Endoscopic lithotripsy combined with drug lithotripsy vs. drug lithotripsy for the treatment of phytobezoars: analysis of 165 cases.

AIM: To analyze efficacy of endoscopic lithotripsy combined with drug lithotripsy as compared with drug lithotripsy for the treatment of phytobezoars. METHODS: We collected and evaluated case records of 165 patients with phytobezoars from 2014 to 2023. And we analyzed demographic and clinical characteristics, imaging features, endoscopic features, complications of phytobezoars, and compared efficacy between endoscopic lithotripsy combined with drug lithotripsy (Group A) and drug lithotripsy (sodium bicarbonate combined with proton pump inhibitor) (Group B). RESULTS: The median age of patients with phytobezoars was 67.84 ± 4.286 years old. Abdominal pain was the most common symptom and peptic ulcers (67.5%) were the most common complication. Bezoar-induced ulcers were more frequent in the gastric angle. The success rate of phytobezoars vanishing in Group A and Group B were similar (92.3% vs. 85.1% within 48 h, 98.7% vs. 97.7% within a week), while the average hospitalization period, average hospitalization cost, second endoscopy rate, and average endoscopic operation time were significantly lower in patients in Group B than in Group A. CONCLUSION: Drug lithotripsy is the preferred effective and safe treatment option for phytobezoars. We advise that an endoscopy should be completed after 48 h for drug lithotripsy.

Septin9 DNA methylation is associated with breast cancer recurrence or metastasis.

OBJECTIVE: We aimed to explore the prognostic value of Septin9 DNA methylation in breast cancer. METHODS: Breast cancer patients with and without recurrence or metastasis and matched non-breast cancer patients were screened retrospectively from 2014 to 2016. Bisulfite conversion and fluorescence quantitative methylation-specific polymerase chain reaction were used to detect the Septin9 methylation status and distribution levels in patient breast tissues. RESULTS: Septin9 DNA methylation was more frequent in breast cancer tissues than in non-breast cancer tissues, but was not significantly correlated with any relevant breast cancer patient clinicopathological characteristic. Septin9 methylation rates were higher in patients with recurrence or metastasis. Septin9 methylation, tumor size, lymph node status, and progesterone receptor (PR) expression could influence prognosis. Septin9 methylation was significantly associated with worse disease-free survival in breast cancer patients, with receiver operating characteristic curve analysis indicating that it had good prognostic ability, with an area under the curve (AUC) value of 0.719. The AUC values increased when Septin9 methylation was combined with tumor size, lymph node status, and PR to predict prognosis. CONCLUSIONS: Septin9 DNA methylation was an independent predictors of breast cancer prognostic risk. This could possibly help improve comprehensive prognosis prediction methods when combined with other risk factors.

Prognostic significance of the systemic inflammation response index in gastrointestinal malignancy patients: a pooled analysis of 10,091 participants.

Background: We performed a meta-analysis to investigate the association of the systemic inflammation response index (SIRI) with long-term survival outcomes in patients with gastrointestinal malignancy. Methods: PubMed, Web of Science and Embase were searched for relevant studies evaluating the prognostic significance of the SIRI in gastrointestinal malignancies until May 2023. Results: 30 studies with 10,091 patients were included. The pooled results identified that patients in the high SIRI group had a worse overall survival and disease-free survival, which was observed across various tumor types, tumor stages and primary treatments. Conclusion: An elevated SIRI is negatively associated with worse survival outcomes of gastrointestinal malignancy patients and can be used as a risk stratification index for gastrointestinal malignancies.

MicroRNA-29a-3p Prevents Drug-Induced Acute Liver Failure through Inflammation-Related Pyroptosis Inhibition.

OBJECTIVE: Little is known about the role of microRNA-29a-3p (miR-29a-3p) in inflammation-related pyroptosis, especially in drug-induced acute liver failure (DIALF). This study aimed to identify the relationship between miR-29a-3p and inflammation-related pyroptosis in DIALF and confirm its underlying mechanisms. METHODS: Thioacetamide (TAA)- and acetaminophen (APAP)-induced ALF mouse models were established, and human samples were collected. The expression levels of miR-29a-3p and inflammation and pyroptosis markers were measured by quantitative real-time polymerase chain reaction (qRT-PCR), Western blotting, or immunochemical staining in miR-29a-3p knock-in transgenic mouse (MIR29A(KI/KI)) DIALF models. In addition, RNA sequencing was conducted to explore the mechanisms. RESULTS: MiR-29a-3p levels were decreased in TAA- and APAP-induced DIALF models. MiR-29a-3p prevented DIALF caused by TAA and APAP. RNA sequencing and further experiments showed that the protective effect of miR-29a-3p on DIALF was mainly achieved through inhibition of inflammation-related pyroptosis, and the inhibition was dependent on activation of the PI3K/AKT pathway. In addition, miR-29a-3p levels were reduced, and pyroptosis was activated in both peripheral blood mononuclear cells and liver tissues of DIALF patients. CONCLUSION: The study supports the idea that miR-29a-3p inhibits pyroptosis by activating the PI3K/AKT pathway to prevent DIALF. MiR-29a-3p may be a promising therapeutic target for DIALF.

CAPRL Scoring System for Prediction of 30-day Mortality in 949 Patients with Coronavirus Disease 2019 in Wuhan, China: A Retrospective, Observational Study.

Background: Coronavirus disease 2019 (COVID-19) is a serious and even lethal respiratory illness. The mortality of critically ill patients with COVID-19, especially short term mortality, is considerable. It is crucial and urgent to develop risk models that can predict the mortality risks of patients with COVID-19 at an early stage, which is helpful to guide clinicians in making appropriate decisions and optimizing the allocation of hospital resoureces. Methods: In this retrospective observational study, we enrolled 949 adult patients with laboratory-confirmed COVID-19 admitted to Tongji Hospital in Wuhan between January 28 and February 12, 2020. Demographic, clinical and laboratory data were collected and analyzed. A multivariable Cox proportional hazard regression analysis was performed to calculate hazard ratios and 95% confidence interval for assessing the risk factors for 30-day mortality. Results: The 30-day mortality was 11.8% (112 of 949 patients). Forty-nine point nine percent (474) patients had one or more comorbidities, with hypertension being the most common (359 [37.8%] patients), followed by diabetes (169 [17.8%] patients) and coronary heart disease (89 [9.4%] patients). Age above 50 years, respiratory rate above 30 beats per minute, white blood cell count of more than10 × 109/L, neutrophil count of more than 7 × 109/L, lymphocyte count of less than 0.8 × 109/L, platelet count of less than 100 × 109/L, lactate dehydrogenase of more than 400 U/L and high-sensitivity C-reactive protein of more than 50 mg/L were independent risk factors associated with 30-day mortality in patients with COVID-19. A predictive CAPRL score was proposed integrating independent risk factors. The 30-day mortality were 0% (0 of 156), 1.8% (8 of 434), 12.9% (26 of 201), 43.0% (55 of 128), and 76.7% (23 of 30) for patients with 0, 1, 2, 3, ≥4 points, respectively. Conclusions: We designed an easy-to-use clinically predictive tool for assessing 30-day mortality risk of COVID-19. It can accurately stratify hospitalized patients with COVID-19 into relevant risk categories and could provide guidance to make further clinical decisions.

Lactic acid induces lactate transport and glycolysis/OXPHOS interconversion in glioblastoma.

The Warburg effect is a dominant phenotype of most tumor cells. Recent reports have shown that the Warburg effect can be reprogrammed by the tumor microenvironment. Lactic acidosis and glucose deprivation are the common adverse microenvironments in solid tumor. The metabolic reprogramming induced by lactic acid and glucose deprivation remains to be elucidated in glioblastoma. Here, we show that, under glucose deprivation, lactic acid can preserve high ATP levels and resist cell death in U251 cells. At the same time, we find that MCT1 and MCT4 are significantly highly expressed. The metabolic regulation factor HIF-1α decreased and C-MYC increased. Nuclear respiratory factor 1 (NRF1) and oxidative phosphorylation (OXPHOS)-related proteins (NDUFB8, ND1) are all distinctly increased. Therefore, lactic acid can induce lactate transport and convert the dominant Warburg effect to OXPHOS. Through bioinformatics analysis, the high expression of HIF-1α, MCT1 or MCT4 indicate a poor prognosis in glioblastoma. In addition, in glioblastoma tissue, HIF-1α, MCT4 and LDH are highly expressed in the interior region, and their expression is decreased in the lateral region. MCT1 can not be detected in the interior region and is highly expressed in the lateral region. Hence, different regions of glioblastoma have diverse energy metabolic pathways. Glycolysis occurs mainly in the interior region and OXPHOS in the lateral region. In general, lactic acid can induce regional energy metabolic reprogramming and assist tumor cells to adapt and resist adverse microenvironments. This study provides new ideas for furthering understanding of the metabolic features of glioblastoma. It may promote the development of new therapeutic strategies in GBM.

MicroRNA-29b-3p prevents Schistosoma japonicum-induced liver fibrosis by targeting COL1A1 and COL3A1.

Schistosomiasis is one of the world's major public health problems in terms of morbidity and mortality, causing granulomatous inflammation and cumulative fibrosis. This study explored in vivo and vitro effects of miR-29b-3p in granulomatous liver fibrosis by targeting COL1A1 and COL3A1 in Schistosoma japonicum infection. Thirty male Balb/c mice were assigned to normal control and model (percutaneous infection of cercariae of S. japonicum) groups. NIH-3T3 mouse embryonic fibroblasts were designated into blank, NC, miR-29b-3p mimic, TGF-ß1, TGF-ß1 + NC, and TGF-ß1 + miR-29b-3p mimic groups. HE and Masson staining were employed to observe the pathological changes and collagenous fibrosis. The expression of α-SMA, COL1A1, COL3A1, TIMP-1 was determined by immunohistochemistry. The RT-qPCR, Western blotting and immunofluorescence staining were conducted to determine expression of miR-29b-3p, COL1A1, and COL3A1. CCK-8 assay and flow cytometry were performed to evaluate viability and apoptosis. The relative expression of miR-29b-3p decreased in the model group. The model group showed marked fibrosis in liver tissues. The expression of α-SMA, COL1A1, COL3A1, TIMP-1 was higher in the model group than that in the normal control group. Dual luciferase reporter gene assay revealed that miR-29b-3p directly targeted COL1A1 and COL3A1. Compared with the blank, NC, TGF-ß1 and TGF-ß1 + NC groups, the miR-29b-3p mimic group exhibited up-regulated expression of miR-29b-3p and MMP-9 but down-regulated expression of TIMP-1, HSP47, α-SMA, COL1A1, and COL3A1; while lower cell viability but higher apoptosis rate showed. It indicated that miR-29b-3p prevents S. japonicum-induced liver fibrosis by inhibiting COL1A1 and COL3A1.

NCAPH plays important roles in human colon cancer.

Colon cancer (CC) is one of the major malignancies worldwide, whose pathogenesis is complex and requires the accumulated alteration of multiple genes and signaling pathways. Condensins are multi-protein complexes that play pivotal roles in chromosome assembly and segregation during mitosis, meiosis and even tumorigenesis. Using tissue microarrays by immunohistochemistry and hematoxylin-eosin staining, we found that non-SMC condensin I complex subunit H (NCAPH) in colon cancerous tissues was higher than that in all corresponding adjacent non-cancerous tissues. We then characterized the exact function of the NCAPH in CC. We provided evidences showing that NCAPH is highly expressed in colorectal cancer cell lines comparing with normal human colonic epithelial cells, and identified many NCAPH mutations in CC patients. We found that depletion of NCAPH inhibits CC cell proliferation, migration in vitro and xenograft tumor formation in vivo. Furthermore, NCAPH knockdown promotes cell apoptosis and cell cycle arrest at G2/M phase. Interestingly, the NCAPH high expression in tumor tissues of colon patients had a significantly better prognosis and survival rate than low-expression patients, suggesting that NCAPH high expression promotes colonic cancerous cell proliferation; on the other hand, it may also sensitize these cells responding to chemo- or radio-therapies. Collectively, these findings reveal an important role of NCAPH in CC, indicating that NCAPH could be used as a new therapeutic target in future.

Clinical metagenomic analysis of bacterial communities in breast abscesses of granulomatous mastitis.

BACKGROUND: Granulomatous mastitis (GM) is a chronic inflammatory breast lesion. Its etiology remains incompletely defined. Although mounting evidence suggests the involvement of Corynebacterium in GM, there has been no systematic study of GM bacteriology using -omics technology. METHODS: The bacterial diversity and relative abundances in breast abscesses from 19 women with GM were investigated using 16S rDNA metagenomic sequencing and Sanger sequencing. A quantitative PCR (qPCR) assay was also developed to identify Corynebacterium kroppenstedtii. RESULTS: A bioinformatic analysis revealed that Corynebacterium was present in the 19 GM patients, with abundances ranging from 1.1% to 58.9%. Of note, Corynebacterium was the most abundant taxon in seven patients (more than a third of the subjects). The predominance of Corynebacterium kroppenstedtii infection (11 of 19 patients, 57.9%) was confirmed with Sanger sequencing and the qPCR assay. CONCLUSIONS: This study profiled the microbiota of patients with GM and indicated an important role for Corynebacterium, and in particular C. kroppenstedtii, in the pathogenesis of this disease.

Clinical and pathological study on patients with primary antineutrophil cytoplasmic autoantibody-associated vasculitis with renal immune complex deposition.

BACKGROUND: Traditionally, antineutrophil cytoplasmic autoantibody-associated vasculitis (AAV) is histologically characterized by pauci-immune glomerulonephritis. However, more and more literature has reported immune complex (IC) deposits to be found in renal specimen from patients with AAV. The role that these IC deposits play in the development of AAV, as well as their clinical and pathological significance, is worthy of studying. OBJECTIVES: The objective of this study was to analyze the clinical and pathological characteristics of Chinese patients with AAV having renal IC deposition. METHODS: A retrospective study was performed on 34 patients with AAV in Shanghai Ruijin Hospital with renal IC deposition. Clinical and pathological data were collected and studied and compared with other 76 AAV patients having classic pauci-immune glomerulonephritis. RESULTS: Thirty-four patients were enrolled in this study, with a mean age of 56.4 ± 16.4 years and a male-female ratio of 1:1.3 (19/15). Twenty-seven patients (79.4%) had impaired renal function, with an average serum creatinine of 4.4 ± 3.2 mg/dL. C3 (82.4%) and immunoglobulin M (50%) were the most common IC deposits observed in the kidneys. During the follow-up (median, 39 months), 6 patients (17.7%) died, and 11 (32.4%) finally progressed to end-stage renal disease despite immunosuppressive therapy. Compared with patients having classic pauci-immune glomerulonephritis, patients with renal IC deposits had similar clinical and laboratory features except for more proteinuria (2374 ± 2221 vs 1444 ± 1956 mg/24 h, P = 0.002), a higher prevalence of nephrotic syndrome (30.3% vs 9.6%, P = 0.007) and hypocomplementemia (86.8 ± 33.1 vs 110 ± 45.5 mg/dL, P = 0.029), and also a higher risk for progressing to end-stage renal disease (32.4% vs 13.1%, P = 0.018). CONCLUSIONS: Patients with AAV with renal IC deposition might have a worse renal prognosis than those having classic pauci-immune glomerulonephritis.

Phytoestrogen α-zearalanol exerts antiapoptotic effects in differentiated pc12 cells via oestrogen receptor α.

Our previous studies have demonstrated that phytoestrogen α-zearalanol (α-ZAL) possesses potential benefits in alleviating cell apoptotic death just like oestrogen. However, the underlying mechanism is not fully understood. This study was designed to test the hypothesis that the neuroprotective effect of α-ZAL is mediated by oestrogen receptor (ER) as α-ZAL owns the benzene ring structure may interact with ER. The present results showed a significant increase in apoptosis in differentiated PC12 cells after a 24-hr exposure to amyloid ß-peptide fragment 25-35 (Aß25-35 ), accompanied by decreasing of bcl-2 expression and increasing bax expression, whereas a pre-treatment with α-ZAL ameliorated these changes induced by Aß25-35 . In addition, the α-ZAL-mediated cytoprotection was abrogated by ERα antagonist but not by ERß antagonist. In summary, these data suggest that α-ZAL intervenes against Aß-induced apoptosis via intersecting bcl-2-bax apoptotic pathway in an ERα-sensitive manner.

Clara cell 10-kDa protein inhibits T(H)17 responses through modulating dendritic cells in the setting of allergic rhinitis.

BACKGROUND: T(H)17 responses have recently been implicated to play a role in allergic airway diseases, but their local expression in the setting of allergic rhinitis (AR) and their regulation in allergic airway diseases remain unclear. OBJECTIVE: We sought to investigate the regulatory role of Clara cell 10-kDa protein (CC10), an endogenous regulator of airway inflammation, on T(H)17 responses in the setting of AR. METHODS: Wild-type and homozygous CC10-null mice were used to establish an ovalbumin (OVA)-induced AR model. Human recombinant CC10 was given during sensitization or challenge. T(H)17 responses in human subjects and mice were examined by using flow cytometry, quantitative RT-PCR assay, immunohistochemistry, and ELISA. The direct effect of CC10 on T(H)17 cells and CD11c(+) dendritic cells (DCs) was studied by means of cell culture. Adoptive transfer was used to examine the influence of CC10-conditioned DCs on airway inflammation. The regulatory effect of CC10 on the expression of the CCL20 gene was tested by using the BEAS-2B cell line. RESULTS: Compared with those of control subjects, T(H)17 responses were enhanced in the nasal mucosa of patients with AR. CC10-null mice with AR showed enhanced T(H)17 responses, and CC10 treatment significantly decreased T(H)17 responses. CC10 had no direct effect on in vitro T(H)17 cell differentiation. CC10 could significantly decrease the expression of OX40 ligand, IL-23, and IL-6 but enhance CD86 and TGF-ß expression in DCs. Importantly, CC10 was able to inhibit T(H)17 cell polarization in the presence of OVA-pulsed DCs. CC10 pretreatment inhibited T(H)17 responses elicited by adoptive transfer of OVA-pulsed DCs. Furthermore, CC10 decreased the expression of CCL20 in BEAS-2B cells induced by inflammatory cytokines. CONCLUSION: T(H)17 responses are enhanced in patients with AR, and CC10 inhibits T(H)17 responses through modulation of the function of DCs.

Berberine alleviates ischemic arrhythmias via recovering depressed I(to) and I(Ca) currents in diabetic rats.

The present study was designed to elucidate the potential mechanism underlying that berberine suppressed ischemic arrhythmias in a rat model of diabetes mellitus (DM). Streptozotocin (STZ)-induced diabetic rats were subjected to ischemia by the occlusion of left anterior descending (LAD) coronary artery. Berberine was orally administered for 7 days before ischemic injury in diabetic rats. Whole-cell patch-clamp was performed to measure the transient outward K⁺ current (I(to)) and L-type Ca²âº current (I(Ca)). Results showed that oral administration of berberine (100 mg/kg) attenuated ischemia-induced arrhythmias in diabetic rats. Berberine significantly shortened the prolonged QTc interval from 214 ± 6ms to 189 ± 5ms in ischemic diabetic rats, and also restored the diminished I(to) and I(Ca) current densities in the same animal model rats. In conclusion, the ability of berberine to protect diabetic rats against cardiac arrhythmias makes it possible to be a prospective therapeutic agent in clinical management of cardiac disease secondary to diabetes.

[Anti-mycobacteria drugs therapy for periductal mastitis with fistula].

OBJECTIVES: To study the etiology, clinical and pathologic characteristics of periductal mastitis with fistula and estimate the effect of anti-mycobacterial agents for periductal mastitis with fistula. METHODS: Totally 27 patients of periductal mastitis with fistula received anti-mycobacteria drugs therapy from December 2008 to September 2011 were analyzed retrospectively. All of the patients were female. The mean age at onset was 28 years (range 15 to 40 years old). The main clinical manifestation of the 27 patients was breast fistula, including 21 patients with single fistula and 6 patients with multiple fistula. Three patients manifested with pure fistula, 14 patients with both fistula and lump, 10 patients with fistula, lump and abscess. The samples including pus or tissues of all patients were underwent bacteria culture and all patients core needle biopsy. All patients were given primary anti-mycobacteria drugs therapy, parts of patients received surgery based on the evaluation of medical treatment. RESULTS: The common bacteria culture of all patients failed to demonstrate any causative microorganism. Four cases were selected randomly to undergo PCR of mycobacteria, only one case was identified as Massiliense in bacteria culture of mycobacteria. Twenty-seven patients with periductal mastitis with fistula were treated with anti-mycobacterial agents (isoniazid, rifampicin and ethambutol or pyrazinamide of triple oral drugs) for 1 to 3 months, the fistula of all 27 patients were closed well. Sixteen patients were treated with the agents only and cured. Eleven patients received surgical treatment after treated with the medical agents. None of the patients were given mastectomy. All patients had no reccurence until now. CONCLUSIONS: The periductal mastitis with fistula has a closely relationship with the infection of nontuberculosis mycobacteria. Those patients could be treated with triple anti-mycobacterial agents and could also avoided mastectomy.

Impact of light variation on development of photoprotection, antioxidants, and nutritional value in Lactuca sativa L.

Lettuce plants were grown at low (LL), middle (ML), and high light (HL) conditions to examine the relationship between photoacclimatory plasticity, light energy utilization, and antioxidant capacity. With the increase in light intensity from LL to ML, the energy flux via DeltapH- and xanthophylls-regulated thermal dissipation, fluorescence and constitutive thermal dissipation, and electron transport for photorespiratory carbon oxidation all increased significantly. However, plants at HL exhibited reduced electron transport for photosynthetic carbon reduction and decreased maximal photochemical efficiency of photosytem II (PSII) as compared to that at ML. Increasing light level significantly increased the alternative electron transport, O(2)(*-) production rate, and H(2)O(2) and malondialdehyde (MDA) contents followed by increased ferric reducing antioxidant power (FRAP) and activities of superoxide dismutase (SOD), catalase (CAT), ascorbate peroxidase (APX), monodehydroascorbate reductase (MDHAR), dehydroascorbate reductase (DHAR), and glutathione reductase (GR). Moreover, plants exposed to HL showed higher nutritional value as indicated by the high contents of ascorbate, glutathione, carotenoids, and alpha-tocopherol. It was concluded that absorption of excess photon energy at high light was associated with increased antioxidant capacity and that produce quality could be improved by short-term exposure to suboptimum irradiance.