Abdominal catheter-induced intussusception following renal transplantation in two pediatric recipients: 2 cases report and literature review.

Background: Intussusception is a frequent abdominal emergency in the pediatric population when the proximal bowel invaginates into the distal bowel. However, catheter-induced intussusception has not previously been described in pediatric renal transplant recipients, and the risk factors need to be investigated. Case Description: We report 2 cases of post-transplant intussusception which were caused by abdominal catheters. Case 1 experienced ileocolonic intussusception 3 months after renal transplantation and presented with intermittent abdominal pain; the intussusception was successfully managed using air enema. However, this child experienced a total of 3 episodes of intussusception within 4 days, which discontinued only after removal of the peritoneal dialysis catheter. No further intussusception recurrence was observed and the patient's intermittent pain disappeared during the follow-up. Case 2 developed ileocolonic intussusception 2 days after renal transplantation and presented currant jelly stools. The intussusception was completely irreducible until the intraperitoneal drainage catheter was eliminated; the patient discharged normal feces during the following days. A search in the databases of PubMed, Web of Science, and Embase yielded 8 similar cases. Our 2 cases had a younger age at disease onset than those retrieved in the search, and abdominal catheter was revealed as a lead point. Possible leading points of the 8 previously reported cases included post-transplant lymphoproliferative disorder (PTLD), acute appendicitis, tuberculosis, lymphocele, and firm adhesions. We noted that our cases were managed successfully with nonoperative treatment, whereas the 8 reported cases underwent surgical intervention. All of the 10 cases of intussusception occurred after renal transplantation and showed that intussusception had been induced by a lead point. Conclusions: Our 2 cases implied that abdominal catheter could be a lead point to induce intussusception, especially in pediatric recipients with abdominal disorder. This experience may be applicable to other surgeries involving indwelling abdominal catheters in children. Health practitioners should consider this pathologic lead point and avoid serious consequences when intussusception occurs.

Chemotherapy with a TP Regimen in Combination with Stereotactic Radiotherapy Could Significantly Optimize the Clinical Efficacy of NSCLC Treatment.

The changes in lifestyle and bad living habits have a significant impact on the health of people, resulting in an increasing prevalence of lung cancer. The most prevalent kind of lung cancer is nonsmall cell lung cancer (NSCLC), which accounts for around 80% of all cases. Chemotherapy is a common treatment method in clinical practice with certain negative effects. The primary goal of this study is to investigate the clinical efficacy of stereotactic radiotherapy in combination with a docetaxel plus cisplatin (TP) chemotherapy regimen in patients with nonsmall cell lung cancer (NSCLC) and their impact on the levels of cytokeratin fragment 21-1 (CYFRA21-1) and metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in NSCLC patients. Eighty patients who were admitted to the hospital between November 2016 and November 2019 were recruited and assigned to receive either chemotherapy with a TP regimen (the control group) or chemotherapy with a TP regimen plus stereotactic radiotherapy (the observation group). The WHO response evaluation criteria (REC) for solid tumors were adopted to analyze short-term efficacy, and the Karnofsky performance status (KPS) score was used to assess the quality of life by recording adverse reactions in the blood system, kidney, gastrointestinal tract, bladder, nervous system, and heart. The levels of CYFRA21-1 and MALAT1 in serum before and after the treatment were determined and compared. As a result, the observation group showed higher total efficacy and MALAT1 level, better quality of life, and lower CYFRA21-1 level than the control group (P < 0.05). Stereotactic radiotherapy plus TP regimen chemotherapy resulted in significantly better progression-free survival, overall survival, survival rate, and long-term prognosis versus chemotherapy alone. Moreover, combined therapy was associated with a lower incidence of hemoglobin reduction, gastrointestinal reaction, and renal impairment versus TP regimen chemotherapy (P < 0.05). Therefore, we concluded that stereotactic radiotherapy plus chemotherapy with a TP regimen significantly optimizes the clinical efficacy of the NSCLC treatment.

Mutation breeding of Aspergillus niger by atmospheric room temperature plasma to enhance phosphorus solubilization ability.

Background: Phosphorus (P) is abundant in soils, including organic and inorganic forms. Nevertheless, most of P compounds cannot be absorbed and used by plants. Aspergillus niger v. Tiegh is a strain that can efficiently degrade P compounds in soils. Methods: In this study, A. niger xj strain was mutated using Atmospheric Room Temperature Plasma (ARTP) technology and the strains were screened by Mo-Sb Colorimetry with strong P-solubilizing abilities. Results: Compared with the A. niger xj strain, setting the treatment time of mutagenesis to 120 s, four positive mutant strains marked as xj 90-32, xj120-12, xj120-31, and xj180-22 had higher P-solubilizing rates by 50.3%, 57.5%, 55.9%, and 61.4%, respectively. Among them, the xj120-12 is a highly efficient P solubilizing and growth-promoting strain with good application prospects. The growth characteristics such as plant height, root length, and dry and fresh biomass of peanut (Arachis hypogaea L.) increased by 33.5%, 43.8%, 43.4%, and 33.6%, respectively. Besides available P, the chlorophyll and soluble protein contents also vary degrees of increase in the P-solubilizing mutant strains. Conclusions: The results showed that the ARTP mutagenesis technology can improve the P solubilization abilities of the A. niger mutant strains and make the biomass of peanut plants was enhanced of mutant strains.

Cilostazol eliminates radiation-resistant glioblastoma by re-evoking big conductance calcium-activated potassium channel activity.

In spite of radio- and chemotherapy, glioblastoma (GBM) develops therapeutic resistance leading to recurrence and poor prognosis. Therefore, understanding the underlying mechanisms of resistance is important to improve the treatment of GBM. To this end, we developed a radiation-resistant cell model by exposure to consecutive periods of irradiation. Simultaneously, single high-dose irradiation was introduced to determine "when" GBM developed consecutive irradiation-induced resistance (CIIR). We found that CIIR promoted TGF-ß secretion, activated pro-survival Akt, and downregulated p21 in a p53-independent manner. Furthermore, CIIR upregulated multidrug-resistant proteins, resulting in temozolomide resistance. CIIR GBM also enhanced cell mobility and accelerated cell proliferation. The big-conductance calcium-activated potassium channel (BK channel) is highly expressed and activated in GBM. However, CIIR diminishes BK channel activity in an expression-independent manner. Cilostazol is a phosphodiesterase-3 inhibitor for the treatment of intermittent claudication and was able to reverse CIIR-induced BK channel inactivation. Paxilline, a BK channel blocker, promoted cell migration and proliferation in parental GBM cells. In contrast, Cilostazol inhibited CIIR-induced cell motility, proliferation, and the ability to form tumor spheres. Moreover, we established a radiation-resistant GBM in vivo model by intracranially injecting CIIR GBM cells into the brains of NOD/SCID mice. We found that Cilostazol delayed tumor in vivo growth and prolonged survival. As such, inactivation of the BK channel assists GBM in developing radiation resistance. Accordingly, restoring BK channel activity may be an effective strategy to improve therapeutic efficacy, and cilostazol could be repurposed to treat GBM.

Postoperative Mycobacteroides abscessus subsp. abscessus endophthalmitis: Clinical analysis of 12 clustered adults and a proposed therapeutic algorithm.

PURPOSE: Postoperative endophthalmitis caused by nontuberculous mycobacterium is a rare but devastating complication after intraocular surgery. However, optimal treatment strategies remain undetermined in view of its rarity. METHODS: We investigated the cases of culture-proven postoperative Mycobacteroides abscessus subsp. abscessus endophthalmitis in southern Taiwan, focusing on clinical manifestations and microbiological study, and aimed to describe clinical staging and to propose a therapeutic modality for this disease. RESULTS: Twelve cases, including two published cases, were treated in two medical centers in southern Taiwan between Aug. 2011 and Dec. 2016, and all ever received cataract surgery at one clinic. Their disease courses could be categorized into four distinct stages, i.e., the initial, quiescent, recurrent, and end stage, and some cases experienced 1-4 cycles of quiescent-recurrent stages. Although all eyes ended up with phthisis or were eviscerated, the affected eyes receiving pars plana vitrectomy (PPV) tended to become quiescent and survived longer than those without PPV (adjusted hazard ratio: 13.9, p < 0.05). Eight isolates of eight patients were available for microbiological study. All isolates were susceptible to amikacin, and inducible clarithromycin resistance was observed in 100% of isolates. CONCLUSION: Despite the preservation of vision in postoperative M.abscessus endophthalmitis remained a challenge, a stage-based approach is proposed, which may facilitate decision-makings for the future study.

Design, synthesis, and biological evaluation of novel tetrahydroprotoberberine derivatives (THPBs) as proprotein convertase subtilisin/kexin type 9 (PCSK9) modulators for the treatment of hyperlipidemia.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) modulators may attenuate PCSK9-induced low-density lipoprotein receptor (LDLR) degradation in lysosome and promote the clearance of circulating low-density lipoprotein cholesterol (LDL-C). A novel series of tetrahydroprotoberberine derivatives (THPBs) were designed, synthesized, and evaluated as PCSK9 modulators for the treatment of hyperlipidemia. Among them, eight compounds exhibited excellent activities in downregulating hepatic PCSK9 expression better than berberine in HepG2 cells. In addition, five compounds 15, 18, 22, (R)-22, and (S)-22 showed better performance in the low-density lipoprotein, labeled with 1,1'-dioctadecyl-3,3,3',3'-tetramethyl-indocarbocyanine perchlorate (DiI-LDL) uptake assay, compared with berberine at the same concentration. Compound 22, selected for in vivo evaluation, demonstrated significant reductions of total cholesterol (TC) and LDL-C in hyperlipidemic hamsters with a good pharmacokinetic profile. Further exploring of the lipid-lowering mechanism showed that compound 22 promoted hepatic LDLR expression in a dose-dependent manner in HepG2 cells. Additional results of human ether-à-go-go related gene (hERG) inhibition assay indicated the potential druggability for compound 22, which is a promising lead compound for the development of PCSK9 modulator for the treatment of hyperlipidemia.

Highly sensitive and selective light-up fluorescent probe for monitoring gallium and chromium ions in vitro and in vivo.

Over the past decades, gallium (Ga) compounds have gained importance in the field of cancer treatment. Gallium acts as an iron mimic and disturbs iron-dependent propagation and other processes in tumor cells. However, the toxicity of gallium was also well documented in vitro and in vivo in animals. Though the oral administration of gallium in humans is less toxic, it has also been shown that a long period of administration could induce tumor fibrosis. Chromium (Cr), a naturally occurring heavy metal, is commonly used in industrial processes and can cause severe health problems in humans. It has been found to be closely involved in the metabolism of nucleic acids, proteins and fats in humans. Cr(iii) salts can be used as micronutrients and dietary supplements. However, similar to gallium (Ga3+), chromium (Cr3+) can build up to an excessive degree that is harmful to the human body. Therefore, it would be of great interest to develop chemosensing for the selective and sensitive detection of gallium and chromium ions in vitro and in vivo. Herein, we reported that an NBD-based (4-chloro-7-nitrobenzo-2-oxa-1,3-diazole) fluorescent probe (NBDT) was fabricated with demonstrated extraordinary specificity and sensitivity. A swift response toward Ga3+ and Cr3+ ions was discovered using fluorescence enhancement over a wide pH range and with cycle stability. Furthermore, lighted up by Ga3+ and Cr3+ ions in vitro, this NBDT sensor was successfully applied to detect exogenous Ga3+ and Cr3+ ions in MDA-MB-231 and HepG2 cells. Additionally, using zebrafish as the in vivo model, we demonstrated the capability of this NBDT for detecting and imaging Ga3+ and Cr3+ ions in zebrafish. Taken together, this NBDT has indicated great potential for detecting and monitoring Ga3+ and Cr3+ ions in vitro and in vivo.

[A clinical trial of treatment of primary insomnia of patients with qi-stagnation constitution by shallow acupuncture combined with ear-acupoint pellet-pressing].

OBJECTIVE: To investigate the clinical effect of shallow acupuncture combined with ear-acupoint pellet-pressing in the treatment of primary insomnia in patients with qi-stagnation constitution. METHODS: A total of 60 primary insomnia outpatients with qi-stagnation constitution were randomly divided into treatment group and control group, with 30 patients in each group. The patients in the control group were given oral Alprazolam tablets once a day, and those in the treatment group given shallow acupuncture of Yintang (EX-HN3), Shangen (inferior to EX-HN3), Anmian (EX-HN16) and bilateral Xingjian (LR2) and bilateral Taichong (LR3), once a day, and combined with pellet-pressing of ear acupoints "Shenmen""Sympathy""Subcortex""Heart" and "Liver" once every other day. Each course of treatment was 10 consecutive days, and both groups were treated for three courses. The sleep quality was assessed using Pittsburgh Sleep Quality Index (PSQI), the emotional status assessed using Self-rating Depression Scale (SDS), and the qi-stagnation state evaluated according to "the Criteria for Classification and Judgement of Constitution of Traditional Chinese Medicine (2009)". The therapeutic effect was evaluated according to "the Criteria for Diagnosis and Evaluation of Therapeutic Effect of Diseases of Traditional Chinese Medicine"．. RESULTS: Of the two 30 cases in the control and treatment groups, 2 (6.7%) and 6 (20.0%) were cured, 6 (20.0%) and 14 (46.7%) experienced marked improvement in their symptoms, 21 (70.0%) and 6 (20.0%) were effective, and 1 (3.3%) and 4 (13.3%) ineffective, with the effective rate being 86.7% and 96.7%, respectively. No significant difference was found between the two groups in the short-term effect (P>0.05). One month's follow-up showed that, of the two 30 cases in the control and treatment groups, 2 (6.7%) and 5 (16.7%) were cured, 4(13.3%) and 14 (46.6%) experienced marked improvement, 10 (33.3%) and 6 (20.0%) were effective, and 14(46.7%) and 5(16.7%) ineffective, with the effective rate being 53.3% and 83.3%, respectively. The long-term therapeutic effect of the treatment group was significantly superior to that of the control group (P<0.05). After the treatment, both PSQI and SDS scores in the two groups, and qi-stagnation score in the treatment group showed a significant reduction in comparison with their own pretreatment (P<0.05), and one-month's follow-up (not the short-term outcome) displayed that the PSQI, SDS and qi-stagnation scores of the treatment group were significantly lower than those of the control group (P<0.05)．. CONCLUSION: Shallow acupuncture combined with ear-acupoint pellet-pressing can significantly improve sleep quality, depression symptoms, and pathological constitution in primary insomnia patients with qi-stagnation constitution, possessing a stable long-term clinical effect.

Autophagy inhibition enhances etoposide-induced cell death in human hepatoma G2 cells.

Induction of autophagy usually acts as a survival mechanism of cancer cells in response to chemotherapy. However, the function and molecular mechanism of autophagy in human hepatoma cells under drug treatment is still not clear. To address this issue, we established an experimental model in which HepG2 cells were treated with etoposide, a widely used anticancer agent. We demonstrate the etoposide-induced accumulation of GFP-LC3 dots by fluorescent microscopy, the up-regulation of LC3-II protein expression by Western blotting and the increased number of autophagic vacuoles by electron microscopy, confirming the activation of autophagy by etoposide in HepG2 cells. Inhibition of autophagy by either 3-methyladenine (3MA) or beclin-1 small interfering RNA enhanced etoposide-induced cell death. Furthermore, activation of p53 and AMPK was detected in etoposide-treated cells and inhibition of AMPK triggered apoptosis through suppression of autophagy. On the other hand, inactivation of p53 promoted cell survival through augmentation of autophagy. Collectively, these findings indicate that etoposide-induced autophagy promotes hepatoma cell adaptation and survival, and that autophagy inhibition improves the chemotherapeutic effect of etoposide. Moreover, AMPK activation is clearly associated with etoposide-induced autophagy. We conclude that manipulation of AMPK may be a promising approach of adjuvant chemotherapy for hepatocellular carcinoma.