Gut microbiota characteristics of colorectal cancer patients in Hubei, China, and differences with cohorts from other Chinese regions.

The research on the correlation or causality between gut microbiota and the occurrence, development, and treatment of colorectal cancer (CRC) is receiving increasing emphasis. At the same time, the incidence and mortality of colorectal cancer vary among individuals and regions, as does the gut microbiota. In order to gain a better understanding of the characteristics of the gut microbiota in CRC patients and the differences between different regions, we initially compared the gut microbiota of 25 CRC patients and 26 healthy controls in the central region of China (Hubei Province) using 16S rRNA high-throughput sequencing technology. The results showed that Corynebacterium, Enterococcus, Lactobacillus, and Escherichia-Shigella were significantly enriched in CRC patients. In addition, we also compared the potential differences in functional pathways between the CRC group and the healthy control group using PICRUSt's functional prediction analysis. We then analyzed and compared it with five cohort studies from various regions of China, including Central, East, and Northeast China. We found that geographical factors may affect the composition of intestinal microbiota in CRC patients. The composition of intestinal microbiota is crucial information that influences colorectal cancer screening, early detection, and the prediction of CRC treatment outcomes. This emphasizes the importance of conducting research on CRC-related gut microbiota in various regions of China.

Small-molecule inhibition of the METTL3/METTL14 complex suppresses neuroblastoma tumor growth and promotes differentiation.

The N6-methyladenosine (m6A) RNA modification is an important regulator of gene expression. m6A is deposited by a methyltransferase complex that includes methyltransferase-like 3 (METTL3) and methyltransferase-like 14 (METTL14). High levels of METTL3/METTL14 drive the growth of many types of adult cancer, and METTL3/METTL14 inhibitors are emerging as new anticancer agents. However, little is known about the m6A epitranscriptome or the role of the METTL3/METTL14 complex in neuroblastoma, a common pediatric cancer. Here, we show that METTL3 knockdown or pharmacologic inhibition with the small molecule STM2457 leads to reduced neuroblastoma cell proliferation and increased differentiation. These changes in neuroblastoma phenotype are associated with decreased m6A deposition on transcripts involved in nervous system development and neuronal differentiation, with increased stability of target mRNAs. In preclinical studies, STM2457 treatment suppresses the growth of neuroblastoma tumors in vivo. Together, these results support the potential of METTL3/METTL14 complex inhibition as a therapeutic strategy against neuroblastoma.

Successful allogeneic fecal microbiota transplantation for severe diversion colitis: a case report.

Ileostomy diverts the flow of feces, which can result in malnutrition in the distal part of the intestine. The diversity of the gut microbiota consequently decreases, ultimately leading to intestinal dysbiosis and dysfunction. This condition can readily result in diversion colitis (DC). Potential treatment strategies include interventions targeting the gut microbiota. In this case study, we effectively treated a patient with severe DC by ileostomy and allogeneic fecal microbiota transplantation (FMT). A 69-year-old man presented with a perforated malignant tumor in the descending colon and an iliac abscess. He underwent laparoscopic radical sigmoid colon tumor resection and prophylactic ileostomy. Follow-up colonoscopy 3 months postoperatively revealed diffuse intestinal mucosal congestion and edema along with granular inflammatory follicular hyperplasia, leading to a diagnosis of severe DC. After two rounds of allogeneic FMT, both the intestinal mucosal bleeding and edema significantly improved, as did the diversity of the gut microbiota. The positive outcome of allogeneic FMT in this case highlights the potential advantages that this procedure can offer patients with DC. However, few studies have focused on allogeneic FMT, and more in-depth research is needed to gain a better understanding.

Exploring the crosstalk of immune cells: The impact of dysregulated RUNX family genes in kidney renal clear cell carcinoma.

Background: Abnormally expressed Runt-associated transcription factor (RUNX) family has been reported in multiple tumors. Nevertheless, the immunological role of RUNX family in kidney renal clear cell carcinoma (KIRC) remains unknown. Methods: We studied the RNA-seq data regarding tumor and healthy subjects from several public databases in detail for evaluating the prognostic and immunological functions owned by three RUNX genes in cancer patients. Quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR) and immunohistochemical (IHC) staining served for detecting their expressions in tumor and normal samples. Results: We observed that KIRC patients presented high expressions of RUNX1, RUNX2, and RUNX3. The expressions of three genes were validated by qRT-PCR, which was same as bioinformatical results. Prognostic analysis indicated that the overexpression of RUNX1 and RUNX2 negatively affects the outcomes in patients with KIRC. Related functional predictions indicated that the RUNXs and co-expression genes were significantly related to the immune response pathway. Moreover, three RUNX members were associated with immune infiltration cells and their related gene markers. The expression of RUNX family in several immune cells is positively or negatively correlated, and its dysregulation is obviously associated with the differential distribution of immune cells. RUNX family genes were abnormally expressed in KIRC patients, and were closely related to the crosstalk of immune cells. Conclusions: Our findings may help to understand the pathogenesis and immunologic roles of the RUNX family in KIRC patients from new perspectives.

Effect of stainless-steel wire internal fixation on intracapsular condylar fracture.

OBJECTIVES: The aim of the study was to investigate the clinical effect of stainless-steel wire fixation on the early mouth-opening movement of an intracapsular fracture involving the condylar process. MATERIALS AND METHODS: In this study, patients who underwent mandibular condylar intracapsular fracture surgery in our hospital from 2012 to 2020 were selected as research subjects. A total of 44 patients received steel wire internal fixation treatment, 32 patients received titanium plate-and-nail rigid internal fixation, and 28 patients underwent conservative non-surgical treatment. RESULTS: For the patients in the stainless-steel wire group, the degree of mouth opening reached normal levels of 3.7 cm approximately 10 days after surgery. The recovery time for the patients in the titanium plate-and-nail rigid internal-fixation group was 21 days, while the patients in the conservative treatment group needed 60 days to recover. CONCLUSION: The treatment of fixation with a stainless-steel wire for intracapsular condylar fracture reduced the time taken to perform mouth-opening exercises and improved the recovery rate of patients.

OBJETIVO: Explorar el efecto clínico de la fijación de alambre de acero inoxidable en el movimiento temprano de apertura de la boca en la fractura interna del cóndilo. MÉTODO: Este estudio seleccionó a pacientes que se sometieron a cirugía de fractura intracapsular de cóndilo en nuestro hospital de 2012 a 2020 como sujetos de investigación. Un total de 44 pacientes recibieron tratamiento de fijación interna de alambre de acero, 32 recibieron placa de titanio y fijación interna con clavos, y 28 recibieron tratamiento conservador no quirúrgico. RESULTADOS: En los pacientes del grupo de alambre de acero inoxidable, alrededor de 10 días después de la cirugía el grado de apertura de la boca alcanzó un valor normal de 3.7 cm. El tiempo de recuperación de los pacientes en el grupo de fijación interna con clavos y placa de titanio fue de 21 días, mientras que los pacientes en el grupo de tratamiento conservador tardaron 60 días en recuperarse. CONCLUSIONES: La fijación con alambre de acero inoxidable para el tratamiento de la fractura intracapsular del cóndilo acorta el tiempo hasta la apertura de la boca y mejora la tasa de recuperación de los pacientes.

Gastroblastoma: a case report and literature review.

Objective: Gastroblastoma is an extremely rare gastric tumor. Its pathogenesis remains unclear and there is a lack of specific clinical symptoms. The aim of this paper is to report a case of gastroblastoma and provide references for the diagnosis, treatment, and prognosis of this disease. Methods: The diagnosis and treatment of a 51-year-old female patient with gastroblastoma were retrospectively reported. Analyzing this case by combining the clinical data such as imaging and pathological results of patients with the relevant literature. Results: The patient's chief complaint was the presence of melena persisted for over two weeks. Abdominal contrast-enhanced CT showed gastric antral nodules, and micro-probe endoscopic ultrasonography was considered as "gastric antral protruding lesions". The initial diagnosis of "gastric stromal tumor" was made after admission, and surgical treatment was performed on September 23, 2021. Postoperative pathology showed that gastric mixed epithelial and stromal tumor, combined with immunohistochemical staining, was suggestive of gastroblastoma. No signs of tumor recurrence or metastasis were observed during the 2-year follow-up. Conclusion: Combined with the existing literature reports, the incidence of gastroblastoma is mainly higher in young men, and the predilection site is gastric antrum. The biological behavior of the tumor tends to be indolent, and the prognosis of most cases is favorable. However, due to the extremely small number of cases, this conclusion still needs a large number of cases and follow-up data to support. Postoperative pathological and immunohistochemical examination results are the only methods for definite diagnosis at present, and surgery is the first choice for treatment.

Dysregulated ANLN reveals immune cell landscape and promotes carcinogenesis by regulating the PI3K/Akt/mTOR pathway in clear cell renal cell carcinoma.

Background: Abnormal anillin (ANLN) expression has been observed in multiple tumours and is closely associated with patient prognosis and clinical features. In this study, we systematically elucidated the clinical significance and biological roles of ANLN in patients with clear cell renal cell carcinoma (ccRCC). Methods: We obtained transcriptome and clinical data of patients with ccRCC from public databases. Multi-omics data and clinical samples were combined to analyse the correlation between ANLN expression and the clinical characteristics of patients with renal cancer. Additionally, the immune cell landscape of ANLN expression was evaluated using different immune algorithms in the tumour microenvironment. The tumour-promoting potential of ANLN was confirmed using in vitro assays, including CCK8 and Transwell assays. Results: Bioinformatics analysis showed that ANLN is over-expressed in patients with ccRCC, as validated by clinical samples. Publicly available clinical data suggest that high ANLN expression may indicate poor outcomes in patients with ccRCC. Moreover, biological function analysis revealed a marked enrichment of the cell cycle and PI3K-Akt pathways. The distribution of immune cells, particularly M2 macrophages, differed in patients with ccRCC. Furthermore, ANLN silencing inhibited the proliferation, migration, and invasion of renal cancer cells in vitro. After ANLN expression was knocked down in 786-O cells, the protein levels of important PI3K signalling pathway components, including PI3K, Akt, and mTOR, drastically decreased. Conclusions: These findings suggest that ANLN is dysregulated in renal cancer tissues and promotes tumour progression by activating the PI3K/Akt/mTOR signalling pathway.

In vitro and in vivo accuracy of autonomous robotic vs. fully guided static computer-assisted implant surgery.

OBJECTIVES: To assess the accuracy of autonomous robotic and fully guided static computer-assisted implant surgery (sCAIS) performed on models and patients. MATERIALS AND METHODS: This study was divided into in vitro and in vivo sections. In vitro, 80 operators were assigned to two groups randomly. Forty operators performed forty autonomous robotic implant (ARI group) surgeries and the remaining forty operators carried out forty fully guided sCAIS (FGI group) surgeries on maxillary models, respectively. Each operator placed an implant in one maxillary model. In vivo, 60 patients with 113 implants from 2019 to 2023 (ARI group: 32 patients, 58 implants; FGI group: 28 patients, 55 implants) receiving implant surgeries were incorporated in this retrospective research. The preoperative and postoperative cone beam computer tomographs (CBCTs) were utilized to estimate the linear deviations and angular deviations in two-dimensional (2D) and three-dimensional (3D) space. The Pearson's chi-square test, Shapiro-Wilk test, Student's t test, Mann-Whitney U test and mixed models were applied, and p <0.05 was considered statistically significant. RESULTS: In vitro, a total of 80 implants were enrolled and significant differences were found between the two groups (p < 0.001): The 3D deviation at the platform of ARI and FGI group was 0.58 ± 0.60 mm and 1.50 ± 1.46 mm, respectively, at the apex was 0.58 ± 0.60 mm and 1.78 ± 1.35 mm, respectively, and angle was 1.01 ± 0.87° and 2.93 ± 1.59°, respectively. Also, except for mesiodistal deviation at the implant platform, the rest linear and angular deviations in the ARI group were significantly lower than those in the FGI group in 2D space (p < 0.001). In vivo, a significantly lower mean of angular deviation (0.95 ± 0.50°, p < 0.001) and the linear deviation at both platform (0.45 ± 0.28 mm, p < 0.001) and apex (0.47 ± 0.28 mm, p < 0.001) were observed in ARI group when compared to the FGI group (4.31 ± 2.60°; 1.45 ± 1.27 mm; 1.77 ± 1.14 mm). CONCLUSIONS: The use of autonomous robotic technology showed significantly higher accuracy than the fully guided sCAIS.

Risk factors for severe low anterior resection syndrome in patients with rectal cancer undergoing sphincter­preserving resection: A systematic review and meta­analysis.

The present study aimed to evaluate the incidence and risk factors of severe low anterior resection syndrome (LARS) in patients with rectal cancer undergoing sphincter-preserving resection, and to provide the clinical basis and reference for the treatment of rectal cancer and the prevention of LARS. Studies on the incidence and risk factors for severe LARS in patients with rectal cancer undergoing sphincter-preserving resection were searched using PubMed, Embase, Cochrane Library, Scopus and Web of Science, according to the inclusion and exclusion criteria. After evaluating the study quality and extracting relevant data, RevMan 5.2 and STATA software were used to conduct a meta-analysis. A total of 12 articles were considered eligible for the present meta-analysis. Within these articles, there were 3,877 cases of sphincter-preserving resection for rectal cancer and 1,589 cases of severe LARS; the incidence of severe LARS was 40.99%. The results of the meta-analysis revealed that sex [female; odds ratio (OR), 6.54; 95% CI, 3.63-11.76; Z, 6.27; P<0.00001], radiotherapy and chemotherapy (OR, 3.45; 95% CI, 2.29-5.21; Z, 5.91; P<0.00001), total mesorectal excision (TME; OR, 4.39; 95% CI, 3.32-5.79; Z, 10.41; P<0.00001), and distance between tumor and anal margin (OR, 2.74; 95% CI, 0.86-8.72; Z, 1.70; P<0.00001) may be the risk factors for severe LARS.

Duplication of the transverse colon in adults: a case report and literature review.

Background: Duplication of the transverse colon is a rare gastrointestinal malformation. Its pathogenesis is still unclear, and it is extremely rare in adults. Patients often present with symptoms of tumor compression such as abdominal mass, abdominal pain, and constipation as the first manifestation. Methods and result: A patient with a duplication of the transverse colon was admitted to the Department of General Surgery of our hospital. Laparoscopic exploration found a mass at the rear of the transverse colon near the splenic flexure, and the root was connected to the middle portion of the transverse colon. Conclusion: Surgery is a radical treatment and reduces the possibility of perforation, bleeding, obstruction, and cancer.

Development and validation of a kidney renal clear cell carcinoma prognostic model relying on pyroptosis-related LncRNAs-A multidimensional comprehensive bioinformatics exploration.

BACKGROUND: Renal cell carcinoma (RCC) is a malignant tumour that may develop in the kidney. RCC is one of the most common kinds of tumours of this sort, and its most common pathological subtype is kidney renal clear cell carcinoma (KIRC). However, the aetiology and pathogenesis of RCC still need to be clarified. Exploring the internal mechanism of RCC contributes to diagnosing and treating this disease. Pyroptosis is a critical process related to cell death. Recent research has shown that pyroptosis is a critical factor in the initiation and progression of tumour formation. Thus far, researchers have progressively uncovered evidence of the regulatory influence that long noncoding RNAs (lncRNAs) have on pyroptosis. METHODS: In this work, a comprehensive bioinformatics approach was used to produce a predictive model according to pyroptosis-interrelated lncRNAs for the purpose of predicting the overall survival and molecular immune specialties of patients diagnosed with KIRC. This model was verified from multiple perspectives. RESULTS: First, we discovered pyroptosis-associated lncRNAs in KIRC patients using the TCGA database and a Sankey diagram. Then, we developed and validated a KIRC patient risk model based on pyroptosis-related lncRNAs. We demonstrated the grouping power of PLnRM through PCA and used PLnRM to assess the tumour immune microenvironment and response to immunotherapy. Immunological and molecular traits of diverse PLnRM subgroups were evaluated, as were clinical KIRC patient characteristics and predictive risk models. On this basis, a predictive nomogram was developed and analyzed, and novel PLnRM candidate compounds were identified. Finally, we investigated possible medications used by KIRC patients. CONCLUSIONS: The results demonstrate that the model generated has significant value for KIRC in clinical practice.

Analysis of risk factors for surgical site infection after colorectal surgery: a cross-sectional study in the east of China pre-COVID-19.

Background: The occurrence of surgical site infection (SSI) can prolong the postoperative hospital stay, increase the economic burden of patients, and even endanger their lives. The purpose of this study was to investigate the incidence, risk factors, and microbiology of SSI after colorectal surgery (CRS) and to provide a basis for the prevention and control of SSI. Methods: A single-center, prospective, cross-sectional study of adult patients undergoing CRS was conducted from 2010-2019. Univariate and multivariate logistic regression models were used to collect and analyze demographic information, hospital characteristics, and potential perioperative risk factors of SSI. Results: A total of 3,302 eligible patients were included in this study, with 213 cases experiencing SSIs, resulting in an infection rate of 6.45%. Notably, the incidence of SSI decreased from 13.33% in 2010 to 3.56% in 2019 (Ptrend < 0.001). Escherichia coli accounted for the majority of isolated microorganisms (37.09%), with 49 strains exhibiting resistance to one or more antibiotics (35.25%). Multivariate analysis showed that diabetes, anastomosis leakage, wound classification (contaminated/dirty), operation duration, blood loss greater than 200 ml, and NNIS risk index score for 2 or 3 were independent risk factors. Conversely, laparoscopic approach, preoperative bowel preparation and preoperative albumin levels emerged as protective factors against SSI after CRS. Furthermore, compared to non-SSI patients, SSI patients had a significantly higher 30-day mortality rate following surgery (0.23% vs. 2.35%, p < 0.05). Conclusion: SSI after CRS was susceptible to many factors, and the pathogen of SSI was mainly Escherichia coli. In clinical practice, measures such as correcting preoperative hypoproteinemia, choosing laparoscopic surgery, preoperative bowel preparation and shortening the duration of surgery should be taken to reduce the incidence of SSI.

[Application and Effect Evaluation of Precision Nursing Care of Enhanced Rehabilitation After Surgery in the Perioperative Period of Colorectal Cancer].

Objective: To examine the effect of perioperative precision nursing care of enhanced recovery after surgery (ERAS) on the postoperative recovery, stress response, and psychological state of colorectal cancer patients. Methods: A total of 100 patients undergoing elective laparoscopic colorectal cancer surgery were randomly assigned to an experimental group and a control group, with 50 patients in each group. The experimental group received systematic, standardized, and specialized precision nursing care in three stages, the preoperative, intraoperative, and postoperative stages, while the control group received routine nursing care. The main outcome indicators compared between the two groups included the time of the first postoperative passage of flatus and stool, ambulation, liquid-diet meal, postoperative length-of-stay, and C-reactive protein (CRP), interleukin-6 (IL-6), and homeostatic model assessment of insulin resistance (HOMR-IR) measured 1 day before surgery and 1, 3, and 5 days after surgery. Secondary outcome indicators included the anxiety and depression levels of patients measured upon admission to the hospital and 48 h after surgery by Self-rating Anxiety Scale (SAS) and Self-rating Sepression Scale (SDS), respectively. Results: In the experimental group, the time of the first postoperative passage of flatus and stool, ambulation, and liquid-diet meal and the postoperative length-of-stay were all lower than those in the control group. The postoperative CRP and IL-6 levels of the two groups were significantly higher than the preoperative levels, and the control group had higher CRP and IL-6 levels than the experimental group did, all showing significant difference ( P<0.05). The two groups presented different stress states at different points of time after surgery, with the CRP and IL-6 levels reaching the highest 3 days after surgery and then dropping to some degree afterwards. The HOMR-IR of the patients in the experimental group was significantly lower than that of the control group and the difference was significant at both 1 d and 3 d after surgery ( P<0.05). Comparison of the difference in the anxiety and the depression scores in the two groups showed significant difference ( P<0.05). Before discharge, patient satisfaction of the experimental group was significantly higher than that of the control group ( P<0.05). Conclusion: The implementation of ERAS precision nursing care can effectively promote the postoperative recovery of colorectal cancer patients, reduce the perioperative stress response, alleviate anxiety and depression, improve patient satisfaction, and hence should be extensively applied in clinical practice.

Macrocyclization via remote meta-selective C-H olefination using a practical indolyl template.

The synthesis of macrocyclic compounds with different sizes and linkages remains a great challenge via transition metal-catalysed intramolecular C-H activation. Herein, we disclose an efficient macrocyclization strategy via Pd-catalysed remote meta-C-H olefination using a practical indolyl template. This approach was successfully employed to access macrolides and coumarins. In addition, the intermolecular meta-C-H olefination also worked well and was exemplified by the synthesis of antitumor drug belinostat from inexpensive and readily available benzenesulfonyl chloride. Notably, catalytic copper acetate and molecular oxygen were used in place of silver salts as oxidants. Furthermore, for the first time, the formation of a macrocyclophane cyclopalladated intermediate was detected through in situ Fourier-transform infrared monitoring experiments and ESI-MS.

Efficacy and safety of Xian-Lian-Jie-Du optimization decoction as an adjuvant treatment for prevention of recurrence in patients with stage IIIB/IIIC colon cancer: study protocol for a multicentre, randomized controlled trial.

INTRODUCTION: Colon cancer remains one of the most prevalent cancers worldwide. Unfortunately, there are no recognized and effective therapeutic strategies to prevent tumor recurrence after radical resection and chemotherapy, and the disease-free survival (DFS) in patients with stage IIIB or IIIC disease remains unsatisfactory. Xian-Lian-Jie-Du optimization decoction (XLJDOD) is a Chinese herbal medicine (CHM) empirical prescription, which has been validated experimentally and clinically that could inhibit the progression of colorectal cancer and ameliorate the symptoms. The purpose of this study is to evaluate the efficacy and safety of XLJDOD in prevention of recurrence of colon cancer. METHODS: This study is a multi-center, double-blind, randomized, placebo-controlled trial conducted at 13 hospitals of China. Following the completion of surgery and adjuvant 5- fluorouracil-based chemotherapy, a total of 730 subjects with stage IIIB or IIIC colon cancer will be randomized in a 1:1 ratio to an intervention group (n = 365; XLJDOD compound granule) and a control group (n = 365; Placebo). Patients will receive 6-month treatments and be followed up with 3 monthly assessments for 2 years. The primary outcome is 2-year DFS rate and the secondary outcomes are 1, 2-year relapse rate (RR), overall survival (OS) and quality of life (QoL). Safety outcomes such as adverse events will be also assessed. A small number of subgroup analysis will be carried out to explore the heterogeneity of effects of XLJDOD. DISCUSSION: The outcomes from this randomized controlled trial will provide objective evidences to evaluate XLJDOD's role as an adjuvant treatment in colon cancer. TRIAL REGISTRATION: www. CLINICALTRIALS: gov , identifier: NCT05709249. Registered on 31 Jan 2023.

Small bowel diverticulum with enterolith causing intestinal obstruction: A case report.

BACKGROUND: Small bowel diverticula are rare in clinics, and small intestinal obstruction caused by coprolites is rarer and difficult to diagnose early. The true incidence of these diverticula may be underestimated due to their clinical symptoms not differing from those of small bowel obstruction resulting from other causes. It is common in the elderly, although it can occur at any age. CASE SUMMARY: This is a case report of a 78-year-old man with epigastric pain for 5 d. Conservative treatment does not effectively relieve pain, inflammatory indicators are elevated, and computed tomography suggests jejunal intussusception and mild ischemic changes in the intestinal wall. Laparoscopic exploration showed that the left upper abdominal loop was slightly edematous, the jejunum mass at the near Flex ligament was palpable, the size was about 7 cm × 8 cm, the local movement was slight, and the diverticulum was seen 10 cm downward, and the local small intestine was dilated and edema. Segmentectomy was performed. After the short parenteral nutrition after surgery, the fluid and enteral nutrition solution were pumped through the jejunostomy tube, and the patient was discharged after the treatment was stable, and the jejunostomy tube was removed in an outpatient clinic one month after the operation. Postoperative pathology: Jejunectomy specimen: (1) Small intestinal diverticulum with chronic inflammation, ulcer with full-thickness activity, and necrosis of the intestinal wall in some areas; (2) also see that the hard object is consistent with stone changes; and (3) the incision margin on both sides shows chronic inflammation of mucosal tissue. CONCLUSION: Clinically, the diagnosis of small bowel diverticulum is difficult to distinguish from jejunal intussusception. Combined with the patient's condition, rule out other possibilities after a timely disease diagnosis. According to the patient's body tolerance adopt personalized surgical methods to achieve better recovery after surgery.

Diallyl trisulfide inhibits gastric cancer stem cell properties through ΔNp63/sonic hedgehog pathway.

Gastric cancer is one of the deadliest malignant tumors, and half of the patients develop recurrences or metastasis within 5 years after eradication therapy. Cancer stem cells (CSCs) are considered to be important in this progress. The sonic hedgehog (SHH) pathway plays an important role in the maintenance of gastric CSCs characteristics. The p63 proteins are vital transcription factors belonging to the p53 family, while their functions in regulating CSCs remain unclear. The preventive effects of dietary diallyl trisulfide (DATS) against human gastric cancer have been verified. However, whether DATS can target gastric CSCs are poorly understood. Here, we investigated the role of ΔNp63/SHH pathway in gastric CSCs and the inhibitory effect of DATS on gastric CSCs via ΔNp63/SHH pathway. We found that ΔNp63 was upregulated in serum-free medium cultured gastric tumorspheres compared with the parental cells. Overexpression of ΔNp63 elevated the self-renewal capacity and CSC markers' levels in gastric sphere-forming cells. Furthermore, we found that ΔNp63 directly bound to the promoter region of Gli1, the key transcriptional factor of SHH pathway, to enhance its expression and to activate SHH pathway. In addition, it was revealed that DATS effectively inhibited gastric CSC properties both in vitro and in vivo settings. Activation of SHH pathway attenuated the suppressive effects of DATS on the stemness of gastric cancer. Moreover, DATS suppression of gastric CSC properties was also diminished by ΔNp63 upregulation through SHH pathway activation. These findings illustrated the role of ΔNp63/SHH pathway in DATS inhibition of gastric cancer stemness. Taken together, the present study suggested for the first time that DATS inhibited gastric CSCs properties by ΔNp63/SHH pathway.

Safety and immunogenicity of a bivalent HPV16/18 vaccine in Chinese females.

As global supply is still inadequate to address the worldwide requirements for HPV vaccines, we assessed the safety and immunogenicity of a new bivalent HPV16/18 vaccine. In this randomized, double-blind, placebo-controlled, phase 2 trial, healthy 9-45-year-old Chinese females in three age cohorts (600 aged 9-17 years; 240 aged 18-26 years; 360 aged 27-45 years) were randomized 1:1 to receive three doses (0,2,6 months) of HPV16/18 vaccine or placebo. We measured neutralizing antibodies against HPV 16 and 18 at 7 months and monitored safety to 12 months in all age cohorts; 9-17-year-old girls were monitored for safety and immunogenicity to 48 months. In vaccinees, 99.8% seroconverted for HPV 16 and 18 types at 7 months; respective GMTs of 5827 (95% CI: 5249, 6468) and 4223 (3785, 4713) were significantly (p < .001) higher than controls for all comparisons. GMTs in the 9-17-year-olds, which were significantly higher than in older women at 7 months, gradually declined to 48 months but remained higher than placebo with seropositivity rates maintained at 98.5% and 97.6% against HPV 16 and 18, respectively. Adverse events occurred at similar rates after vaccine and placebo (69.8% vs. 72.5%, p = .308), including solicited local reactions and systemic adverse events which were mainly mild-to-moderate. The bivalent HPV16/18 vaccine was well tolerated and induced high levels of neutralizing antibodies in all age groups which persisted at high levels to 48 months in the 9-17-year-old age group which would be the target for HPV vaccination campaigns.

Three-port approach vs conventional laparoscopic radical cystectomy with orthotopic neobladder: a single-center retrospective study.

BACKGROUND: This study aimed to compare the clinical outcomes of patients who underwent three-port laparoscopic radical cystectomy (LRC) with orthotopic neobladder (ONB) and traditional five-port method. METHODS: From January 2017 to November 2020, 100 patients underwent LRC + ONB at a third-level grade A hospital. RESULTS: Our study included 55 patients who underwent three-port LRC and 45 patients who underwent the five-port method. There were no significant differences in perioperative data such as operation time (253.00 ± 43.89 vs. 259.07 ± 52.31 min, P = 0.530), estimated blood loss (EBL)(97.64 ± 59.44 vs. 106.67 ± 55.35 min, P = 0.438), day to flatus (2.25 ± 1.49 vs. 2.76 ± 1.77 days, P = 0.128), day to regular diet (7.07 ± 2.99 vs. 7.96 ± 3.32 days, P = 0.165), day to pelvic drain removal (9.58 ± 3.25 vs. 10.53 ± 3.80 days, P = 0.180), and hospital stay after operation (11.62 ± 3.72 vs. 11.84 ± 4.37 days, P = 0.780) between the two groups. The only significant difference was in the treatment cost (P = 0.035). Similarly, postoperative complications, quality of life, and tumor outcomes were not significantly different between the two groups (P > 0.05). CONCLUSIONS: The three-port method is safe and feasible for patients suitable for traditional five-port LRC with an orthotopic neobladder.