.The left upper lung tissues were removed for examination of the pathological changes which were scored with a light microscope.Results Compared with the baseline at T1,OI was significantly decreased,and RI,concentrations of IL-6,IL-1β and TNF-α in serum and pathological scores of lung tissues were increased at T3 in CPB,LI and IGF-1 groups (P＜0.05).Compared with group S,OI was significantly decreased,and RI,concentrations of IL-6,IL-1β and TNF-α in serum and pathological scores of lung tissues were increased at T3 in CPB,LI and IGF-1 groups (P＜0.05).Compared with group CPB,OI was significantly decreased,and RI,concentrations of IL-6,IL-1β and TNF-α in serum and pathological scores of lung tissues were increased at T3 in group LI (P＜0.05).Compared with group LI,OI was significantly increased,RI,concentrations of IL-6 and IL-1β in serum and pathological scores of lung tissues were decreased at T3,and the concentration of serum TNF-α was increased at T3 in group IGF-1 (P＜0.05).Conclusion IGF-1 pretreatment can reduce lung injury in rats undergoing CPB,and the mechanism is related to inhibiting inflammatory responses.

Objective To study the medication law of Professor Qian Ying in the treatment of primary liver cancer based on data mining technology;To provide ideas for the clinical treatment of primary liver cancer.Methods Outpatient TCM prescriptions of Professor Qian Ying for the treatment of liver cancer from November 2008 to August 2020 were collected,and a data table was established after sorting.The drug frequency,property and taste and tropism were analyzed using Excel 2019.The medical case analysis module of the Great Physician Inheritance Platform was used to analyze the core drugs,the symbiosis analysis between drug pairs,the drug association analysis,and the drug clustering analysis of the screened TCM prescriptions.Results Totally 108 prescriptions were included,involving 188 kinds of Chinese materia medica,with a total frequency of 1 322 times.High-frequency drugs included Hedyotis Sinensis,Angelicae Sinensis Radix,Visci Herba,Curcumae Radix,Salviae Miltiorrhizae Radix et Rhizoma,etc.The medicinal properties were mainly cold,mild and warm,and the tastes were mainly bitter,sweet and pungent,and the main meridians were liver meridians,spleen meridians,kidney meridians and stomach meridians.There were 9 pairs of high frequency drug combinations in drug association,such as Curcumae Radix-Polygoni Orientalis Fructus,Visci Herba-Curcumae Rhizoma.In the correlation analysis of drug disease,the ones with higher correlations include"stomachache-Salviae Miltiorrhizae Radix et Rhizoma""abdominal mass-Paeoniae Radix Rubra and Citri Reticulatae Pericarpium""tinnitus-Adenophorae Radix,Lycii Fructus,Visci Herba""prolonged sublingual collaterals-Curcumae Rhizoma,Polygoni Orientalis Fructus,Salviae Miltiorrhizae Radix et Rhizoma"and so on.Drug clustering could be divided into three potential drug clusters.Conclusion Professor Qian Ying often uses heat-clearing drugs,tonifying drugs,and promoting qi and blood circulation drugs to treat liver cancer,with Huqi Powder as the main formula and modified according to the syndromes.Clearing heat and detoxifying,soothing liver and relieving depression,removing blood stasis and regulating collatrals are used to treat its symptoms,and tonifying qi and invigorating spleen,regulating liver and nourishing liver and kidney are used to treat its essence.