Washed microbiota transplantation for Crohn's disease: A metagenomic, metatranscriptomic, and metabolomic-based study.

BACKGROUND: Fecal microbiota transplantation (FMT) is a promising therapeutic approach for treating Crohn's disease (CD). The new method of FMT, based on the automatic washing process, was named as washed microbiota transplantation (WMT). Most existing studies have focused on observing the clinical phenomena. However, the mechanism of action of FMT for the effective management of CD-particularly in-depth multi-omics analysis involving the metagenome, metatranscriptome, and metabolome-has not yet been reported. AIM: To assess the efficacy of WMT for CD and explore alterations in the microbiome and metabolome in response to WMT. METHODS: We conducted a prospective, open-label, single-center clinical study. Eleven CD patients underwent WMT. Their clinical responses (defined as a decrease in their CD Activity Index score of > 100 points) and their microbiome (metagenome, metatranscriptome) and metabolome profiles were evaluated three months after the procedure. RESULTS: Seven of the 11 patients (63.6%) showed an optimal clinical response three months post-WMT. Gut microbiome diversity significantly increased after WMT, consistent with improved clinical symptoms. Comparison of the metagenome and metatranscriptome analyses revealed consistent alterations in certain strains, such as Faecalibacterium prausnitzii, Roseburia intestinalis, and Escherichia coli. In addition, metabolomics analyses demonstrated that CD patients had elevated levels of various amino acids before treatment compared to the donors. However, levels of vital amino acids that may be associated with disease progression (e.g., L-glutamic acid, gamma-glutamyl-leucine, and prolyl-glutamine) were reduced after WMT. CONCLUSION: WMT demonstrated therapeutic efficacy in CD treatment, likely due to the effective reconstruction of the patient's microbiome. Multi-omics techniques can effectively help decipher the potential mechanisms of WMT in treating CD.

Evaluation of Chongqing Tuo Tea at Different Grades: An Integrated Approach by Artificial and Intelligent Sensory, Non-Volatile, and Volatile Compounds Analysis.

This study aims to investigate the relationship between the grades of Tuo tea and the quality of compounds. A combination of artificial sensory evaluation, intelligent sensory technologies (electronic nose and electronic tongue), gas chromatography-mass spectrometry (GC-MS), high-performance liquid chromatography (HPLC), chemical-physical analysis, and multivariate statistical analysis were employed to examine the differences among three grades of Tuo tea (SG, 1G, and 2G). The results of artificial sensory evaluation, electronic tongue, and electronic nose revealed that the aroma and taste of different grades of Tuo tea varied greatly. A total of 112 volatile compounds and 44 non-volatile compounds were identified. In order to elucidate the key components that cause differences in the quality of Tuo tea, 2 partial least squares discriminant analysis (PLS-DA) models with excellent parameters (volatile, R2Y = 0.999 and Q2 = 0.996; non-volatile, R2Y = 0.992 and Q2 = 0.972) were established. A total of 80 key differential volatile compounds were identified with the double selection criterion of variable importance in projection (VIP) greater than 1 and p < 0.05. Among these, 43 compounds with OAV > 1 were further identified as the odor-active compounds in all three grades of Tuo. Moreover, 22 key non-volatile compounds that contribute to the quality differences have been screened out. This investigation implied that the volatile and non-volatile compounds of Tuo tea could serve as indicators of its quality. The results provided a new approach to distinguish the grades of Tuo tea.

Removal of a guide-wire sliding into abdominal cavity via transgastric natural orifice transluminal endoscopic surgery: A case report.

BACKGROUND: Guidewire slippage into the peritoneal cavity during clinical operations is extremely rare. Therefore, this paper aims to report a successful case of guidewire removal using transgastric natural orifice transluminal endoscopic surgery (NOTES). The goal is to enhance physicians' understanding of the management plan for this unique scenario and provide a valuable reference for clinical practice. CASE SUMMARY: A 64-year-old man presented with abdominal distension and was diagnosed with cirrhosis combined with massive ascites. To proceed with treatment, the patient underwent ultrasound-guided peritoneal puncture and underwent catheterization and drainage. Unfortunately, a 0.035-inch guidewire slipped into the abdominal cavity during the procedure. Following a comprehensive evaluation and consultation by a multidisciplinary team, the guidewire was successfully removed using NOTES. CONCLUSION: This case highlights the potential consideration of transgastric NOTES removal when encountering a foreign body, such as a guidewire, within the abdominal cavity.

Introduction of hospital-based health technology assessment in China: experiences from seven pilot hospitals.

OBJECTIVES: This study aimed to introduce a pilot program for hospital-based health technology assessment (HB-HTA) in China and present the participants' experiences based on seven case studies from seven tertiary hospitals. METHODS: One-year pilot projects were initiated at the beginning of 2018. Seven pilot hospitals were closely followed from the beginning until the completion of their pilot HTA project. Regular interviews were conducted with the hospital managers leading the HB-HTA projects and key members of the special HTA teams. Observations were made based on field trips and written HTA reports. RESULTS: Three pilot projects evaluated the use of medical consumables, three evaluated the use of surgical or medical interventions, and one evaluated an innovative management model for ventilators. Real-world data were collected from all the pilot projects to assist with the assessments. Most HB-HTA pilot projects achieved remarkable results such as improvements in economic efficiency; however, there were also obvious deficiencies such as the lack of a necessary cost-effectiveness analysis. CONCLUSIONS: The results varied among the seven HB-HTA pilot projects. The HB-HTA pilot program was implemented to promote the use of HB-HTA in hospital decision making in China. At the same time, HB-HTA in China faces challenges. We have made some policy recommendations based on the findings of the pilot projects.

A retrospective study on improving the accuracy of radiotherapy for patients with breast cancer with lymph node metastasis using Styrofoam.

BACKGROUND: To retrospectively analyze the accuracy of radiotherapy using cone beam computed tomography (CBCT), Styrofoam fixation, and breast bracket fixation in the chest wall target area and supraclavicular lymphatic drainage area (supraclavicular target area) of patients with breast cancer.and compare the setting efficiency and comfort satisfaction. PATIENTS AND METHODS: A total of 65 patients with postoperative lymphatic metastasis of breast cancer, including 36 cases of Styrofoam fixation and 29 cases of breast bracket fixation, were recruited from March 2021 to August 2022 and retrospectively analyzed. All the patients underwent CBCT scans weekly, and the setup errors of the chest wall and supraclavicular target volume were compared and recorded. The planning target volume (PTV) margins of the two groups were calculated using the correlation MPTV = 2.5Σ + 0.7σ. The setup time and comfort satisfaction scores of the two groups were recorded and analyzed. The correlations among errors in each direction were analyzed using the Pearson correlation analysis. RESULTS: There was a significant difference in the left-right direction (X) axis of the chest wall target area between the Styrofoam and breast bracket groups (1.59 ± 1.47 mm vs. 2.05 ± 1.64 mm, P = 0.012). There were statistical differences in the ventrodorsal direction (Z) and bed angle of the supraclavicular target area, the data were (1.36 ± 1.27 mm vs. 1.75 ± 1.55 mm, P = 0.046; 0.47 ± 0.47° vs. 0.66 ± 0.59°, P = 0.006, respectively). In the X, Y, and Z directions, the respective PTV margins of the two groups in the chest wall target area were 5.01 mm, 5.99 mm, and 5.47 mm in the Styrofoam group, while those in the breast bracket group were 6.10 mm, 6.34 mm, and 6.10 mm, respectively. Moreover, the PTV margins of the supraclavicular target in the three directions were 3.69 mm, 3.86 mm, and 4.28 mm in the Styrofoam group, while those in the breast bracket group were 3.99 mm, 3.72 mm, and 5.45 mm, respectively. The setup time of the two groups was 3.4 ± 1.1 min and 5.5 ± 3.1 min (P = 0.007). The subjective comfort satisfaction scores of the two groups were 27.50 ± 1.24 and 25.44 ± 1.23 (P < 0.001). CONCLUSIONS: The application of Styrofoam fixation in radiotherapy of breast cancer in the supraclavicular lymph node area has several advantages as compared to breast bracket fixation, including higher positioning accuracy, smaller external expansion boundary, improved work efficiency, and patients' comfort, which might provide a reference for clinical work.

A prospective comparative study on bladder volume measurement with portable ultrasound scanner and CT simulator in pelvic tumor radiotherapy.

OBJECTIVE: The consistency of bladder volume is very important in pelvic tumor radiotherapy, and portable bladder scanner is a promising device to measure bladder volume. The purpose of this study was to investigate whether the bladder volume of patients with pelvic tumor treated with radiotherapy can be accurately measured using the Meike Palm Bladder Scanner PBSV3.2 manufactured in China and the accuracy of its measurement under different influencing factors. METHODS: A total of 165 patients with pelvic tumor undergoing radiotherapy were prospectively collected. The bladder volume was measured with PBSV3.2 before simulated localization. CT simulated localization was performed when the bladder volume was 200-400ml. The bladder volume was measured with PBSV3.2 immediately after localization and recorded. The bladder volume was then delineated on CT simulation images and recorded. To compare the consistency of CT simulation bladder volume and bladder volume measured by PBSV3.2. To investigate the accuracy of PBSV3.2 in different sex, age, treatment purpose, and bladder volume. RESULTS: There was a significant positive correlation with bladder volume on CT and PBSV3.2 (r = 0.874; p < 0.001). The mean difference between CT measured values and PBSV3.2 was (-0.14 ± 50.17) ml. The results of the different variables showed that the overall mean of PBSV3.2 and CT measurements were statistically different in the age ≥ 65 years, bladder volumes > 400ml and ≤ 400ml groups (p = 0.028, 0.002, 0.001). There was no statistical significance between the remaining variables. The volume difference between PBSV3.2 measurement and CT was 12.87ml in male patients, which was larger than that in female patients 3.27ml. Pearson correlation analysis showed that the correlation coefficient was 0.473 for bladder volume greater than 400ml and 0.868 for bladder volume less than 400ml; the correlation coefficient of the other variables ranged from 0.802 to 0.893. CONCLUSION: This is the first large-sample study to evaluate the accuracy of PBSV3.2 in a pelvic tumor radiotherapy population using the convenient bladder scanner PBSV3.2 made in China. PBSV3.2 provides an acceptable indicator for monitoring bladder volume in patients with pelvic radiotherapy. It is recommended to monitor bladder volume with PBSV3.2 when the planned bladder volume is 200-400ml. For male and patients ≥ 65 years old, at least two repeat measurements are required when using a bladder scanner and the volume should be corrected by using a modified feature to improve bladder volume consistency.

Surgical resection for second primary colorectal cancer: a population-based study.

Background: Second primary colorectal cancer (CRC) is attributed to a crucial component of the CRC population. Still, its treatments remain unclear due to the troublesome conditions originating from multiple primary cancers and the lack of quality evidence. This study aimed to determine that which type of surgical resection is the eligible treatment for second primary CRC among patients with a prior cancer history. Methods: This cohort study retrospectively collected patients with second primary stage 0-III CRC in the Surveillance, Epidemiology, and End Results database from 2000 to 2017. Prevalence of surgical resection in second primary CRC, overall survival (OS) and disease-specific survival (DSS) of patients who received different surgical interventions were estimated. Results: A total of 38,669 patients with second primary CRC were identified. Most of the patients (93.2%) underwent surgical resection as initial treatment. Approximately 39.2% of the second primary CRCs (N = 15,139) were removed with segmental resection, while 54.0% (N = 20,884) were removed through radical colectomy/proctectomy. Surgical resection was associated with a significantly favorable OS and DSS compared to those not receiving any surgical operations for second primary CRC [OS: adjusted Hazard ratios (adjusted HR): 0.35; 95% CI: 0.34-0.37, p < 0.001; DSS: adjusted HR: 0.27; 95% CI: 0.25-0.29, p < 0.001]. Segmental resection considerably outperformed radical resection in terms of OS and DSS (OS: adjusted HR: 0.97; 95% CI: 0.91-1.00, p = 0.07; DSS: adjusted HR: 0.92; 95% CI: 0.87-0.97, p = 0.002). Segmental resection was also associated with a significantly reduced cumulative mortality of postoperative non-cancer comorbidities. Conclusion: Surgical resection demonstrated excellent oncological superiority for second primary CRC and was used to remove the vast majority of second primary CRCs. In comparison to radical resection, segmental resection offered a better prognosis and reduced postoperative non-cancer complications. The second primary colorectal cancers should be resected if the patients can afford surgical operations.

Ilaprazole-amoxicillin dual therapy at high dose as a first-line treatment for helicobacter pylori infection in Hainan: a single-center, open-label, noninferiority, randomized controlled trial.

OBJECTIVES: This study aimed to evaluate the efficacy, adverse events, patient compliance, and cost of dual therapy with Ilaprazole-amoxicillin (IA) at high dose versus Ilaprazole-amoxicillin-furazolidone-bismuth (IAFB) quadruple therapy for the Helicobacter pylori (H.pylori) infection among Chinese patients. METHODS: 200 patients who had tested positive for H. pylori and undergoing upper gastrointestinal endoscopy after being diagnosed with chronic gastritis participated in this open-label randomized controlled clinical trial. Patients were randomized to Group A and Group B: the 14-day IA dual treatment group (101) and IAFB quadruple treatment group (99). The 13 C urea breath test was conducted to determine whether H. pylori had been eliminated 4-6 weeks after the treatment. Eradication rates, drug-related adverse events, patient compliance, and drug costs were compared between the two treatment groups. RESULTS: Eradication rates in group A were 92.1% and 94.9%, depending on the intention-to-treat (ITT), per-protocol (PP), respectively, which was similar to group B (91.9% and 93.6%). There was no significant difference observed in adverse events between the two groups (P = 0.518). Interestingly, compliance was significantly higher in group A compared to the group B (P = 0.031). In addition, drug costs were significantly lower for group A in comparison to the group B. CONCLUSIONS: IA dual therapy was found to be equally effective, safer and less costly than IAFB quadruple therapy. Therefore, these therapies can be potentially considered as first-line regimens for empirical treatment.

Clinical value of styrofoam fixation in intracranial tumor radiotherapy.

Objective: To analyze the application value of two postural fixation techniques.(styrofoam combined with head mask and fixed headrest combined with head mask) in intracranial tumor radiotherapy via cone beam computed tomography (CBCT). Methods: This study included 104 patients with intracranial tumors undergoing radiotherapy. The patients were divided into two groups: Group A (54 cases with styrofoam fixation) and Group B (50 cases with fixed headrest fixation). The positional deviation in 3D space between the two groups was compared using CBCT. The set-up errors were expressed as median (25th percentile, 75th percentile)or M(p25, p75) since the set-up errors in all directions were not normally distributed,The Mann-Whitney U test was performed. Results: The age and gender of patients in the two groups were not significantly different. The set-up errors of A in lateral (X), longitudinal (Y), vertical (Z), and yaw(Rtn) axes were 1.0 (0,1) mm, 1.0 (0,1) mm, 1.0 (0,2) mm, and 0.4 (0.1, 0.8) degrees, respectively while the set-up errors of B were 1.0 (0,1) mm, 1.0 (1,2) mm, 1.0 (0,2) mm, and 0.5 (0.15,0.9) degrees, respectively. Moreover, patients in the styrofoam group had significantly smaller set-up errors in the Y-axis than patients in the headrest group (p=0.001). However, set-up errors in the X, Z, and Rtn axes were not significantly different between the two groups. The expansion boundaries of the target area in the X, Y, and Z directions were 1.77 mm, 2.45 mm, and 2.47 mm, respectively. The outer expansion boundaries of the headrest group were 2.03 mm, 3.88 mm, and 2.57 mm in X, Y, and Z directions, respectively. The set-up times of groups A and B were (32.71 ± 5.21) seconds and (46.57 ± 6.68) seconds, respectively (p=0.014). Patients in group A had significantly better comfort satisfaction than patients in group B (p=0.001). Conclusion: Styrofoam plus head thermoplastic mask body fixation technique has a higher positional accuracy in intracranial tumor radiotherapy than headrest plus head thermoplastic mask fixation. Besides, styrofoam plus head thermoplastic mask body fixation technique is associated with improved positioning efficiency, and better comfort than headrest plus head thermoplastic mask fixation, and thus can be effectively applied for intracranial tumor radiotherapy positioning.

Krüppel-Like Factor 2 Is a Gastric Cancer Suppressor and Prognostic Biomarker.

Gastric cancer (GC) is a common digestive tract tumor. Due to its complex pathogenesis, current diagnostic and therapeutic effects remain unsatisfactory. Studies have shown that KLF2, as a tumor suppressor, is downregulated in many human cancers, but its relationship and role with GC remain unclear. In the present study, KLF2 mRNA levels were significantly lower in GC compared to adjacent normal tissues, as analyzed by bioinformatics and RT-qPCR, and correlated with gene mutations. Tissue microarrays combined with immunohistochemical techniques showed downregulation of KLF2 protein expression in GC tissue, which was negatively correlated with patient age, T stage, and overall survival. Further functional experiments showed that knockdown of KLF2 significantly promoted the growth, proliferation, migration, and invasion of HGC-27 and AGS GC cells. In conclusion, low KLF2 expression in GC is associated with poor patient prognosis and contributes to the malignant biological behavior of GC cells. Therefore, KLF2 may serve as a prognostic biomarker and therapeutic target in GC.

The initiation, exploration, and development of hospital-based health technology assessment in China: 2005 ‒ 2022.

A hospital-based health technology assessment (HB-HTA) can provide the evidence needed to inform clinical decisions at the administrative level. With the implementation of a new round of medical and health care system reforms in China, such as the abolition of medical mark-ups, adoption of modern hospital management systems, reform of diagnosis related groups (DRGs) payment, and performance evaluations for public hospitals, medical institutions increasingly need HB-HTA. The development of HB-HTA in China can be divided into three phases: An initiation phase (2005-2014), a preliminary exploratory phase (2015-2017), and a rapid development phase (2018-present). HB-HTA has been used to manage medical consumables, medical devices, and medicines, but there are still problems and challenges in terms of concept recognition, the mode of development, and limited professionals and data. To promote and use HB-HTA in developing countries, we have identifies the development paths and recommendations for implementation based on a case study in China, which can be summarized as follows: enhancing the top-level design of HB-HTA, formulating HB-HTA guidelines, further promoting the main ideas of HB-HTA, concentrating on the training of evaluation personnel, establishing an HB-HTA network and paying attention to the flexibility of HB-HTA in the application process, and multi- stakeholder participation.

The association of blood ctDNA levels to mutations of marker genes in colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) is a deadly and commonly diagnosed cancer. Cell-free circulating tumor DNAs (ctDNA) have been used in the diagnosis and treatment of CRC, but there are open questions about the relationship between ctDNAs and CRC. Although mutations of genes detected by ctDNA in CRC have been studied, the quantitative relationship between ctDNA mutations and ctDNA concentration has not been addressed. AIMS: We hypothesized that there was an association between mutations of genes identified in ctDNAs and ctDNA concentration. His study examined this association in a population of CRC patients. METHODS: In 85 CRC patients, we sampled 282 mutations in 36 genes and conducted an association study based on a Random forest model between mutations and ctDNA concentrations in all patients. RESULTS: This association study showed that mutations on five genes, ALK, PMS2, KDR, MAP2K1, and MSH2, were associated with the ctDNA concentrations in CRC patients' blood samples. Because ctDNA mutations correlate with ctDNA level, we can infer the tumor burden or tumor size from ctDNA mutations, as well as the survival time for prognosis. CONCLUSION: Our findings shed light on the associations between mutations of genes identified in ctDNAs and ctDNA concentration in the blood of CRC patients. This discovery provides information regarding the tumor burden or tumor size based on ctDNA mutations.

Role of gut microbiota in the pathogenesis and therapeutics of minimal hepatic encephalopathy via the gut-liver-brain axis.

Minimal hepatic encephalopathy (MHE) is a frequent neurological and psychiatric complication of liver cirrhosis. The precise pathogenesis of MHE is complicated and has yet to be fully elucidated. Studies in cirrhotic patients and experimental animals with MHE have indicated that gut microbiota dysbiosis induces systemic inflammation, hyperammonemia, and endotoxemia, subsequently leading to neuroinflammation in the brain via the gut-liver-brain axis. Related mechanisms initiated by gut microbiota dysbiosis have significant roles in MHE pathogenesis. The currently available therapeutic strategies for MHE in clinical practice, including lactulose, rifaximin, probiotics, synbiotics, and fecal microbiota transplantation, exert their effects mainly by modulating gut microbiota dysbiosis. Microbiome therapies for MHE have shown promised efficacy and safety; however, several controversies and challenges regarding their clinical use deserve to be intensively discussed. We have summarized the latest research findings concerning the roles of gut microbiota dysbiosis in the pathogenesis of MHE via the gut-liver-brain axis as well as the potential mechanisms by which microbiome therapies regulate gut microbiota dysbiosis in MHE patients.

Altered gut microbiota is associated with sleep disturbances in patients with minimal hepatic encephalopathy caused by hepatitis B-related liver cirrhosis.

BACKGROUND: Sleep disturbances are prevalent in patients with minimal hepatic encephalopathy (MHE). This study aimed to evaluate the association between sleep disturbances and altered gut microbiota in patients with MHE caused by hepatitis B-related liver cirrhosis. RESEARCH DESIGN AND METHODS: Ninety-eight and 45 patients with MHE were included in exploration and validation cohorts, respectively. Sleep disturbances were assessed using the Chinese version of the Pittsburgh Sleep Quality Index (PSQI) questionnaire. Microbiota in fecal samples were analyzed via amplicon sequencing of bacterial 16S ribosomal RNA genes. RESULTS: The gut microbiomes of MHE patients with sleep disturbances were characterized by lower bacterial diversity and distinct bacterial composition. Relative abundances of Streptococcus salivarius and Veillonella were independent predictors of sleep disturbances in MHE patients and well-distinguished MHE patients with and without sleep disturbances in both the exploration and validation cohorts. Moreover, the relative abundances of S. salivarius were positively correlated with plasma ammonia levels, and functional modules associated with protein digestion and absorption and lipopolysaccharide biosynthesis were enriched in the microbiomes of MHE patients with sleep disturbances. CONCLUSIONS: Both S. salivarius and Veillonella were associated with sleep disturbances in patients with MHE caused by hepatitis B-related liver cirrhosis.

Scorpion Neurotoxin Syb-prII-1 Exerts Analgesic Effect through Nav1.8 Channel and MAPKs Pathway.

Trigeminal neuralgia (TN) is a common type of peripheral neuralgia in clinical practice, which is usually difficult to cure. Common analgesic drugs are difficult for achieving the desired analgesic effect. Syb-prII-1 is a ß-type scorpion neurotoxin isolated from the scorpion venom of Buthus martensi Karsch (BmK). It has an important influence on the voltage-gated sodium channel (VGSCs), especially closely related to Nav1.8 and Nav1.9. To explore whether Syb-prII-1 has a good analgesic effect on TN, we established the Sprague Dawley (SD) rats' chronic constriction injury of the infraorbital nerve (IoN-CCI) model. Behavioral, electrophysiological, Western blot, and other methods were used to verify the model. It was found that Syb-prII-1 could significantly relieve the pain behavior of IoN-CCI rats. After Syb-prII-1 was given, the phosphorylation level of the mitogen-activated protein kinases (MAPKs) pathway showed a dose-dependent decrease after IoN-CCI injury. Moreover, Syb-prII-1(4.0 mg/kg) could significantly change the steady-state activation and inactivation curves of Nav1.8. The steady-state activation and inactivation curves of Nav1.9 were similar to those of Nav1.8, but there was no significant difference. It was speculated that it might play an auxiliary role. The binding mode, critical residues, and specific interaction type of Syb-prII-1 and VSD2rNav1.8 were clarified with computational simulation methods. Our results indicated that Syb-prII-1 could provide a potential treatment for TN by acting on the Nav1.8 target.

Circular RNA 0001666 inhibits colorectal cancer cell proliferation, invasion and stemness by inactivating the Wnt/ß-catenin signaling pathway and targeting microRNA-1229.

A previous bioinformatics study suggested that circular RNA 0001666 (circ_0001666) and its target microRNA (miR)-1229 were associated with colorectal cancer (CRC) pathogenesis. However, the role of this interaction in the regulation of CRC cell malignancy remains unclear. Thus, the aim of the present study was to examine the interaction between circ_0001666 and miR-1229, and its effects on CRC cell malignancy. circ_0001666 overexpression or knockdown plasmids were transfected into the HT-29 and HCT-116 cell lines. In addition, in rescue experiments, circ_000166 or miR-1229 overexpression plasmids were transfected into the HT-29 cell line, either alone or in combination. Following transfection, cell proliferation, apoptosis, invasion and the number of CD133+ cells were analyzed. The protein expression level of proteins in the Wnt/ß-catenin pathway was also examined. In both HT-29 and HCT-116 cell lines, circ_0001666 overexpression increased apoptosis, whilst inhibiting cell proliferation and invasion, and reducing the frequency of CD133+ cells. By contrast, circ_0001666 knockdown reduced apoptosis, but increased cell proliferation and the number of CD133+ cells. However, cell invasion remained unaffected. In addition, circ_0001666 expression levels negatively regulated those of miR-1229, whereas miR-1229 expression did not affect circ_0001666, in both the HT-29 and HCT-116 cell lines. Furthermore, a luciferase reporter assay confirmed that miR-1229 directly bound to circ_0001666. In the HT-29 cell line, miR-1229 overexpression activated the Wnt/ß-catenin pathway, and promoted cell proliferation, invasion and stemness, while suppressing cell apoptosis. In addition, miR-1229 overexpression reversed the effects of circ_0001666 overexpression. In conclusion, circ_0001666 suppresses CRC cell proliferation, invasion and stemness by inhibiting the Wnt/ß-catenin signaling pathway by targeting miR-1229, and may represent a potential target for CRC treatment.

More work is needed on cost-utility analyses of robotic-assisted surgery.

OBJECTIVE: To comprehensively analyze the cost-utility of robotic surgery in clinical practice and to investigate the reporting and methodological quality of the related evidence. METHODS: Data on cost-utility analyses (CUAs) of robotic surgery were collected in seven electronic databases from the inception to July 2021. The quality of the included studies was assessed using the CHEERs and QHES checklists. A systematic review was performed with the incremental cost-effectiveness ratio as the outcome of interest. RESULTS: Thirty-one CUAs of robotic surgery were eligible. Overall, the identified CUAs were fair to high quality, and 63% of the CUAs ranked the cost-utility of robotic surgery as "favored," 32% categorized as "reject," and the remaining 5% ranked as "unclear." Although a high heterogeneity was present in terms of the study design among the included CUAs, most studies (81.25%) consistently found that robotic surgery was more cost-utility than open surgery for prostatectomy (ICER: $6905.31/QALY to $26240.75/QALY; time horizon: 10 years or lifetime), colectomy (dominated by robotic surgery; time horizon: 1 year), knee arthroplasty (ICER: $1134.22/QALY to $1232.27/QALY; time horizon: lifetime), gastrectomy (dominated by robotic surgery; time horizon: 1 year), spine surgery (ICER: $17707.27/QALY; time horizon: 1 year), and cystectomy (ICER: $3154.46/QALY; time horizon: 3 months). However, inconsistent evidence was found for the cost-utility of robotic surgery versus laparoscopic surgery and (chemo)radiotherapy. CONCLUSIONS: Fair or high-quality evidence indicated that robotic surgery is more cost-utility than open surgery, while it remains inconclusive whether robotic surgery is more cost-utility than laparoscopic surgery and (chemo)radiotherapy. Thus, an additional evaluation is required.

BmK DKK13, A Scorpion Toxin, Alleviates Pain Behavior in a Rat Model of Trigeminal Neuralgia by Modulating Voltage-Gated Sodium Channels and MAPKs/CREB Pathway.

BmK DKK13 (DKK13) is a mutated recombinant peptide, which has a significant antinociception in a rat model of the inflammatory pain. The purpose of this study was to evaluate the antinociceptive effect of DKK13 on trigeminal neuralgia (TN) in rats. Male Sprague-Dawley (SD) rats were treated with the chronic constriction injury of the infraorbital nerve (IoN-CCI) model to induce stable symptoms of TN. DKK13 (1.0 mg/kg, 2.0 mg/kg and 4.0 mg/kg, i.v.) or morphine (4.0 mg/kg, i.v.) was administered by tail vein once on day 14 after IoN-CCI injury. Behavioral tests, electrophysiology and western blotting were performed to investigate the role and underlying mechanisms of DKK13 on IoN-CCI model. Behavioral test results showed that DKK13 could significantly increase the mechanical pain and thermal radiation pain thresholds of IoN-CCI rats and inhibit the asymmetric spontaneous pain scratching behavior. Electrophysiological results showed that DKK13 could significantly reduce the current density of Nav1.8 in the ipsilateral side of trigeminal ganglion (TG) neurons in IoN-CCI rats, and the steady-state activation and inactivation curves of Nav1.8 shifted, respectively, to the direction of hyperpolarization and depolarization. Western blotting results showed that DKK13 significantly reduced the expression of Nav1.8 and the phosphorylation levels of key proteins of MAPKs/CREB pathway in TG tissues of IoN-CCI rats. In brief, DKK13 has a significant antinociceptive effect on IoN-CCI rats, which may be achieved by changing the dynamic characteristics of Nav1.8 channel and regulating the protein phosphorylation in MAPKs/CREB pathway.

Economic Evaluation of Cognitive Behavioral Therapy for Depression: A Systematic Review.

OBJECTIVES: This study aimed to conduct a systematic review of cost-utility studies of internet-based and face-to-face cognitive behavioral therapy (CBT) for depression from childhood to adulthood and to examine their reporting and methodological quality. METHODS: A structured search for cost-utility studies concerning CBT for depression was performed in 7 comprehensive databases from their inception to July 2020. Two reviewers independently screened the literature, abstracted data, and assessed quality using the Consolidated Health Economic Evaluation Reporting Standards and Quality of Health Economic Studies checklists. The primary outcome was the incremental cost-effectiveness ratio (ICER) across all studies. To make a relevant comparison of the ICERs across the identified studies, cost data were inflated to the year 2020 and converted into US dollars. RESULTS: Thirty-eight studies were included in this review, of which 26 studies (68%) were deemed of high methodological quality and 12 studies (32%) of fair quality. Despite differences in study designs and settings, the conclusions of most included studies for adult depression were general agreement; they showed that face-to-face CBT monotherapy or combination therapy compared with antidepressants and usual care for adult depression were cost-effective from the societal, health system, or payer perspective (ICER -$241 212.4/quality-adjusted life-year [QALY] to $33 032.47/QALY, time horizon 12-60 months). Internet-based CBT regardless of guided or unguided also has a significant cost-effectiveness advantage (ICER -$37 717.52/QALY to $73 841.34/QALY, time horizon 3-36 months). In addition, CBT was cost-effective in preventing depression (ICER -$23 932.07/QALY to $26 092.02/QALY, time horizon 9-60 months). Nevertheless, the evidence for the cost-effectiveness of CBT for children and adolescents was still ambiguous. CONCLUSIONS: Fair or high-quality evidence showed that CBT monotherapy or combination therapy for adult depression was cost-effective; whether CBT-related therapy was cost-effective for children and adolescents depression remains inconclusive.

Application analysis of omental flap isolation and modified pancreaticojejunostomy in pancreaticoduodenectomy (175 cases).

BACKGROUND: To explore the application value of free omental wrapping and modified pancreaticojejunostomy in pancreaticoduodenectomy (PD). METHODS: The clinical data of 175 patients who underwent pancreaticoduodenectomy from January 2015 to December 2020 were retrospectively analysed. In total, 86 cases were divided into Group A (omental wrapping and modified pancreaticojejunostomy) and 89 cases were divided into Group B (control group). The incidences of postoperative pancreatic fistula and other complications were compared between the two groups, and univariate and multivariate logistic regression analyses were used to determine the potential risk factors for postoperative pancreatic fistula. Risk factors associated with postoperative overall survival were identified using Cox regression. RESULTS: The incidences of grade B/C pancreatic fistula, bile leakage, delayed bleeding, and reoperation in Group A were lower than those in Group B, and the differences were statistically significant (P < 0.05). Group A had an earlier drainage tube extubation time, earlier return to normal diet time and shorter postoperative hospital stay than the control group (P < 0.05). The levels of C-reactive protein (CRP), interleukin-6 (IL-6), and procalcitonin (PCT) inflammatory factors 1, 3 and 7 days after surgery also showed significant. Univariate and multivariate logistic regression analyses showed that a body mass index (BMI) ≥ 24, pancreatic duct diameter less than 3 mm, no isolation of the greater omental flap and modified pancreaticojejunostomy were independent risk factors for pancreatic fistula (P < 0.05). Cox regression analysis showed that age ≥ 65 years old, body mass index ≥ 24, pancreatic duct diameter less than 3 mm, no isolation of the greater omental flap isolation and modified pancreaticojejunostomy, and malignant postoperative pathology were independent risk factors associated with postoperative overall survival (P < 0.05). CONCLUSIONS: Wrapping and isolating the modified pancreaticojejunostomy with free greater omentum can significantly reduce the incidence of postoperative pancreatic fistula and related complications, inhibit the development of inflammation, and favourably affect prognosis.