Characteristics and immune checkpoint inhibitor effects on non-smoking non-small cell lung cancer with KRAS mutation: A single center cohort (STROBE-compliant)

Kirsten rat sarcoma (KRAS) mutation (KRASm) is associated with poor prognosis in non-small cell lung cancer (NSCLC) patients. We have aimed to survey NSCLC patients harboring KRASm in Taiwan, where never-smoking lung adenocarcinoma predominates, and analyze the immune checkpoint inhibitor effect on NSCLC harboring KRASm.NSCLC patients with KRASm were enrolled and tested on programmed death-ligand 1 (PD-L1) expression using available tissue. We analyzed their clinical features, PD-L1 status, responses to ICIs, and overall survival (OS).We studied 93 patients with a median age 66.0 years, 23.7% of whom were women, and 22.6% were never-smokers. The results showed that G12C (36.6%) was the most common KRASm. In 47 patients with available tissue for PD-L1 testing, PD-L1 expression was positive in 66.0% of patients, while PD-L1 ≥50% was higher in ever-smokers (P = .038). Among 23 patients receiving ICI treatment, those with PD-L1 ≥50% experience a 45.5% response rate to ICI. There were benefits from ICI treatment on OS compared with no ICI treatment (median OS 35.6 vs 9.8 months, P = .002) for all of our patients, and for patients with PD-L1 ≥50% (median OS not-reached vs 8.4 months, P = .008). There were no differences in survival across different KRAS subtypes (P = .666).Never-smokers composed more than one-fifth of KRASm in NSCLC in Taiwan. A high PD-L1 expression was related to smoking history and responded well to ICI. ICI treatment improved the OS in NSCLC patients with KRASm, particularly those with PD-L1 ≥50%.     

Correction: Discovery of 8-prenylnaringenin from hop (Humulus lupulus L.) as a potent monoacylglycerol lipase inhibitor for treatments of neuroinflammation and Alzheimer’s disease

Correction for ‘Discovery of 8-prenylnaringenin from hop (Humulus lupulus L.) as a potent monoacylglycerol lipase inhibitor for treatments of neuroinflammation and Alzheimer’s disease’ by Min-Che Tung et al., RSC Adv., 2021, 11, 31062–31072, https://doi.org/10.1039/D1RA05311F.

The authors regret that the name of one of the authors (Hsing-Mien Hsu) was shown incorrectly in the original article. The corrected author list is as shown above.The authors also regret an incorrect version of Fig. 7 was included in the original article. The correct version of Fig. 7 is presented below.Open in a separate windowFig. 7The dose-dependent inhibitions of the identified inhibitors against hMAGL.The Royal Society of Chemistry apologises for these errors and any consequent inconvenience to authors and readers.     

Hepatitis D virus infection in children with acute or chronic hepatitis B virus infection in Taiwan

To investigate the prevalence and clinical features of hepatitis D virus infection (HDV) in childhood, total antibody to hepatitis D antigen (anti-HD) in serum samples from 247 children (29 with acute hepatitis B, 68 with chronic hepatitis B, and 150 with asymptomatic hepatitis B surface antigen (HBsAg) carriers with normal liver function profiles) were studied using solid-phase competitive radioimmunoassay. Anti-HD was detected in three of the 29 children with acute hepatitis B and in only one of the 68 with chronic hepatitis B; none of the serum specimens from 150 asymptomatic carriers with normal liver function profile showed detectable anti-HD. All three children with HDV coinfection cleared HBsAg and seroconverted to anti-HBs, whereas one with superinfection finally had normal liver function without clearance of HBsAg. To identify possible sources of HDV infection, HBV markers and anti-HD in family members were also examined. One 4-month-old infant boy became infected through a blood transfusion from his hepatitis B e antigen (HBeAg)-positive carrier father, who had anti-HD. A 4-month-old infant girl was infected through close contact with her HBeAg-negative carrier father, who had HDV superinfection. The infection sources remained undefined in another two patients. The mothers of these four children were seronegative for anti-HD, indicating that perinatal transmission is not the usual mode of HDV infection in Taiwan. The natural course of either acute or chronic HBV infections in childhood in Taiwan may be more closely related to HBV itself, or to some other yet unrecognized factor, rather than to HDV infection.     

Laparoscopic-assisted vaginal hysterectomy with in situ morcellation for large uteri

STUDY OBJECTIVE: To estimate whether laparoscopic in situ morcellation (LISM) can facilitate laparoscopic-assisted vaginal hysterectomy (LAVH) for large uteri. DESIGN: Prospective study (Canadian Task Force classification II-1). SETTING: University-affiliated hospital. PATIENTS: In all, 147 women with myoma or adenomyosis weighing more than 500 g from January 2004 through December 2007 were enrolled. The patients were divided into 4 subgroups: patients with uteri weighing 500 to 749 g who had traditional LAVH without LISM (group 1A, n = 69) or with LISM (group 1B, n = 16); and patients with uteri weighing 750 g or more who were treated by traditional LAVH without LISM (group 2A, n = 38) or with LISM (group 2B, n = 24). INTERVENTIONS: Laparoscopic-assisted vaginal hysterectomy with or without LISM. MEASUREMENT AND MAIN RESULTS: No significant differences existed in age, body mass index, preoperative diagnoses, complications, or duration of hospital stay among groups. The mean uterine weights were 608 +/- 75, 597 +/- 66, 989 +/- 179, and 935 +/- 226 g for groups 1A, 1B, 2A, and 2B, respectively. The operative time (120 +/- 16 vs 157 +/- 36 minutes, p <.001; 140 +/- 19 vs 224 +/- 57 minutes, p <.001) were significantly shorter in patients with LISM than without in both groups 1 and 2. The estimated blood loss was highest in group 2A. Six (16%) patients lost more than 500 mL of blood and 3 (8%) of them needed blood transfusions. Conversion to laparotomy occurred in 1 (2.6%) of 38 patients in group 2A. No repeated surgery or surgical mortality occurred. CONCLUSION: Laparoscopic-assisted vaginal hysterectomy with LISM was an efficient and safe procedure for removal of large uteri during LAVH.     

Tumor necrosis factor-alpha converting enzyme in the human placenta throughout gestation

Ectodomain shedding of epidermal growth factor receptor ligands such as transforming growth factor- alpha (TGF-alpha), heparin-binding epidermal growth factor-like growth factor (HBEGF), and amphiregulin (AREG) is considered to be important during implantation. Tumor necrosis factor-alpha converting enzyme (TACE) has been suggested as the major sheddase for these molecules. The objectives of this study are (1) to characterize the expression of TACE in the human placenta throughout gestation; (2) to determine the association between the expression of TACE with TGF-alpha, HBEGF, and AREG; (3) to ascertain whether TACE mediates TGF-alpha, HBEGF, and AREG shedding; and (4) to examine the effect of hypoxia on the expression of TACE. By analyzing a total of 55 villous samples representing different gestational ages, the authors found that TACE was continuously expressed in the placentas throughout gestation and that the levels of TACE were positively correlated with the levels of TGF-alpha, HBEGF, and AREG. Preadministration of a TACE inhibitor in villous explant cultures or transfection of cytotrophoblastic cells with TACE-specific small interference RNA decreased the shedding of HBEGF and AREG. Moreover, hypoxia (2% O(2)) caused an increase in the levels of TACE mRNA and protein in villous explants and primary cytotrophoblastic cells in vitro. These results indicate that oxygen regulates the expression of TACE and that TACE may be important for placental development during human pregnancy.     

Therapeutic effects of baicalin on lipopolysaccharide-induced acute lung injury in rats

Baicalin is a flavonoid present in many traditional Chinese medicines. A number of studies show that baicalin has anti-inflammatory actions and protects against a variety of tissue and organ injuries. The effect of baicalin in lipopolysaccharide (LPS)-induced acute lung injury is not well studied. In this study, typically acute lung injury was induced in rat by intratracheal injection of LPS, which increased lactate dehydrogenase activity and protein content in bronchoalveolar lavage fluid, wet/dry lung weight ratio, Evan's blue dye leakage, and neutrophil infiltration. Baicalin (20 mg/kg) was administrated 1 hour before or 30 min after LPS injection. Both pre and post-treatment with baicalin attenuated the increase of these parameters and improved histological finding. Our results suggest that baicalin has a therapeutic effect on LPS-induced acute lung injury.     

Primary aortoduodenal fistula caused by tuberculous aortitis presenting as recurrent massive gastrointestinal bleeding

Upper gastrointestinal bleeding from primary aortoduodenal fistula (PADF) is unusual and fatal. The etiology of PADF from tuberculous aortitis is rare. We report a 69-year-old male patient who suffered recurrent hematemesis and hematochezia with hypovolemic shock of unknown origin. Initial endoscopy failed to lead to a diagnosis. A bleeder over the third portion of the duodenum was found after the third endoscopy. Exploratory laparotomy showed a ruptured aortic pseudoaneurysm with an aortoduodenal fistula. Dacron graft repair of the aorta and simple closure of the duodenal fistula were carried out. Pathologic examination revealed tuberculous aortitis. The patient survived and was symptom-free following operation and antituberculous therapy. Review of the literature revealed that the clinical presentations in this disorder are insidious. The endoscopic findings are atypical. We conclude that so-called "herald bleeding", a history of tuberculous infection or aortic aneurysm and a high degree of suspicion are critical for successful diagnosis. Early diagnosis and surgical exploration are needed for timely and successful management.