ObjectiveMethylthioadenosine phosphorylase (MTAP) is found to be frequently deleted in malignant cancers, but the role of MTAP underlying metastasis and stemness of liver cancer remains far from clear. 5-fluorouracil (5-Fu) is clinically used in treating advanced liver cancer, however, chemoresistance is one of the major barriers impeding its efficacy. Liver cancer stem cells are considered to be the reservoir for tumor progression and chemoresistance. This study aims to explore the role of MTAP in regulating stemness and chemoresistance of 5-Fu in liver cancer. It is designed to elucidate the molecular mechanisms underlying MTAP-manipulated stemness. How MTAP influences metastasis and chemoresistance against 5-Fu in liver cancer is also elaborated. MethodsThe correlation of MTAP expression with stemness marker CD133 was evaluated by flow cytometry. Colony formation assays were conducted to analyze the tumorigenic ability. Western blot assays were applied to delineate the molecular mechanisms underlying MTAP-regulated stemness. Trans-well assays were conducted to analyze the metastatic potential of liver cancer cells.In vivo experiments were performed using subcutaneous xenograft and lung metastasis model on nude mice. Tumor size and weight were analyzed upon 5-Fu treatment. Metastatic nodules on lungs were evaluated. Immunohistochemical and TUNNEL assays were performed on slides obtained from tumor tissues. ResultsMTAP overexpression inhibited expression of CD133 and colony formation, which is further ablated by MTAP inhibitor. MTAP deprivation augmented stemness and colony formation, which is reversed by protein arginine methyltransferase 5 (PRMT5) overexpression but not its catalytically inactive counterparts. Critically, SRY-box transcription factor 2 (SOX2) was found to be a downstream regulator of MTAP/PRMT5, leading to stemness of liver cancer cells. MTAP overexpression suppressed SOX2 expression, while MTAP inhibition augmented expression of SOX2. Critically, MTAP overexpression inhibited migration and invasion of liver cancer cells. In vivo experiments in animal model found that MTAP deprivation promotes tumor growth and metastatic nodules of liver cancer. Additionally, MTAP overexpression inhibits tumor growth. Moreover, MTAP deprivation contributes to chemoresistance shown by increased tumor size and weight treated by 5-Fu. In contrast, MTAP overexpression led to further decline in tumor size and weight elicited by 5-Fu treatment. Accordingly, SOX2 was inhibited in tumor tissues after MTAP overexpression. Marker of proliferation Ki67 (Ki67) expression was dampened while apoptosis was found in MTAP-overexpressed tumor tissues. ConclusionIn this study, plethora of experimental studies collectively demonstrated that MTAP deprivation enhances stemness of liver cancer by regulating SOX2, exerting anti-cancer and chemoresistant role against 5-Fu in liver cancer. It is also worth noting that MTAP inhibition promoted metastasis of liver cancer. MTAP overexpression augmented tumor shrinking elicited by 5-Fu and SOX2 was involved in this process. These results concluded that MTAP/PRMT5/SOX2 signaling axis was involved in regulating stemness and chemoresistance of liver cancer. These findings help to exploit novel therapies by targeting stemness in MTAP-depleted liver cancer. It shed novel light on unveiling MTAP-regulated stemness in antagonizing 5-Fu treatment in liver cancer. It also adds mounting evidence to the theoretical basis for accomplishing personalized chemotherapy of liver cancer patients by targeting MTAP or its downstream PRMT5/SOX2.

Objective:To investigate the prognostic value of aldosterone synthase (CYP11B2) immunohistochemical expression in adrenal specimens for surgical outcomes of primary aldosteronism (PA).Methods:The clinical data of 99 patients who underwent total unilateral adrenalectomy from June 2022 to January 2023 at Beijing Anzhen Hospital was retrospectively analysed. The clinical data of 99 patients who underwent unilateral total adrenalectomy at Beijing Anzhen Hospital from June 2022 to January 2023 were retrospectively analyzed.There were 59 patients in the PA group, age (53.02±10.56) years, body mass index (BMI) (26.28±4.33) kg/m 2, preoperative aldosterone 29.0(15.9, 61.5)ng/dl, plasma renin 1.3(0.6, 2.8)μIU/ml, aldosterone renin ratio (ARR) 19.3(9.1, 59.2) μg/μIU, preoperative potassium (3.60±0.69) mmol/L, and systolic blood pressure (156.54±21.39) mmHg (1 mmHg=0.133 kPa).There were 40 cases in the nonfunctioning adenoma (NFA) group, age (57.23±9.39) years, BMI (27.07±3.46) kg/m 2, preoperative aldosterone 9.0(7.2, 14.1) ng/dl, plasma renin 18.0(5.2, 47.6)μIU/ml, ARR 0.6(0.2, 1.4) μg/μIU, preoperative potassium (4.17±0.41) mmol/L, and systolic blood pressure (157.97±26.87) mmHg. The differences between the two groups were statistically significant for potassium ( P<0.01), aldosterone ( P=0.012), renin ( P<0.01), and ARR ( P<0.01).Surgical outcomes were assessed using the Consensus on the Outcome of Surgery for Primary Aldosteronism (PASO) (complete/partial/no success for clinical and biochemical outcomes). CYP11B2 expression was evaluated by immunohistochemistry using the 2022 World Health Organization's histopathology of primary aldosteronism (HISTALDO) criteria. The correlation between the expression of CYP11B2 and surgical outcomes was assessed. Results:The mean follow-up of 99 patients was (11.73±4.92) months. Of these, 36 out of 59 PA patients had positive CYP11B2 expression in their adrenal specimens, while 23 were negative; all 40 NFA patients were negative for CYP11B2. Among the 36 CYP11B2-positive PA patients, there were 19 cases of aldosterone-producing adenomas, 3 aldosterone-producing nodules, 4 aldosterone-producing micronodules, 8 multiple aldosterone-producing micronodules, and 2 aldosterone-producing diffuse hyperplasia. 36 cases of CYP11B2-positive PA patients had complete clinical success in 15 cases, partial success in 20 cases, and no success in 1 case, and complete biochemical success in 24 cases, partial success in 11 cases, and no success in 1 case; 23 CYP11B2-negative PA patients had complete clinical success in 4 cases, partial success in 15 cases, and no success in 4 cases, and complete biochemical success in 6 cases, partial success in 15 cases, and no success in 2 cases. Adrenal specimens from CYP11B2-positive PA patients had significantly better clinical ( P=0.038) and biochemical ( P=0.008) success rates than CYP11B2-negative PA patients. Patients with aldosterone-producing adenomas had complete clinical success in 8 cases, partial success in 11 cases, and no success in 0 cases, and biochemical success was completely achieved in 16 cases, partially achieved in 2 cases, and not successful in 1 case. They also had significantly higher clinical ( P=0.028) and biochemical ( P<0.01) success rates compared to CYP11B2-negative PA patients. Conclusions:Patients with PA who had immunohistochemical staining for CYP11B2 positivity and high expression in adrenal specimens had a better postoperative clinical and biochemical prognosis. Patients with aldosterone-producing adenomas had the greatest postoperative outcome of all pathological subtypes of PA.

Turning to critical illness is a common stage of various diseases and injuries before death. Patients usually have complex health conditions, while the treatment process involves a wide range of content, along with high requirements for doctor′s professionalism and multi-specialty teamwork, as well as a great demand for time-sensitive treatments. However, this is not matched with critical care professionals and the current state of medical care in China. Telemedicine, which shortens the distance of medical professionals and the gap of disease diagnosis and treatments in various regions through electronic information, can effectively solve the current problem. Therefore, there is an urgent need to develop a standardized, high-quality visualization telemedicine round system .Therefore, experts have been organized to search domestic and foreign literature on telemedicine round for critically ill patients and to form this consensus based on clinical experiences so as to further improve the level of critical care treatments in regions.

Purpose: This study compared the outcomes of haploidentical-related donor (HRD) and umbilical cord blood (UCB) hematopoietic stem cell transplantation (HSCT) in pediatric patients with hematologic malignancies. Methods: Data on patients who underwent HRD HSCT with post-transplant cyclophosphamide (n = 41) and UCB HSCT (n = 24) after targeted busulfan-based myeloablative conditioning with intensive pharmacokinetic monitoring between 2009 and 2018 were retrospectively analyzed. Results: The median follow-up durations in the HRD and UCB groups were 7.0 and 10.9 years, respectively. The cumu‑ lative incidence of acute graft-versus-host disease (GVHD) grades II–IV and moderate-to-severe chronic GVHD did not differ significantly between the groups. However, the HRD group demonstrated significantly lower rates of acute GVHD grades III–IV (4.9% vs. 29.2%, p = 0.009) and non-relapse mortality (2.6% vs. 34.2%, p < 0.001) but a higher relapse incidence (32.1% vs. 8.8%, p = 0.004) than the UCB group. The 5-year event-free and overall survival rates were 65.8% and 54.2% (p = 0.204) and 78.0% and 65.7% (p = 0.142) for the HRD and UCB groups, respectively. Multivariate analysis identified disease status as a significant risk factor for overall survival (hazard ratio, 3.24; p = 0.016). Additionally, UCB HSCT exhibited a trend toward worse event-free survival compared to HRD HSCT (hazard ratio, 2.63; p = 0.05). Conclusions These findings indicate that HRD HSCT with post-transplant cyclophosphamide provides promising outcomes compared to UCB HSCT in pediatric patients, with a trend toward improved survival over a long-term follow-up period exceeding a median of 7 years. Thus, HRD HSCT may be a valuable option for pediatric patients with‑ out human leukocyte antigen-matched donors.

The single photon counting imaging detector based on microchannel plate(MCP)has the characteristics of high sensitivity and low dark count rate,and has been applied to the optical remote sensing detection of weak ultraviolet spectral signals in space.In this work,by using planar array single photon counting imaging detector as the detector,flat-field concave grating as the splitter,and electrodeless discharge lamp(EDL)as the excitation light source,a dispersion detection system suitable for hydride generation-atomic fluorescence spectrometry(HG-AFS)was developed.The wavelength calibration of the system was carried out,and the negative high pressure and EDL stability time of the planar array single photon counting imaging detector were analyzed and optimized.The characteristic emission spectral lines of As and Bi elements excited in the wavelength range of 180-320 nm were analyzed,and the scattering interference in the wavelength range of 257.3-306.7 nm was discussed.The results showed that the AFS dispersion detection system based on the planar array single photon counting imaging detector could detect and analyze the HG-AFS fluorescence signal initially,and the influence of scattering interference on the detection results was effectively avoided.The system had the advantages including simple structure,no refrigeration and temperature control,no moving parts and simultaneous measurement of multi-band.

By summarizing the mass spectrometric fragmentation patterns of oxyphenisatin substances,an analytical method was established for screening of illegally added oxyphenisatin compounds in weight-loss health foods using high performance liquid chromatography-in-source-fragmentation-quadrupole time-of-flight mass spectrometry(HPLC-ISF-QTOF-MS),along with a quantitative method for 11 kinds of oxyphenisatin compounds.Based on the developed screening method,an oxyphenisatin derivative was discovered in the reference standards,which was tentatively identified as 4-(3-(4-hydroxyphenyl)-2-oxoindolin-3-yl)phenyl acetate and confirmed by MS/MS analysis.The results showed that all 11 kinds of oxyphenisatin compounds had correlation coefficients greater than 0.9971,with limits of detection(LODs)ranging from 0.12 to 0.68 μg/L and limits of quantification(LOQ)from 0.21 to 2.29 μg/L.The LODs for 11 kinds of characteristic ions ranged from 0.45 to 9.11 μg/kg.At spiking levels of 25,50 and 100 μg/kg,the recoveries ranged from 78.9%to 117.3%.The instrumental precision,intra-day method precision and inter-day method precision were 0.23%?1.70%,0.7%?2.4%,and 1.1%?3.3%,respectively.The developed targeted and non-targeted detection method demonstrated high sensitivity,strong stability,rapid analysis,and an expanded screening range for oxyphenisatin substances,and provided robust technical support for regulatory authorities in combating illegal adulteration.

Background: Small cell lung cancer (SCLC) is called ‘smoker’s disease’ because it is strongly associated with smoking and most cases occur in smokers. However, it can also occur in never smokers. We investigated the clinical features of never smokers with SCLC and compared their treatment outcomes with those of smokers with SCLC. Methods: We retrospectively reviewed the clinical data of patients who had proven SCLC and had received chemotherapy at a single cancer center between July 2002 and April 2021. Results: Of 1,643 patients, 1,416 (86.2%) were enrolled in this study. A total of 162 (11.4%) and 1,254 (88.6%) patients were never smokers and smokers, respectively. There were more female never smokers than smokers (n=130; 80.2% vs. 79, 6.3%, p=0.000), and the incidence of ischemic heart disease was lower among never smokers than among smokers (4/1,416, [2.5%] vs. 83/1,416 [6.6%], p=0.036). Never smokers showed less symptoms at diagnosis than smokers (80.9% vs. 87.2%, p=0.037); however, they showed more toxicity after first-line treatment (61.7% vs. 47.8%, p=0.001). The objective response rate (ORR) was significantly higher in never smokers (74.1% vs. 59.6%, p=0.000). In the multivariate analysis, never smoking and second-line treatment were associated with a better ORR. However, progression-free survival and overall survival were not significantly different between never smokers and smokers. Conclusion In conclusion, never smokers accounted for 11.4% of patients with SCLC. They had distinguishing clinical characteristics and showed better chemotherapeutic responses than smokers.

Purpose: This study compared the outcomes of haploidentical-related donor (HRD) and umbilical cord blood (UCB) hematopoietic stem cell transplantation (HSCT) in pediatric patients with hematologic malignancies. Methods: Data on patients who underwent HRD HSCT with post-transplant cyclophosphamide (n = 41) and UCB HSCT (n = 24) after targeted busulfan-based myeloablative conditioning with intensive pharmacokinetic monitoring between 2009 and 2018 were retrospectively analyzed. Results: The median follow-up durations in the HRD and UCB groups were 7.0 and 10.9 years, respectively. The cumu‑ lative incidence of acute graft-versus-host disease (GVHD) grades II–IV and moderate-to-severe chronic GVHD did not differ significantly between the groups. However, the HRD group demonstrated significantly lower rates of acute GVHD grades III–IV (4.9% vs. 29.2%, p = 0.009) and non-relapse mortality (2.6% vs. 34.2%, p < 0.001) but a higher relapse incidence (32.1% vs. 8.8%, p = 0.004) than the UCB group. The 5-year event-free and overall survival rates were 65.8% and 54.2% (p = 0.204) and 78.0% and 65.7% (p = 0.142) for the HRD and UCB groups, respectively. Multivariate analysis identified disease status as a significant risk factor for overall survival (hazard ratio, 3.24; p = 0.016). Additionally, UCB HSCT exhibited a trend toward worse event-free survival compared to HRD HSCT (hazard ratio, 2.63; p = 0.05). Conclusions These findings indicate that HRD HSCT with post-transplant cyclophosphamide provides promising outcomes compared to UCB HSCT in pediatric patients, with a trend toward improved survival over a long-term follow-up period exceeding a median of 7 years. Thus, HRD HSCT may be a valuable option for pediatric patients with‑ out human leukocyte antigen-matched donors.

Background: Small cell lung cancer (SCLC) is called ‘smoker’s disease’ because it is strongly associated with smoking and most cases occur in smokers. However, it can also occur in never smokers. We investigated the clinical features of never smokers with SCLC and compared their treatment outcomes with those of smokers with SCLC. Methods: We retrospectively reviewed the clinical data of patients who had proven SCLC and had received chemotherapy at a single cancer center between July 2002 and April 2021. Results: Of 1,643 patients, 1,416 (86.2%) were enrolled in this study. A total of 162 (11.4%) and 1,254 (88.6%) patients were never smokers and smokers, respectively. There were more female never smokers than smokers (n=130; 80.2% vs. 79, 6.3%, p=0.000), and the incidence of ischemic heart disease was lower among never smokers than among smokers (4/1,416, [2.5%] vs. 83/1,416 [6.6%], p=0.036). Never smokers showed less symptoms at diagnosis than smokers (80.9% vs. 87.2%, p=0.037); however, they showed more toxicity after first-line treatment (61.7% vs. 47.8%, p=0.001). The objective response rate (ORR) was significantly higher in never smokers (74.1% vs. 59.6%, p=0.000). In the multivariate analysis, never smoking and second-line treatment were associated with a better ORR. However, progression-free survival and overall survival were not significantly different between never smokers and smokers. Conclusion In conclusion, never smokers accounted for 11.4% of patients with SCLC. They had distinguishing clinical characteristics and showed better chemotherapeutic responses than smokers.

PURPOSE: Bone cement-reinforced fenestrated pedicle screws (FPSs) have been widely used in the internal fixation and repair of the spine with osteoporosis in recent years and show significant improvement in fixation strength and stability. However, compared with conventional reinforcement methods, the advantages of bone cement-reinforced FPSs remain undetermined. This article compares the effects of fenestrated and conventional pedicle screws (CPSs) combined with bone cement in the treatment of osteoporosis. METHODS: A clinical control study of FPSs and CPSs combined with bone cement reinforcement in osteoporotic vertebral internal fixation was performed using the database PubMed, Embase, Cochrane Library, CNKI, the Wanfang, and the China Biomedical Literature Service System. Two evaluators screened the relevant literature in strict accordance with the inclusion criteria (diagnosis of participants, type of clinical study, treatment with FPS and CPS, and outcome indicators) and exclusion criteria (duplicate literature and missing or incorrect data) and independently conducted data extraction and quality evaluation. Clinical control studies of direct comparison between FPS and CPS combined with bone cement reinforcement in patients who were definitively diagnosed with thoracolumbar fractures or spinal degenerative diseases were included. Quality evaluation was conducted using the Cochrane risk bias evaluation tool for randomized controlled studies and using the Newcastle-Ottawa scale for retrospective case-control studies. RevMan software (version 5.3) was used for the meta-analysis to compare the clinical efficacy, radiological results, and related complications of the 2 methods. RESULTS: A total of 13 articles were included, including 7 randomized controlled studies and 6 retrospective case-control studies. There were 909 patients in these studies, 451 in the FPS and polymethyl methacrylate (FPS & PMMA) group and 458 in the CPS and polymethyl methacrylate (CPS & PMMA) group. The results of the meta-analysis showed that there was no significant difference between the 2 groups in operation time, hospital stay, visual analogue score, Japanese orthopaedic association score, Oswestry disability index score, Cobb angle, vertebral body deformation index and fusion rate (p > 0.05). The mean difference of intraoperative bleeding volume was -10.45, (95% confidence intervals (CI) (-16.92, -3.98), p = 0.002), the mean difference of loss height of the anterior edge of the vertebral body after surgery was -0.69 (95% CI (-0.93, -0.44), p < 0.001), and the relative risk (RR) of overall complication rate was 0.43 (95% CI (0.27, 0.68), p < 0.001), including the RR of bone cement leakage rate was 0.57 (95% CI (0.39, 0.85), p = 0.005). The screw loosening rate (RR = 0.26, 95% CI (0.13, 0.54), p < 0.001) of the FPS group was significantly lower than that of the CPS group. CONCLUSION The existing clinical evidence shows that compared with the CPS combined with bone cement, the use of FPS repair in the internal fixation of an osteoporotic vertebral body can reduce the amount of intraoperative bleeding, be more conducive to maintaining the height of the vertebral body, and significantly reduce the incidence of postoperative complications such as bone cement leakage and screw loosening.
Humans ; Pedicle Screws ; Bone Cements ; Spinal Fractures/surgery* ; Osteoporotic Fractures/surgery* ; Fracture Fixation, Internal/instrumentation*