s:Aim To study the effects of total gluco-sides of paeony ( TGP) on the differentiation of co-cul-tured osteoclasts and the mechanisms of how TGP influ-ences the osteoclasts. Methods The synovial fibro-blasts and monocytes of peripheral blood in adjuvant-induced arthritic rats were separated and co-cultured to induce osteoclasts. The cells were treated with different TGP dosages (5, 50, 500, 5 000 mg·L-1 , and 50 g ·L-1 ) for 48 h. The proliferation, the TRAP activi-ty, and the bone resorption of osteoclasts were ob-served. The levels of IL-1,TNF-α,M-CSF and RANKL in the supernatants of osteoclasts were detected using ELISA. Meanwhile, the expression of ERK, JNK and p38 was detected by real time PCR. Results The ex-periments revealed that 50, 500, 5 000 mg·L-1 TGP inhibited the osteoclast growth, the TRAP activity, and the resorption pit area in a dose-dependent manner. TGP also inhibited the levels of IL-1 , TNF-α, M-CSF and RANKL in the supernatants and the expression of ERK, JNK and p38 in osteoclasts. The appropriate concentrations were 50 mg·L-1 to 5 000 mg·L-1 and had dose-dependent effects within this range. Conclu-sions TGP regulates the differentiation and activity of co-cultured osteoclasts. The effects of TGP are related to its inhibiting the cytokines secretion of synovial fi-broblasts and the activity of MAPK pathways.

Background Nanoemulsions (NEs) is one of the most popular ophthalmic colloidal drug delivery system due to its long-term stability, low toxicity and irritancy, considerable capacity for solubilization of lipophilic drug molecules and great potential in bioavailability improvement.The cornea pathway is the main route of intraocular absorption after topical use of NEs.Though NEs possess numerous physiological and physicochemical advantages,the use of NEs cannot always obtain satisfactory results.Objective This study was to investigate the impacts of epithelium and stroma on the corneal permeation of topical ophthalmic terbinafine hydrochloride nanoemulsions (TH-NEs).Methods TH-NEs was prepared by the self-emulsification method.The size and Zeta potential of the oil droplets in the formulation were analyzed using a dynamic light-scattering particle size analyzer.The high performance liquid chromatography (HPLC) was used for the in vitro release study.Sixty New Zealand albino rabbits were randomly divided into intact cornea group and cornea epithelium debrided group.The cornea epithelium of the left eyes was debrided in the cornea epithelium debrided group.The TH-NEs were instilled into the lower conjunctival sac of left eyes.Six rabbits were executed from each group 15,30,60,120 and 240 minutes after dosing,respectively.The corneas were collected and analyzed by HPLC.The fluorescein diacetate (FDA) was used to label the TH-NEs.Two C57BL/6 mice with left cornea epithelium debrided and 2 normal mice were used for the fluorescence tracing study.The fluorescence distribution of FDA labeled TH-NEs was observed by a two-photon laser confocal scanning microscope 30 minutes and 60 minutes after single instillation.Results The average size and Zeta potential of the oil droplets were 51.37 nm and-0.232 7 mV respectively,and 0.482％ of encapsulated drugs was released from the TH-NEs after 12 hours.The peak concentrations of TH in the intact cornea and epithelium debrided cornea were (17.85 ± 2.79) μg/g and (4.40± 1.75) μg/g respectively, which occurred 15 minutes postdose.The drug concentrations in the intact cornea were significantly higher than that in the debrided cornea 15,30,60 and 120 minutes after dosing, with significant differences between them (t =9.998,8.658,6.903,7.576;all at P=0.000).The fluorescence was observed in the cornea epithelium when the cornea was intact.The fluorescence intensity in the superior layer of corneal epithelium was obviously higher than that in the deep layers of corneal epithelium 30 minutes and 60 minutes after dosing.No fluorescence was observed in the cornea stroma of both eyes.Conclusions The cornea epithelium is the main of absorption and distribution position of TH-NEs.The cornea stroma is the dominating permeation barrier for the intraocular transportation of the TH-NEs.The cornea stroma may stop the permeation of TH-NEs by molecular exclusion mechanism.

Objective:To observe the effect of abdominal electroacupuncture(EA)on intestinal function in patients with constipation after stroke. Methods:A total of 100 patients with post-stroke constipation were divided into an observation group and a control group by the random number table method,with 50 cases in each group.The control group was treated with oral lactulose,10 mL each time,3 times a day,for 2 consecutive weeks.The observation group was treated with additional abdominal EA at Tianshu(ST25),Fushe(SP13),and Daheng(SP15)on the basis of oral lactulose,30 min for needle retention each time,once a day,for 2 consecutive weeks.The total effective rate after treatment,constipation symptom score,the score of patient assessment of constipation quality of life scale(PAC-QOL),serum motilin(MTL)level,and the score of mini-mental state examination(MMSE)were compared between the two groups. Results:After 2 weeks of treatment,the total effective rate was 93.5%in the observation group and 76.1%in the control group,and the difference between the two groups was statistically significant(P<0.05).The constipation symptom score,PAC-QOL score,MMSE score,and MTL level changed significantly after treatment in both groups(P<0.05).After treatment,the constipation symptom score and PAC-QOL score in the observation group were lower than those in the control group,while the MMSE score and MLT level were higher than those in the control group,and the differences between the two groups were statistically significant(P<0.05). Conclusion:On the basis of oral lactulose,EA at abdominal points can significantly improve the intestinal and cognitive function of stroke patients simultaneously.

Objective:To investigate the clinical efficacy of partial excision of nail matrix combined with phenolic ablation in the treatment of ingrowing toenail.Methods:115 patients(148 toenails) with ingrowing toenail treated in the Central hospital of Wuhan from October 2004 to May 2013 were selected for this study.The patients were divided into two groups,53 patients(67 toenails) admitted from October 2004 to December 2007 were considered as the observation group and treated with Partial excision of nail matrix,62 patients(81 toenails) admitted from January 2008 to May 2013 were considered as the control group and treated with Partial excision of nail matrix and phenolic ablation.The bleeding time,pain relief time,healing time,recurrences after one year and satisfaction rate of two groups were compared.Results:The wounds of 148 toenails were healing.The Bleeding time,pain relief time,recurrences after one year in the control group (1.85:±:0.42days,13.25± 2.17hours) were lower than the observation group (2.69± 0.53 days,21.54± 2.56hours),and healing time in the control group (11.32± 2.37days) were longer than the observation group (8.93± 2.06 days)(P＜0.05),the recurrence rate and overall satisfaction rate of observation group and control group were 6.15％,12.5％ and 97.06％,91.07％.Conclusion:Partial excision of nail matrix combined with phenolic ablation was more effective in the treatment of ingrowing toenail than surgical excisional techniques.

[Objective]To summarize the advances in research on animal model of deficiency syndrome of traditional Chinese medicine(TCM) of the present stage, to provide the ideas for the establishment of animal model of TCM. [Methods] The article discusses the animal model with Qi deficiency, blood deficiency, Yin deficiency, Yang deficiency syndrome from the TCM etiology, western medicine etiology and pathology, model of western disease combined with syndrome. [Results] After active exploration of scholars over the years, TCM deficiency syndrome animal model has made great progress, researchers have made many TCM syndrome animal models using different methods, which have the characteristics of TCM syndrome. The molding method of traditional etiology of TCM has the advantages of conforming to the TCM etiology, but has the disadvantages of instability. Animal model made by western medicine etiology and pathology has the advantages of stability, practicality and repeatability, but has the disadvantages of disjointing with TCM theory. Animal models combined with disease and syndrome are ideal animal models at the moment. [Conclusion] Under the guidance of Chinese medicine theory, creating a more unified, more scientific method and evaluation system by means of modern science and technology and providing a more solid foundation for the scientific research of traditional Chinese medicine are very important.

Objective:To investigate the influencing factors for celiac lymph node metastasis in thoracic esophageal squamous cell carcinoma (TE-SCC), construct a prediction model of celiac lymph node metastasis in TE-SCC, and stratify the probability of celiac lymph node metastasis.Methods:The retrospective case-control study was conducted. The clinicopathological data of 443 patients with TE-SCC who underwent thoracoscopic and laparoscopic esophagectomy with systematic lymph node dissection in the First Affiliated Hospital of Zhengzhou University between March 2015 and April 2019 were collected. There were 259 males and 184 females, aged from 41 to 81 years, with a median age of 64 years. The nomogram prediction model was constructed based on the results of multivariate analysis of influencing factors for celiac lymph node metastasis in TE-SCC, of which calibration curve and decision curve were drawed. The predictive performance was evaluated using the concordance index. The score for celiac lymph node metastasis in TE-SCC predicted by nomogram model was used for further recursive partitioning analysis, and patients were stratified into risk subgroups using the decision-making tree model. Observation indicators: (1) celiac lymph node metastasis in TE-SCC; (2) analysis of influencing factors for celiac lymph node metastasis in TE-SCC; (3) construction of nomogram prediction model of celiac lymph node metastasis in TE-SCC; (4) construction of decision-making tree model of celiac lymph node metastasis in TE-SCC and risk subgroup analysis of celiac lymph node metastasis probability. Measurement data with skewed distribution were represented as M (range). Count data were represented as absolute numbers and percentages, and comparison between groups was analyzed using the chi-square test. Comparison of ordinal data between groups was analyzed using the nonparametric rank sum test. Multivariate analysis was performed using the Logistic regression model. Based on Logistic regression model multivariate analysis, a new nomogram model was constructed using the RStudio 3.4 software. Results:(1) Celiac lymph node metastasis in TE-SCC: celiac lymph node metastasis was found in 89 of the 443 patients, with a celiac lymph node metastasis rate of 20.09%(89/443). (2) Analysis of influencing factors for celiac lymph node metastasis in TE-SCC. Results of univariate analysis showed that tumor location, tumor length, tumor differentiation degree, pathological T staging, nerve invasion, vessel invasion, and thoracic lymph node metastasis were related factors for celiac lymph node metastasis in TE-SCC ( χ2=12.177, Z=-2.754, -4.218, -4.254, χ2=3.908, 33.025, 30.387, P<0.05). Results of multivariate analysis showed that tumor location, vessel invasion, and thoracic lymph node metastasis were independent influencing factors for celiac lymph node metastasis in TE-SCC ( odds ratio=2.165, 3.442, 2.876, 95% confidence interval: 1.380-3.396, 1.787-6.633, 1.631-5.071, P<0.05). (3) Construction of nomogram prediction model of celiac lymph node metastasis in TE-SCC: based on the factors screened by multivariate analysis, including tumor location, vessel invasion, and thoracic lymph node metastasis, the nomogram prediction model of celiac lymph node metastasis in TE-SCC was established, with the concordance index of 0.846. The calibration curve showed a high consistency between the celiac lymph node metastasis probability estimated by the prediction model and the actual rate of celiac lymph node metastasis. The decision curve showed that the nomogram prediction model of celiac lymph node metastasis in TE-SCC had a good prediction value when the probability threshold was 0.001-0.819.(4) Construction of decision-making tree model of celiac lymph node metastasis in TE-SCC and risk subgroup analysis of celiac lymph node metastasis probability: patients were stratified into six risk subgroups using the decision-making tree model based on the celiac lymph node metastasis probability. The group A included patients with no vessel invasion+negative thoracic lymph node, group B included patients with no vessel invasion+the number of positive thoracic lymph nodes of 1-3, group C included patients with no vessel invasion+the number of positive thoracic lymph nodes of ≥4, group D included patients with vessel invasion+the number of positive thoracic lymph nodes of 0-2+upper or middle thoracic esophageal carcinoma, group E included patients with vessel invasion+the number of positive thoracic lymph nodes of 0-2+lower thoracic esophageal carcinoma, group F included patients with vessel invasion+the number of positive thoracic lymph nodes of ≥3. The group A was low-risk group with the celiac lymph node metastasis probability of 11%, group B and D were intermediate low-risk groups with the celiac lymph node metastasis probability of 27% and 21%, group C and E were the intermediate high-risk groups with the celiac lymph node metastasis probability of 56% and 55%, and group F was high-risk group with the celiac lymph node metastasis probability of 80%. Conclusions:The tumor location, vessel invasion, and thoracic lymph node metastasis are independent influencing factors for celiac lymph node metastasis in TE-SCC. Vessel invasion has the dominant influence on celiac lymph node metastasis, followed by the number of positive thoracic lymph nodes, and then the tumor location. Patients can be stratified into six risk subgroups based on the nomogram prediction model and decision-making tree model of celiac lymph node metastasis in TE-SCC.

Objective To introduce the detailed surgical procedure of parachute-like-suture double-pouch pancreaticojejunostomy in laparoscopic pancreaticoduodenectomy (LPD),and to study its clinical results.Methods A retrospective study was conducted on 31 patients who underwent parachute-like-suture double-pouch pancreaticojejunostomy in laparoscopic pancreaticoduodenectomy between January 2016 and June 2018 in our department.Results Of 31 patients who underwent total laparoscopic pancreaticoduodenectomy,5 patients underwent two-dimensional (2D) LPD and 26 underwent three-dimensional (3D) LPD.Total mesopancreas excision (TMpE) was performed in 12 patients,including 2 patients combined with PV-SMV segmental resection and reconstruction.The mean operative duration,and mean estimated blood loss,post-operative hospital stay were 412.8 ± 102.4 min,462.8 ± 396.7 ml,14.7 ± 8.9 d,respectively.The operating time of parachute-like-suture double-pouch pancreaticojejunostomy was 29.7 ± 6.8 min (20 ～45 min).Post-operative complications occurred in 8 patients (25.8％),3 of whom suffered from more than two types of complications.There were 2 patients (6.5％) with postoperative B/C grade pancreatic fistula,4 patients with postoperative biliary leakage (12.9％),3 patients with delayed gastric emptying (9.7％),1 patient with portal vein thrombosis (3.2％) and 1 patient with peritoneal effusion (3.2％).One patient died during perioperative period due to gastrointestinal hemorrhage.Conclusions Parachute-like-suture double-pouch pancreaticojejunostomy in laparoscopic pancreaticoduodenectomy was a simple,convenient,reliable method.It is worthy of clinical promotion and further studied.

Objective:To summarize the technical points of laparoscopic pancreaticoduodenectomy (LPD) carried out in a single center.Methods:The clinical data of 102 patients who underwent laparoscopic pancreaticoduodenectomy in 2018 at the Department of Hepatobiliary Surgery of the Second Hospital of Hebei Medical University were retrospectively analyzed, and the general conditions, operation time, intraoperative blood loss, and surgical operation were analyzed. Post-operative complications, hospital stay and other indicators were studied.Results:Of the 102 patients who were included, there were 57 males and 45 females, aged 15.0 to 79.0 (59.9±11.8) years old, with a body mass index (23.6±3.6) kg/m 2. For the 102 patients who underwent LPD, 6 were total pancreatic resection. Three were combined with vascular resection in the form of portal vein-superior mesentery vein segmental resection. The operation time was (376.6±87.2) min, the intraoperative blood loss was 350 (100, 800) ml, and the postoperative hospital stay was (17.0±5.9) days. Postoperative complications occurred in 26 of the 102 patients (25.5%), and more than two complications occurred in 17 patients. B/C grade pancreatic fistula occurred in 9 patients (9.4%), abdominal bleeding in 8 patients (7.8%), gastrointestinal bleeding in 2 patients (2.0%), biliary fistula in 4 patients (3.9%), and gastric emptying disorder in 5 patients (4.9%), 8 patients had pulmonary infection (7.8%). Five patients (4.9%) died during the perioperative period. Conclusion:The main technical points of LPD included en bloc resection, pancreaticojejunostomy, and vascular reconstruction. The basis of LPD is en bloc resection. Combined resection and reconstruction of vascular segments is a sign of maturity of LPD technology and a prerequisite for further development as a routine procedure.

Objective:To study the single purse-string parachute suturing technique for pancreaticojejunostomy in laparoscopic pancreaticoduodenectomy, and to determine its feasibility and safety.Methods:The clinical data of 71 patients who underwent laparoscopic pancreaticoduodenectomy using the single purse-string parachute suturing technique for pancreaticojejunostomy from October 2018 to October 2021 at the Second Hospital of Hebei Medical University were retrospectively analyzed. There were 41 males and 30 females, with age (59.1±9.7) years old. The operative time, intraoperative blood loss, complication rate and other data were analyzed.Results:All 71 patients successfully underwent total laparoscopic pancreaticoduodenectomy, with 5 patients who underwent 2D laparoscopic surgery and 66 patients 3D laparoscopic surgery. There were additional vascular resection and reconstruction in 2 patients. The operative time was (388.9±92.9) min, the intraoperative blood loss was (411.3±176.9) ml, and the postoperative hospital stay was (14.1±5.8) d. The operation time of 71 patients who underwent the single purse-string parachute technique of pancreaticojejunostomy was (26.9±6.8) min. Postoperative complications occurred in 18 patients (25.4%). Grade B pancreatic fistula occurred in 2 patients (2.8%), and the longest time for removal of abdominal drain was 17 days after operation. Among the 71 patients, complications including biliary fistula occurred in 6 patients (8.5%), delayed gastric emptying in 5 patients (7.0%), pulmonary infection in 4 patients (5.6%), non-pancreatic fistula-related abdominal infection in 4 patients (5.6%), non-pancreatic fistula-related abdominal bleeding in 1 patient (1.4%), biliary tract bleeding in 1 patient (1.4%), and chylous leakage in 2 patients (2.8%).Conclusion:The single purse-string parachute technique of pancreaticojejunostomy in laparoscopic pancreaticoduodenectomy had the advantages of being safe and reliable. The procedure is worthy of furthers promotion.

Objective To review our experience in laparoscopic pancreaticoduodenectomy combined with major vascular resection and reconstruction.Methods Of 183 patients who underwent laparoscopic pancreaticoduodenectomy in our department from November 2013 to January 2017,major vascular resection and reconstruction using the SMA first approach for total mesopancreas excision was performed in 7 patients.The clinical data of these 7 patients were retrospectively analyzed.Results Total 3D laparoscopic surgery was performed in all these 7 patients.The mean operation time,mean blood loss and blood flow occlusion time were (551.4 ± 83.8) min,(671.3 ± 256.3) ml and (45.8 ± 6.7) min,respectively.Six out of 7 patients were pathologically diagnosed to have pancreatic adenocarcinoma with negative surgical margins.Two patients had lymphatic metastasis (the number of metastatic lymph node was 1 in each patient).The mean number of lymph nodes resected was (12.7 ± 5.8).The portal vein-superior mesenteric vein (PV-SMV) was segmentally resected and reconstructed using an end to end anastomosis following the preoperative plan in 4 patients.These included 2 patients who underwent total pancreatectomy.The portal vein was wedge-resected and reconstructed by venorrhaphy in 2 patients.The remaining 1 patient was histopathologically diagnosed to have a mass-type chronic pancreatitis.Only 1 patient was treated in the ICU for 1 day after surgery.Post-operative complications occurred in 2 patients and they were managed with nonsurgical treatment (PV-SMV thrombosis and gastric emptying disorder in 1 and a pancreatic leakage (level A) in 1).The mean length of post-operative hospital stay was (13.7 ± 3.2) days with no in-hospital mortality.Seven patients were alive by April 2017.The mean follow-up for the 6 patients with pancreatic adenocarcinoma was 4.5 (3.5 ～9) months.Conclusions Based on our experience in skillful and masterly major vascular resection and reconstruction in open surgery and on our experience in standard laparoscopic pancreaticoduodenectomy,laparoscopic pancreatieoduodenectomy combined with major vascular resection and reconstruction was feasible and safe.This surgery requires very mature skills in laparoscopic surgery.