Objective: To systematically evaluate the association between random urinary electrolyte levels and hypertension among children and adolescents in Guizhou Province, so as to provide evidence for region specific dietary guidance and interventions. Methods: In 2023, a total of 2 480 children and adolescents aged 6 to 17 years were recruited from a nine-year coherent style school in Guizhou Province in a children health cohort, with follow ups conducted in 2024 and 2025. Random urine samples were collected to measure urinary sodium, potassium, calcium, and chloride, and the urinary sodium to potassium ratio (Na/K) was calculated. The diagnosis of hypertension was based on the criteria established by the Chinese Guidelines for Hypertension Prevention and Treatment (2024 revised edition) and relevant research. Linear mixed models and multinomial Logistic regression were used to assess the associations of urinary electrolytes with systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), and the risk of hypertension. Results: At baseline, SBP, DBP, and MAP were 102.33 (94.33, 110.33), 61.33 (56.33, 67.00) and 75.22 (69.67, 81.33)mmHg among children and adolescents, respectively. After adjusting for potential confounders and two follow-ups, higher urinary Na/K ratio was positively associated with higher of SBP ( β=0.054, 95%CI =0.028- 0.081 ) and MAP ( β=0.038, 95%CI =0.010-0.066), as well as higher risks of hypertension ( OR=1.248, 95%CI =1.006-1.548) (all P <0.05). Higher of urinary chloride levels were positively associated with higher of SBP ( β=0.088, 95%CI = 0.009- 0.167), whereas higher of urinary potassium (SBP: β=-0.062, 95%CI =-0.096 to -0.028; MAP: β=-0.041, 95%CI = -0.078 to -0.005) and calcium levels (SBP: β=-0.036, 95%CI =-0.065 to -0.007) were negatively associated with blood pressure (all P < 0.05 ). Conclusion The urinary Na/K, as a comprehensive electrolyte marker, more stably reflects sodium load and excretory pressure in children and adolescents, and may serve as an early predictor of hypertension risk.

Objective:To investigate the anti-fatigue effect of Dendrobium and Panax Quinquefolius Granules(DPQG)on the overtrained mice,and to clarify its possible mechanism.Methods:A total of 48 mice were randomly divided into control group(equal volume of distilled water),low dose of DPQG group(400 mg·kg-1 DPQG),medium dose of DPQG group(800 mg·kg-1 DPQG),and high dose of DPQG group(1 600 mg·kg-1 DPQG).The DPQG were administered by gavage for 35 d,and the rotarod test and swimming endurance test were performed 30 min after last administration.Serum,liver tissue,and muscle tissue were collected from the mice in various groups.ELISA method was used to detect the serum lacticacid(LAC)levels and lactate dehydrogenase(LDH)activities,and the malondialdehyde(MDA)levels,superoxide dismutase(SOD)and glutathione peroxidase(GSH-Px)activities,and the liver glycogen and muscle glycogen levels in muscle tissue of the mice in various groups;HE staining was used to observe the pathomorphology of muscle tissue of the mice.Transcriptomics and metabolomics technologies were used to identify the key genes and metabolites in muscle tissue of the mice in control group and high dose of DPQG group and to analyze the correlations between differentially expressed genes(DEGs)and differentially expressed metabolites.Results:Compared with control group,the rod turning exhaustion time of the mice in different doses of DPQG groups were significantly increased(P＜0.05),and the swimming exhaution time of the mice in high dose of DPQG group was increased(P＜0.05).Compared with control group,the LDH,SOD,and GSH-Px activities of the mice in medium and high doses of DPQG groups were increased(P＜0.01).Compared with control group,the levels of MDA and liver glycogen of the mice in medium and high doses of DPQG groups were decreased(P＜0.05 or P＜0.01).The transcriptomics sequencing results showed that DPQG mainly acted on DEGs such as Trib3 and Olfr495;the Gene Ontology(GO)functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)signaling pathway enrichment analysis results showed that the DEGs were mainly enriched in olfactory-related processes and signaling pathways;the metabolomics KEGG analysis results showed that the differential metabolites were mainly enriched in the regulation pathway of inflammatory mediators on tryptophan(TRP);the combined analysis of transcriptomics and metabolomics results showed that the piezo1 gene had high correlations with the differential metabolites β1-solamarine(r=-1,P＜0.05)and tilidine(r=1,P＜0.05).Conclusion:DPQG can exert an anti-fatigue effect on the overtrained mice by modulating LAC metabolism and glycogen homeostasis,as well as maintaining the oxidative/antioxidant balance in the body;its anti-fatigue mechanism is related to the Olfr495 and piezo1 genes and the regulation pathway of inflammatory mediators on TRP channels.

Purpose/Significance The data security management system is built based on the big data of medical alliance to achieve the purpose of enhancing data protection,reducing security risks and improving data security.Method/Process By analyzing the busi-ness scenario of medical alliance,data security policies and application security technologies are established in the full life cycle of collec-tion,transmission,storage,processing,sharing and destruction,and the construction of data security system is improved.Result/Con-clusion The data security management system is a"safety belt"for the business of medical alliance.With a clear security system and standards as the outline,it provides an effective path for the legal and compliant development of hospital business and establishes a feed-back mechanism.

To study the biological characteristics and gene function of Ligilactobacillus salivarius CICC23174 strain,a strain isolated from chicken intestines.The next generation sequencing plat-form HiSeq2000 was used for sequencing,and bioinformatics software was employed to assemble and optimize the raw data.Functional annotation,bacteriocin and signal peptide,gene collinearity comparison,and phylogenetic analysis were performed on its gene information.Our results indica-ted that the linear genome of Ligilactobacillus salivarius CICC23174 was 203 542 bp in length,with a GC content of 32.84％,encoding 1 890 genes,containing 3 bacteriocins,and 50 signal pep-tides.Importantly,the Ligilactobacillus salivarius CICC23174 included into 27 unique genes,forming four systems:the Type Ⅰ CRISPR Cas defense system,the Type Ⅱ toxin antitoxin system,the tumor escaped inhibitory gene,and the protein secretion pathway.Moreover,collinearity analy-sis showed that CICC23174 strain was most similar to the Ligilactobacillus salivarius UCC118,but 16S rRNA phylogenetic analysis indicted that CICC23174 strain was genetically close to FZJTZ9M6 strain.The results of this study lay the foundation for enriching the species evolution-ary library of Lactobacillus salivarius and exploring the potential probiotic functions of Lactoba-cillus salivarius.

Background and purpose:In 2016 the National Cancer Institute(NCI)decided stopping to use NCI-60 cell lines for drug screening,suggesting that tumor cell lines were losing their value as a tool for drug discovery and basic research.The reason for NCI-60 cells'retirement'was that the preclinical studies based on traditional cellular and animal models did not obtain the corresponding expected efficacy in clinical trials.Since the major cancer behaviors,such as proliferation and metastasis,are fundamentally altered with long-term culture,the tumor cell lines are not representative of the characteristics of cancer in patients.Currently,scientists hope to create a new cancer model that are derived from fresh patient samples and tagged with details about their clinical past.Our purpose was to create patient-derived breast cancer primary cell lines as new cancer model for drug screening and basic research.Methods:Breast cancer tissues were collected in the Department of Breast Surgery,Affiliated Hospital of Guizhou Medical University.The collection of tumor tissue samples was approved by the Ethics Committee of the Affiliated Hospital of Guizhou Medical University(approval number:2022 ethics No.313),and the collection and use of tumor tissues complied with the Declaration of Helsinki.The primary breast cancer cell lines were isolated from the patient's breast cancer tissues and cultured in BCMI medium.After the cells proliferated,the media were replaced with DEME medium.Cell line STR genotyping was done to determine cell-specific genetic markers and identification.Clone formation assay and transplantation assay were done to analyze the ability of breast cancer primary cell lines to form tumors.Results:We created 6 primary breast cancer cell lines.The 6 primary breast cancer cell lines from the patients were tagged with the definitively clinicopathological features,clinical diagnosis,therapeutic regimens,clinical effectiveness and prognostic outcomes.The STR genotyping assays identified the genetic markers and determined the identities of the 6 primary breast cancer cell lines.Clone formation assays and transplantation assay showed that the proliferative capacities of the patient-derived primary breast cancer cell lines were significantly greater compared with the conventional breast cancer cell lines.Conclusion:We created a panel of 6 patient-derived primary breast cancer cell lines as new cancer model for drug screening and basic research in breast cancer.

Objective:To explore the safety and efficacy of radiofrequency in the treatment of overactive bladder(OAB).Methods:A prospective, multicenter, non-randomized controlled trial was conducted. Eligible patients were divided into test group and control group in Zhejiang Provincial People’Hospital, The First Affiliated Hospital of Wenzhou Medical University, and Sir Run Run Shaw Hospital affiliated to Zhejiang University School of Medicine from March 2019 to June 2020. Inclusion criteria: patients diagnosed with OAB, and bladder capacity>100ml. Exclusion criteria: pregnant and lactating women; patients with secondary OAB symptoms such as urinary tract obstruction; patients with uncontrolled urinary tract infection within 1 week; patients in stable stage by using other treatment methods; patients implanted with any nerve stimulator, cardiac pacemaker or implantable defibrillator; patients with malignant tumors, serious cardiovascular, cerebrovascular diseases, renal insufficiency or received BTX treatment in recent 12 months. The patients were allocated to test group and the control group in a ratio of 2∶1 according to the time sequence of the visit. The patients in the test group were treated with radiofrequency treatment. After entering the group, they were treated for 4 times at the 1st, 2nd, 7th and 8th week respectively. In the control group, the energy was turned off during the radiofrequency treatment. The patients were followed-up every week until the end of the 12th week. The treatment success rate [the average frequency of urination in 24 h was reduced more than 50% from the baseline or returned to the normal (≤8 times/day) or the average frequency of urgent urination in 24 h was reduced more than 50% from the baseline], the frequency of urination, urgent urination and nocturnal urination before and after treatment, the residual urine volume of the bladder, the quality of life (QOL) score and the occurrence of catheter related adverse events in two groups were compared.Results:114 patients were enrolled in the study, including 76 patients in the test group and 38 patients in the control group. There were no significant differences in the age [(44.2±12.8) vs. (41.7 ± 12.1) years old], male female ratio (13/63 vs. 4/34), average course of disease [2.0(1.2, 5.0) vs. 2.0 (1.0, 4.0) years], the frequency of urination[12.8 (10.6, 16.8) vs. 12.8 (10.3, 17.0) times], urgency urination [11.8(9.3, 15.8) vs. 11.8 (9.0, 17.0) times], nocturia [2.7 (1.3, 3.7) vs. 2.3(0.7, 3.3) times], residual urine volume of bladder [12.0 (3.0, 28.0) vs. 14.0 (3.7, 20.0) ml ] and the QOL score [5.0(4.0, 5.0) vs. 4.0(4.0, 5.0)]before the treatment between the two groups ( P>0.05). The treatment success rate in the test group was 76.3% (58/76), while 26.3% (10/38) in the control group, with a statistically significant difference ( P<0.01). There were significant differences between the test group and control group in the frequency of urination [9.7 (7.7, 12.0) vs. 12.9 (9.6, 15.7) times], urgent urination [7.3 (5.0, 10.0) vs. 11.7 (7.3, 15.3) times], nocturia [1.3 (0.7, 2.0) vs. 1.7 (1.0, 3.0) times] and the QOL score of the patients[3.0(1.0, 3.0) vs. 4.0(3.0, 4.5)]after the treatment(all P<0.05). The frequency of urination, urgency urination, nocturia, the residual urine volume and the QOL score in the test group were significantly improved ( P<0.05) after the treatment.The frequency of urination, nocturia, residual urine volume and the QOL score in the control group were improved ( P<0.05) after the treatment. 13 (11.4%) patients had catheter related adverse events. In the test group and the control group, there were 7 cases of macroscopic hemorrhage caused by the placement of instruments (5/76 vs. 2/38), 5 cases of acute urinary tract infection within 3 days (3/76 vs. 2/38), and 1 case of instrument breakage (catheter breakage) (0/76 vs. 1/38). There were no significant differences in the adverse events between the two groups ( P> 0.05). Conclusions:Radiofrequency treatment of OAB can effectively improve the symptoms of patients, improve the QOL of patients, and has low incidence of adverse events, with good efficacy and safety.

Objective:To determine the impact of body mass index (BMI) on perioperative and oncological outcomes after robot-assisted radical cystectomy (RARC) with intracorporeal urinary diversion.Methods:Clinical data of bladder cancer patients undergoing robot-assisted radical cystectomy with intracorporeal urinary diversion in Zhejiang Provincial People's Hospital from January 2017 to January 2020 were retrospectively analyzed. Patients were divided into three groups according to BMI, including 61 cases in normal group (<25.0 kg/m2), 52 cases in overweight group (25.0-29.9 kg/m2) and 33 cases in obese group (≥30.0 kg/m2). In the normal group, the median age was 73.6(59, 79), including 45 male(73.8%), with 51 cases(83.6%) of ASA score 0-2, 10 cases (16.4%)of 3 or higher, and 10 cases (16.4%) undergoing neoadjuvant chemotherapy. Past medical history included smoking in 34 cases (55.7%), hypertension in 19 cases (31.1%), diabetes in 10 cases (16.4%), heart disease in 12 cases (19.7%), and abdominal surgery in 6 cases (9.8%). In the overweight group, the median age was 69.7(60, 78), including 38 male (73.1%), with 25 cases (48.1%)of ASA score 0-2, 27 cases (51.9%) of 3 or higher, and 9 cases (17.3%) undergoing received neoadjuvant chemotherapy. Past medical history included smoking in 30 cases (57.7%), hypertension in 20 cases (38.5%), diabetes in 10 cases (19.2%), heart disease in 9 cases (17.3%), and abdominal surgery in 5 cases (9.6%). In the obses group, the median age was 69.9(61, 78), including 21 male(63.7%), with 20 cases (60.6%)of ASA score 0-2, 13 cases(39.4%) of 3 or higher, 9 cases (27.3%) undergoing neoadjuvant chemotherapy. Past medical history included smoking in 18 cases (54.5%), hypertension in 17 cases (51.5%), diabetes in 19 cases (57.6%), heart disease in 7 cases (21.2%), and abdominal surgery in 4 cases (12.1%). After statistical comparison among the three groups, it was found that the proportion of patients with hypertension and diabetes in the obesity group and overweight group was higher than that in the normal group (all P<0.05), but there was no significant difference in other factors (all P>0.05). During the surgical process, robot-assisted radical cystectomy and bilateral pelvic lymph node dissection were performed firstly. The scope of lymph node dissection was divided into standard range and expanded range, and the diversion was divided into orthotopic neobladder and ileal bladder. During the orthotopic neobladder process, 40-50 cm ileum at the distance of 15 cm away from ileocecum was obtained by stapler, and then the U-shaped neobladder was made, and the new bladder was anastomosed with urethra and bilateral ureter. For ileal bladder, the ileum was cut off 15cm away from the ileocecum with stapler to obtain the 15 cm ileum to prepare the ileal conduit and restore the continuity of the ileum. The bilateral ureteral spacing 3cm was implanted on the ileal conduit. In the normal group, standard range lymphatic dissection was performed in 20 cases (32.8%), enlarged dissection in 41 cases (67.2%), orthotopic neobladder in 22 cases(36.1%), and ileal conduit in 39 cases (63.9%). In the overweight group, standard range lymphatic dissection was performed in 12 cases (23.1%), enlarged dissection in 40 cases (76.9%), orthotopic neobladder in 26 cases (49.1%), and ileal conduit in 26 cases (50.9%). In the obesity group, the standard range of lymphatic dissection was performed in 7 cases (21.2%), enlarged dissection in 26 cases (78.7%), orthotopic neobladder in 7 cases (21.2%), and ileal conduit in 26 cases (78.8%). There was no significant difference among the three groups (all P>0.05). Compared the operation time, intraoperative blood loss, postoperative exhaust time, postoperative time of taking solid food, postoperative hospital stay, postoperative complications (according to the Clavien-Dindo grading system, postoperative complications are reported inⅠ-Ⅱ grade as mild complications and above Ⅲ grade as serious complications) and pathology results in three groups. Results:All cases successfully underwent robotically without conversion or major intraoperative complications. The operation time in overweight and obsess group were longer than that of normal group with RARC or orthotopic neobladder [310(250, 350) min, 370(310, 420) min, 250(230, 310) min, ( P<0.05)], but there was no significant difference in RARC and ileal conduit[270(220, 300) min, 280(230, 300) min, 240(220, 290)min, P>0.05]. The estimated blood loss in overweight and obsess group was more than that in normal group [230(150, 450)ml, 310(250, 600)ml, 190(100, 350)ml, P<0.05], but there was no difference in blood transfusion rate [4(7.7%), 2(6.1%), 5(8.2%), P>0.05]. The exhaust time [2(1, 3) days, 2(1, 4)days, 2(1, 4)days], postoperative solid food intake time [4(3, 5)days, 4(3, 6)days, 4(3, 6)days] and the hospital stay[10(5, 16)days, 10(6, 17)days, 12(6, 20)days] were not different in three groups(all P>0.05). The mild complication rates in 90 days were significant higher in overweight and obsess groups[28 (53.8%), 16(48.5%), 20(32.8%), P<0.05], but the total and severe complication rates were not significantly different. The incidences of urinary system complications and incision complications in obese and overweight patients were significantly higher than those in normal group ( P<0.05). There was no significant difference in the incidence of gastrointestinal complications and ureteral anastomosis-related complications (stricture or urinary leakage)( P>0.05). There was no significant difference in the number of dissected lymph node, positive lymph node, positive rate of incisional margin and postoperative pathological stage among three different BMI groups(all P>0.05). Conclusion:Robot-assisted radical cystectomy combined with intracorporeal urinary diversion is a safe and effective method for the treatment of overweight, obese and even morbidly obese patients with bladder cancer. The recovery of intestinal function and the oncological results are not affected by body mass index. However, laparoscopic radical cystectomy for overweight and obese patients, especially for orthotopic neobladder, has the risk of long operation time, large amount of intraoperative bleeding and increased risk of minor postoperative complications.

Objective:To investigate the surgical efficacy of split liver transplantation.Methods:Patients who underwent liver transplantation at the Affiliated Hospital of Qingdao University between January 2015 and December 2022 were retrospectively analyzed. They were divided into split liver transplantation group ( n=60) and whole liver transplantation group ( n=765)according to graft types.In the split liver transplantation group, there were 23 males and 37 females, aged (52.5±10.2) years, and the body mass index was (22.4±3.3) kg/m 2. In the whole liver transplantation group, there were 630 males and 135 females, aged (51.2±9.6) years, and body mass index was (24.5±3.7) kg/m 2.The basic data of the two groups were matched 1∶1 using the propensity score matching method. The independent sample t test and χ2 test were used to compare the intraoperative and postoperative recovery of the two groups of donors and recipients. The overall survival rate and the graft survival rate of the two groups were analyzed by Kaplan-Meier method and the cumulative survival rate was compared by the Log-rank test. Results:Fifty-one well-matched pairs of data with similar baseline characteristics were obtained. The ratio of graft mass to recipient body weight in the matched split liver transplantation group was (1.78±0.55)%. Operation time( M(IQR))(10.8(1.5)hours vs. 8.0(1.9)hours, U=6.608, P<0.01) and cold ischaemia time(5.4(1.3)hours vs. 4.6(2.2)hours, U=2.825, P=0.005) were significantly longer in the split liver transplantation group than those in the whole liver transplantation group. Intra-operative anhepatic phase(53.0(15.0)minutes vs. 57.0(24.0)minutes, U=1.048, P=0.295),bleeding volume(1 000(1 400)ml vs. 1 200(1 200)ml, U=0.966, P=0.334) and intraoperative instillation of red blood cells(9.0(6.5)U vs. 11.0(11.0)U, U=1.732, P=0.083) were not significantly different between the two groups. However,the split liver transplantation group showed significantly longer postoperative intensive care unit stay(5.0(3.0)days vs. 4.0(4.0)days, U=2.677, P=0.007) and postoperative hospital stay(30.0(15.0)days vs. 26.0(15.0)days, U=2.237, P=0.025) and significantly higher incidence of postoperative complications(56.8%(29/51) vs. 36.6%(19/51), χ2=3.935, P=0.047) than the whole liver transplantation group. Furthermore,levels of alanine transaminase and aspartate aminotransferase were significantly higher on postoperative days 1,4 and 7 in the split liver transplantation group(all P<0.05) than in the whole liver transplantation group;however,there were no significant differences in these levels on postoperative days 14 and 28. The time to restoration of normal liver function in both groups(12.5(13.7)days vs. 9.0(12.5)days, U=1.607, P=0.108) was not statistically significant. Furthermore,the median follow-up time after surgery was 25.6 months in both groups. In postoperative years 1,2,3 and 5, the graft survival rates were 88.1%,80.8%,77.8% and 66.7% in the whole liver transplantation group and 80.3%,70.3%,67.3% and 60.5% in the split liver transplantation group( P=0.171),respectively. The patient survival rates in post-operative years 1,2,3 and 5 were 88.1%,80.8%,77.8% and 66.7% in the whole liver transplantation group and 80.3%,75.9%,70.3% and 63.3% in the split liver transplantation group,respectively( P=0.252). However,the differences of graft survival rates and patient survival rates between the two groups were not significant. Conclusion:Although it affects the early recovery of patients after liver transplantation,split liver transplantation has no effect on long-term survival rates and demonstrates surgical efficacy similar to that of whole liver transplantation.

Objective:To investigate the surgical efficacy of split liver transplantation.Methods:Patients who underwent liver transplantation at the Affiliated Hospital of Qingdao University between January 2015 and December 2022 were retrospectively analyzed. They were divided into split liver transplantation group ( n=60) and whole liver transplantation group ( n=765)according to graft types.In the split liver transplantation group, there were 23 males and 37 females, aged (52.5±10.2) years, and the body mass index was (22.4±3.3) kg/m 2. In the whole liver transplantation group, there were 630 males and 135 females, aged (51.2±9.6) years, and body mass index was (24.5±3.7) kg/m 2.The basic data of the two groups were matched 1∶1 using the propensity score matching method. The independent sample t test and χ2 test were used to compare the intraoperative and postoperative recovery of the two groups of donors and recipients. The overall survival rate and the graft survival rate of the two groups were analyzed by Kaplan-Meier method and the cumulative survival rate was compared by the Log-rank test. Results:Fifty-one well-matched pairs of data with similar baseline characteristics were obtained. The ratio of graft mass to recipient body weight in the matched split liver transplantation group was (1.78±0.55)%. Operation time( M(IQR))(10.8(1.5)hours vs. 8.0(1.9)hours, U=6.608, P<0.01) and cold ischaemia time(5.4(1.3)hours vs. 4.6(2.2)hours, U=2.825, P=0.005) were significantly longer in the split liver transplantation group than those in the whole liver transplantation group. Intra-operative anhepatic phase(53.0(15.0)minutes vs. 57.0(24.0)minutes, U=1.048, P=0.295),bleeding volume(1 000(1 400)ml vs. 1 200(1 200)ml, U=0.966, P=0.334) and intraoperative instillation of red blood cells(9.0(6.5)U vs. 11.0(11.0)U, U=1.732, P=0.083) were not significantly different between the two groups. However,the split liver transplantation group showed significantly longer postoperative intensive care unit stay(5.0(3.0)days vs. 4.0(4.0)days, U=2.677, P=0.007) and postoperative hospital stay(30.0(15.0)days vs. 26.0(15.0)days, U=2.237, P=0.025) and significantly higher incidence of postoperative complications(56.8%(29/51) vs. 36.6%(19/51), χ2=3.935, P=0.047) than the whole liver transplantation group. Furthermore,levels of alanine transaminase and aspartate aminotransferase were significantly higher on postoperative days 1,4 and 7 in the split liver transplantation group(all P<0.05) than in the whole liver transplantation group;however,there were no significant differences in these levels on postoperative days 14 and 28. The time to restoration of normal liver function in both groups(12.5(13.7)days vs. 9.0(12.5)days, U=1.607, P=0.108) was not statistically significant. Furthermore,the median follow-up time after surgery was 25.6 months in both groups. In postoperative years 1,2,3 and 5, the graft survival rates were 88.1%,80.8%,77.8% and 66.7% in the whole liver transplantation group and 80.3%,70.3%,67.3% and 60.5% in the split liver transplantation group( P=0.171),respectively. The patient survival rates in post-operative years 1,2,3 and 5 were 88.1%,80.8%,77.8% and 66.7% in the whole liver transplantation group and 80.3%,75.9%,70.3% and 63.3% in the split liver transplantation group,respectively( P=0.252). However,the differences of graft survival rates and patient survival rates between the two groups were not significant. Conclusion:Although it affects the early recovery of patients after liver transplantation,split liver transplantation has no effect on long-term survival rates and demonstrates surgical efficacy similar to that of whole liver transplantation.

The p21 activated kinase 4 (PAK4) is serine/threonine protein kinase that is critical for cancer progression. Guided by X-ray crystallography and structure-based optimization, we report a novel subseries of C-3-substituted 6-ethynyl-1H-indole derivatives that display high potential and specificity towards group II PAKs. Among these inhibitors, compound 55 exhibited excellent inhibitory activity and kinase selectivity, displayed superior anti-migratory and anti-invasive properties against the lung cancer cell line A549 and the melanoma cell line B16. Compound 55 exhibited potent in vivo antitumor metastatic efficacy, with over 80% and 90% inhibition of lung metastasis in A549 or B16-BL6 lung metastasis models, respectively. Further mechanistic studies demonstrated that compound 55 mitigated TGF-β1-induced epithelial-mesenchymal transition (EMT).