Artificial intelligence-based drug development: current progress and future challenges / 中国药科大学学报

@#In recent years, artificial intelligence (AI) has been widely applied in the field of drug discovery and development.In particular, natural language processing technology has been significantly improved after the emergence of the pre-training model.On this basis, the introduction of graph neural network has also made drug development more accurate and efficient.In order to help drug developers more systematically and comprehensively understand the application of artificial intelligence in drug discovery, this article introduces cutting-edge algorithms in AI, and elaborates on the various applications of AI in drug development, including drug small molecule design, virtual screening, drug repurposing, and drug property prediction, finally discusses the opportunities and challenges of AI in future drug development.

Feasibility and safety of simultaneous integrated boost in volumetric modulated arc therapy for early breast cancer after breast-conserving surgery / 肿瘤研究与临床

Objective:To investigate the feasibility and adverse reactions of simultaneous integrated boost (SIB) in volumetric modulated arc therapy (VMAT) for early breast cancer after breast-conserving surgery.Methods:A total of 67 patients with early breast cancer after breast-conserving surgery at Zhongshan People's Hospital from September 2019 to May 2021 were enrolled. All patients received VMAT-SIB to the whole breast and tumor bed. The total breast dose and tumor bed dose were 40.5Gy/15 times every 3 weeks and 48 Gy/15 every 3 weeks respectively. The exposure dose of organs at risk and acute adverse reactions of radiotherapy were evaluated.Results:The average doses of planning target volume of the whole brease (PTV WB) and planning target volume of the boost(PTV BOOST) were (42.0±2.1) Gy and (49.9±0.8) Gy, respectively. The V 95% and V 105% of PTV WB and PTV BOOST were (98.8±1.2)% and (31.4±11.3)%, (99.8±0.6)% and (22.9±10.2)%, respectively. The V 5Gy, V 20Gy, V 30Gy and mean dose (D mean) of ipsilateral lung were (52.4±12.0)%, (15.3±4.5)%, (6.7±2.2)% and (11.0±2.4) Gy respectively. The V 18Gy, V 40Gy and D mean of heart were 3.80% (0.48%,9.60%), 0 (0,0.16%) and (6.7±2.1) Gy respectively. At the end of radiotherapy, 19 patients (29%) of all 67 patients had no acute skin toxicity, 41 patients (61%) showed radiation erythema, 5 patients (7%) had radioactive dry peeling and 2 patients (3%) had wet peeling mainly located in the nipple, areola area and breast folds. None of the patients had grade 3-4 acute skin reactions. Breast swelling and breast pain were found respectively in 9 patients (13%) and 7 patients (10%). No local recurrence or distant metastases were observed during the follow-up period. The 2-year disease-free survival rate was 100%. Conclusions:VMAT combined with SIB is feasible in the treatment of early breast cancer. The adverse reactions of radiotherapy are mild and well tolerated.

Laparoscopic versus open hepatectomy in the treatment of recurrent hepatobiliary stones / 中华普通外科杂志

Objective To compare laparoscopic hepatectomy to open surgery in recurrent hepatolithiasis.Methods From Jan 2014 to Feb 2016,106 cases of recurrent hepatolithiasis eligible for hepatectomy were prospectively randomized into laparoscopic group (53cases) and open group (53 cases).The perioperative variables,postoperative morbidity and outcomes were analyzed and compared between the 2 groups.Results The statistical results show that the laparoscopic group and open group had similar intraoperative rate of blood loss ＞400 ml,wound infection,abdominal infection,Grade B bile leakage,score of Clavien classification system,stone clearance rate and hospitalization cost (P ＞ 0.05).The laparoscopy group had longer operation time (P ＜ 0.05),and shorter postoperative hospital stay (P ＜0.05).Binary logistic analysis showed that decreased preoperative platelet count,longer operation time,and hepatectomy in difficult places are risk factors for intraoperative blood loss ＞ 400 ml (OR ＞ 1,P ＜0.05);type of past biliary tract operation,positive bile culture during surgery and residual stones are risk factors for grade B bile leakage (OR ＞ 1,P ＜ 0.05).Conclusions Laparoscopic hepatectomy for recurrent hepatolithiasis is safe and feasible.

Risk factors for delayed gastric emptying after pancreaticoduodenectomy / 中华胰腺病杂志

Objective To analyze the related risk factors for delayed gastric emptying ( DGE) after pancreaticoduodenectomy .Methods Clinical data on 308 patients who underwent pancreaticoduodenectomy at Ningbo Lihuili hospital from January 2009 to December 2014 were retrospectively analyzed , and patients were divided into DGE group and non-DGE group.Univariate analysis and multivariate logistic regression analysis were used to study the risk factors associated with DGE during perioperative period .Results DGE occurred in 55 patients (17.9%).The incidences of grade A, grade B and grade C DGE were 7.1%(22/308), 6.2%(19/308) and 4.5%(14/308), respectively.The univariate analysis showed the method of pancreatic digestive tract reconstruction ( pancreaticogastrostomy or pancreaticojejunostomy ) , postoperative pancreatic fistula, postoperative biliary fistula and postoperative intraabdominal infection were risk factors for DGE after surgery. Multivariate analysis indicated that the method of pancreatic digestive tract reconstruction (OR=1.19, P=0.046), postoperative pancreatic fistula ( OR=1.33, P=0.014), postoperative biliary fistula (OR=1.43, P=0.047) and postoperative intraabdominal infection (OR=1.51, P=0.001) were independently associated with DGE . Postoperative pancreatic fistula (OR=3.692, P=0.021) and intraabdominal infection (OR=3.725,P=0.003)were also the independent risk factors for Grade B and Grade C DGE. Conclusions DGE after pancreaticoduodenectomy was strongly related to the postoperative complications .Postoperative pancreatic fistula , biliary fistula and intraabdominal infection were associated with increased risk of DGE , while pancreaticogastrostomy reduced the incidence of DGE by decreasing the incidence of pancreatic or biliary fistula .

Protect the submandibular gland in patients with nasopharyngeal carcinoma treated with intensity-modulated radiotherapy: a preliminary study / 肿瘤研究与临床

Objective To investigated the protective ways of intensity modulated radiotherapy (IMRT)for submandibular gland function in patients with nasopharyngeal carcinoma.Methods From March 2010 to November 2012,101 patients with nasopharyngeal carcinoma were enrolled into study.They were treated with IMRT and evaluated by face to face dry mouth questionnaire during the follow-up of 3,6,12,18,24 and more than 24 months,meanwhile,their dose volume histogram of submandibular gland were taken into consideration.Results The average contralateral median dose and that of ipsilateral submandibular gland were (45.69±7.22) Gy and (51.64±8.20) Gy,respectively,and the V35,V40,V45,V50 were 95.82 ％,69.99 ％,46.90 ％,25.50 ％,and 100 ％,96.50 ％,82.24 ％,60.98 ％,respectively.There were positive relationship between the xerostomia grading of 3,6,and 12 months after radiotherapy and the average dose of submandibular gland or the V35,V40,V45,V50.After 6 month,the xerostomia in 77.2 ％ (78/101) was significantly improved,and after 12 months,less than 5 ％ of patient complained about G3 or more grade of xerostomia.Conclusions When using IMRT in nasopharyngeal carcinoma,it' s necessary to reduce the irradiated volume and the dose of submandibular gland.It is confined that the median dose of contralateral submandibular gland should be less than 40-45 Gy,and V40 or V45 ≤66.7 ％ or ≤50 ％,which can effectively protect the function of salivary gland.

Protective effect of intensity-modulated radiation therapy on salivary gland function in nasopharyngeal carcinoma patients / 中国肿瘤临床

Objective:To investigate the protective effect of intensity-modulated radiotherapy (IMRT) on salivary gland function in nasopharyngeal carcinoma (NPC) patients. Methods:In total, 101 NPC patients who were admitted from March 2010 to November 2012 were enrolled in this study. The parotid gland, the submandibular gland, and the oral cavity were sketched as the organs at risk (OARs). The patients were treated with IMRT and were evaluated through a face-to-face interview using a dry mouth assessment ques-tionnaire during the follow-up visits at 3, 6, 12, 18, and 24 months. The dose volume histogram of the salivary gland of the patients was also considered. Results:The mean doses (MDs) in the parotid gland were 37.4 and 33.8 Gy in the affected and uninjured sides, respec-tively. Meanwhile, the MDs in the submandibular glands were 51.6 and 45.7 Gy in the affected and uninjured sides, respectively. The MD of the oral cavity was 38.2 Gy. At 6 months after the treatment, the symptom of xerostomia was significantly improved in 77.2%of the patients (78/101). One year later, only less than 5%of the patients complained of having G3 or higher-grade xerostomia. Conclu-sion:With time, xerostomia significantly improved after the radiotherapy. At least one of the V30 to V35 of the parotid gland was≤50.0%, whereas at least one of the V40 to V45 of the submandibular glands was≤66.7%~50.0%. The MD for the oral cavity should be<40 Gy to effectively protect salivary gland function.

Preoperative diabetes mellitus and postoperative morbidity of pancreatoduodenectomy for pancreatic adenocarcinoma / 中华普通外科杂志

Objective To investigate the influence of preoperative diabetes mellitus (DM) on postoperative morbidity of pancreatoduodenectomy for pancreatic ductal adenocarcinoma.Methods The clinical data of 302 pancreatic ductal adenocarcinoma patients who underwent pancreatoduodenectomy from January 1,2005 to August 31,2012 were retrospectively analyzed.Results 113 patients (37.4％)had preoperative DM among the total 302 patients.The percentage of the major complication including pancreatic fistulas,delayed gastric emptying,infections,acute kidney injury and mortality accounted for 19.9％,12.9％,25.9％,36.0％,3.2％ and 3.5％ respectively.In the DM group,firm pancreatic texture was more common than that in non-DM group (x2 =15.175,P ＜ 0.01).While pancreatic fistula in the DM group developed less frequently(x2 =7.811,P =0.005) than that in non-DM group.Delayed gastric emptying,infections,acute kidney injury,hemorrhage,pulmonary,cardiovascular and neurologic complications,as well as length of stay in hospital and mortality were in similar frequency in the two groups (P ＞ 0.05).Binary Logistic regression analysis showed DM(OR =0.358,P =0.035) and firm pancreatic texture(OR =0.395,P =0.032) were protective factors against pancreatic fistula while preoperative jaundice(OR =3.819,P =0.010) and intraoperative blood transfusion (OR =1.268,P =0.001) were predisposing factors for pancreatic fistula.Conclusions With good control of perioperative glucose level,DM does not increase operation risk in pancreatoduodenectomy for pancreatic ductal adenocarcinoma.

As2O3toxicity on rat liver during retrograde isolated hepatic perfnsion / 中华普通外科杂志

Objective To study As2O3toxicity on rat liver in a retrograde isolated hepatic perfusion model. Methods In this study 104 male Sprague-Dawley rats weighing between 300 and 400 g were used. Eight male SD rats were used for preoperatively normal control and the remaining rats were randomly divided into 4 subgroups receiving As2O3at dosage of 0 mg/kg,0.75 mg/kg, 1.5 mg/kg, 3 mg/kg respectively. Modified RIHP was used in which As2O3was infused through hepatic artery. Ringer's lactate was retrogradly infused through hepatic veins and the portal vein was used as the outflow tract. Hepatic function, pathology and liver enzymes were assessed at different time points. As2O3concentration was monitered during the perfusion in rats of subgroup C. Results Serum ALT and AST rose to the peak on the first day, returning to normal after 3 or 7 days in all four subgroups. There was no difference between the peak levels of serum ALT and AST between subgroup A and B. Differences in serum ALT、AST level between subgroup A and C, A and D, B and C, B and D, C and D were all statistically significant (FALT=40.811,P<0.01;FAST= 48.212,P <0.01). On day 7, ALT and AST in subgroup D were still statistically higher when compared with that of other subgroups and normal control (FALT=13.928, P<0.01;FAST=17.942, P<0.01), and the hepatic pathology showed necrosis of the hepatocyte. The peak levels of As2O3were 13.21±0.82(μg/ ml) and 0.09±0.008 (μg/ml)in rats liver and systemic circulation in subgroup C during isolated perfuision. There were significant differences between the peak levels of concentration of As2O3in rats liver and systemic circulation (t=35.758,P<0.01). Conclusions The hepatic toxicity is reversible caused by As2O3when given at a dosage of 1.5 mg/kg of As2O3in a murine model of RIHP.

Grafted liver preservation / 国际外科学杂志

Maintaining organ viability after donation until transplantation is critically important for optimal graft function and survival. To date, static cold storage is the moot widely used form of liver preservation in clinical practice. Although simple and effective, it is questionable whether this method is able to prevent deterioration of organ quality in the present with increasing numbers of organs retrieved from older, more marginal, and even non-heart-beating donors. This review describes the history and progress of liver preservation and preservation solution, including hypothermic machine perfusion. Despite the fact that hypothermic machine perfusion might be superior to static cold storage preservation, liver are still exposed to hypothermia induced damage. Therefore, recently some groups have pointed at the beneficial effects of normothermic machine perfusion as a new perspective in liver preservation and transplantation.