1.Antiviral therapy for chronic hepatitis B with mildly elevated aminotransferase: A rollover study from the TORCH-B trial
Yao-Chun HSU ; Chi-Yi CHEN ; Cheng-Hao TSENG ; Chieh-Chang CHEN ; Teng-Yu LEE ; Ming-Jong BAIR ; Jyh-Jou CHEN ; Yen-Tsung HUANG ; I-Wei CHANG ; Chi-Yang CHANG ; Chun-Ying WU ; Ming-Shiang WU ; Lein-Ray MO ; Jaw-Town LIN
Clinical and Molecular Hepatology 2025;31(1):213-226
Background/Aims:
Treatment indications for patients with chronic hepatitis B (CHB) remain contentious, particularly for patients with mild alanine aminotransferase (ALT) elevation. We aimed to evaluate treatment effects in this patient population.
Methods:
This rollover study extended a placebo-controlled trial that enrolled non-cirrhotic patients with CHB and ALT levels below two times the upper limit of normal. Following 3 years of randomized intervention with either tenofovir disoproxil fumarate (TDF) or placebo, participants were rolled over to open-label TDF for 3 years. Liver biopsies were performed before and after the treatment to evaluate histopathological changes. Virological, biochemical, and serological outcomes were also assessed (NCT02463019).
Results:
Of 146 enrolled patients (median age 47 years, 80.8% male), 123 completed the study with paired biopsies. Overall, the Ishak fibrosis score decreased in 74 (60.2%), remained unchanged in 32 (26.0%), and increased in 17 (13.8%) patients (p<0.0001). The Knodell necroinflammation score decreased in 58 (47.2%), remained unchanged in 29 (23.6%), and increased in 36 (29.3%) patients (p=0.0038). The proportion of patients with an Ishak score ≥ 3 significantly decreased from 26.8% (n=33) to 9.8% (n=12) (p=0.0002). Histological improvements were more pronounced in patients switching from placebo. Virological and biochemical outcomes also improved in placebo switchers and remained stable in patients who continued TDF. However, serum HBsAg levels did not change and no patient cleared HBsAg.
Conclusions
In CHB patients with minimally raised ALT, favorable histopathological, biochemical, and virological outcomes were observed following 3-year TDF treatment, for both treatment-naïve patients and those already on therapy.
2.Antiviral therapy for chronic hepatitis B with mildly elevated aminotransferase: A rollover study from the TORCH-B trial
Yao-Chun HSU ; Chi-Yi CHEN ; Cheng-Hao TSENG ; Chieh-Chang CHEN ; Teng-Yu LEE ; Ming-Jong BAIR ; Jyh-Jou CHEN ; Yen-Tsung HUANG ; I-Wei CHANG ; Chi-Yang CHANG ; Chun-Ying WU ; Ming-Shiang WU ; Lein-Ray MO ; Jaw-Town LIN
Clinical and Molecular Hepatology 2025;31(1):213-226
Background/Aims:
Treatment indications for patients with chronic hepatitis B (CHB) remain contentious, particularly for patients with mild alanine aminotransferase (ALT) elevation. We aimed to evaluate treatment effects in this patient population.
Methods:
This rollover study extended a placebo-controlled trial that enrolled non-cirrhotic patients with CHB and ALT levels below two times the upper limit of normal. Following 3 years of randomized intervention with either tenofovir disoproxil fumarate (TDF) or placebo, participants were rolled over to open-label TDF for 3 years. Liver biopsies were performed before and after the treatment to evaluate histopathological changes. Virological, biochemical, and serological outcomes were also assessed (NCT02463019).
Results:
Of 146 enrolled patients (median age 47 years, 80.8% male), 123 completed the study with paired biopsies. Overall, the Ishak fibrosis score decreased in 74 (60.2%), remained unchanged in 32 (26.0%), and increased in 17 (13.8%) patients (p<0.0001). The Knodell necroinflammation score decreased in 58 (47.2%), remained unchanged in 29 (23.6%), and increased in 36 (29.3%) patients (p=0.0038). The proportion of patients with an Ishak score ≥ 3 significantly decreased from 26.8% (n=33) to 9.8% (n=12) (p=0.0002). Histological improvements were more pronounced in patients switching from placebo. Virological and biochemical outcomes also improved in placebo switchers and remained stable in patients who continued TDF. However, serum HBsAg levels did not change and no patient cleared HBsAg.
Conclusions
In CHB patients with minimally raised ALT, favorable histopathological, biochemical, and virological outcomes were observed following 3-year TDF treatment, for both treatment-naïve patients and those already on therapy.
3.Antiviral therapy for chronic hepatitis B with mildly elevated aminotransferase: A rollover study from the TORCH-B trial
Yao-Chun HSU ; Chi-Yi CHEN ; Cheng-Hao TSENG ; Chieh-Chang CHEN ; Teng-Yu LEE ; Ming-Jong BAIR ; Jyh-Jou CHEN ; Yen-Tsung HUANG ; I-Wei CHANG ; Chi-Yang CHANG ; Chun-Ying WU ; Ming-Shiang WU ; Lein-Ray MO ; Jaw-Town LIN
Clinical and Molecular Hepatology 2025;31(1):213-226
Background/Aims:
Treatment indications for patients with chronic hepatitis B (CHB) remain contentious, particularly for patients with mild alanine aminotransferase (ALT) elevation. We aimed to evaluate treatment effects in this patient population.
Methods:
This rollover study extended a placebo-controlled trial that enrolled non-cirrhotic patients with CHB and ALT levels below two times the upper limit of normal. Following 3 years of randomized intervention with either tenofovir disoproxil fumarate (TDF) or placebo, participants were rolled over to open-label TDF for 3 years. Liver biopsies were performed before and after the treatment to evaluate histopathological changes. Virological, biochemical, and serological outcomes were also assessed (NCT02463019).
Results:
Of 146 enrolled patients (median age 47 years, 80.8% male), 123 completed the study with paired biopsies. Overall, the Ishak fibrosis score decreased in 74 (60.2%), remained unchanged in 32 (26.0%), and increased in 17 (13.8%) patients (p<0.0001). The Knodell necroinflammation score decreased in 58 (47.2%), remained unchanged in 29 (23.6%), and increased in 36 (29.3%) patients (p=0.0038). The proportion of patients with an Ishak score ≥ 3 significantly decreased from 26.8% (n=33) to 9.8% (n=12) (p=0.0002). Histological improvements were more pronounced in patients switching from placebo. Virological and biochemical outcomes also improved in placebo switchers and remained stable in patients who continued TDF. However, serum HBsAg levels did not change and no patient cleared HBsAg.
Conclusions
In CHB patients with minimally raised ALT, favorable histopathological, biochemical, and virological outcomes were observed following 3-year TDF treatment, for both treatment-naïve patients and those already on therapy.
4.Impact of sutureless dorsal venous complex combined with robotic-assisted laparoscopic prostatectomy on sexual function in patients with prostatic cancer.
Wei ZHENG ; Xin-Mian HUANG ; Xiao-Bo XU ; Ke-Bing YANG ; Xiao-Long QI ; Da-Hong ZHANG
National Journal of Andrology 2025;31(9):807-811
OBJECTIVE:
To evaluate the impact of sutureless approach to the dorsal venous complex (DVC) combined with robotic-assisted laparoscopic prostatectomy on sexual function of patients with prostatic cancer.
METHODS:
This study included 114 prostate cancer patients who underwent robot-assisted laparoscopic radical prostatectomy at our hospital from January 2021 to January 2024. The patients were randomly divided into a control group (n=57) and an observation group (n=57). The control group received conventional "figure-of-eight" suture ligation of the dorsal venous complex (DVC), while the observation group underwent direct DVC transection using monopolar electrocautery scissors after increasing pneumoperitoneum pressure.Surgical duration, intraoperative blood loss, positive surgical margin rates, and positive apical margin rates were recorded. The continence rates and rates of morning erections at 1, 3 and 6 months after the operation were compared between groups. Sexual function was assessed pre-operatively and at 6 months post-operation by using the IIEF-5 and PEDT.
RESULTS:
The operative time in the observation group was significantly longer than that in the control group ([115.71 ± 19.42] min vs [103.42 ± 12.78] min, P<0.05). While no significant differences were observed in intraoperative blood loss, positive surgical margin rate, or positive apical margin rate between the two groups (P>0.05). At 3 and 6 months after the operation, the observation group exhibited higher urinary continence rates and morning erection recovery rates compared to the control group (P<0.05). Furthermore, at 6 months postoperatively, the observation group demonstrated significantly higher IIEF-5 scores and lower PEDT scores than those of control group(P<0.05).
CONCLUSION
The use of a sutureless DVC technique in robotic-assisted laparoscopic radical prostatectomy protects the post-operative sexual function in patients.
Humans
;
Male
;
Prostatectomy/methods*
;
Laparoscopy/methods*
;
Prostatic Neoplasms/surgery*
;
Robotic Surgical Procedures/methods*
;
Middle Aged
;
Operative Time
;
Aged
5.A photodynamic nanohybrid system reverses hypoxia and augment anti-primary and metastatic tumor efficacy of immunotherapy.
Haitao YUAN ; Xiaoxian WANG ; Xin SUN ; Di GU ; Jinan GUO ; Wei HUANG ; Jingbo MA ; Chunjin FU ; Da YIN ; Guohua ZENG ; Ying LONG ; Jigang WANG ; Zhijie LI
Acta Pharmaceutica Sinica B 2025;15(6):3243-3258
Photodynamic immunotherapy is a promising strategy for cancer treatment. However, the dysfunctional tumor vasculature results in tumor hypoxia and the low efficiency of drug delivery, which in turn restricts the anticancer effect of photodynamic immunotherapy. In this study, we designed photosensitive lipid nanoparticles. The synthesized PFBT@Rox Lip nanoparticles could produce type I/II reactive oxygen species (ROS) by electron or energy transfer through PFBT under light irradiation. Moreover, this nanosystem could alleviate tumor hypoxia and promote vascular normalization through Roxadustat. Upon irradiation with white light, the ROS produced by PFBT@Rox Lip nanoparticles in situ dysregulated calcium homeostasis and triggered endoplasmic reticulum stress, which further promoted the release of damage-associated molecular patterns, enhanced antigen presentation, and stimulated an effective adaptive immune response, ultimately priming the tumor microenvironment (TME) together with the hypoxia alleviation and vessel normalization by Roxadustat. Indeed, in vivo results indicated that PFBT@Rox Lip nanoparticles promoted M1 polarization of tumor-associated macrophages, recruited more natural killer cells, and augmented infiltration of T cells, thereby leading to efficient photodynamic immunotherapy and potentiating the anti-primary and metastatic tumor efficacy of PD-1 antibody. Collectively, photodynamic immunotherapy with PFBT@Rox Lip nanoparticles efficiently program TME through the induction of immunogenicity and oxygenation, and effectively suppress tumor growth through immunogenic cell death and enhanced anti-tumor immunity.
6.Efficacy and safety of recombinant human anti-SARS-CoV-2 monoclonal antibody injection(F61 injection)in the treatment of patients with COVID-19 combined with renal damage:a randomized controlled exploratory clinical study
Ding-Hua CHEN ; Chao-Fan LI ; Yue NIU ; Li ZHANG ; Yong WANG ; Zhe FENG ; Han-Yu ZHU ; Jian-Hui ZHOU ; Zhe-Yi DONG ; Shu-Wei DUAN ; Hong WANG ; Meng-Jie HUANG ; Yuan-Da WANG ; Shuo-Yuan CONG ; Sai PAN ; Jing ZHOU ; Xue-Feng SUN ; Guang-Yan CAI ; Ping LI ; Xiang-Mei CHEN
Chinese Journal of Infection Control 2024;23(3):257-264
Objective To explore the efficacy and safety of recombinant human anti-severe acute respiratory syn-drome coronavirus 2(anti-SARS-CoV-2)monoclonal antibody injection(F61 injection)in the treatment of patients with coronavirus disease 2019(COVID-19)combined with renal damage.Methods Patients with COVID-19 and renal damage who visited the PLA General Hospital from January to February 2023 were selected.Subjects were randomly divided into two groups.Control group was treated with conventional anti-COVID-19 therapy,while trial group was treated with conventional anti-COVID-19 therapy combined with F61 injection.A 15-day follow-up was conducted after drug administration.Clinical symptoms,laboratory tests,electrocardiogram,and chest CT of pa-tients were performed to analyze the efficacy and safety of F61 injection.Results Twelve subjects(7 in trial group and 5 in control group)were included in study.Neither group had any clinical progression or death cases.The ave-rage time for negative conversion of nucleic acid of SARS-CoV-2 in control group and trial group were 3.2 days and 1.57 days(P=0.046),respectively.The scores of COVID-19 related target symptom in the trial group on the 3rd and 5th day after medication were both lower than those of the control group(both P<0.05).According to the clinical staging and World Health Organization 10-point graded disease progression scale,both groups of subjects improved but didn't show statistical differences(P>0.05).For safety,trial group didn't present any infusion-re-lated adverse event.Subjects in both groups demonstrated varying degrees of elevated blood glucose,elevated urine glucose,elevated urobilinogen,positive urine casts,and cardiac arrhythmia,but the differences were not statistica-lly significant(all P>0.05).Conclusion F61 injection has initially demonstrated safety and clinical benefit in trea-ting patients with COVID-19 combined with renal damage.As the domestically produced drug,it has good clinical accessibility and may provide more options for clinical practice.
7.Role of Glucose-6-phosphate Dehydrogenase in Viral Infection
Dong-Xue CHEN ; Yun-Long LI ; Da-Qiao WEI ; Fen HUANG
Progress in Biochemistry and Biophysics 2024;51(8):1788-1796
Glucose-6-phosphate dehydrogenase (G6PD) is the first rate-limiting enzyme of the pentose phosphate pathway, which regulates the production of nicotinamide adenine dinucleotide phosphate (NADPH) in cells, and plays an important role in redox reactions. In addition, NADPH is necessary for biosynthesis reactions and is an essential hydrogen donor in the biosynthesis of cholesterol, fatty acids, and sex hormones. NADPH also plays an important role in maintaining intracellular redox homeostasis, converting intracellular oxidized glutathione into reduced glutathione (GSH), which is the main intracellular antioxidant. Therefore, G6PD plays an important role in maintaining intracellular redox homeostasis. Studies have shown that the decrease in G6PD activity can lead to a breakdown of the redox balance in the cells and tends to the oxidation state, which not only leads to dysregulation of cell growth and signaling, but also makes the host more susceptible to viruses. Previous studies have focused on the molecular characteristics of G6PD, anemia caused by G6PD deficiency, and the relationship between malignant tumors and G6PD. In recent years, more attentions have been paid to the importance of G6PD at the cellular level, development, and disease progression. To explore the effects of G6PD on viral life cycle, the relationship between G6PD and viral infections, including the clinical symptoms and virus-host interactions of hepatitis B virus (HBV), human papilloma virus (HPV), hepatitis E virus (HEV), influenza virus and dengue fever virus (DENV) will be reviewed, which will benefit the antiviral drugs development. Many studies had proved that patients with deficient G6PD are more susceptible to HBV infection. It has been reported that HBV infection activates the glycolytic pathway, promotes pentose phosphate pathway, and accelerates citric acid cycle to enhance nucleotide and fat biosynthesis, thereby promoting viral replication. During HPV infection, miR-206 up-regulates the expression of G6PD to facilitate viral replication. Thus, G6PD may be a new target for anti-cervical cancer therapy. It was reported that patients with G6PD deficiency are more susceptible to HEV infection, and more serious HEV infection-associated diseases are developed. However, the mechanism of why and how the deficiency of G6PD affect HEV infection is still unclear. The oxidative stress caused by G6PD deficiency provides a suitable environment for influenza virus replication. Furthermore, patients with G6PD deficiency are more susceptible to SARS-CoV-2 infection and lead to more severe clinical symptoms with a higher risk of thrombosis and hemolysis than general population. There is a correlation between DENV infection and G6PD deficiency, which increase the risk of hemolysis, however, the pathogenesis is still unknown. The deficiency of G6PD promotes HCoV 229E infection, possibly because the NF-κB signal pathway is suppressed when G6PD deficiency, which results in decreased innate antiviral immune, and increased susceptibility to HCoV 229E, finally leads to increased viral replication. Thus, the deficiency of G6PD play an important role during viruses’ infection, especially the susceptibility. More studies should be performed on the relicationship between G6PD deficiency and specific viral susceptibility, and more attentions shoud be paid to G6PD deficient patients, which will benefit the treatment of viral infection and the development of antiviral drugs.
8.Research progress in the regulation of host antiviral signaling pathways by hepatitis E virus infection
Guo ZHONG ; Dong-Xue CHEN ; Da-Qiao WEI ; Fen HUANG
Chinese Journal of Zoonoses 2024;40(8):782-789
Innate immunity is the first line of defense against viral infection.Hepatitis E virus(HEV)infection usually cau-ses acute self-limiting diseases in immunocompetent patients,but results in chronic infection in immunocompromised patients or pregnant people.After HEV infects host cells,pattern recognition receptors(PRRs)recognize the viral genome,thus indu-cing rapid activation of multiple antiviral signal pathways in the host immune system,and the expression of interferons(IFNs)and interferon stimulated genes(ISGs),and consequently inhibiting viral replication.To escape host antiviral responses,HEV encoded proteins regulate host antiviral signal pathways and subsequently inhibit antiviral responses,such as those involving cytokines or chemokines.The regulation of host signal pathways by HEV infection and the escape of HEV from host innate im-munity are reviewed herein.
9.Development of multicolor photoelectroencephalography evoked flash for selection of naval aircraft pilots
Yong-Sheng CHEN ; Jing HUANG ; Da-Wei TIAN ; Fei YU ; Hui-Bian ZHANG ; Lin ZHANG ; Ying-Juan ZHENG ; Xiao-Quan ZHU
Chinese Medical Equipment Journal 2024;45(7):112-114
Objective To develop a multicolor photoelectroencephalography evoked flash to identify photosensitive epilepsy patients during the selection of naval aircraft pilots.Methods The multicolor photoelectroencephalography evoked flash was composed of a main body,a control box and a bracket.There were four rows of LED lights in the main body,which emitted four colors of light including red,yellow,green and orange,respectively;there were three sockets for signal,light and power and one color changeover switch on the body of the control box,and a control circuit board was fixed at the bottom inside the control box;the bracket had a double-jointed arm folding structure.The flash developed was compared with the coventional photoelectroencephalography evoked flash to verify its effect for inducing photosensitive epilepsy.Results There were no significant differences between the two flashes in the numbers of identified cases with photosensitive epilepsy when the subjects were under awake and closed-eye conditions(P>0.05).Condusion The flash developed can make up for the deficiency of the coventional photoelectroencephalography evoked flash when selecting naval aircraft pilots.[Chinese Medical Equipment Journal,2024,45(7):112-114]
10.Chinese expert consensus on the diagnosis and treatment of traumatic supraorbital fissure syndrome (version 2024)
Junyu WANG ; Hai JIN ; Danfeng ZHANG ; Rutong YU ; Mingkun YU ; Yijie MA ; Yue MA ; Ning WANG ; Chunhong WANG ; Chunhui WANG ; Qing WANG ; Xinyu WANG ; Xinjun WANG ; Hengli TIAN ; Xinhua TIAN ; Yijun BAO ; Hua FENG ; Wa DA ; Liquan LYU ; Haijun REN ; Jinfang LIU ; Guodong LIU ; Chunhui LIU ; Junwen GUAN ; Rongcai JIANG ; Yiming LI ; Lihong LI ; Zhenxing LI ; Jinglian LI ; Jun YANG ; Chaohua YANG ; Xiao BU ; Xuehai WU ; Li BIE ; Binghui QIU ; Yongming ZHANG ; Qingjiu ZHANG ; Bo ZHANG ; Xiangtong ZHANG ; Rongbin CHEN ; Chao LIN ; Hu JIN ; Weiming ZHENG ; Mingliang ZHAO ; Liang ZHAO ; Rong HU ; Jixin DUAN ; Jiemin YAO ; Hechun XIA ; Ye GU ; Tao QIAN ; Suokai QIAN ; Tao XU ; Guoyi GAO ; Xiaoping TANG ; Qibing HUANG ; Rong FU ; Jun KANG ; Guobiao LIANG ; Kaiwei HAN ; Zhenmin HAN ; Shuo HAN ; Jun PU ; Lijun HENG ; Junji WEI ; Lijun HOU
Chinese Journal of Trauma 2024;40(5):385-396
Traumatic supraorbital fissure syndrome (TSOFS) is a symptom complex caused by nerve entrapment in the supraorbital fissure after skull base trauma. If the compressed cranial nerve in the supraorbital fissure is not decompressed surgically, ptosis, diplopia and eye movement disorder may exist for a long time and seriously affect the patients′ quality of life. Since its overall incidence is not high, it is not familiarized with the majority of neurosurgeons and some TSOFS may be complicated with skull base vascular injury. If the supraorbital fissure surgery is performed without treatment of vascular injury, it may cause massive hemorrhage, and disability and even life-threatening in severe cases. At present, there is no consensus or guideline on the diagnosis and treatment of TSOFS that can be referred to both domestically and internationally. To improve the understanding of TSOFS among clinical physicians and establish standardized diagnosis and treatment plans, the Skull Base Trauma Group of the Neurorepair Professional Committee of the Chinese Medical Doctor Association, Neurotrauma Group of the Neurosurgery Branch of the Chinese Medical Association, Neurotrauma Group of the Traumatology Branch of the Chinese Medical Association, and Editorial Committee of Chinese Journal of Trauma organized relevant experts to formulate Chinese expert consensus on the diagnosis and treatment of traumatic supraorbital fissure syndrome ( version 2024) based on evidence of evidence-based medicine and clinical experience of diagnosis and treatment. This consensus puts forward 12 recommendations on the diagnosis, classification, treatment, efficacy evaluation and follow-up of TSOFS, aiming to provide references for neurosurgeons from hospitals of all levels to standardize the diagnosis and treatment of TSOFS.

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