Consistent signatures in the human gut microbiome of old- and young-onset colorectal cancer.

The incidence of young-onset colorectal cancer (yCRC) has been increasing in recent decades, but little is known about the gut microbiome of these patients. Most studies have focused on old-onset CRC (oCRC), and it remains unclear whether CRC signatures derived from old patients are valid in young patients. To address this, we assembled the largest yCRC gut metagenomes to date from two independent cohorts and found that the CRC microbiome had limited association with age across adulthood. Differential analysis revealed that well-known CRC-associated taxa, such as Clostridium symbiosum, Peptostreptococcus stomatis, Parvimonas micra and Hungatella hathewayi were significantly enriched (false discovery rate <0.05) in both old- and young-onset patients. Similar strain-level patterns of Fusobacterium nucleatum, Bacteroides fragilis and Escherichia coli were observed for oCRC and yCRC. Almost all oCRC-associated metagenomic pathways had directionally concordant changes in young patients. Importantly, CRC-associated virulence factors (fadA, bft) were enriched in both oCRC and yCRC compared to their respective controls. Moreover, the microbiome-based classification model had similar predication accuracy for CRC status in old- and young-onset patients, underscoring the consistency of microbial signatures across different age groups.

Clinical effect of pulmonary rehabilitation in patients with mechanical ventilation: A meta-analysis.

OBJECTIVE: To systematically evaluate the clinical efficacy of pulmonary rehabilitation in patients with mechanical ventilation in an intensive care unit (ICU). METHODS: Relevant studies were identified in the PubMed, Web of Science, National Library of Medicine, China National Knowledge Infrastructure and Wanfang databases. A meta-analysis was performed after screening based on the inclusion and exclusion criteria, data extraction and literature quality evaluation. RESULTS: In total, 19 studies involving 2181 participants were included. The results of the meta-analysis revealed that compared with patients with conventional rehabilitation measures, patients with pulmonary rehabilitation measures had a higher offline success rate (relative risk (RR) = 1.16; 95% confidence interval (CI): 1.09, 1.24; p < 0.00001) and higher arterial oxygen partial pressure levels (mean difference (MD) = 8.96; 95%CI: 5.98, 11.94; p < 0.0001) and these measures significantly shortened the duration of mechanical ventilation (standardised MD (SMD) = -1.08; 95%CI: -1.58, -0.59; p < 0.0001) and ICU stay (SMD = -1.41; 95%CI: -1.94, -0.88; p < 0.0001). Aspiration significantly reduced the incidence of ventilator-associated pneumonia (RR = 0.35; 95%CI: 0.24, 0.51; p < 0.00001) and deep vein thrombosis (RR = 0.32; 95%CI: 0.13, 0.76; p = 0.01) in ICU patients with mechanical ventilation. CONCLUSION: Pulmonary rehabilitation measures can improve the success rate of weaning from mechanical ventilation in ICU patients, shorten the time of mechanical ventilation and ICU hospitalisation and reduce the incidence of related adverse reactions, but the impact on mortality requires further study.

Small Papillae Regulated by SPD25 are Critical for Balancing Photosynthetic CO2 Assimilation and Water Loss in Rice.

BACKGROUND: The leaf epidermis plays an important role in the transmission of light and the regulation of water and gas exchange, which influences the photosynthesis of mesophyll cells. Small papillae (SP) are one of the important structural elements of the leaf epidermis. The mechanism of the effect that small papillae have on rice leaf photosynthetic performance remains unclear. RESULTS: In this study, a small papilla deficient 25 (spd25) mutant was isolated from japonica rice Longjin1. Small papillae were absent on the adaxial and abaxial leaf surfaces of the spd25 mutant and the silicon and cuticular wax content in the spd25 mutant leaves decreased. Map-based cloning and functional analysis revealed that SPD25, encoding a guanine nucleotide exchange factor for Rop, is a novel allele of OsRopGEF10. The spd25 mutant showed an increased water loss rate and reduced relative water content. The lower stomatal conductance in the spd25 mutant prevented water loss but decreased the intercellular CO2 concentration and net assimilation rate. The fluorescence parameters showed that the inhibited CO2 assimilation reaction feedback regulated the photochemical electron-transfer reaction, but the performance of Photosystem II was stable. Further analysis indicated that the excess light energy absorbed by the spd25 mutant was dissipated in the form of non-photochemical quenching to avoid photodamage through the optical properties of small papillae. CONCLUSIONS: SPD25 regulates the development of small papillae on the surface of rice leaves, which play an important role in balancing photosynthetic gas exchange and water loss. This study deepens our understanding of the physiological mechanisms by which small papillae affect photosynthetic performance.

Comparison of Definitive Radiotherapy-Based Treatment and Surgical-Based Treatment for Locally Advanced Head and Neck Soft Tissue Sarcoma.

Background: Head and neck soft-tissue sarcomas are rare but aggressive malignancies. Definitive radiotherapy might be an alternative treatment choice in patients unfit for surgery with preservation of organ function and facial morphology. Whether definitive radiotherapy is comparable with surgery has not been fully demonstrated. In this study, we compared the prognosis of patients with radiotherapy-based treatment and with surgery-based treatment. Methods: From May 2014 to February 2021, patients with locally advanced head and neck soft-tissue sarcoma treated with either definitive radiotherapy-based treatment or radical surgery-based treatment were retrospectively enrolled. Clinical outcomes including tumor response, patients' survival and acute treatment-related toxicities were evaluated. Kaplan-Meier curves with log-rank test were used to compare survival data. Cox regression analysis was used to explore prognostic factors. Results: A total of 24 patients (12 males and 12 females, 3 to 61 years old) were eligible for analysis. The median follow-up time was 49 (range: 6-96) months. In 16 patients receiving definitive radiotherapy-based treatment, 6 reached complete response. The survival curve showed that there was no statistically significant difference in overall survival (OS), distant metastasis-free survival (DMFS), loco-regional relapse-free survival (LRRFS) and progression-free survival (PFS) between the two groups of patients (p = 0.35, p = 0.24, p = 0.48, p = 0.1, respectively). COX regression analysis showed that older age was associated with poor DMFS. There was no significant difference in grade 3-4 toxicities between the two groups. Conclusions: In cases of contradictions to surgery, refusal to surgery or failure to complete resection, chemoradiotherapy might be an alternative treatment option.

Surgery After Conversion Therapy With PD-1 Inhibitors Plus Tyrosine Kinase Inhibitors Are Effective and Safe for Advanced Hepatocellular Carcinoma: A Pilot Study of Ten Patients.

BACKGROUND AND AIMS: Immunotherapy with PD-1 inhibitors combined with tyrosine kinase inhibitors (TKIs) has been proven to be effective against advanced hepatocellular carcinoma (HCC). The aim of this study was to identify the feasibility and safety of subsequent salvage surgery after this combination therapy. METHODS AND PATIENTS: A retrospective analysis was performed on patients with primary HCC with major vascular invasion between 2018 and 2019. All cases were treated with a combination of a PD-1 inhibitor and TKI agents and subsequent surgery. RESULTS: A total of 10 HCC cases with major vascular invasion met the successful conversion criteria after the combination therapy, and eight patients underwent subsequent salvage surgery after both radiology and 3D quantitative oncological assessment. Partial response (PR) was recorded in 7 of 10 patients and complete response (CR) in 3 of 10 patients before salvage surgery. Salvage surgery included right hepatectomy, left hepatectomy, and anatomic segmental hepatectomy. The mean intraoperative blood loss was 1,650 ml (50-3,000 ml). No complications beyond Clavien-Dindo level III or postoperative mortality were observed. The viable tumor cell rate of the PR cases (modified response evaluation criteria in solid tumors, mRECIST) varied from 1.5% to 100%, and only one patient had pathology-proven pathological complete response (pCR). The postoperative median follow-up time was 19.7 months (9.1-24.9 months). The 12-month recurrence-free survival rate of all cases who underwent salvage surgery was 75%. CONCLUSION: Salvage surgery was effective and safe after conversion therapy with PD-1 inhibitors plus TKIs and may increase the long-term oncological benefit for patients with unresectable HCC.

Suppression of circDcbld1 Alleviates Intimal Hyperplasia in Rat Carotid Artery by Targeting miR-145-3p/Neuropilin-1.

We replicated the rat common carotid artery (CCA) intima hyperplasia model and found the expression of a circular RNA, circRNA_009723 (circDcbld1), was markedly increased in the CCA with intimal hyperplasia. In vitro, the suppression of circDcbld1 in rat vascular smooth muscle cells (VSMCs) led the increase of contractile smooth muscle cell markers and the decrease of cell migration. In vivo, the injection of chemically modified circDcbld1 small interfering RNA (siRNA) lessened the formation of neointima in rat CCA after balloon injury. Further experiments proved that circDcbld1, as a competing endogenous RNA, interacted with miR-145-3p and upregulated the level of neuropilin-1 (Nrp1), thereby regulating the migration of VSMCs. In this study, we demonstrated a new mechanism by which circular RNA promotes intimal hyperplasia. We deem that intervention in the circDcbld1-miR-145-3p/Nrp1 pathway might be a feasible approach to alleviate the post-injury intimal hyperplasia.

Two cases of intrahepatic cholangiocellular carcinoma with high insertion-deletion ratios that achieved a complete response following chemotherapy combined with PD-1 blockade.

BACKGROUND: Insertion-deletion mutations (indels) may generate more tumour-specific neoantigens with high affinity to major histocompatibility complex class I. A high indel ratio is also related to a good response to programmed death-1 (PD-1) checkpoint blockade in melanoma and renal cell carcinoma. However, the correlation between a high indel ratio and the immunotherapy response in intrahepatic cholangiocarcinoma (ICC) is unknown. CASE PRESENTATION: Two patients with relapsed ICC at stage IIIb were treated with PD-1 blockade combined with chemotherapy. After 7 and 4 months of chemotherapy and PD-1 blockade (3 and 15 cycles, and 5 and 6 cycles, respectively), magnetic resonance imaging and positron emission tomography with computed tomography imaging showed that both patients achieved a complete response (CR), which has lasted up to nearly 16 and 13 months to date, respectively. Whole-exome sequencing and immunohistochemistry analysis showed that both patients had cancers with microsatellite stability (MSS) and mismatch repair (MMR) proficiency, weak PD-L1 expression, and a tumour mutation burden (TMB) of 2.95 and 7.09 mutations/Mb, respectively. Patient 2 had mutations of TP53 and PTEN that are known to confer sensitivity to immunotherapy, and the immunotherapy-resistant mutation JAK2, whereas patient 1 had no known immunotherapy response-related mutations. However, the indel ratios of the two patients (48 and 66.87%) were higher than the median of 12.77% determined in a study of 71 ICC patients. Moreover, comparison to six additional ICC patients who showed a partial response, stable disease, or progressive disease after PD-1 blockade treatment alone or in combination with chemotherapy demonstrated no difference in PD-L1 expression, TMB, MSI, and MMR status from those of the two CR patients, whereas the indel frequency was significantly higher in the CR patients. CONCLUSIONS: These two cases suggest that indels might be a new predictor of PD-1 blockade response for ICC patients beside PD-L1 expression, TMB, MSI, and dMMR, warranting further clinical investigation.

Proper surgical technique approved for early laparoscopic cholecystectomy for non-critically ill elderly patients with acute cholecystitis.

BACKGROUND/AIMS: Either percutaneous cholecystostomy or cholecystectomy are definitive recommendations regarding treatment of elderly or critically ill patients with acute cholecystitis (AC). In this study, we investigated whether early laparoscopic cholecystectomy (ELC) is appropriate for non-critically ill elderly patients with AC with modified surgical technique. METHODOLOGY: A total of 230 non-critically ill elderly patients, who had undergone laparoscopic cholecystectomy (LC) with "suction-curettage" dissection or "open-gallbladder" technique, were retrospectively reviewed, and were divided into three groups based on the length of time from onset of symptoms to surgical intervention (from ELC to delayed intervention). Among the three groups, the operative difficulty, morbidity, mortality, conversion rate, postoperative hospitalization and total hospital stay were compared. RESULTS: There were no significant differences among the three groups with respect to clinical characteristics, conversion rate, the incidences of major postoperative complications and mortality rate. However, the mean operative time and in-hospital stay were significantly shorter, and the estimated blood loss was significantly less in the ELC group than in the delay group (p<0.01). CONCLUSIONS: With "suction-curettage" dissection or "open-gallbladder" technique, LC is a safe and effective treatment for AC in elderly patients at any time. There is no advantage to postponing an early operation in elderly patients with AC.