Peptide receptor radionuclide therapy (PRRT) with radiolabeled SSTR2 agonists is a treatment option that is highly effective in controlling metastatic and progressive neuroendocrine tumors (NETs). Previous studies have shown that an SSTR2 agonist combined with albumin binding moiety Evans blue (denoted as ¹⁷⁷Lu-EB-TATE) is characterized by a higher tumor uptake and residence time in preclinical models and in patients with metastatic NETs. This study aimed to enhance the in vivo stability, pharmacokinetics, and pharmacodynamics of ¹⁷⁷Lu-EB-TATE by replacing the maleimide-thiol group with a polyethylene glycol chain, resulting in a novel EB conjugated SSTR2-targeting radiopharmaceutical, ¹⁷⁷Lu-LNC1010, for PRRT. In preclinical studies, ¹⁷⁷Lu-LNC1010 exhibited good stability and SSTR2-binding affinity in AR42J tumor cells and enhanced uptake and prolonged retention in AR42J tumor xenografts. Thereafter, we presented the first-in-human dose escalation study of ¹⁷⁷Lu-LNC1010 in patients with advanced/metastatic NETs. ¹⁷⁷Lu-LNC1010 was well-tolerated by all patients, with minor adverse effects, and exhibited significant uptake and prolonged retention in tumor lesions, with higher tumor radiation doses than those of ¹⁷⁷Lu-EB-TATE. Preliminary PRRT efficacy results showed an 83% disease control rate and a 42% overall response rate after two ¹⁷⁷Lu-LNC1010 treatment cycles. These encouraging findings warrant further investigations through multicenter, prospective, and randomized controlled trials.

Esophagogastric variceal bleeding (EGVB) is one of the main complications of decompensated portal hypertension, especially in patients with liver cirrhosis, and it often has a high mortality rate. Medication combined with endoscopy is the main prevention and treatment method for EGVB, while transjugular intrahepatic portosystemic shunt (TIPS) combined with variceal embolization can also be selected for some high-risk patients, and individualized diagnosis and treatment of portal hypertension based on hepatic venous pressure gradient should become the latest consensus and the main strategy. This article mainly reviews endoscopic therapy and TIPS for the prevention and treatment of EGVB patients with decompensated portal hypertension in terms of selection of indications, incidence rate of complications, and respective advantages and disadvantages.

Objective:To investigate the clinical utility of 68Ga-labeled fibroblast activation protein inhibitor (FAPI) PET/CT in the detection of primary and metastatic gastric signet-ring cell carcinoma (GSRCC) and compared the results with those of 18F-FDG PET/CT. Methods:A total of 21 patients (10 males, 11 females, average age 52 years) with primary and metastatic GSRCC who underwent 68Ga-FAPI and 18F-FDG PET/CT at the First Affiliated Hospital of Xiamen University from June 2020 to May 2022 were retrospectively analyzed. Pathological results of surgery and (or) biopsy were used as the " gold standard" for final diagnosis. In cases whose surgery or tissue biopsies were not available, clinical and radiographic follow-up results were used as the reference standards. Wilcoxon signed-rank test was used to compare the SUV max of 18F-FDG and 68Ga-FAPI. McNemar χ2 test was used to compare the detection rate between 18F-FDG and 68Ga-FAPI PET/CT. Results:68Ga-FAPI PET/CT showed higher SUV max than 18F-FDG in primary tumors (5.3(2.4, 15.7) vs 2.4(1.8, 2.5); z=2.31, P=0.021), local recurrences (7.8(6.0, 8.9) vs 2.4(1.9, 3.4); z=2.20, P=0.028), lymph nodes metastases (7.7(4.5, 12.2) vs 2.4(1.9, 3.6); z=6.01, P<0.001) and bone/visceral metastases (6.7(5.3, 11.1) vs 2.4(2.0, 3.4); z=11.36, P<0.001). Regarding diagnostic accuracy, 68Ga-FAPI PET/CT showed higher sensitivities than 18F-FDG for primary tumors (7/9 vs 2/9; χ2=3.20, P=0.063) and local recurrences (7/7 vs 2/7; χ2=3.20, P=0.063). It also demonstrated higher lesion detection rates than 18F-FDG for suspicious lymph node metastases (86%(65/76) vs 32%(24/76); χ2=31.37, P<0.001) and bone/visceral metastases (99%(184/185) vs 39%(73/185); χ2=107.08, P<0.001). Conclusions:68Ga-FAPI PET/CT showed higher tumor uptake and lesion detection rate than 18F-FDG in the primary and metastatic GSRCC. 68Ga-FAPI PET/CT demonstrates good diagnostic performance for tumor detection, staging, and restaging of GSRCC, which is helpful to further guide clinical treatment strategy.

Objective To investigate the potential of ginkgolide B(GB)in mitigating vascular endothelial injury by antagonizing endoplasmic reticulum stress(ERS)and elucidate its underlying molecular mechanism.Methods An injury model of human bone marrow-derived endothelial progenitor cells(EPCs)induced by tunica-mycin(TM)was established.Cell proliferation was assessed using MTS assay,while cell viability was determined through Calcein-AM/EthD-I double staining.Transwell assay was employed to evaluate cell migration ability.DCFH-DA staining was utilized to measure intracellular ROS levels,and NADPH activity was quantified via ELISA.JC-1 and DiOC6 staining were performed for qualitative and quantitative assessment of mitochondrial membrane potential respectively.Qrt-pcr analysis was conducted to determine mRNA expression levels,whereas western blot analysis enabled detection of protein expression levels in the cells.Results GB dose-dependently attenuated tunicamycin-induced ERS-mediated endothelial injury in hEPCs,as evidenced by decreased cell viability,impaired cell migration,and angiogenesis inhibition(P<0.01).Furthermore,GB treatment significantly reduced ROS production and NADPH levels within the cells(P<0.01),while also inhibiting ERS-mediated decline in mitochondrial membrane potential concentration-dependently(P<0.01).Additionally,GB inhibited the expression of ERS-related proteins such as GRP78,ATF4,CHOP etc.,regulated apoptosis-related protein Bcl-xl,Bax cleaved caspase-4 cytochrome c;thereby effectively counteracting endoplasmic reticulum stress-induced cellular damage.Conclusions GB exerts a protective effect on vascular endothelium by antagonizing endoplasmic reticulum stress;this mechanism may be attributed to its ability to reduce intracellular reactive oxygen species levels.It also suppresses the expression of ERS-related proteins(CHOP78 and ATF4),and modulates apoptosis-associated proteins(Bcl-xl,Bax,cleaved caspase-4,and cytochrome c).

How to improve the performance of circulating tumor DNA (ctDNA) signal acquisition and the accuracy to authenticate ultra low-frequency mutation are major challenges of minimal residual disease (MRD) detection in solid tumors. In this study, we developed a new MRD bioinformatics algorithm, namely multi-variant joint confidence analysis (MinerVa), and tested this algorithm both in contrived ctDNA standards and plasma DNA samples of patients with early non-small cell lung cancer (NSCLC). Our results showed that the specificity of multi-variant tracking of MinerVa algorithm ranged from 99.62% to 99.70%, and when tracking 30 variants, variant signals could be detected as low as 6.3 × 10 ^-5 variant abundance. Furthermore, in a cohort of 27 NSCLC patients, the specificity of ctDNA-MRD for recurrence monitoring was 100%, and the sensitivity was 78.6%. These findings indicate that the MinerVa algorithm can efficiently capture ctDNA signals in blood samples and exhibit high accuracy in MRD detection.
Humans ; Carcinoma, Non-Small-Cell Lung/genetics* ; Lung Neoplasms/genetics* ; Neoplasm, Residual/pathology* ; Biomarkers, Tumor/genetics* ; Computational Biology

Objective:This paper intends to explore the clinical efficacy and safety of the refined extroperitoneal intrafascial laparoscopic radical prostatectomy in patients with localized prostate cancer.Methods:The data of 107 patients with localized prostate cancer who were underwent laparoscopic radical prostatectomy in our hospital from July 2013 to January 2020 were analyzed retrospectively. According to the operation methods, the patients were divided into two groups: the refined intra fascial resection group (59 cases) and the conventional interfascial neurovascular bundle reservation group(48 cases). There was no significant different comparing the age [(61.8±8.9) years vs. (62.2±8.1) years, P=0.71], body mass index (BMI) [(24.8±1.3) kg/m 2 vs.(24.3±1.4) kg/m 2, P=0.89], preoperative total prostate specific antigen (PSA) [(6.8±0.9) ng/ml vs. (7.2±1.1) ng/ml, P=0.44], prostate volume [(47.9±18.4) ml vs. (48.3±17.9) ml, P=0.67] between the modified group and the conventional group. The clinical stage of the two groups was both in cT 1-T 2aN 0M 0, and the preoperative Gleason score was less than or equal to 7 ( P=0.76). In the improved group, the bilateral pelvic floor fascia was not dissected, the dorsal deep vein complex was not sutured, the denonvillier fascia was kept intact, the prostate was dissected by intrafascial technique, and the bilateral vascular and nerve bundles were completely preserved. After anastomosing the urethra and bladder neck, the bilateral prostate fascia, the pubic bladder-prostate ligament, DVC and the anterior wall of bladder neck were continuously sutured with 3-0 barbed wire in order to anatomically reconstructe the anterior suspension system. The preoperative data, intraoperative condition, postoperative pathological stage, positive margin rate and postoperative 6-month's follow-up, especially incontinence and erectile function were compared between the two groups. Results:There was no significant difference between the two groups in the basic clinical data, intraoperative bleeding volume[(90.6±26.4)ml vs.(105.3±34.1)ml, P>0.05], prostate-specific antigen 6 weeks after operation[(0.08±0.06)ng/ml vs.(0.09±0.07) ng/ml, P>0.05], postoperative pathological stage and positive margin rate(12.5% vs. 11.9%, P>0.05). In the early postoperative stage, patients performed a significantly better continence. Continence rate in 1 week: 16.7%(8/48) vs. 52.5%(31/59)( P<0.05), in 1 month: 29.2%(14/48)vs. 64.4%(38/59)( P<0.05), and in 3 month 52.1%(25/48) vs. 77.9%(46/59)( P<0.05). And also a better erectile function recovery rate in 1 month: 8.3%(4/48) vs. 23.7%(14/59)( P<0.05), in 3 month: 27.1%(13/48) vs. 49.2%(29/59)( P<0.05), in refined intrafascial group, but that was not significant different between the two groups 6 months after operation. Conclusion:The refined intrafascial laparoscopic radical prostatectomy can completely reconstruct the anatomic structure adjacent to urethra, and preserve utmostly the pelvic floor muscle, prostate fascia and neurovascular bundle, which are supposed to facilitate the revovery of urinary incontinence and erectile dysfunction in the early postoperative period.

Cases of 2019-nCoV nucleic acid and antibody (IgM and IgG total antibody) after discharge from a hospital in Chongqing were continuously monitored. It was found that 5 cases of "re-positive" phenomenon, 5 cases of antibody were positive, and there was a trend of increasing with time. "Re-Positive" may be related to the following three factors. Children with asymptomatic infection had a long time of fecal detoxification.There were two consecutive nucleic acid tests "false negative" caused by various reasons.The virus clearance in patients was not complete, and the discharge standard was not conservative enough. The analysis of the causes of "Re-Positive" patients and the discussion of its infection will help us reveal more characteristics of this virus, and to provide a new basis for the discharge standard in the constantly updated diagnosis and treatment programme.

Objective: To understand the possible transmission route of a family cluster of COVID-19 in Zhengzhou and the potential infectivity of COVID-19 in incubation period, and provide scientific evidence for the timely control of infectious source and curb the spread of the epidemic. Methods: Epidemiological investigation was conducted for a family cluster of COVID-19 (8 cases) with descriptive epidemiological method, and respiratory tract samples of the cases were collected for the nucleic acid detection of 2019-nCoV by RT-PCR. Results: Two primary cases, which occurred on 31 January and 1 February, 2020, respectively, had a common exposure history in Wuhan. The other six family members had onsets on 30 January, 31 January, 1 February (three cases) and 3 February, 2020. Conclusions In this family cluster of COVID-19, six family members were infected through common family exposure to the 2 primary cases. Five secondary cases had onsets earlier than or on the same day as the primary cases, indicating that COVID-19 is contagious in incubation period, and the home isolation in the early phase of the epidemic might lead to the risk of family cluster of COVID-19.

To compare carbon nanoparticles with methylene blue for sentinel lymph nodes mapping in laparoscopic staging of early endometrial carcinoma.Forty five patients with stage I or stage Ⅱ endometrial carcinoma undergoing laparoscopic operation from January 2016 to January 2018 were randomly divided into two groups:methylene blue was applied in 20 cases and carbon nanoparticies were applied in 25 cases for sentinel lymph node (SLN) mapping in laparoscopic staging;and the images of two tracers were compared.The development time of nano-carbon group was shorter[(16.4±3.4) min vs.(21.0±5.9)min,t=3.26,P=0.02] and duration was longer [(73.1 ± 14.3) min vs.(54.6 ± 14.9)min,t=5.41,P=0.04] than those of methylene blue group.In lymphatic mapping,the detection rate of SLN in nano-carbon group was significantly higher than that of methylene blue group [95％ (21/22)vs.5/18].For detection of metastatic SLN,the sensitivity of methylene blue group was 1/2 and that of nano-carbon group was 4/4 (x2=66.70,P＜0.01).The results indicate that both methylene blue and Nano-carbon tracer can be used for SLN mapping in laparoscopic staging of early endometrial carcinoma,and nano-carbon tracer is recommended as the first choice to predict pelvic lymph node metastasis in endometrial carcinoma surgery.

Objective: To summarized the experience in laparoscopic duodenum-preserving pancreatic head resection (LDPPHR). Methods: The clinical data of four patients who underwent LDPPHR from February 2017 to June 2018 in Hunan Provincial People’s Hospital were retrospectively analyzed. The Clinical characteristics, operation time, intraoperative blood loss, biliary fistula rate, pancreatic fistula rate and follow-up data were analyzed. Results: The four patients included one patient with a solid pseudopapillary tumor and three patients with a serous cystadenoma. Two patients underwent duodenum-preserving total pancreatic head resection, and two patients underwent duodenum-preserving subtotal pancreatic head resection. The operation time of the four patients was (525.8±121.8) minutes, and the blood loss (250.0±191.5) ml. Biliary duct drainage was carried out in 2 patients: one patient developed biochemical bile leakage, while another had no postoperative complication. The two patients without biliary drainage developed grade B pancreatic leakage, delayed bile leakage, abdominal bleeding and infection. All the three patients who developed postoperative complications were treated conservatively and they recovered well. Conclusions LDPPHR was designed to better preserve the integrity and function of digestive tract. However, the perioperative complications were high. This operation should only be carried out in large pancreatic centers. Routine biliary drainage is recommended to surgeons with little experience in this operation.