Objective To evaluate the efficacy and safety of enteric-coated metformin hydrochloride capsules(Junlida?)in patients with T2DM and poor glycemic control under lifestyle interventions.Methods In this study,419 patients with T2DM were recruited from 15 research centers from July 2020 to March 2022,and randomly divided into observation(Obs)group(n=209)and control group(Con,n=210)using a multicenter,randomized,double-blind,non-inferiority trial design.Patients in the Obs group were treated with enteric-coated Metformin hydrochloride capsules(Junlida?),and patients in the Con group were treated with Metformin hydrochloride tablets(Glucophage?).The optimal effective dose of 2 g/d was achieved within 4 weeks,and the reasonable dose was maintained until the end of treatment.The treatment period was 24 weeks.HbA1c and its compliance rate,FPG,and body weight were compared between the two groups in full analysis set(FAS)and protocol set(PPS).Safety and adverse events(AE)were evaluated in safety set(SS).Results A total of 414 participants were randomized(207 cases in Obs group and 207 cases in Con group).414 cases in FAS population(207 cases in Obs group and 207 cases in Con group),and 328 cases in PPS population(164 cases in Obs group and 164 cases in Con group),and 414 cases in SS population(207 cases in Obs group and 207 cases in Con group).After treatment,HbA1c,FPG and body weight were lower in both groups(P<0.05)in FAS and PPS.HbA1c compliance rate was not significantly different between the two groups in FAS and PPS(P>0.05).The results of non-inferiority test showed that the lower limit was>-0.4%in both FAS(-0.154,95%CI-0.384～0.069)and PPS(-0.139,95%CI-0.390～0.112),and the Obs group reached non-inferiority end point.The achievement rate,compliance rate,safety index and incidence of AE were not significantly different between the two groups(P>0.05).Conclusions Junlida? demonstrated non-inferiority to Glucophage? in glycemic control and can be safely and effectively used in patients with diabetes.

Objective To evaluate the efficacy and safety of enteric-coated metformin hydrochloride capsules(Junlida?)in patients with T2DM and poor glycemic control under lifestyle interventions.Methods In this study,419 patients with T2DM were recruited from 15 research centers from July 2020 to March 2022,and randomly divided into observation(Obs)group(n=209)and control group(Con,n=210)using a multicenter,randomized,double-blind,non-inferiority trial design.Patients in the Obs group were treated with enteric-coated Metformin hydrochloride capsules(Junlida?),and patients in the Con group were treated with Metformin hydrochloride tablets(Glucophage?).The optimal effective dose of 2 g/d was achieved within 4 weeks,and the reasonable dose was maintained until the end of treatment.The treatment period was 24 weeks.HbA1c and its compliance rate,FPG,and body weight were compared between the two groups in full analysis set(FAS)and protocol set(PPS).Safety and adverse events(AE)were evaluated in safety set(SS).Results A total of 414 participants were randomized(207 cases in Obs group and 207 cases in Con group).414 cases in FAS population(207 cases in Obs group and 207 cases in Con group),and 328 cases in PPS population(164 cases in Obs group and 164 cases in Con group),and 414 cases in SS population(207 cases in Obs group and 207 cases in Con group).After treatment,HbA1c,FPG and body weight were lower in both groups(P<0.05)in FAS and PPS.HbA1c compliance rate was not significantly different between the two groups in FAS and PPS(P>0.05).The results of non-inferiority test showed that the lower limit was>-0.4%in both FAS(-0.154,95%CI-0.384～0.069)and PPS(-0.139,95%CI-0.390～0.112),and the Obs group reached non-inferiority end point.The achievement rate,compliance rate,safety index and incidence of AE were not significantly different between the two groups(P>0.05).Conclusions Junlida? demonstrated non-inferiority to Glucophage? in glycemic control and can be safely and effectively used in patients with diabetes.

Chronic hepatitis B virus (HBV) infection is a global public health concern. Existing antiviral drugs, including nucleos(t)ide analogs and interferon-α, can suppress HBV replication and improve the prognosis. However, the persistence of covalently closed circular DNA (cccDNA), the integration of HBV-DNA into the host genome, and compromised immune responses impede the successful treatment of hepatitis B. While achieving a functional cure of HBV remains elusive with the current treatment methods, this is the goal of new therapeutic approaches. Therefore, developing novel antiviral drugs is necessary for achieving a functional or complete cure for chronic hepatitis B. In recent years, substantial progress has been made in drug discovery and development for HBV infection. Direct-acting antiviral agents such as entry inhibitors, capsid assembly modulators, subviral particle release inhibitors, cccDNA silencers, and RNA interference molecules have entered clinical trials. In addition, several immunomodulatory agents, including toll-like receptor agonists, therapeutic vaccines, checkpoint inhibitors, and monoclonal antibodies, are also making their way toward clinical use. In this review, we summarize the recent progress and limitations of chronic hepatitis B treatment and discuss perspectives on approaches to achieving functional cure. Although it will take some time for these new antiviral drugs to be widely used in clinical practice, combination therapy may become a preferable treatment option in the future.
Humans ; Antiviral Agents/therapeutic use* ; Hepatitis B, Chronic/drug therapy* ; Hepatitis B virus/genetics*

Diabetes, hypertension, and dyslipidemia, collectively referred to the " Three Highs, " represent increasingly prevalent metabolic risk factors in China. Many individuals experience all three conditions concurrently, significantly heightening the risk of cardiovascular disease and mortality. Although the National Metabolic Management Center(MMC) has been established for over eight years and has its unique features, the awareness, treatment, and control rates of these diseases in China remain low, and the efficiency of community management is insufficient. According to the previous two editions of management guidelines and the most recent domestic and international diagnostic and treatment guidelines, this paper conducts an in-depth analysis of the operational experience and management strategies of the MMC. Its aim is to improve the efficiency of grassroots MMC mode management for " Three Highs" patients and ensure that patients receive more standardized management.

Diabetes, hypertension, and dyslipidemia, collectively referred to the " Three Highs, " represent increasingly prevalent metabolic risk factors in China. Many individuals experience all three conditions concurrently, significantly heightening the risk of cardiovascular disease and mortality. Although the National Metabolic Management Center(MMC) has been established for over eight years and has its unique features, the awareness, treatment, and control rates of these diseases in China remain low, and the efficiency of community management is insufficient. According to the previous two editions of management guidelines and the most recent domestic and international diagnostic and treatment guidelines, this paper conducts an in-depth analysis of the operational experience and management strategies of the MMC. Its aim is to improve the efficiency of grassroots MMC mode management for " Three Highs" patients and ensure that patients receive more standardized management.

The latest epidemiological data suggests that the situation of adult diabetes in China is severe, and metabolic diseases have become significant chronic illnesses that have a serious impact on public health and social development. After more than six years of practice, the National Metabolic Management Center(MMC) has developed distinctive approaches to manage metabolic patients and has achieved a series of positive outcomes, continuously advancing the standardized diagnosis and treatment model. In order to further improve the efficiency, based on the first edition, the second edition guideline was composed by incorporating experience of the past six years in conjunction with the latest international and domestic guidelines.

Objective Thresholds for auditory brain stem responses (ABRs) to tone burst and tone burst in notched noises of two different intensities were tested in adults with sensorineural hearing loss.The relationship between ABR and puretone thresholds was analyzed to identify an acoustic stimuli with better frequency-specificity.Methods Thirty-eight adults with sensorineural hearing loss (totally 45 ears) were included in the study.Tone burst used to elicit ABRs had 2.5 cycles on the rise and fall and no plateau.Notched noises of two different intensities were used to mask tone burst ipsilaterally when recording ABRs.Those two kinds of notched noises were 25 dB (intensity A) and 15 dB (intensity B) lower than tone burst in intensity respectively.Tone burst ABRs without masking were named tb-ABR,while tone burst ABRs in notched noises of intensity A and B named as amtb-ABR and bmtb-ABR.Thresholds for tb ABR,amtb ABR and bmtb-ABR were tested and analyzed.Results The regression coefficients between puretone thresholds and thresholds for tb-ABR,amtb-ABR and bmtb-ABR of all frequencies were greater than 0.8.The mean differences between ABR and puretone thresholds were all less than 10 dB.Tb-ABR thresholds the were the closest to puretone thresholds at 500 Hz,while bmtb ABR thresholds were the closest at the other three frequencies.Bmtb-ABR thresholds were more close to puretone thresholds in patients with steeply sloping hearing loss.Conclusion Thresholds for all those three ABRs could be used to predict puretone thresholds.In most condition,tb-ABR thresholds were able to estimate puretone thresholds.In some condition,different stimuli could be chosen to elicit ABR at different frequencies.It was reasonable to choose bmtb -ABR for puretone thresholds estimation in patients with steeply sloping hearing loss.

Objective To investigate the relationship between the expression patterns of fibronectin (Fn) and its receptors-α5β1 and αVβ3 integrins and angiogenesis after cerebral ischemia in aged mice. Methods Both young (2 months) and aged (18 months) C57BL6 male mice were subject to middle cerebral artery occlusion. The brain endothelial cells (BECs) proliferation was assessed by using dual-immunofluorescent staning (IF) for Ki67 and CD31 and the vessel density was quantified by counting the number of CD31-positive vessels per field of view. The expression patterns of Fn,α5β1 and αVβ3 on blood vessels was assessed by using dual-IF for CD31/ɑ5,CD31/β3 and CD31/Fn. Results The number of CD31/Ki67 dual-positive cells in the penumbra at day 7 after cerebral ischemia of was significantly lower in the aged mice than in the young mice (4.7±0.8/field, P<0.05). The number of CD31-positive vessels in the penumbra at day 7 and 14 of was both significantly lower in aged mice than in the young mice (38.3±3.9/field, 45±4.4/field, both P<0.01). Furthermore, the expression of Fn, α5 and β3 on blood vessels in the penumbra at day 7 after cerebral ischemia was significantly lower in age mice than in the young mice (P<0.05). Conclusions The cerebral angiogenesis after ce?rebral ischemia is impaired in the aged stroked mice, which is associated with the low expression of fibronectin and its receptors-α5β1 andαVβ3 integrins on blood vessels.

Radl7 is an early replication checkpoint protein which sensing DNA lesions during DNA replication and halting progression ofreplication fork in cell cycle.It plays an important role in insuring the integrality and stability of DNA.Recent researches reveal that its functional defect and high expression may correlate with cell carcinogenesis and progression of carcinoma.

Objective To compare the accuracy of auditory brain stem response (ABR) thresholds to tone burst and tone burst ipsilaterally masked by notched noise in estimating puretone thresholds of adults with normal hearing.To study characteristics of ABRs evoked by tone burst and tone burst in notched noise of two different intensities.These three kinds of ABRs were named as follows:tb-ABR,amtb-ABR and bmtb-ABR.Methods Puretone audiometry,ABRs to tone burst and tone burst ipsilaterally masked by notched noise of different intensities were tested in 20 adults (totally 40 ears) with normal hearing.Results ①Thresholds for tb-ABR,amtb-ABR and broth-ABR of each frequency all approximated each other,and there were no statistically significant differences between them.②The mean differences between puretone thresholds and thresholds for tb-ABR,amtb -ABR and bmtb-ABR of each frequency were all less than 15 dB.Those mean differences of different ABRs of the same frequency were approximate to each other and had no statistically differences.③No matter what kind of ABR was tested,the latencies of wave V shortened with increase of frequency in each ABR at the same intensity.When the intensity and frequency of the tone burst were the same,the latency of wave V of tb-ABR was always statistically shorter than that of amtb-ABR.The latter was also always statistically shorter than that of bmtb-ABR.Conclusion Thresholds for ABRs to tone burst and tone burst ipsilaterally masked by notched noise were useful in predicting puretone thresholds.