BACKGROUND:Croton cream can activate ERK pathways and have anti-apoptotic effects on neuronal cells.It is not clear whether it synergistically exerts anti-apoptotic effects by inhibiting the activation of JNK and p38 pathways. OBJECTIVE:To explore the effects and mechanisms of croton cream on neuronal damage and apoptosis in the ischemic cortex of rats with cerebral ischemia-reperfusion injury. METHODS:(1)Ninety Sprague-Dawley rats were randomly divided into sham operation group,model group,croton cream low-dose group,croton cream medium-dose group,croton cream high-dose group and nimodipine group,with 15 rats in each group.Except for the sham operation group,animal models of middle cerebral artery occlusion were prepared in rats by the thread method.Rats in the three croton cream groups were given 20,40,and 60 mg/kg croton cream,respectively.Rats in the sham operation and model groups were given the same amount of normal saline,once a day,for 7 consecutive days.The optimal concentration of croton cream,namely the high dose of croton cream,was selected based on neurological deficit score,TTC staining,brain tissue water content,hematoxylin-eosin staining and Nissl staining.(2)Another 120 Sprague-Dawley rats were randomly divided into sham operation group,model group,croton cream group,JNK inhibitor group,croton cream+JNK inhibitor group,p38 MAPK inhibitor group,croton cream+p38 MAPK inhibitor group,and nimodipine group,with 15 rats in each group.Animal models of middle cerebral artery occlusion were prepared using the thread method in all the groups except in the sham operation group.Thirty minutes before modeling,10 μL of SP600125(JNK inhibitor)and 10 μL of SB203580(p38 MAPK inhibitor)were injected into the lateral ventricle of the rats,respectively.Rats in croton cream groups were intragastrically given 60 mg/kg croton cream.Seven days later,the JNK/p38 MAPK signaling pathway,apoptosis-related proteins and cell apoptosis were detected by western blot,TUNEL staining and flow cytometry,respectively. RESULTS AND CONCLUSION:(1)Compared with the sham operation group,neurological deficit score,cerebral water content,cerebral infarction volume and apoptosis rate were significantly increased in the model group(P<0.05),where nerve cells showed scattered distribution.Compared with the model group,neurological deficit score,water content of brain tissue and cerebral infarction volume were significantly decreased in the croton cream medium-dose group,high-dose group and nimodipine group(P<0.05),and the pathological morphology of nerve cells was significantly improved.(2)Compared with the JNK inhibitor group,p-JNK/JNK,p-p38/p38 and Bax expressions in rat brain tissue and the apoptotic rate were significantly decreased in the croton cream+inhibitor groups(P<0.05),while the expression of and Bcl-2 was significantly increased(P<0.05).To conclude,croton cream may inhibit the activation of JNK/p38 MAPK signaling pathway and reduce neuronal apoptosis to achieve neuroprotective effects in rats with cerebral ischemia-reperfusion injury.

Objective:To establish contact dermatitis pruritus model and detect itch,anxiety and depression-like behaviors.To observe the activation of the medial prefrontal cortex(mPFC)neurons and provide morphological evi-dence for its involvement in the regulation of itch perception information.Methods:A model of contact dermatitis pruri-tus was constructed with diphenylcyclopyrenone(DCP)applied on the neck and back of the mouse,and the itch per-ception video tracking system was used to detect the scratching behavior.Open field and suspended tail behavioral ex-periments were conducted to explore the anxiety and depression-like behaviors of mice under contact dermatitis.The dis-tribution of c-Fos and p-ERK1/2 positive cells in the mPFC of contact dermatitis model mice was investigated by immu-nofluorescence staining.Results:The contact dermatitis pruritus model was successfully established,and the bouts of scratching in the contact dermatitis model group was significantly higher than that in the control group(P＜0.05).The results of open field test showed that the time and distances were significantly reduced in the central area of the contact dermatitis model group.The results of the tail suspension experiment suggested that the time of immobility increased sig-nificantly in the contact dermatitis model group(P＜0.05).There were more c-Fos positive and p-ERK1/2 positive cells in the mPFC compared with the control group(P＜0.05).Conclusion:Bouts of scratching were increased in the contact dermatitis group and the mice had anxiety and depression-like behaviors.In the contact dermatitis state,mPFC neurons were activated,providing morphological evidence for the involvement of mPFC neurons in contact dermatitis pruritus and accompanying affective disorders such as anxiety and depression.

Objective:To analyze the activation of primary somatosensory cortex(S1)neurons in post-traumatic stress disorder(PTSD)mice after tactile stimulation of whiskers and the changes of S1 cortical neurons in PTSD mice.Methods:Using the neuron cytoskeleton-associated protein(Arc)labeling strategy and immunofluorescence staining technique,the Arc of S1 cortical neurons in PTSD mice and control mice after whisker stimulation was marked and ob-served.By analyzing the difference in the spatial expression position of Arc labeled neurons and the number of positive cells,the activation level of S1 cortical neurons in the two groups was compared and analyzed.The pyramidal neurons of S1 cortex were labeled by sparse virus labeling method,and the number of dendrites and the morphology and number distribution of dendritic spines were compared between the two groups.Results:After whisker stimulation,it was found that Arc positive neurons were distributed from shallow layer to deep layer of S1,and more densely distributed in layersⅡ/Ⅲ and V.Compared with the control group,the number of positive neurons in different layers of the PTSD group was significantly increased.The results of cell morphology and structure analysis showed that,compared with the control group,the density of dendritic spines in layer Ⅱ/Ⅲ of mice with PTSD increased,and the number of mushroom dendrit-ic spines increased,while the number of filamentous pseudopod dendritic spines decreased.The number of dendritic spines of Si V layer mushroom type and slender type was higher,but the total number of dendritic spines was not sig-nificantly different.Conclusion:After whisker stimulation in PTSD mice,S1 neurons were over-activated,and the structure and morphology of neurons changed significantly.

Objective:To analyze the influencing factors of low liver regeneration in patients with hilar cholangiocarcinoma (HCCA) after portal vein embolization (PVE).Method:Clinical data of 62 patients with HCCA undergoing PVE at Henan Provincial People's Hospital (People's Hospital of Zhengzhou University) from January 2019 to March 2024 were retrospectively analyzed, including 33 males and 29 females, aged (59.1±10.3) years. Patients were divided into two groups based on the median regeneration rate of remnant liver volume (28.6%) three weeks after PVE: low regeneration ( n=31, <28.6%) and high regeneration group ( n=31, ≥28.6%). The proportion of lymph node metastasis, history of alcohol consumption, liver fibrosis, biliary tract infection, alkaline phosphatase (ALP), and tumor necrosis factor-α (TNF-α) were compared between two groups. Multivariate logistic regression analysis was used to indentify the influencing factors of low liver regeneration in patients with HCCA after PVE surgery. Results:The proportion of lymph node metastasis, history of alcohol consumption, liver fibrosis, biliary tract infection, ALP, and level of TNF-α were higher in the low regeneration group than those in the high regeneration group (all P<0.05). Multivariate logistic regression analysis showed that patients with regional lymph node metastasis ( OR=2.561, 95% CI: 1.265-5.185), history of alcohol consumption ( OR=2.616, 95% CI: 1.321-5.181), liver fibrosis ( OR=2.351, 95% CI: 1.265-4.369), biliary tract infection ( OR=2.461, 95% CI: 1.226-4.940), elevated level of ALP ( OR=2.687, 95% CI: 1.351-5.344), and elevated level of TNF-α ( OR=2.781, 95% CI: 1.452-5.326) had an increased risk of low liver regeneration after PVE (all P<0.05). Conclusion:Regional lymph node metastasis, history of alcohol consumption, liver fibrosis, biliary tract infection, and elevated ALP and TNF-α are risk factors for low liver regeneration in patients with HCCA after PVE surgery, which should be noted in clinical practice.

Objective:To investigate the clinical effect of proper management of inferior pancreaticoduodenal artery (IPDA) in laparoscopic pancreaticoduodenectomy (LPD).Methods:This is a retrospective case series study. The clinical and pathological data of 70 patients who received LPD due to pancreatic head tumors, periampullary tumors, or distal common bile duct tumors in the Pancreatic Center of the Second Clinical College of Guangzhou University of Chinese Medicine from January to December 2022 were retrospectively collected. There were 47 males(67.1%) and 23 females(32.9%),aged (59.9±12.8)years(range:13 to 87 years).The procedure of IPDA exposure was as follows:a middle approach was utilized to expose the right half of superior mesenteric artery(SMA) and its right branches between the SMA and superior mesenteric vein(SMV) in superior colonic region. In the subcolonic region,SMA trunk exposure via dissection along the jejunal artery from feet to head and identification the association between IPDA and jejunal artery were prior to IPDA root ligation and dissection. The safety and efficacy of intraoperative IPDA handling were assessed based on surgical videos. Follow-up was carried out in outpatient clinic or by telephone, and outpatient follow-up was conducted once every 1 to 3 months after surgery.Results:The percentage of total LPD was 98.6%(69/70),with all patients achieving R0 resection. Nine cases(12.9%) were involved in combined vascular resection and reconstruction,with 1 case (1.4%) requiring additional upper abdominal incision for vascular and gastrointestinal reconstruction,while the remaining eight cases (11.4%) were completed laparoscopically. The operative time was (432.7±115.4)minutes(range:282 to 727 minutes), and the blood loss was (140.0±125.7)ml(range:20 to 800 ml). Only two patients(2.9%) received fresh frozen plasma transfusion,with an average volume of 650 ml. Reliable ligation and safe handling of the IPDA were achieved in 91.4%(64/70) of cases, with 8.6%(6/70) suffering from IPDA injury-related bleeding. No one was converted to opened surgery. Pathologically,the mean tumor size was (3.3±1.6)cm (range:1 to 7 cm),and the mean number of harvested lymph nodes was 17.0±7.3(range:0 to 46). Lymph node metastasis was observed in 13 cases (18.6%). Five cases (13.2%) developed grade B pancreatic fistula,while no grade C pancreatic fistula occurred. Other complications included bile leakage in one case(1.4%),delayed gastric emptying in two cases(2.9%), lymphatic leakage in 2 cases(2.9%),intra-abdominal infection in 9 cases(12.9%),and fat liquefaction of surgical incision in 1 case(1.4%). Two cases(2.9%) experienced postoperative intra-abdominal bleeding,one due to mesangial bleeding of lesser curvature of the stomach and the other due to oozing from the hepatic arterial sheath. These bleeding events were not concerned with IPDA. The average length of postoperative hospital stay was (15.2±4.6)days(range:9 to 28 days).Conclusion:Proper intraoperative management of IPDA in LPD might reduce IPDA-related bleeding during and after surgery and improve the safety of LPD.

Objective:To investigate the clinical effect of proper management of inferior pancreaticoduodenal artery (IPDA) in laparoscopic pancreaticoduodenectomy (LPD).Methods:This is a retrospective case series study. The clinical and pathological data of 70 patients who received LPD due to pancreatic head tumors, periampullary tumors, or distal common bile duct tumors in the Pancreatic Center of the Second Clinical College of Guangzhou University of Chinese Medicine from January to December 2022 were retrospectively collected. There were 47 males(67.1%) and 23 females(32.9%),aged (59.9±12.8)years(range:13 to 87 years).The procedure of IPDA exposure was as follows:a middle approach was utilized to expose the right half of superior mesenteric artery(SMA) and its right branches between the SMA and superior mesenteric vein(SMV) in superior colonic region. In the subcolonic region,SMA trunk exposure via dissection along the jejunal artery from feet to head and identification the association between IPDA and jejunal artery were prior to IPDA root ligation and dissection. The safety and efficacy of intraoperative IPDA handling were assessed based on surgical videos. Follow-up was carried out in outpatient clinic or by telephone, and outpatient follow-up was conducted once every 1 to 3 months after surgery.Results:The percentage of total LPD was 98.6%(69/70),with all patients achieving R0 resection. Nine cases(12.9%) were involved in combined vascular resection and reconstruction,with 1 case (1.4%) requiring additional upper abdominal incision for vascular and gastrointestinal reconstruction,while the remaining eight cases (11.4%) were completed laparoscopically. The operative time was (432.7±115.4)minutes(range:282 to 727 minutes), and the blood loss was (140.0±125.7)ml(range:20 to 800 ml). Only two patients(2.9%) received fresh frozen plasma transfusion,with an average volume of 650 ml. Reliable ligation and safe handling of the IPDA were achieved in 91.4%(64/70) of cases, with 8.6%(6/70) suffering from IPDA injury-related bleeding. No one was converted to opened surgery. Pathologically,the mean tumor size was (3.3±1.6)cm (range:1 to 7 cm),and the mean number of harvested lymph nodes was 17.0±7.3(range:0 to 46). Lymph node metastasis was observed in 13 cases (18.6%). Five cases (13.2%) developed grade B pancreatic fistula,while no grade C pancreatic fistula occurred. Other complications included bile leakage in one case(1.4%),delayed gastric emptying in two cases(2.9%), lymphatic leakage in 2 cases(2.9%),intra-abdominal infection in 9 cases(12.9%),and fat liquefaction of surgical incision in 1 case(1.4%). Two cases(2.9%) experienced postoperative intra-abdominal bleeding,one due to mesangial bleeding of lesser curvature of the stomach and the other due to oozing from the hepatic arterial sheath. These bleeding events were not concerned with IPDA. The average length of postoperative hospital stay was (15.2±4.6)days(range:9 to 28 days).Conclusion:Proper intraoperative management of IPDA in LPD might reduce IPDA-related bleeding during and after surgery and improve the safety of LPD.

Objective:To analyze the effect of Croton leaf on ERK1/2 pathway in hippocampal of rats with cerebral ischemia-reperfusion.Methods:A total of 216 SD male rats were divided into sham operation group, model group, nimodipine group, low-dose, medium-dose and high-dose groups of croton leaf according to random nubmer table method, with 36 rats in each group. The MACO model of rats was prepared by the method of wire embolization. The high, medium and low dose groups were intragastrated with the water decoction 0.06 g/ml, 0.12 g/ml and 0.18 g/ml of Croton leaf; nimodipine group was intragastrated with nimodipine suspension 1.08 g/L; sham operation group and model group were intragastrated with equal volume of normal saline. Garcia JH score was used to conduct neurological function score, and HE staining was used to observe the morphology of hippocampal neurons after 7 days of continuous administration. Apoptosis of hippocampal CA3/DG region was detected by TUNEL assay. Western Blot was used to detect the expression of ERK1/2 and p-ERK1/2 proteins.Results:Compared with the model group at simultaneous point, the neurological function scores of low-dose, medium-dose and high-dose groups of Croton leaf increased ( P<0.01), the number of apoptotic cells decreased ( P<0.01), the expression of p-ERK1/2 / ERK1/2 [1 d: (0.22±0.03, 0.34±0.02, 0.46±0.01 vs. 0.19±0.02); 3 d: (0.38±0.02, 0.50±0.02, 0.68±0.02 vs. 0.27±0.02); 7 d: (0.29±0.03, 0.43±0.02, 0.59±0.02 vs. 0.21±0.03)] in hippocampus of the low-dose, medium-dose and high-dose groups of Croton leaf significantly increased ( P<0.01). Conclusion:Croton leaf could regulate the expression of ERK1/2 pathway protein upward, effectively improve the neural function and resist the apoptosis of hippocampal CA3/DG area of rats with cerebral ischemia-reperfusion injury.

Objective:To study the preliminary clinical results of the No-touch technique in laparoscopic pancreaticoduodenectomy for pancreatic head cancer.Methods:A retrospective analysis was consulted on 11 patients who underwent laparoscopic pancreaticoduodenectomy for pancreatic head cancer at the Pancreas Center of Guangdong Provincial Hospital of Traditional Chinese Medicine from April 2019 to April 2020. There were 5 males and 6 females, with a Mean±SD age of (63.6±12.2) years. Preoperative evaluation showed all patients were diagnosed to have resectable pancreatic head carcinoma with no local invasion into adjacent arteries and veins, and without metastasis. The surgical strategy consisted of no initial Kocher manoeuvre with no flipping or pulling of the pancreaticoduodenal area. Through unwinding of the pancreatic uncinate process, the pancreatic blood vessels, nerves and lymphatic vessels were completely detached to isolate the tumor. Finally, the pancreaticoduodenal area was totally resected and the digestive tract was reconstructed using the Child’s method. The operation time, intraoperative blood loss, postoperative complications, postoperative pathology and follow-up data of the patients were evaluated.Results:All patients completed the laparoscopic operation without any need for conversion to laparotomy. The operation time of the 11 patients was (422.2±102.2) min, and the bleeding volume was (102.7±65.4) ml. There were 2 patients who developed pancreatic fistula, with 1 patient having a biochemical fistula and 1 patient a grade B fistula. There was no grade C fistula. Other complications included 1 patient with delayed gastric emptying. There were no biliary fistula, no postoperative abdominal bleeding, and no perioperative death. Postoperative pathology showed 6 patients had lymph node metastases, with a positive lymph nodes rate of (4.8±4.4)%. All patients had R 0 resection. The follow-up survival data of the 11 patients showed one patient to develop intrahepatic metastasis 1 month after operation and he died 9 months after operation. Another patient developed liver metastases 2 months after operation. The remaining patients were tumor-free. Conclusion:Laparoscopic pancreaticoduodenectomy using the No-touch isolation and resection technique could achieve complete resection of tumors, and it can safely and effectively be applied to patients with pancreatic head cancer.

Pancreaticoduodenectomy is one of the most difficult abdominal operations, and the difficulty in resection and complicated digestive tract reconstruction have brought great challenges for surgeons. At present, laparoscopic pancreaticoduodenectomy has been widely used in clinical practice, and compared with traditional 2D laparoscopy, 3D laparoscopy has the features of high magnification, high definition, and three-dimensional vision, which enables surgeons to see more clearly and operate more accurately, and thus it has great potential to be widely used in pancreaticoduodenectomy.

Objective:To examine the surgical approach, practical cognition as well as clinical effect of the orthotopic resection for laparoscopic pancreatoduodenectomy(OLPD).Methods:From March 2019 to December 2019, 32 cases were treated with laparoscopic pancreatoduodenectomy (LPD) in a novel approach without mobilization of pancreatoduodenum in Pancreas Center of the Second Affiliated Hospital of Guangzhou University of Chinese Medicine.There were 16 male patients and 16 female patients.The mean age was (64.8±9.5) years old.Body mass index was 14.9 to 31.0 kg/m 2.All patients were diagnosed as ampullary or pancreatic head tumors and were not unresectable cases.In the surgical strategy, Kocher′s dissociation, turning and pulling of the pancreaticoduodenal region, was not performed first.Anatomy in situ, separation of vessels which enter and exit from pancreas, separation of lymphatics and isolation of tumors were carried out in priority through the combined middle and left posterior approaches.Finally, the pancreatic head and duodenum region was mobilized and the entire resection of pancreas in situ was carried out.Digestive tract reconstruction was performed through Child method. Results:Postoperative pathology showed that 27 cases were pancreatic or ampullary malignant tumors and five cases were benign tumors among 32 patients.The operative time was (357.3±64.3) minutes.The diameter of pancreatic ducts was (3.0±1.0) mm. The pancreas of 20 cases (62.5%) were soft. Five patients suffered from pancreatic fistula (Grade B) and one patient suffered from intra-abdominal hemorrhage postoperatively.No other complications like pancreatic fistula (Grade C) or biliary fistula delayed gastric emptying or mortality were encountered.The postoperative hospital day was (13.7±3.6) days.Conclusions:Combining the multi-angle of the laparoscopic approaches and excising the pancreaticoduodenal specimen in situ, OLPD is a kind of surgical method which can realize the concept of no touch tumor surgery.Patients who undergo the OLPD can receive better treatments and results.