OBJECTIVES: To investigate the prognostic significance of PDZ-binding kinase (PBK) in pan-cancer and its potential as a therapeutic target for pancreatic cancer. METHODS: PBK expression levels were investigated in 33 cancer types based on data from TCGA, GEO and CPTAC databases. RT-PCR and Western blotting were employed to examine PBK expression in clinical pancreatic cancer specimens and cell lines. The diagnostic and prognostic value of PBK in pancreatic cancer was evaluated using survival analysis, Cox regression analysis, ROC curve analysis, and clinical correlation studies. Gene enrichment and immune correlation analyses were conducted to explore the potential role of PBK in tumor microenvironment, and its correlation with drug sensitivity was investigated using GDSC and CTRP datasets. In pancreatic cancer BXPC-3 cells, the effects of lentivirus-mediated PBK knockdown on cell proliferation, migration, and invasion were examined using CCK-8, colony formation, and Transwell assays. The interaction between PBK and non-SMC condensin II complex subunit G2 (NCAPG2) was analyzed using co-immunoprecipitation and Western blotting. RESULTS: PBK was overexpressed in multiple cancer types, including pancreatic cancer. A high PBK expression was associated with a poor prognosis of the patients and correlated with immune infiltration and alterations in the tumor microenvironment. Elevated PBK expression was positively correlated with the sensitivity to MEK inhibitors (Trametinib) and EGFR inhibitors (Afatinib) but negatively with the sensitivity to Bcl-2 inhibitors (TW37) and niclosamide. In BXPC-3 cells, PBK knockdown significantly suppressed NCAPG2 expression and inhibited cell proliferation, migration, and invasion. Co-immunoprecipitation confirmed a direct binding between PBK and NCAPG2. CONCLUSIONS PBK is a key regulator of pancreatic cancer and interacts with NCAPG2 to promote tumor progression, suggesting its value as a potential biomarker and therapeutic target for pancreatic cancer.
Humans ; Pancreatic Neoplasms/genetics* ; Prognosis ; Biomarkers, Tumor/genetics* ; Cell Line, Tumor ; Cell Proliferation ; Adenocarcinoma/metabolism* ; Tumor Microenvironment ; Cell Movement ; Mitogen-Activated Protein Kinase Kinases

Immune repertoire is defined as the sum of T cells and B cells, which possesses high diversity and enables immune system to respond to various antigen stimuli. With the development of sequencing technique, immune repertoire sequencing can be utilized to deeply understand the changes of lymphocyte clones when rejection occurs at the gene level, and also provide the possibility for the emergence of novel non-invasive diagnostic techniques based on immune repertoire sequencing. In recent years, more and more attempts have been made to apply immune repertoire sequencing in solid organ transplantation, especially in the fields of kidney transplantation, liver transplantation, heart transplantation and post-transplantation infection. In this article, research progresses on the application of immune repertoire sequencing in these fields were reviewed, and current status of immune repertoire sequencing in organ transplantation and its potential as a novel technique for early non-invasive diagnosis of rejection were summarized, aiming to provide reference for subsequent development and clinical application of this technique.

Internet medical services provide a more convenient communication channel between doctors and patients.Doctors can communicate with patients through online consultation,telephone and other ways to understand the patient's condition and provide treatment suggestions.This kind of communication mode can enable patients to trust doctors more and establish a good doctor-patient relationship.Therefore,this paper analyzes the development of Internet medical services in hospitals,analyzes the development of services from the perspective of pre diagnosis,in-process and post diagnosis services,and puts forward countermeas-ures for the development of Internet medical services from the perspective of patient satisfaction in view of the lack of perfect policy guarantees,the inability to effectively feedback the needs of patients,the lack of mature service models and other issues.

OBJECTIVE To analyse the prognosis and laryngeal function retention of patients undergoing minimally invasive and open surgery after induction chemotherapy.METHODS The clinical data of 54 hypopharyngeal carcinoma patients who received induction chemotherapy and underwent laryngeal preservation surgery in Beijing Tongren Hospital from 2016 to 2022 were retrospectively analyzed.The laryngeal function recovery and survival rate were compared between the two groups.RESULTS Twenty-eight patients underwent transoral minimally invasive surgery and 26 patients underwent partial laryngectomy and/or partial laryngectomy via external cervical approach.The 3-year survival rates of the two groups were 63%and 59%,respectively,and the difference was not statistically significant(P＞0.05).The differences were statistically significant(P＜0.05).CONCLUSION In patients with downstaged hypopharyngeal carcinoma after induction chemotherapy,the survival rate of transoral minimally invasive surgery is similar to that of open surgery,and the laryngeal function recovery of transoral minimally invasive surgery is better.

Objective To investigate the expression of 8-hydroxy deoxy guanosine(8-OHdG)and nectin-4 in the serum of primary liver cancer(PLC),and to evaluate the efficacy of transcatheter chemoembolization(TACE)for PLC.Methods From January 2021 to June 2022,180 patients with primary liver cancer with TACE were studied.According to the efficacy of TACE patients,they were separated into a good group(n=137)and an adverse group(n=43).The general clinical data and the serum expression levels of 8-OHdG and nectin-4 were compared between the two groups;multivariate Logistic regression was applied to analyze the influencing factors of postoperative efficacy in TACE for primary liver cancer;receiver operating characteristic was applied to analyze the value of serum 8-OHdG and nectin-4 levels in evaluating the efficacy of TACE for primary liver cancer.Results There were no significant differences in age,sex,BMI,Child-Pugh grade,tumor location,tumor number,tumor diameter,tumor contour,degree of differentiation,tumor envelope,vascular cancer thrombus,bile duct cancer thrombus and lymph node metastasis between the poor postoperative efficacy group and the good efficacy group after TACE for primary liver cancer(P＞0.05).The expression levels of serum 8-OHdG and nectin-4 in the poor postoperative efficacy group after TACE for primary liver cancer were obviously higher than those in the good efficacy group(P＜0.05).Multivariate Logistic regression analysis showed that serum 8-OHdG,nectin-4,tumor diameter,TNM staging and Lymph node metastasis were all independent influencing factors for the postoperative efficacy of TACE in primary liver cancer(P＜0.05).The AUC of the combined evaluation of serum 8-OHdG and nectin-4 for the postoperative efficacy of TACE in primary liver cancer was 0.930,with a sensitivity of 86.05％and a specificity of 94.16％,which was superior to their respective individual evaluations(Zcombination-8-OHdG=2.033,Zcombination-nectin-4=3.221,P=0.042,0.001).Conclusion The serum levels of 8-OHdG and nectin-4 are obviously increased in the poor postoperative efficacy group after TACE for primary liver cancer.The combination of the two has a good evaluation effect on the postoperative efficacy of TACE for primary liver cancer.

Objective:To investigate the characteristics of congenital hypothyroidism (CH) in premature infants and analyze the predictors of transient congenital hypothyroidism(TCH) and permanent CH (PCH).Methods:A retrospective study was conducted on the preterm infants with CH born in Beijing from January 2008 to June 2018. They were screened, diagnosed and treated by the Beijing Neonatal Disease Screening Center. They were assigned into TCH and PCH groups according to the clinical prognosis. Univariate analysis and Logistic regression analyses were used to determine the predictors of PCH, and the receiver operating characteristic curve (ROC) was drawn to determine the best cut-off point.Results:A total of 2 216 892 newborns were screened, 15 382 were initially screened positive, the median time of screening was 4(4,10) d after birth, and the median time of postnatal reexamination was 30(22,42) d after birth, 14 576 newborns were reexamined, the reexamination rate was 94.8%. A total of 92 preterm infants were diagnosed with CH, of which 60 were TCH, accounting for 65.2%; 28 were PCH, accounting for 30.4%; and 4 were lost to follow-up, accounting for 4.3%. Univariate analysis showed that in the PCH group, the abnormal rate of thyroid B-ultrasound, levothyroxine (LT4) dose at 1-year old, thyrotropin (TSH) level at 2 years old, LT4 dose at 2 years old, LT4 dose and free thyroxine (FT4) level at 3 years old were higher than those in the TCH group. Logistic regression analysis revealed that abnormal B-ultrasound ( OR=12.184,95% CI 2.270~65.403), and elevated TSH level at 2 years old ( OR=2.033,95% CI 1.280~3.228),increased LT4 dose at 3 year old ( OR=21.435,95% CI 3.439~133.584) are the risk factors for PCH. The maximum area under ROC curve was 0.798 at 3 years old (95% CI 0.680~0.916), the best cut-off point was 1.3 μg/(kg·d) for the 3-year-old drug dose; followed by 2-year-old TSH level, which was 0.683 (95% CI 0.548~0.817), the best cut-off point was 4.51 μIU/ml. Conclusions:TCH accounted for a large proportion of preterm infants with CH. During the follow-up, the increased LT4 dose at 3 years old and the elevated TSH level at 2 years old were the early predictors of PCH.

Objective:To evaluate the mid-term complication rates of the Hui-Jing one-stage procedure (lingual mucosa combined with longitudinal preputial island flap onlay urethroplasty + tubularized incised plate glansplasty)versus the classic Bracka staged surgery for children with severe hypospadias.Methods:A retrospective analysis was conducted on clinical data of 75 children with proximal hypospadias who were treated at the Seventh Medical Center of PLA General Hospital from March 2017 to June 2022. Of these patients, 31 cases (15 cases penoscrotal type and 16 cases perineal type) were underwent the Bracka two-stage surgery with a median age of 38 months (24.0, 44.5) and 44 cases underwent the Hui-Jing one-stage procedure (23 cases penoscrotal type and 21 perineal type) with a median age of 40.5 months (20.75, 90.5). The length of urethral plate defect after correction of penile curvature was (4.30±0.84)cm in the Bracka group and (4.56±0.79)cm in the Hui-Jing group, which also showed no significant difference.There was no statistically significant difference of the median age and the position of preoperative urethral opening between the two groups( P=0.47, P=0.74). The first stage of Bracka repair consists of orthoplasty and urethral bed substitution with free preputial graft. After 6 months, the urethral plate created from free graft was tabularized to form neourethra; Hui-Jing procedure group used the free lingual mucosal as urethral plate substitution, then we conducted longitudinal preputial island flap Onlay and Snodgrass phalloplasty. The incidence of postoperative urethral fistula, urethral stricture and urethral diverticulum was compared between the two groups of cases and the difference in efficacy between the two procedures was assessed. Results:Among the 75 patients included in the study, there was no statistically significant difference in age or location of urethral meatus between the Bracka and Hui-Jing groups. In Bracka group, 9 cases of urethral stricture (29.0%), 6 case of urethral fistula (19.4%), and 2 cases of urethral diverticulum (6.5%) occurred after surgery, while 12 cases of urethral fistula (27.3%) and 3 case of urethral fistula (6.8%) occurred in the Hui-Jing group. No urethral stricture occurred in Hui-Jing group. There was no statistically significant difference in overall incidence of complications between the two groups [17/31(54.8%) vs.15/44(34.1%), P=0.12]. The incidence of urethral fistula and urethral diverticulum show no significant differences between two groups(19.4% vs 27.3, P=0.61, 6.5% vs. 6.8%, P=0.13). The number of operation in Bracka group was (2.68±1.03) and the hospitalization cost was (12 984.63±3 808.15) Yuan, while the number of operation in Hui-Jing group was (1.36±0.53) and the hospitalization cost was (8 490.54±3 136.84) Yuan. Conclusions:The Hui-Jing one-stage procedure can be used for the surgical treatment of children with severe hypospadias. There is no urethral stricture happened in Hui-Jing group, while the general complication incidence and incidence of urethral fistula and diverticulum show no differences.

ObjectiveTo investigate the effect of supplemented Buyang Huanwutang on kidney tissue， nuclear factor-κB （NF-κB） pathway， and fibrosis factors in diabetic kidney disease （DKD） mice. MethodA total of 24 db/db mice （11-12 weeks old） were randomized into the model group （equivalent volume of distilled water， once/day， 8 weeks）， supplemented Buyang Huanwutang group （16.0 g·kg^-1， once/day， 8 weeks）， and irbesartan group （13.5 mg·kg^-1， once/day， 8 weeks） after adaptive feeding for 1 week and positive urinary protein monitoring， with 8 in each group. Another 8 db/m mice （11-12 weeks old） were included in the normal group （equivalent volume of distilled water， once/day， 8 weeks）. Then samples were collected， and the levels of fasting blood glucose （FBG）， total cholesterol （TC）， triglyceride （TG）， blood urea nitrogen （BUN）， serum creatinine （SCr）， and urinary microalbumin （mALB） were detected. The mRNA expression of tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， and monocyte chemoattractant protein-1 （MCP-1） was determined by real-time polymerase chain reaction （Real-time PCR）. The expression of nuclear factor-κB （NF-κB）， NF-κB inhibitor α （IκBα）， phosphorylated IκBα （p-IκBα）， transforming growth factor-β₁ （TGF-β₁）， α-smooth muscle actin （α-SMA）， and fibronectin （FN） in kidney tissue was measured by Western blot. The expression of NF-κB in renal tissue was detected by immunofluorescence. The pathological changes of kidney were observed under light microscope. ResultCompared with the normal group， the model group showed glomerular hypertrophy， increase in extracellular matrix， thickening of basement membrane， small cystic lumen， interstitial inflammatory cell infiltration， and some interstitial fibrosis （P<0.01）. Moreover， the model group had higher content of FBG， mALB， TC， TG， BUN， and SCr （P<0.01）， higher expression of inflammatory factors TNF-α， IL-1β， and MCP-1， and fibrosis-related proteins TGF-β₁， α-SMA， and FN （P<0.01）， and stronger activation of NF-κB pathway in renal tissue （P<0.01） than the normal group. Compared with the model group， supplemented Buyang Huanwutang alleviated the pathological injury in kidney （P<0.01）， decreased the content of mALB， TC， and TG， the content of BUN and SCr （P<0.01）， and the content of TNF-α， IL-1β， and MCP-1 （P<0.05， P<0.01）， and inhibited the activation of NF-κB pathway and the expression of fibrosis factors in renal tissue （P<0.05， P<0.01）， but had no significant effect on blood glucose level. ConclusionBy inhibiting NF-κB pathway and the expression of fibrosis factors in renal tissue， supplemented Buyang Huanwutang can exert anti-inflammatory and anti-fibrosis effect and alleviate the pathological damage in kidney tissue， thereby protecting the kidney.

Objective To develop a magnetic anastomosis device for infrahepatic inferior vena cava and verify its feasibility and safety in rat models. Methods According to the anatomical characteristics of rat inferior vena cava, a magnetic device suitable for end-to-end anastomosis of infrahepatic inferior vena cava was designed and manufactured. The device consisted of the inner and outer rings. The inner ring was a coated neodymium-iron-boron magnetic ring, and the outer ring was made of polyetheretherketone by 3D printing. Ten fine holes are evenly distributed on the outer ring, of which 5 fine holes were used to load the fine needles, and the other 5 fine holes were mutually connected with the fine needles of the contralateral anastomosis ring during anastomosis. The outer ring was uniformly loaded with fine needles and then bonded with the inner ring to form a magnetic anastomosis complex. Bilateral ends of vessels passed through the anastomosis ring and were fixed to the fine needles, and then end-to-end vascular anastomosis was performed by mutual attraction of two magnetic anastomosis rings. Twenty SD rats were selected and received end-to-end anastomosis of infrahepatic inferior vena cava with magnetic anastomosis device. The time of vascular occlusion, postoperative survival, postoperative anastomotic patency, gross observation and histological examination of anastomotic stoma were analyzed. Results All rats successfully completed end-to-end magnetic anastomosis of the infrahepatic inferior vena cava, and the time of vascular occlusion was 4~6 min. One rat died at 10 d after operation, and the other rats survived within postoperative 2 months. The patency rates of anastomotic stoma in surviving rats at postoperative 1 d, 3 d, 1 month and 2 months were 100%, 100%, 95% and 95%, respectively. At 2 months after operation, no obvious displacement and angulation of the anastomosis device were seen. No signs of corrosion and cracking of the anastomosis rings were observed. No evident hyperplasia and edema of surrounding tissues were noted. Bilateral ends of vessels were completely healed, and no obvious stenosis or thrombosis was found at the anastomotic stoma. Histological examination showed high continuity of bilateral vascular walls of anastomotic stoma, the inner surface of anastomotic stoma was covered by endothelial cells, and no thrombus or fibrous tissue was attached. Conclusions It is safe and feasible to utilize the self-designed magnetic anastomosis device to perform end-to-end magnetic anastomosis of infrahepatic inferior vena cava in rat models.