Background/Aims: Four-week treatment of linvencorvir (RO7049389) was generally safe and well tolerated, and showed anti-viral activity in chronic hepatitis B (CHB) patients. This study evaluated the efficacy, safety, and pharmacokinetics of 48-week treatment with linvencorvir plus standard of care (SoC) in CHB patients. Methods: This was a multicentre, non-randomized, non-controlled, open-label phase 2 study enrolling three cohorts: nucleos(t)ide analogue (NUC)-suppressed patients received linvencorvir plus NUC (Cohort A, n=32); treatment-naïve patients received linvencorvir plus NUC without (Cohort B, n=10) or with (Cohort C, n=30) pegylated interferon-α (Peg-IFN-α). Treatment duration was 48 weeks, followed by NUC alone for 24 weeks. Results: 68 patients completed the study. No patient achieved functional cure (sustained HBsAg loss and unquantifiable HBV DNA). By Week 48, 89% of treatment-naïve patients (10/10 Cohort B; 24/28 Cohort C) reached unquantifiable HBV DNA. Unquantifiable HBV RNA was achieved in 92% of patients with quantifiable baseline HBV RNA (14/15 Cohort A, 8/8 Cohort B, 22/25 Cohort C) at Week 48 along with partially sustained HBV RNA responses in treatment-naïve patients during follow-up period. Pronounced reductions in HBeAg and HBcrAg were observed in treatment-naïve patients, while HBsAg decline was only observed in Cohort C. Most adverse events were grade 1–2, and no linvencorvir-related serious adverse events were reported. Conclusions 48-week linvencorvir plus SoC was generally safe and well tolerated, and resulted in potent HBV DNA and RNA suppression. However, 48-week linvencorvir plus NUC with or without Peg-IFN did not result in the achievement of functional cure in any patient.

As intelligent production of traditional Chinese medicine （TCM） has been inevitable， informatization and automation of the production process have become the precondition for realizing intelligent manufacturing of TCM， of which the accumulation of critical material attribute and the critical quality attribute are the basis. The study of material properties is of great significance to achieve the quality control of the final product in the process， but there is a lack of systematic induction and summary of the research on the attribute of TCM pills. Therefore， the authors analyzed and summarized the attributes of raw materials， excipients and intermediates in the pill unit process according to the classification of powder properties， rheological properties and texture properties. What’s more， the impact of material attributes on the quality of the final product was summarized. Besides， this review summarized the attribute characterization techniques involved in the pill process and provided some suggestions for the characterization of product quality attributes. Finally， based on the concept of quality by design （QbD）， the authors proposed that the study of material attribute should be combined with process analytical technology （PAT）， and the focus of drug quality control should be moved forward to guide equipment upgrading， so as to realize intelligent continuous manufacturing of TCM pills.

Objective To explore the clinical characteristics and treatment of Pseudomonas peritoneal dialysis-associated peritonitis(PsP). Methods The data of patients receiving peritoneal dialysis in four tertiary hospitals in Jilin province from 2015 to 2019 were retrospectively analyzed.According to the etiological classification,the patients with peritoneal dialysis-associated peritonitis(PDAP)were classified into PsP group and non-PsP group.The incidence of PsP was calculated,and the clinical characteristics and treatment outcomes of the two groups were compared.Kaplan-Meier method was used to draw the survival curve,and Cox regression was performed to analyze the risk factors affecting the technical failure of PsP.The treatment options of Pseudomonas aeruginosa-caused PDAP and the drug sensitivity of PsP were summarized. Results A total of 1530 peritoneal dialysis patients with complete data were included in this study,among which 439 patients had 664 times of PDAP.The incidence of PsP was 0.007 episodes/patient-year.PsP group had higher proportion of refractory peritonitis(41.38% vs.19.69%,P=0.005),lower cure rate(55.17% vs.80.79%, P=0.001),and higher extubation rate(24.14% vs.7.09%,P=0.003)than non-PsP group.The technical survival rate of PsP group was lower than that of non-PsP group(P<0.001).Multivariate Cox regression analysis showed that Pseudomonas aeruginosa was an independent risk factor for technical failure in patients with PsP(HR=9.020,95%CI=1.141-71.279,P=0.037).Pseudomonas was highly sensitive to amikacin,meropenem,and piperacillin-tazobactam while highly resistant to compound sulfamethoxazole,cefazolin,and ampicillin. Conclusion The treatment outcome of PsP is worse than that of non-PsP,and Pseudomonas aeruginosa is an independent risk factor for technical failure of PsP.
Humans ; Peritoneal Dialysis/adverse effects* ; Peritonitis/etiology* ; Pseudomonas ; Retrospective Studies ; Treatment Outcome

The novel coronavirus disease (COVID-19) pandemic is emerging as a global health threat and shows a higher risk for men than women. Thus far, the studies on andrological consequences of COVID-19 are limited. To ascertain the consequences of COVID-19 on sperm parameters after recovery, we recruited 41 reproductive-aged male patients who had recovered from COVID-19, and analyzed their semen parameters and serum sex hormones at a median time of 56 days after hospital discharge. For longitudinal analysis, a second sampling was obtained from 22 of the 41 patients after a median time interval of 29 days from first sampling. Compared with controls who had not suffered from COVID-19, the total sperm count, sperm concentration, and percentages of motile and progressively motile spermatozoa in the patients were significantly lower at first sampling, while sperm vitality and morphology were not affected. The total sperm count, sperm concentration, and number of motile spermatozoa per ejaculate were significantly increased and the percentage of morphologically abnormal sperm was reduced at the second sampling compared with those at first in the 22 patients examined. Though there were higher prolactin and lower progesterone levels in patients at first sampling than those in controls, no significant alterations were detected for any sex hormones examined over time following COVID-19 recovery in the 22 patients. Although it should be interpreted carefully, these findings indicate an adverse but potentially reversible consequence of COVID-19 on sperm quality.
Adult ; Asthenozoospermia/virology* ; COVID-19/physiopathology* ; China ; Gonadal Steroid Hormones/blood* ; Humans ; Male ; Progesterone/blood* ; Prolactin/blood* ; SARS-CoV-2 ; Semen/physiology* ; Semen Analysis ; Sperm Count ; Sperm Motility ; Spermatozoa/physiology* ; Time Factors

OBJECTIVE: To establish and evaluate the model of chronic obstructive pulmonary disease (COPD) with osteoporosis induced by elastase in mice. METHODS: Twenty four healthy female 8-week-old C57BL / 6 mice (weighing about 18 g) were randomly divided into three groups. The control group was given intratracheal drip of normal saline, the experimental group 1 and the experimental group 2 were given intratracheal drip of elastase, the control group and the experimental group 1 were kept for 8 weeks and then killed, the experimental group 2 was kept for 12 weeks and then killed. HE staining was used to evaluate the histopathological changes of lung and tibia in the control and experimental groups. The levels of serum inflammatory factors and broncho alveolar lavage factors (BALF) were detected by ELISA. Micro CT was used to detect the bone mass related parameters of mouse femur. The expression of osteoclastic and osteogenic genes was detected by real-time fluorescence quantitative PCR. RESULTS: Lung histopathology showed that the structure of alveoli in the experimental group was disordered, the walls of alveoli became thin or broken, and the alveoli cavity expanded. IL-6 and TNF-α in BALF were significantly higher than those in control group (<0.001), while IL-1β and TNF-α in serum inflammatory factors were significantly higher than those in control group (<0.001). BV / TV(bone volume fraction), TB.Th(average bone trabecular thickness) and TB.N(average bone trabecular number) in the experimental group were significantly lower than those in the control group (<0.05), TB.Sp (average bone trabecular separation) and BS / BV (bone surface area fraction) in the experimental group were significantly higher than those in the control group (<0.01). Compared with the control group, the expression of osteoclast related marker genes increased in the experimental group (<0.05), but decreased in the experimental group(<0.05). The results of experiment 1 and experiment 2 were time-dependent. CONCLUSION In this study, elastase was used to construct a COPD model with osteoporosis successfully, which provides a suitable animal model for the future study of the pathogenesis of COPD with osteoporosis.
Animals ; Bone Density ; Female ; Mice ; Mice, Inbred C57BL ; Osteoporosis ; etiology ; Pancreatic Elastase ; Pulmonary Disease, Chronic Obstructive ; complications

Objectives: To compare the effect of 2 different occlusion devices for treating cryptogenic stroke (CS) patients combining patent foramen ovale (PFO) and large right-to-left shunt (RLS). Methods: A total of 123 CS patients combining PFO and large RLS treated in our hospital from 2013-05 to 2016-08 were enrolled. All patients received percutaneous PFO interventional closure, based on different occlusion devices, the patients were divided into 2 groups: Cardi-O-fix PFO occluder group, n=80 and Amplatzer PFO occluder group, n=43. CS diagnosis was confirmed by 3 experienced neurologists via medical imaging examination; PFO and large RLS were diagnosed by transthoracic echocardiography and right heart contrast echocardiography. The baseline features, clinical symptoms, operation and follow-up data were reviewed to observe the efficacy of 2 occlusion devices. Results: Each group had 1 patient suffered from paroxysmal atrial fibrillation after the operation; 1 patient in Cardi-O-fix PFO occluder group had inguinal hematoma. No stroke recurrence, no death during follow-up period; the residual shunt was similar between 2 groups. Conclusions: PFO occlusion was beneficial for preventing stroke recurrence in CS patients combining PFO and large RLS. The safety and efficacy were similar in Cardi-O-fix and Amplatzer PFO occlusion devices.

Objective To study the mechanism induced by exogenous H2 S on rat glioma formation.Methods Fourty adult SD rats were ran-domly divided into control group , NaHS group , tumor group , tumor +NaHS group of four groups , each group 10.Tumor group , tumor+NaHS group injected rat striatum C 6 glioma cells to established glioma model . Control group, NaHS group received no treatment.Four groups of rats fed normally , three weeks after taking the brain sensitive sulfur electrode applied to detect the rat brain tumor and H 2 S content of its decapitated . The cystathionine -beta-synthase ( CBS ) , mRNA transcription level of 3-mercaptopyruvate sulfurtransferase (3MST) were determined by real time PCR assay. The hypoxia -inducible transcription factors -1α(HIF-1α), vascular endothelial growth factor (VEGF) and the expre-ssion of matrix metallo proteinase-9 ( MMP-9 ) by ELISA and Western blot.The intratumoral micro vessel density ( MVD ) was counted by CD105 -MVD. Results Compared with the control group , NaHS group, tumor group, tumor +NaHS group were clearly visible tumor tissue, significantly increased the number of tumor capillaries .Tumor+NaHS group has more CBS , 3MST, HIF-α, VEGF expression of MMP -9.And tumor +NaHS group was significantly higher than the NaHS group , tumor group ( P<0.01 ) .Conclusion Exogenous H 2 S may induce and promote angiogenesis in rat glioma within its mechanism of H2S promote CBS, 3MST, closely related to the HIF-αVEGF expression of matrix metalloproteinase MMP -9.

The paradigm of a real world study has become the frontiers of clinical researches, especially in the field of Chinese medicine, all over the world in recent years. In this paper, ethical issues which probably exist in real-world studies are raised and reviewed. Moreover, some preliminary solutions to these issues such as protecting subjects during the process of real-world studies and performing ethical review are raised based on recent years' practices to enhance the scientificity and ethical level of real-world studies.
Biomedical Research ; ethics ; methods ; Humans

BACKGROUNDData on the epidemiology of hypertension in Chinese non-dialysis chronic kidney disease (CKD) patients are limited. The aim of the present study was to investigate the prevalence, awareness, treatment, and control of hypertension in the non-dialysis CKD patients through a nationwide, multicenter study in China.

METHODSThe survey was performed in 61 tertiary hospitals in 31 provinces, municipalities, and autonomous regions in China (except Hong Kong, Macao, and Taiwan). Trained physicians collected demographic and clinical data and measured blood pressure (BP) using a standardized protocol. Hypertension was defined as systolic BP ≥ 140 mmHg and/or diastolic BP ≥ 90 mmHg, and/or use of antihypertensive medications. BP < 140/90 mmHg and < 130/80 mmHg were used as the 2 thresholds of hypertension control. In multivariate logistic regression with adjustment for sex and age, we analyzed the association between CKD stages and uncontrolled hypertension in non-dialysis CKD patients.

RESULTSThe analysis included 8927 non-dialysis CKD patients. The prevalence, awareness, and treatment of hypertension in non-dialysis CKD patients were 67.3%, 85.8%, and 81.0%, respectively. Of hypertensive CKD patients, 33.1% and 14.1% had controlled BP to < 140/90 mmHg and < 130/80 mmHg, respectively. With successive CKD stages, the prevalence of hypertension in non-dialysis CKD patients increased, but the control of hypertension decreased (P < 0.001). When the threshold of BP < 130/80 mmHg was considered, the risk of uncontrolled hypertension in CKD 2, 3a, 3b, 4, and 5 stages increased 1.3, 1.4, 1.4, 2.5, and 4.0 times compared with CKD 1 stage, respectively (P < 0.05). Using the threshold of < 140/90 mmHg, the risk of uncontrolled hypertension increased in advanced stages (P < 0.05).

CONCLUSIONSThe prevalence of hypertension Chinese non-dialysis CKD patients was high, and the hypertension control was suboptimal. With successive CKD stages, the risk of uncontrolled hypertension increased.

Adult ; Aged ; Awareness ; Female ; Humans ; Hypertension ; complications ; epidemiology ; therapy ; Male ; Middle Aged ; Prevalence ; Renal Insufficiency, Chronic ; complications

OBJECTIVETo study the phenotype and tumorigenicity of SHG-44 glioma stem cell spheres and the pathological characteristics of their xenograft tumors.

METHODSSHG-44 glioma cells were cultured under neural stem cell medium and glioma stem cell spheres were collected. Immunocytochemistry was used to dectet the expression of CD133, nestin, A2B5, vimentin, VEGFR-2 and IDH R132H. Cell spheres were induced using serum-containing medium, and the expression of CD133, nestin, vimentin, GFAP, β-III tubulin and GalC in the cell spheres were detected. The expression of CD133, nestin, VEGFR-2, GFAP, S-100 and CD34 in the intracranial xenograft tumor tissues was detected using immunohistochemistry. The pathological characteristics of orthotopic xenograft tumors generated from the SHG-44 glioma cells and SHG-44 glioma stem cell spheres were compared.

RESULTSSHG-44 glioma stem cell spheres were collected successfully after cultured under neural stem cell medium. The ratio of CD133(+) cells in the passage 10 SHG-44 glioma stem cell spheres was (71.63 ± 5.92)%, significantly higher than that in the SHG-44 glioma cells [(1.95 ± 1.45)%]. Immunocytochemistry showed that in the SHG-44 glioma cell spheres, the ratio of nestin(+) cells was (84.06 ± 7.58)%, vimentin(+) cells (29.11 ± 3.44)%, VEGFR 2(+) cells (64.44 ± 3.69)%, and A2B5(+) cells (14.08 ± 2.19)%. A subpopulation of cells with mutation of IDH R132H was detected harboring in the SHG-44 glioma cell spheres. After induction of differentiation with serum-containing medium, the ratio of CD133(+) cells was (1.89 ± 1.27)%, nestin(+) cells (6.67 ± 2.75)%, vimentin(+) cells (93.75 ± 2.95)%, GFAP (+) cells (91.33 ± 4.75)%, β-III tubulin(+) cells (82.36 ± 4.02)%, and GalC(+) cells (8.92 ± 3.19)%. Immunohistochemistry showed positive expression of GFAP, S-100, VEGFR-2, and negative of CD133 and nestin in the orthotopic xenograft tumors. A very small amount of human-specific CD34 cells formed a tubular structure. Compared with the SHG-44 glioma cell-formed xenograft tumor, the SHG-44 glioma stem cell-formed xenograft tumor exhibited a higher local invasiveness.

CONCLUSIONSSHG-44 glioma cell spheres are successfully collected after cultured under neural stem cell medium. They belong to the CD133(+)A2B5(-) GSC subpopulation, highly expressing VEGFR-2, possess the ability of both self-renewal and multi-directional differentiation, and may participate in the formation of vasculogenic mimicry.

Animals ; Brain Neoplasms ; metabolism ; pathology ; Cell Line, Tumor ; Cells, Cultured ; Glial Fibrillary Acidic Protein ; metabolism ; Glioma ; metabolism ; pathology ; Humans ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Neoplasm Invasiveness ; Neoplasm Transplantation ; Neoplastic Stem Cells ; metabolism ; pathology ; S100 Proteins ; metabolism ; Vascular Endothelial Growth Factor Receptor-2 ; metabolism