Chronic infection of hepatitis B virus(HBV)presents one of the serious public health challenges worldwide.Current treatment of chronic hepatitis B(CHB)is limited,and is composed of interferon and nucleoside/nucleotide reverse transcriptase inhibitors(NRTI).Interferon is poorly tolerated and is only responsive in a small fraction of CHB patients and NRTIs often face the problem of emergence of drug resistance during long-term treatment.The current treatment of CHB earl be improved in several ways including genotyping mutations associated with drug resistance before treatment to guide the choice of NRTIs and suitable combinations among NRTIs and interferon.It is important to continue research in the identification of novel therapeutic targets in the life cycle of HBV or in the host immune system to stimulate the development of new antiviral agents and immunotherapies.Several antivirai agents targeting HBV entry,cecDNA,capsid formation,viral morphogenesis and virion secretion,as well as two therapeutic vaccines are currently being evaluated in preclinical studies or in clinical trials to assess their anti-HBV efficacy.

Objective To study the clinical effect of qi supplementation combined with rehabilitation on the severity of fatigue after ischcmic stroke in patients with qi deficiency. Methods Ninety ischemic stroke patients with qi deficiency were randomly divided into 3 groups of 30. The treatment group was treated with an oral decoction of qi-supplementing Chinese medicine and also rehabilitation. The Western medicine control group was treated with a Chinese medicine placebo, Western medicine and rehabilitation. The blank control group was treated with the Chinese medicine placebo and rehabilitation. All groups were evaluated using a stroke-specific quality of life scale ( SSQOL) and a fatigue severity scale (FSS) before and 4 weeks after treatment. Results After treatment, the average SS-QOL and FSS scores had improved significantly compared with those before treatment, especially in the two treatment groups. There was a significant difference between the treatment group and the Western medicine control group,and between the treatment group and the blank control group on both scales. There was also a significant difference between the Western medicine control group and the blank control group in terms of SS-QOL scores, but not FSSscores. Conclusion All 3 treatments alleviated fatigue in ischemic stroke patients with a qi deficiency. Qi supplementation combined with rehabilitation was the most effective, followed by Western medicine combined with rehabilitation.

Objective To study the clinical efficacy and operative skill of multi-endoscopic technique in treatment of post-traumatic urethrostenosis in male patients.Methods A retrospective analysis was done on clinical data of 47 male patients with post-traumatic urethrostenosis treated with direct visional incision urethrotomy combined with transurethral resection of scar tissue and ureteroscopic incision.There were 29 patients with anterior urethral strictures and 18 with posterior urethral strictures.Results Of all,43 patients underwent successful endoscopic surgeries at the first time but one underwent secondary surgery because of unsuccessful endoscopic incision.These patients achieved satisfactory results without urinary incontinence,fistula or reoperation.The left three patients underwent open surgeries because of unsuccessful endoscopic incision,in which one patient could micturate at maximal flow rate of 9-12 ml/s,without therapeutic urethral dilation,one could micturate under regular therapeutic dilation and the other one could not micturate.Conclusions With the advantages of safety,high success rate and good long-term efficiency,multi-endoscopic technique can be used as an initial treatment for male patients with post-traumatic urethrostenosis and is worthy to be popularized.

Fanconi's anemia (FA) is an autosomal recessive disease featuring a great diversity of clinical symptoms, including congenital malformation, growth retardation and bone marrow failure. Cells obtained from FA patients show a specific hypersensitivity to crosslinking agents such as mitomycin C (MMC). In this study, MMC-induced chromosome breakage tests have been done on 27 healthy controls and 51 patients with bone marrow failure [including 48 patients with aplastic anemia (AA) and 3 patients with FA before cytogenetic analysis]. The results showed that: (1) Diagnosis of 4 FA cases was confirmed, and one of them was the correction of clinical misdiagnosis; bone marrow failure combined with congenital malformation was observed in a few of non-FA aplastic anemia patients, while 1 FA patient lacked congenital abnormality and underdiagnosed before cytogenetic analysis. The data confirmed that misdiagnosis or underdiagnosis of FA could be caused without cytogenetic study. (2) Spontaneous chromosome breakages observed in FA patients were the same as those in AA patients and healthy controls. MMC-induced chromosome breakages observed in FA patient cells were much higher than those in AA patients and healthy controls, especially, metaphases containing more than 5 breakages were easily found in FA lymphocytes treated with 50 ng MMC. (3) Mosaic was found in one of the 4 FA patients. MMC-induced chromosome breakage test at different MMC concentrations could help to dignosis of FA mosaic patient.

At present, there are still about 250 million people with chronic hepatitis B virus (HBV) infection around the world, which seriously threatens human life and health. Chronic hepatitis B (CHB) can develop into liver diseases such as liver fibrosis, liver cirrhosis, and hepatocellular carcinoma; however, there is still a limited number of antiviral drugs and an extremely low cure rate in clinical practice, and thus it is urgent to develop new antiviral drugs. HBV has strong hepatotropism and only infects a few primates such as humans and chimpanzees under natural conditions. Whether immune response (innate immunity and adaptive immunity) can effectively recognize and eliminate or inhibit HBV is an important factor leading to different outcomes after virus infection, and cytokines play an important immunoregulatory role in this process. This article summarizes and discusses the research advances in some key cytokines in CHB infection and treatment.

Betacoronavirus ; isolation & purification ; pathogenicity ; Bile Acids and Salts ; metabolism ; Bile Ducts, Intrahepatic ; pathology ; virology ; Cell Culture Techniques ; Coronavirus Infections ; complications ; pathology ; Cytokine Release Syndrome ; etiology ; physiopathology ; Cytopathogenic Effect, Viral ; Epithelial Cells ; enzymology ; pathology ; virology ; Humans ; Hyperbilirubinemia ; etiology ; Liver ; pathology ; Organoids ; pathology ; virology ; Pandemics ; Peptidyl-Dipeptidase A ; analysis ; Pneumonia, Viral ; complications ; pathology ; Receptors, Virus ; analysis ; Serine Endopeptidases ; analysis ; Viral Load

OBJECTIVETo explore the safety and efficacy of pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) in preventing chemotherapy-induced neutropenia in patients with breast cancer and non-small cell lung cancer (NSCLC), and to provide the basis for clinical application.

METHODSAccording to the principle of open-label, randomized, parallel-group controlled clinical trial, all patients were randomized by 1∶1∶1 into three groups to receive PEG-rhG-CSF 100 μg/kg, PEG-rhG-CSF 6 mg, or rhG-CSF 5 μg/kg, respectively. The patients with breast cancer received two chemotherapy cycles, and the NSCLC patients received 1-2 cycles of chemotherapy according to their condition. All patients were treated with the combination chemotherapy of TAC (docetaxel+ epirubicin+ cyclophosphamide) or TA (docetaxel+ epirubicin), or the chemotherapy of docetaxel combined with carboplatin, with a 21 day cycle.

RESULTSThe duration of grade 3-4 neutropenia in the PEG-rhG-CSF 100 μg/kg and PEG-rhG-CSF 6 mg groups were similar with that in the rhG-CSF 5 μg/kg group (P>0.05 for all). The incidence rate of grade 3-4 neutropenia in the PEG-rhG-CSF 100 μg/kg group, PEG-rhG-CSF 6 mg group, and G-CSF 5 μg/kg group were 69.7%, 68.4%, and 69.5%, respectively, with a non-significant difference among the three groups (P=0.963). The incidence rate of febrile neutropenia in the PEG-rhG-CSF 100 μg/kg group, PEG-rhG-CSF 6 mg group and G-CSF 5 μg/kg group were 6.1%, 6.4%, and 5.5%, respectively, showing no significant difference among them (P=0.935). The incidence rate of adverse events in the PEG-rhG-CSF 100 μg/kg group, PEG-rhG-CSF 6 mg group and G-CSF 5 μg / kg group were 6.7%, 4.1%, and 5.5%, respectively, showing a non-significant difference among them (P=0.581).

CONCLUSIONSIn patients with breast cancer and non-small cell lung cancer (NSCLC) undergoing TAC/TA chemotherapy, a single 100 μg/kg injection or a single fixed 6 mg dose of PEG-rhG-CSF at 48 hours after chemotherapy show definite therapeutic effect with a low incidence of adverse events and mild adverse reactions. Compared with the continuous daily injection of rhG-CSF 5 μg/kg/d, a single 100 μg/kg injection or a single fixed 6 mg dose of PEG-rhG-CSF has similar effect and is more advantageous in preventing chemotherapy-induced neutropenia.

Antineoplastic Agents ; adverse effects ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; Breast Neoplasms ; drug therapy ; Carboplatin ; administration & dosage ; adverse effects ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; Cyclophosphamide ; administration & dosage ; adverse effects ; Epirubicin ; administration & dosage ; adverse effects ; Female ; Granulocyte Colony-Stimulating Factor ; therapeutic use ; Humans ; Incidence ; Induction Chemotherapy ; Lung Neoplasms ; drug therapy ; Neutropenia ; chemically induced ; epidemiology ; prevention & control ; Polyethylene Glycols ; Recombinant Proteins ; administration & dosage ; Taxoids ; administration & dosage ; adverse effects

Humans ; SARS-CoV-2 ; COVID-19 ; Antibodies ; Antibodies, Viral/therapeutic use* ; Antibodies, Neutralizing/therapeutic use*

The development of broad-spectrum antivirals against human coronaviruses (HCoVs) is critical to combat the current coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its variants, as well as future outbreaks of emerging CoVs. We have previously identified a polyethylene glycol-conjugated (PEGylated) lipopeptide, EK1C4, with potent pan-CoV fusion inhibitory activity. However, PEG linkers in peptide or protein drugs may reduce stability or induce anti-PEG antibodies in vivo. Therefore, we herein report the design and synthesis of a series of dePEGylated lipopeptide-based pan-CoV fusion inhibitors featuring the replacement of the PEG linker with amino acids in the heptad repeat 2 C-terminal fragment (HR2-CF) of HCoV-OC43. Among these lipopeptides, EKL1C showed the most potent inhibitory activity against infection by SARS-CoV-2 and its spike (S) mutants, as well as other HCoVs and some bat SARS-related coronaviruses (SARSr-CoVs) tested. The dePEGylated lipopeptide EKL1C exhibited significantly stronger resistance to proteolytic enzymes, better metabolic stability in mouse serum, higher thermostability than the PEGylated lipopeptide EK1C4, suggesting that EKL1C could be further developed as a candidate prophylactic and therapeutic for COVID-19 and other coronavirus diseases.

Humans ; COVID-19/genetics* ; SARS-CoV-2/genetics* ; Clustered Regularly Interspaced Short Palindromic Repeats/genetics* ; CRISPR-Cas Systems/genetics* ; RNA, Viral/genetics*