A biosynthetic gene cluster for the bioactive fungal sesterterpenoids variecolin ( 1) and variecolactone ( 2) was identified in Aspergillus aculeatus ATCC 16872. Heterologous production of 1 and 2 was achieved in Aspergillus oryzae by expressing the sesterterpene synthase VrcA and the cytochrome P450 VrcB. Intriguingly, the replacement of VrcB with homologous P450s from other fungal terpenoid pathways yielded three new variecolin analogues ( 5- 7). Analysis of the compounds' anticancer activity in vitro and in vivo revealed that although 5 and 1 had comparable activities, 5 was associated with significantly reduced toxic side effects in cancer-bearing mice, indicating its potentially broader therapeutic window. Our study describes the first tests of variecolin and its analogues in animals and demonstrates the utility of synthetic biology for creating molecules with improved biological activities.

Background/Aims: Chronic hepatitis C (CHC) patients who failed antiviral therapy are at increased risk for hepatocellular carcinoma (HCC). This study assessed the potential role of metformin and statins, medications for diabetes mellitus (DM) and hyperlipidemia (HLP), in reducing HCC risk among these patients. Methods: We included CHC patients from the T-COACH study who failed antiviral therapy. We tracked the onset of HCC 1.5 years post-therapy by linking to Taiwan’s cancer registry data from 2003 to 2019. We accounted for death and liver transplantation as competing risks and employed Gray’s cumulative incidence and Cox subdistribution hazards models to analyze HCC development. Results: Out of 2,779 patients, 480 (17.3%) developed HCC post-therapy. DM patients not using metformin had a 51% increased risk of HCC compared to non-DM patients, while HLP patients on statins had a 50% reduced risk compared to those without HLP. The 5-year HCC incidence was significantly higher for metformin non-users (16.5%) versus non-DM patients (11.3%; adjusted sub-distribution hazard ratio [aSHR]=1.51; P=0.007) and metformin users (3.1%; aSHR=1.59; P=0.022). Statin use in HLP patients correlated with a lower HCC risk (3.8%) compared to non-HLP patients (12.5%; aSHR=0.50; P<0.001). Notably, the increased HCC risk associated with non-use of metformin was primarily seen in non-cirrhotic patients, whereas statins decreased HCC risk in both cirrhotic and non-cirrhotic patients. Conclusions Metformin and statins may have a chemopreventive effect against HCC in CHC patients who failed antiviral therapy. These results support the need for personalized preventive strategies in managing HCC risk.

Purpose: The incidence of deep vein thrombosis (DVT) following total hip arthroplasty (THA) without chemoprophylaxis could be as high as 50% in Caucasians. However, according to several subsequent studies, the incidence of venous thromboembolic events (VTE) in Asians was much lower. The routine use of chemoprophylaxis, which could potentially cause increased bleeding, infection, and wound complications, has been questioned in low-incidence populations. The objective of this study is to determine the incidence of VTE after primary THA without chemoprophylaxis in an Asian population using a fast-track rehabilitation protocol and to verify the safety profile for use of ‘mechanical prophylaxis alone’ in patients with standard risk of VTE. Materials and Methods: This is a retrospective cohort study of 542 Hong Kong Chinese patients who underwent primary THA without chemoprophylaxis. All patients received intermittent pneumatic compression and graduated compression stockings as mechanical prophylaxis. Multimodal pain management was applied in order to facilitate early mobilisation. Routine duplex ultrasonography was performed between the fourth and seventh postoperative day for detection of proximal DVT. Results: All patients were Chinese (mean age, 63.0±11.9 years). Six patients developed proximal DVT (incidence rate, 1.1%). None of the patients had symptomatic or fatal pulmonary embolism. Conclusion The incidence of VTE after primary THA without chemical prophylaxis can be low in Asian populations when following a fast-track rehabilitation protocol. Mechanical prophylaxis alone can be regarded as a reasonably safe practice in terms of a balanced benefit-to-risk ratio for Asian patients with standard risk of VTE.

BACKGROUNDVon Hippel-Lindau (VHL) syndrome is an autosomal dominant familial cancer syndrome predisposing the affected individuals to multiple tumours in various organs. The genetic basis of VHL in Southern Chinese is largely unknown. In this study, we characterized the mutation spectrum of VHL in nine unrelated Southern Chinese families.

METHODSNine probands with clinical features of VHL, two symptomatic and eight asymptomatic family members were included in this study. Prenatal diagnosis was performed twice for one proband. Two probands had only isolated bilateral phaeochromocytoma. The VHL gene was screened for mutations by polymerase chain reaction, direct sequencing and multiplex ligation-dependent probe amplification (MLPA).

RESULTSThe nine probands and the two symptomatic family members carried heterozygous germline mutations. Eight different VHL mutations were identified in the nine probands. One splicing mutation, NM_000551.2: c.463+1G > T, was novel. The other seven VHL mutations, c.233A > G [p.Asn78Ser], c.239G > T [p.Ser80Ile], c.319C > G [p.Arg107Gly], c.481C > T [p.Arg161X], c.482G > A [p.Arg161Gln], c.499C > T [p.Arg167Trp] and an exon 2 deletion, had been previously reported. Three asymptomatic family members were positive for the mutation and the other five tested negative. In prenatal diagnosis, the fetuses were positive for the mutation.

CONCLUSIONSGenetic analysis could accurately confirm VHL syndrome in patients with isolated tumours such as sporadic phaeochromocytoma or epididymal papillary cystadenoma. Mutation detection in asymptomatic family members allows regular tumour surveillance and early intervention to improve their prognosis. DNA-based diagnosis can have an important impact on clinical management for VHL families.

Asian Continental Ancestry Group ; DNA Mutational Analysis ; Humans ; Polymerase Chain Reaction ; Sequence Analysis, DNA ; Von Hippel-Lindau Tumor Suppressor Protein ; genetics ; von Hippel-Lindau Disease ; genetics

INTRODUCTIONCone beam computed tomography (CBCT) is a relatively new technological innovation that utilises fl at-panel detector technology to obtain CT-like images. The key strength of a CBCT system is that cross-sectional imaging can be obtained using the angiographic fl at panel unit without having to move the patient, allowing the radiologist to obtain soft tissue imaging during the procedure. This allows treatment planning, guidance, and assessment of outcome to be performed in one interventional suite.

MATERIALS AND METHODSFrom December 2008 to June 2009, 24 CBCT scans were performed during vascular interventional procedures on our department's newly installed multi-axis fl at panel angiographic unit.

RESULTSTen cases were performed for hepatic trans-arterial chemoembolisation, 9 cases for hepatic arterial Yttrium-90 infusion, while 5 cases were for other indications. CBCT was found to be useful in 20 of the 24 cases.

CONCLUSIONOur early experience showed that CBCT was useful in impacting decisions during selected vascular interventional procedures. As CBCT technology improves, we can foresee wider applications of this technology.

Aged ; Angiography ; Cone-Beam Computed Tomography ; standards ; Embolization, Therapeutic ; Female ; Humans ; Male ; Medical Audit ; Middle Aged ; Radiology, Interventional ; methods ; Retrospective Studies

Objective To observe the effect of early hyperbaric oxygen (HBO) therapy on cerebral resuscitation and to provide good evidence and method for the treatment of cerebral resuscitation.Methods The patients responded to cardiac pulmonary resuscitation (CPR) were divided into 2 groups,the early HBO group( within one week of onset) and the delayed HBO group (after 1 week of onset).All the patients were given routine medicinal treatment coupled with HBO therapy.The exposure pressure of HBO and the course of treatment were all the same,only the time point of HBO intervention was different.Evaluation was made by using "the Revised 2001 PVS Criteria for Diagnosis and Treatment" ( the Nanjing Criteria).Consciousness of the patients was evaluated both before HBO therapy and 6 months after onset.Results Of the 18 patients who received early HBO therapy,4 patients recovered and returned to normal life (effective),5 patients became fully conscious,but with minor disability (effective),and 9 patients became vegetable (ineffective),with a total effective rate of 50.0％.Of the 53 patients with delayed HBO therapy,9 patients recovered and returned to normal life (effective),15 patients became fully conscious,but with minor disability (effective),and 29 patients became vegetable (ineffective),with a total effective rate of 45.3％.No significant differences could be seen in effective rates between the 2 groups (P ＞0.05).However,statistical significance could be noted,when effective rates of the 2 groups were compared with those presented in domestic and international reports (2％-10％ ) ( P ＜ 0.05 ).Conclusions In-time HBO therapy could improve prognosis of some patients following cardiac resuscitation,protect neural cells,and improve the intelligence of patients,however,early and ultra-early HBO therapy could not increase the effective rate of cerebral resuscitation.

Objective To observe the effect of early hyperbaric oxygen (HBO) therapy on cerebral resuscitation and to provide good evidence and method for the treatment of cerebral resuscitation.Methods The patients responded to cardiac pulmonary resuscitation (CPR) were divided into 2 groups,the early HBO group( within one week of onset) and the delayed HBO group (after 1 week of onset).All the patients were given routine medicinal treatment coupled with HBO therapy.The exposure pressure of HBO and the course of treatment were all the same,only the time point of HBO intervention was different.Evaluation was made by using "the Revised 2001 PVS Criteria for Diagnosis and Treatment" ( the Nanjing Criteria).Consciousness of the patients was evaluated both before HBO therapy and 6 months after onset.Results Of the 18 patients who received early HBO therapy,4 patients recovered and returned to normal life (effective),5 patients became fully conscious,but with minor disability (effective),and 9 patients became vegetable (ineffective),with a total effective rate of 50.0％.Of the 53 patients with delayed HBO therapy,9 patients recovered and returned to normal life (effective),15 patients became fully conscious,but with minor disability (effective),and 29 patients became vegetable (ineffective),with a total effective rate of 45.3％.No significant differences could be seen in effective rates between the 2 groups (P ＞0.05).However,statistical significance could be noted,when effective rates of the 2 groups were compared with those presented in domestic and international reports (2％-10％ ) ( P ＜ 0.05 ).Conclusions In-time HBO therapy could improve prognosis of some patients following cardiac resuscitation,protect neural cells,and improve the intelligence of patients,however,early and ultra-early HBO therapy could not increase the effective rate of cerebral resuscitation.

OBJECTIVETo assess the safety and efficacy of hyaluronic acid-based gel of non-animal origin (NASHA gel [Restylane]; Q-Med AB, Uppsala, Sweden)for correcting nasolabial folds in Chinese.

METHODSPatients with moderate or severe nasolabial fold (Wrinkle Severity Rating Scale, WSRS) were recruited to receive NASHA gel injection ( < 1.5 ml). The patients were followed up for 6 months. The efficacy was assessed by physicians and patients, respectively. Adverse events (AEs) were recorded and laboratory tests were performed before and after operation.

RESULTS86 patients were treated. 6 months after injection, improved esthetic results was assessed by patients and physicians independently. 52 AEs happened in 32 cases (37.2%). Most of them were local injection reaction and minor, which were recovered spontaneously. No systemic reaction was found.

CONCLUSIONSNASHA gel can improve the nasolabial folds. It is very safe and tolerated.

Adult ; Asian Continental Ancestry Group ; Female ; Humans ; Hyaluronic Acid ; adverse effects ; analogs & derivatives ; therapeutic use ; Male ; Middle Aged ; Rhytidoplasty ; methods ; Skin Aging ; Young Adult