Purpose: Patients with advanced biliary tract cancer (BTC) have a poor survival. We aim to evaluate the efficacy and safety of nab-paclitaxel plus gemcitabine and cisplatin regimen in Chinese advanced BTC patients. Materials and Methods: Eligible patients with locally advanced or metastatic BTC administrated intravenous 100 mg/m2 nab-paclitaxel, 800 mg/m2 gemcitabine, and 25 mg/m2 cisplatin every 3 weeks. The primary endpoint was progression-free survival (PFS). The secondary endpoints included overall survival (OS) and adverse events, while exploratory endpoint was the association of biomarkers with efficacy. Results: After the median follow-up of 25.0 months, the median PFS and OS of 34 enrolled patients were 7.1 months (95% confidence interval [CI], 5.4 to 13.7) and 16.4 months (95% CI, 10.9 to 23.6), respectively. The most common treatment-related adverse events at ≥ 3 grade were neutropenia (26.5%) and leukopenia (26.5%). Survival analyses demonstrated that carcinoembryonic antigen (CEA) levels could monitor patients’ survival outcomes. A significant increase in the number of infiltrating CD4+ cells (p=0.008) and a decrease in programmed death-1–positive (PD-1+) cells (p=0.032) were observed in the response patients. Conclusion In advanced BTC patients, nab-paclitaxel plus gemcitabine and cisplatin regimen showed therapeutic potential. Potential prognostic factors of CEA levels, number of CD4+ cells and PD-1+ cells may help us maximize the efficacy benefit.

Objectives: To examine the short-term and mid-term effects of surgical treatment of obstructive hypertrophic cardiomyopathy (HCM) in one center. Methods: The perioperative data and short-term follow-up outcomes of 421 patients with obstructive HCM who received surgical treatment at Department of Cardiac Surgery, Zhongshan Hospital, Fudan University from January 2017 to December 2021 were analyzed retrospectively. There were 207 males and 214 females, aged (56.5±11.7) years (range: 19 to 78 years). Preoperative New York Heart Association (NYHA) classification included 45 cases of class Ⅱ, 328 cases in class Ⅲ, and 48 cases in class Ⅳ. Fifty-eight patients were diagnosed with latent obstructive HCM and 257 patients had moderate or more mitral regurgitation with 56 patients suffering from intrinsic mitral valve diseases. All procedures were completed by a multidisciplinary team, including professional echocardiologists involving in preoperative planning for proper mitral valve management strategies and intraoperative monitoring. A total of 338 patients underwent septal myectomy alone, and 59 patients underwent mitral valve surgery along with myectomy. A single transaortic approach was used in 355 patients, and a right atrial-atrial septal/atrial sulcus approach was used in 51 other patients. Long-handled minimally invasive surgical instruments were used for the procedures. Student t test, Wilcoxon rank sum test, χ² test or Fisher exact test were used to compare the data before and after surgery. Results: The aortic cross-clamping time of septal myectomy alone was (34.3±8.5) minutes (range: 21 to 94 minutes). Eighteen patients had intraoperative adverse events and underwent immediate reoperation, including residual obstruction (10 patients), left ventricular free wall rupture (4 patients), ventricular septal perforation (3 patients), and aortic valve perforation (1 patient). Four patients died during hospitalization, and 11 patients developed complete atrioventricular block requiring permanent pacemaker implantation. After discharge, 384 (92.1%) patients received a follow-up visit with a median duration of 9 months. All follow-up patients survived with significantly improved NYHA classifications: 216 patients in class Ⅰ and 168 patients in class Ⅱ (χ²=662.73, P<0.01 as compared to baseline). At 6 months after surgery, follow-up echocardiography showed that the thickness of the ventricular septum ((13.6±2.5) mm vs. (18.2±3.0) mm, t=23.51, P<0.01) and the peak left ventricular outflow tract gradient ((12.0±6.3) mmHg vs. (93.4±19.8) mmHg, 1 mmHg=0.133 kPa, t=78.29, P<0.01) were both significantly lower than baseline values. Conclusion: The construction of the surgical team (including echocardiography experts), proper mitral valve management strategies, identification and management of sub-mitral-valve abnormalities, and application of long-handled minimally invasive surgical instruments are important for the successful implementation of septal myectomy with satisfactory short-and medium-term outcomes.
Male ; Female ; Humans ; Retrospective Studies ; Atrial Fibrillation ; Treatment Outcome ; Cardiomyopathy, Hypertrophic/surgery* ; Mitral Valve Insufficiency/surgery* ; Ventricular Septum

The advancement of the next generation sequencing (NGS) technology has promoted the development of ancient DNA research. Ancient DNA has made outstanding contributions in various fields such as human origin, animal evolution, etc. How to effectively extract and mine the genetic information from fossil and sub-fossil remains excavated from specific locations is a prerequisite for optimizing their important roles in many fields. In this study, we correlated the two main indicators of DNA damage (terminal base replacement rate, average fragment length) with the possible factors such as the burial time, geological epochs, tissue types, and sequencing library construction methods. The results show that the end base replacement rate of ancient DNA from Northeastern China is positively correlated with the water content of the environment and the ages of the samples. Among samples of different geological epochs, ancient DNA end base replacement rates have significant differences. On the contrary, different tissue types of the remains have no significant effects on the end base replacement rate of ancient DNA. The average fragment size of the molecules has no obvious correlation with the factors mentioned above. The results provide both solid data for investigating the characteristics of ancient DNA from specimens collected in Northeastern China, and valuable information for collecting appropriate samples from different geographical locations and the downstream storage before wet lab procedures after excavation.

ObjectiveTo investigate the prevalence and epidemiological characteristics of norovirus in adult cases with infectious diarrhea in Putuo District of Shanghai， and provide scientific evidence for the prevention and control of infectious diarrhea caused by norovirus. MethodsFecal samples， clinical information and epidemiological data were collected from January 2013 through December 2019 in surveillance hospitals in Putuo District of Shanghai. Norovirus was examined by real-time fluorescent quantitative reverse transcription polymerase chain reaction （rRT-PCR）. ResultsIn 1 389 adult cases with infectious diarrhea， norovirus positive rate was 25.41%， which was significantly higher in male （27.16%） than female （23.89%）. Furthermore， in 353 cases positive for norovirus， GⅡ group was the most common （77.98%）.The positive rate was highest in the cases aged 30-44 years. Spring， autumn and winter were the seasons with higher incidence of norovirus （September to May）. The norovirus-infected cases had more nausea， vomiting， hyperactivity of bowel sounds， and watery stool， compared to the negative cases （P<0.05）. ConclusionThe detection rate of norovirus remains high in adult cases with infectious diarrhea in Putuo District of Shanghai， of which GII is predominant. Seasonality may be spring， autumn and winter. Therefore， it warrants the countermeasures， such as surveillance and health education， for prevention and control of norovirus in susceptible population during epidemic seasons.

A method for quantitative detection of florfenicol by colloidal gold lateral flow immunoassay was developed.The experimental conditions including pH value, concentrations of antibody in the process of conjugation between the colloidal gold and antibody, amount of gold-labeled antibody, concentration of the antigen sprayed on test lines (T line), and detection time were optimized.With a colloidal gold strip reader, the signal intensity of T lines and control lines (C line) on lateral flow strips was recorded.The T/C ratio of negative control and positive samples was defined as B0 and Bx, and the standard curve was established by plotting the Bx/B0 ratio against the concentration of florfenicol.This assay showed a good linear range from 0.1 to 1.5 ng/mL with the limit of detection of 0.08 ng/mL, while the result could be obtained within 15 min.The result showed that this quantitative method was convenient and rapid, and could be used in screening a large amount of samples on site.

OBJECTIVETo observe the regulatory effects of electroacupuncture with different acupoints combinations on blood lipid and atherosclerosis index (AI) in rats with hyperlipemia, so as to make a preliminary screening for the optimal acupoints combination for hyperlipemia.

METHODSOne hundred and five clean-grade SD male rats were randomly divided into 9 groups, including a normal group, a model group, a Quchi group, a Zhongwan group, a Fenglong group, a Quchi+Zhongwan group, a Quchi+Fenglong group, a Zhongwan+Fenglong group and a Quchi+Zhongwan+Fenglong group (three acupoints group), 17 rats in the normal group and 11 rats in the rest groups. The normal group was fed with normal diet, while the rest groups were fed with high-fat diet for 3 weeks to prepare the hyperlipemia model. All the rats were given unlimited water. After the establishment of model, the normal group was fed freely without any treatment; the model group was bundled and immobilized everyday; the rest groups were bundled, immobilized and treated with electroacupuncture at corresponding acupoints with disperse-dense wave, 20 min per time, once a day. After 4 weeks, the blood examples were collected from abdominal aorta to measure the total cholesterol (TC), triglyceride (TG), high-density lipoprotein (HDL-C) and low-density lipoprotein (LDL-C), and analyzed the AI in each group.

RESULTSAfter the treatment, TC, TG, HDL-C, LDL-C and AI in each acupuncture group were all lower than those in the model group (P<0.05, P<0.01). Compared with single acupoint group and the Quchi+Zhongwan group, the content of TC in the three acupoints group was lower (P<0.01). The differences of content of TG among each acupuncture group were not significant (all P>0.05). Compared with the rest 6 acupuncture groups, the content of HDL-C and AI in the three acupoints group were significantly different (all P<0.05). The content of LDL-C in the three acupoints group was decreased as compared with the Quchi group and the Zhong-wan group.

CONCLUSIONThe electroacupuncture at "Quchi" (LI 11), "Zhongwan" (CV 12) and "Fenglong" (ST 40) has more advantages on regulating the content of HDL-C and LDL-C as well as improving AI in hyperlipemia rats, and it has superior effects on blood lipid metabolism.

Acupuncture Points ; Animals ; Electroacupuncture ; Humans ; Hyperlipidemias ; blood ; therapy ; Lipids ; blood ; Male ; Rats ; Rats, Sprague-Dawley

Aged ; Drug-Related Side Effects and Adverse Reactions ; blood ; therapy ; Emergency Treatment ; Female ; Hemoperfusion ; Humans ; Hypnotics and Sedatives ; poisoning ; Male ; Middle Aged ; Serum ; chemistry

To investigate the expression and localization of various functional domains of ORF1 polyprotein and ORF3 protein of hepatitis E virus in host cells, the coding sequences of the various functional domains (RdRp, HEL, MET, PLP, X) of ORF1 were separately cloned into pcDNA3. 1-GFP vectors for constructing the recombinant plasmids which were verified by enzyme digestion and sequencing. The exact expression of the fusion proteins were detected by Western Blot, and the distribution and localization were observed by the laser scanning confocal microscope(LSCM). In huh7 cells, GFP-RdRp proteins were found mainly in the nuclei, GFP-HEL proteins were distributed vesicularly around the nucleus, GFP-MET proteins were distributed granularly both in the nuclei and the cytoplasm, GFP-PLP proteins had polar distribution around the nucleus, and unknown GFP-X proteins were distributed uniformly both in the nuclei and the cytoplasm. Different localization of these proteins verified the previous data obtained from in vitro studies, providing a support for further research on the biological functions of various proteins coded by HEV genome.
Blotting, Western ; Cells, Cultured ; Hepatitis E virus ; genetics ; Humans ; Open Reading Frames ; Viral Proteins ; genetics ; physiology

Objective To express the recombinant caspid of genotype 4 hepatitis E virus(HEV) ORF2. Methods HEV recombinant capsid protein D66 was expressed in E. coli, using the ORF2 fragment (aa368-606, obtained from swine bile) of genotype 4 HEV. Results The recombinant capsid proteins D66 self-assemble to be particle with a radius of 13 nm through dimeric form in neutral solution. Coated particles reacted well with sera obtained from patients during acute or recovered phase of HEV infection. Immunofluorescence and immnoblot assay suggested that D66 bound and penetrated HepG2 cell lines, and the process of attachment was blocked by sera collected from patients during acute or recovered phase of HEV infection.Conclusion Recombinant D66 particles simulate the structure at the surface of genotype 4 HEV well and specifically adhere and penetrate the host cells, which lays the foundation for the investigation of the molecular mechanism of genotype 4 HEV infection.

OBJECTIVETo investigate the effect of M(5) muscarinic receptor subtype on the locomotor sensitization induced by heroin priming, and it's effect on the FosB expression in the nucleus accumbens (NAc) and the hippocampus in the heroin sensitized rats.

METHODSLocomotor activity was measured every 10 min for 1 h after subcutaneous injection of heroin. FosB expression was assayed by immunohistochemistry, and the antisense oligonucleotides (AS-ONs) targeting M(5) muscarinic receptor was transferred with the lipofectin.

RESULTSMicroinjection of AS-ONs targeting M(5) muscarinic receptor in the ventral tegmental area (VTA) blocked the expression of behavioral sensitization induced by heroin priming in rats. Meanwhile, the expression of FosB-positive neurons in either the NAc or the dentate gyrus (DG) of the hippocampus increased in heroin-induced locomotor sensitized rats. The enhancement of FosB-positive neurons in the NAc or DG could be inhibited by microinjection of M(5) muscarinic receptor AS-ONs into the VTA before the heroin-induced locomotor sensitization was performed. In contrast, microinjection of M(5) muscarinic receptor sense oligonucleotide (S-ONs) into the VTA did not block the expression of behavioral sensitization or the expression of FosB in the NAc or DG in the heroin sensitized rats.

CONCLUSIONBlocking M(5) muscarinic receptor in the VTA inhibits the expression of heroin-induced locomotor sensitization, which is associated with the regulation of FosB expression in the NAc and hippocampus neurons. M(5) muscarinic receptor may be a useful pharmacological target for the treatment of heroin addiction.

Acetylcholine ; metabolism ; Animals ; Brain ; drug effects ; metabolism ; physiopathology ; Heroin ; adverse effects ; Heroin Dependence ; drug therapy ; metabolism ; physiopathology ; Hippocampus ; drug effects ; metabolism ; Immunohistochemistry ; Male ; Microinjections ; Motor Activity ; drug effects ; physiology ; Narcotics ; adverse effects ; Neural Pathways ; drug effects ; metabolism ; physiopathology ; Neurons ; drug effects ; metabolism ; Nucleus Accumbens ; drug effects ; metabolism ; physiopathology ; Oligonucleotides, Antisense ; pharmacology ; Proto-Oncogene Proteins c-fos ; drug effects ; metabolism ; Rats ; Rats, Sprague-Dawley ; Receptor, Muscarinic M5 ; antagonists & inhibitors ; genetics ; metabolism ; Synaptic Transmission ; drug effects ; physiology ; Ventral Tegmental Area ; drug effects ; metabolism ; physiopathology