Are popular books about diet and health written based on scientific evidence? A comparison of citations between the USA and Japan.

OBJECTIVES: To describe and compare the references cited in popular books about diet and health between the USA and Japan. DESIGN: Books were selected based on their best-seller rankings in the diet and health category of online bookstores. We identified references throughout all pages of the books and examined the number of references, reference format (identifiable or not) and presence of specific types of references, such as systematic reviews of human research. We compared the characteristics of references between the two countries and examined related factors to citation. SETTING: Cross-sectional study. PARTICIPANTS: Books (n 100 in each country). RESULTS: Among 100 books from each country, sixty-five US and sixty-six Japanese books had references. Forty-five US books cited more than 100 references, against only five Japanese books. The number of books that cited systematic reviews of human research differed between the USA (n 49) and Japan (n 9). Additionally, the number of books that provided identifiable information for all references was significantly higher in the USA (n 63) than in Japan (n 42). Books whose first authors have licences of medical doctors were more likely to cite references than those without in both countries. CONCLUSIONS: Two-thirds of books about diet and health cited references in both the USA and Japan, but Japanese books cited fewer references and were less likely to cite systematic reviews and provide identifiable references than US books. Further research into the scientific reliability of information in books about diet and health is warranted.

Inhibition of integrin binding to ligand arg-gly-asp motif induces AKT-mediated cellular senescence in hepatic stellate cells.

BACKGROUND & AIMS: Hepatic stellate cells (HSCs) play an essential role in liver fibrogenesis. The induction of cellular senescence has been reported to inhibit HSC activation. Previously, we demonstrated that CWHM12, a small molecule arginine-glycine-aspartic acid (RGD) peptidomimetic compound, inhibits HSC activation. This study investigated whether the inhibitory effects of CWHM12 on HSCs affected cellular senescence. METHODS: The immortalized human HSC lines, LX-2 and TWNT-1, were used to evaluate the effects of CWHM12 on cellular senescence via the disruption of RGD-mediated binding to integrins. RESULTS: CWHM12 induces cell cycle arrest, senescence-associated beta-galactosidase activity, acquisition of senescence-associated secretory phenotype (SASP), and expression of senescence-associated proteins in HSCs. Further experiments revealed that the phosphorylation of AKT and murine double minute 2 (MDM2) was involved in the effects of CWHM12, and the inhibition of AKT phosphorylation reversed these effects of CWHM12 on HSCs. CONCLUSIONS: Pharmacological inhibition of RGD-mediated integrin binding induces senescence in activated HSCs.

Simvastatin inhibits hepatic stellate cells activation by regulating the ferroptosis signaling pathway.

BACKGROUND & AIMS: Ferroptosis is a form of regulated cell death and its promotion in hepatic stellate cells (HSCs) attenuates liver fibrosis. Statins, which are 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors, may induce ferroptosis via the downregulation of glutathione peroxidase 4 (GPX4) by inhibiting the mevalonate pathway. However, little evidence is available regarding the association between statins and ferroptosis. Therefore, we investigated the association between statins and ferroptosis in HSCs. METHODS: Two human HSC cell lines, LX-2 and TWNT-1, were treated with simvastatin, an HMG-CoA reductase inhibitor. Mevalonic acid (MVA), farnesyl pyrophosphate (FPP), and geranylgeranyl pyrophosphate (GGPP) were used to determine the involvement of the mevalonate pathway. We performed a detailed analysis of the ferroptosis signaling pathway. We also investigated human liver tissue samples from patients with nonalcoholic steatohepatitis to clarify the effect of statins on GPX4 expression. RESULTS: Simvastatin reduced cell mortality and inhibited HSCs activation, accompanied by iron accumulation, oxidative stress, lipid peroxidation, and reduced GPX4 protein expression. These results indicate that simvastatin inhibits HSCs activation by promoting ferroptosis. Furthermore, treatment with MVA, FPP, or GGPP attenuated simvastatin-induced ferroptosis. These results suggest that simvastatin promotes ferroptosis in HSCs by inhibiting the mevalonate pathway. In human liver tissue samples, statins downregulated the expression of GPX4 in HSCs without affecting hepatocytes. CONCLUSIONS: Simvastatin inhibits the activation of HSCs by regulating the ferroptosis signaling pathway.

CSNK2B modulates IRF1 binding to functional DNA elements and promotes basal and agonist-induced antiviral signaling.

Interferon regulatory factor 1 (IRF1) is a critical component of cell-intrinsic innate immunity that regulates both constitutive and induced antiviral defenses. Due to its short half-life, IRF1 function is generally considered to be regulated by its synthesis. However, how IRF1 activity is controlled post-translationally has remained poorly characterized. Here, we employed a proteomics approach to identify proteins interacting with IRF1, and found that CSNK2B, a regulatory subunit of casein kinase 2, interacts directly with IRF1 and constitutively modulates its transcriptional activity. Genome-wide CUT&RUN analysis of IRF1 binding loci revealed that CSNK2B acts generally to enhance the binding of IRF1 to chromatin, thereby enhancing transcription of key antiviral genes, such as PLAAT4 (also known as RARRES3/RIG1/TIG3). On the other hand, depleting CSNK2B triggered abnormal accumulation of IRF1 at AFAP1 loci, thereby down-regulating transcription of AFAP1, revealing contrary effects of CSNK2B on IRF1 binding at different loci. AFAP1 encodes an actin crosslinking factor that mediates Src activation. Importantly, CSNK2B was also found to mediate phosphorylation-dependent activation of AFAP1-Src signaling and exert suppressive effects against flaviviruses, including dengue virus. These findings reveal a previously unappreciated mode of IRF1 regulation and identify important effector genes mediating multiple cellular functions governed by CSNK2B and IRF1.

Rifaximin Improves Liver Functional Reserve by Regulating Systemic Inflammation.

Rifaximin, a non-absorbable antibiotic, has been demonstrated to be effective against hepatic encephalopathy (HE); however, its efficacy on liver functional reserve remains unknown. Here, we evaluated the efficacy of rifaximin on the liver functional reserve and serological inflammation-based markers in patients with cirrhosis. A retrospective study was conducted on patients who received rifaximin for more than three months at our hospital between November 2016 and October 2021. The recurrence and grade of HE, serological ammonia levels, Child-Pugh score (CPS), and serological inflammation-based markers such as the neutrophil-lymphocyte ratio (NLR), lymphocyte-monocyte ratio (LMR), platelet-lymphocyte ratio (PLR), C-reactive protein (CRP), and CRP to albumin ratio (CAR) were evaluated. The correlations between serological inflammation-based markers and liver functional reserve were evaluated. HE grades, serum ammonia levels, and inflammation-based markers significantly improved at three months compared with those at baseline. Patients with improved albumin levels showed significantly higher CRP improvement rates at both 3 and 12 months. Patients with an improvement in CAR at 3 months demonstrated a significant improvement in CPS at 12 months. Rifaximin improved the liver functional reserve in patients with cirrhosis. Improvements in inflammation-based markers, particularly CRP and albumin, may be involved in this process.

Hepatic Angiosarcoma with Peliosis Hepatis.

A 59-year-old woman presented to our hospital with liver dysfunction. Imaging revealed multiple lesions in the liver. The patient was diagnosed with peliosis hepatis using percutaneous and laparoscopic biopsies. However, her condition worsened with the appearance of new, obvious mass-forming lesions. Therefore, she underwent a second percutaneous biopsy of these lesions and was diagnosed with hepatic angiosarcoma. Her condition progressed rapidly, and she died two weeks after the diagnosis. Diagnosis of hepatic angiosarcoma in the early stages is difficult. It should be noted that hepatic angiosarcoma may be associated with the development of peliosis hepatis.

Use of Polyglycolic Acid Sheets for the Prevention of Pancreatic Fistula after Laparoscopic Gastrectomy: A Single-Center Retrospective Study.

BACKGROUND: Laparoscopic gastrectomy (LG) indications have been extended to advanced gastric cancer requiring expansive lymph node dissection. Despite the huge benefits of this minimally invasive surgery, major complications such as postoperative pancreatic fistula (POPF) remain a concern. With technical advances in surgical procedures, the treatment outcomes of gastric cancer surgery have improved. However, effective methods for preventing POPF have not yet been established. Herein, we examined the usefulness of polyglycolic acid (PGA) sheets for preventing POPF after LG. METHODS: We retrospectively assessed 142 patients who underwent curative LG at our institution between January 2017 and August 2022. The 142 patients were divided into 2 groups; PGA group (n = 61): the site of lymph node dissection at the superior margin of the pancreas and pancreatic head was covered with PGA sheets, and nPGA group (n = 81): the site was not covered. We retrospectively compared the short-term surgical outcomes including POPF incidence. RESULTS: There was no significant difference in the background factors between the 2 groups and in the incidence of Grade II or higher postoperative complications according to the Clavien-Dindo (CD) classification. However, the incidence of CD Grade II or higher POPF was significantly lower in the PGA group than in the nPGA group (.0% vs 2.3%, respectively, P = .007). CONCLUSIONS: There was no POPF in any of the 61 patients in the PGA group. This outcome suggests that POPF incidence may be reduced by covering the lymph node dissection site with PGA sheets after LG.

[Multiple Intestinal Perforations Caused by Diffuse Large B-Cell Lymphoma-A Case Report].

A 83-year-old man was diagnosed with diffuse large B-cell lymphoma and scheduled for treatment. However, he developed abdominal pain, and computed tomography revealed a gastrointestinal perforation. Emergency surgery was performed, upon which we identified perforations in the small intestine, and we therefore performed resection of the small intestine. R-CHOP therapy was performed postoperatively, resulting in successful tumor shrinkage. Malignant lymphoma of the small intestine often causes intestinal perforations, and the prognosis of patients with perforations is unfavorable. We report a case of a patient with multiple intestinal perforations owing to malignant lymphoma of the small intestine, in whom minimal surgery was performed and intervention in the early postoperative period was successful.

Arg-Gly-Asp-binding integrins activate hepatic stellate cells via the hippo signaling pathway.

BACKGROUND & AIMS: Liver fibrosis characterizes advanced chronic liver disease, and persistent activation of hepatic stellate cells (HSCs) is the primary cause of excessive hepatic fibrogenesis. CWHM12, an analog of the arginine-glycine-aspartic acid (RGD) amino acid sequence found in specific integrins, improves liver fibrosis; however, the detailed mechanisms remain unclear. This study aimed to clarify the cell signaling mechanisms of CWHM12 in activated HSCs. METHODS: Immortalized human HSC lines, LX-2 and TWNT-1, were used to evaluate the effects of CWHM12 on intracellular signaling via the disruption of RGD-binding integrins. RESULTS: CWHM12 strongly promoted phosphorylation and inhibited the nuclear accumulation of Yes-associated protein (YAP), which is a critical effector of the Hippo signaling pathway, leading to the inhibition of proliferation, suppression of viability, promotion of apoptosis, and induction of cell cycle arrest at the G1 phase in activated HSCs. Further investigations revealed that inhibition of TGF-ß was involved in the consequences of CWHM12. Moreover, CWHM12 suppressed focal adhesion kinase (FAK) phosphorylation; consequently, Src, phosphatidylinositol 3-kinase, pyruvate dehydrogenase kinase 1, and serine-threonine kinase phosphorylation led to the translocation of YAP. These favorable effects of CWHM12 on activated HSCs were reversed by inhibiting FAK. CONCLUSIONS: These results indicate that pharmacological inhibition of RGD-binding integrins suppresses activated HSCs by blocking the Hippo signaling pathway, a cellular response which may be valuable in the treatment of hepatic fibrosis.

Long-term surgical outcomes of gastric neuroendocrine carcinoma and mixed neuroendocrine-non-neuroendocrine neoplasms.

BACKGROUND: Neuroendocrine carcinoma (NEC) and mixed neuroendocrine-non-neuroendocrine neoplasm (MiNEN) are extremely rare subtypes of gastric cancer. MiNEN is a mix of carcinomatous components and neuroendocrine neoplasm in the same lesion. NEC and MiNEN have a poor prognosis, are difficult to diagnose, and have no established treatment. Herein, we assessed the clinicopathological characteristics and long-term surgical outcomes of gastric NEC and MiNEN patients in our hospital. METHODS: We retrospectively assessed 1538 patients pathologically diagnosed with gastric cancer and who underwent curative surgical resection at our institution between January 1999 and October 2021. Of these patients, 25 (1.6%) were pathologically diagnosed with neuroendocrine neoplasms. From these 25 patients, we retrospectively analyzed the clinicopathological characteristics and surgical outcomes of 13 (0.8%) patients pathologically diagnosed with NEC or MiNEN. RESULTS: The NEC and MiNEN patients consisted of 11 men and 2 women [mean age, 74 (62-84) years]. The preoperative histological diagnoses were NEC (n = 4) and adenocarcinoma (n = 9). The final pathological diagnoses were large cell neuroendocrine carcinoma (LCNEC; n = 7) and MiNEN (n = 6). Total gastrectomy was the most common surgical procedure (9/13, 69.2%), followed by distal gastrectomy (3/13, 23.1%) and proximal gastrectomy (1/13, 7.7%). Immunohistochemical staining showed 8 CD56-positive patients. All 13 patients were positive for chromogranin A and synaptophysin. The mean Ki-67 value was 64.8 (0-95)%, and the mean mitotic score was 107.9 (0-400). Nine patients survived without recurrence postresection. The median postresection overall survival time was 68.7 (8.0-129) months. The 5-year survival rate was 0.75 ([95% CI] 0.408-0.912). CONCLUSION: The surgical treatment outcomes of NEC and MiNEN patients were relatively favorable. Although evidence concerning the effectiveness of surgery alone is meager, radical resection as part of multidisciplinary treatment including chemotherapy can potentially improve prognosis.

[A Case of Combined Modality Therapy for Progressive Esophagus Cancer with Perforation Due to Preoperative Chemotherapy].

A nearby doctor sensed incongruity in deglutition as a chief complaint from a 56-year-old man. A middle intrathoracic esophagus cancer was subsequently diagnosed and referred to our department. We started FP therapy based on the preoperative chemotherapy guidelines, but perforation of esophageal cancer developed. We conducted chest drainage, and attempted to improve the patient's overall status with antibiotic medical treatment and hyperalimentation; single-stage operations were performed. As tumor invaded the left pleura, surgery occurred for R2 resection of the left lung. Subsequently, we started nivolumab therapy because we give DCF therapy and detected a liver metastasis and we continue it now and survive.

FADS2-dependent fatty acid desaturation dictates cellular sensitivity to ferroptosis and permissiveness for hepatitis C virus replication.

The metabolic oxidative degradation of cellular lipids severely restricts replication of hepatitis C virus (HCV), a leading cause of chronic liver disease, but little is known about the factors regulating this process in infected cells. Here we show that HCV is restricted by an iron-dependent mechanism resembling the one triggering ferroptosis, an iron-dependent form of non-apoptotic cell death, and mediated by the non-canonical desaturation of oleate to Mead acid and other highly unsaturated fatty acids by fatty acid desaturase 2 (FADS2). Genetic depletion and ectopic expression experiments show FADS2 is a key determinant of cellular sensitivity to ferroptosis. Inhibiting FADS2 markedly enhances HCV replication, whereas the ferroptosis-inducing compound erastin alters conformation of the HCV replicase and sensitizes it to direct-acting antiviral agents targeting the viral protease. Our results identify FADS2 as a rate-limiting factor in ferroptosis, and suggest the possibility of pharmacologically manipulating the ferroptosis pathway to attenuate viral replication.

[Combined Modality Therapy for HER2-Positive Progressive Stomach Cancer Metastasis Achieving Treatment Response-A Case Report].

The patient was a 73-year-old man whose chief complaint was a 1-month history of anorexia and weight loss. Pyloric stenosis due to a circumferential type 2 lesion was detected on the pylorus ring from the gastric angle. Close inspection revealed a diagnosis of progressive stomach cancer cT3N+M0, stage Ⅲ. We judged that perioperative radical excision would be impossible and performed gastrojejunal bypass surgery. Postoperatively, the patient was treated with 2 courses of SOX plus trastuzumab and 7 courses of S-1. PR was identified, and a distal-side gastrectomy plus D2 lymph node dissection were performed as conversion surgery. The patient was discharged on postoperative day 9. For 1 year postoperative, no recurrence was noted. The prognosis of the unresectable gastric cancer is poor, but chemotherapy and conversion surgery in this case resulted in a favorable prognosis.

[A Case of Esophageal Malignant Melanoma during Follow-Up of Esophageal Melanosis Metastasis].

Man 62-years-old as for the case. In 2019, he was diagnosed with right hypopharyngeal cancer, and esophageal melanosis was noted on upper gastrointestinal endoscopy before treatment. We did a follow-up upper gastrointestinal endoscopy every year. At a follow-up upper gastrointestinal endoscopy performed in February 2021, he was histologically diagnosed with an esophageal primary malignant melanoma. Computed tomography showed no metastatic lesions. He underwent esophagectomy. He is currently being followed on an outpatient basis and has had no recurrence. Careful follow-up for esophageal melanocytosis is important for early diagnosis of esophageal primary malignant melanoma.

[Duodenal Stent Placement against Anastomotic Stenosis after Esophageal Cancer Resection-A Case Report].

A 53-year-old man was diagnosed as esophageal cancer, and esophagectomy was performed. Anastomotic stenosis was caused due to lymphorrhea and anastomotic leakage after surgery. Dilation was performed, though stenosis did not improved, we placed esophageal stent across the stenotic lesion. Pharyngitis occurred after indwelling esophageal stent, we hence removed the stent. Passage disorder was developed, we placed duodeneal stent which is more flexible. Stenosis is now palliated after placing duodeneal stent. Duodeneal stent could be an option for the tratment of anastomotic stenosis after esophageal surgery.

Azathioprine-induced severe myelosuppression accompanied by massive hair loss and painful oral ulcer in an autoimmune hepatitis patient with NUDT15 minor variant: A case report.

This report highlights azathioprine-induced severe myelosuppression in the patient with NUDT15 minor variant. This case report is particularly instructive because several typical symptoms are the clues to this critical adverse drug reaction.

Total Synthesis of Thuggacin cmc-A and Its Structure Determination.

The first total synthesis of thuggacin cmc-A and the determination of the absolute structure are described. The thuggacin family of antibiotics is of great interest due to the antibiotic activity against Mycobacterium tuberculosis. Based on the assumption that seven stereogenic centers in thuggacin cmc-A would share the same stereochemistry as thuggacin-A, all stereogenic centers of thuggacin cmc-A were strictly constructed in a stereocontrolled manner. The total synthesis allowed its stereostructure to be fully confirmed.