1.New drugs for the functional cure of hepatitis B: Focusing on antisense oligonucleotides and small interfering RNAs
Xieer LIANG ; Zhihong LIU ; Jinlin HOU
Journal of Clinical Hepatology 2025;41(1):7-14
Existing nucleos(t)ide analogues and pegylated interferon exhibit limited efficacy in the functional cure of hepatitis B. Recently, small nucleic acid drugs, such as antisense oligonucleotides and small interfering RNAs, have brought unprecedented breakthroughs in the functional cure of hepatitis B with their brand-new mechanisms of action and remarkable efficacy in early clinical studies. Small nucleic acid drugs, such as antisense oligonucleotides and small interfering RNAs, can reduce the level of HBsAg and strive to achieve HBsAg seroclearance. The reduction in HBsAg may restore the hepatitis B-specific immune function of the body to some extent and may further transform the simple clearance of HBsAg into hard endpoints with clinical value, such as reducing hepatitis B-related liver events. By meticulously analyzing the dynamic trajectory of HBsAg alterations within the context of new drug applications and further optimizing combined treatment strategies and regimens, it is expected to transform the functional cure of hepatitis B into the ultimate goal of improving survival rates and quality of life.
2.Impact of GA/ALB on the prognosis of heart failure in patients with coronary heart disease
Chenchen LIU ; Haoran WANG ; Huifang XING ; Hongli LI ; Zhihong GUO ; Lele ZHANG ; Dong YANG ; Hongping LIANG
International Journal of Laboratory Medicine 2025;46(19):2311-2318
Objective To explore the potential clinical value of the ratio of glycated albumin to albumin(GA/ALB)in the occurrence of heart failure(HF)among patients with coronary atherosclerotic heart disease(CHD).Methods A total of 337 CHD patients admitted to the Department of Cardiology in Shanxi Provincial People's Hospital from July 2023 to June 2024 were selected in this study.CHD patients were divided into HF group and non-HF group based on whether they progressed to HF.The clinical data and laboratory parame-ters of the two groups were compared.Restricted cubic spline curve was used to analyze the relationship be-tween GA/ALB levels and the risk of HF in CHD patients.Receiver operating characteristic curve was applied to evaluate the diagnostic efficacy of GA/ALB,GA,platelet to lymphocyte ratio(PLR),and monocyte to lym-phocyte ratio(MLR)in CHD patients with the occurrence of HF.Logistic regression was used to explore the relationship between serum GA/ALB levels and the risk of CHD patients occurrence of HF,and to analyze the degree of influence and stability of subgroup variables on results.Results There were statistically significant differences in GA/ALB,GA,PLR,MLR,and other indicators between the HF group and the non-HF group in CHD patients(P<0.05).A non-linear relationship was observed between GA/ALB levels and the risk of HF in CHD patients.When the value of GA/ALB multiplied by 10 was less than 5.751,the risk of HF in CHD pa-tients increased with the increase of GA/ALB levels(P<0.001).GA/ALB was an effective predictor for HF occurrence in CHD patients.Multivariable Logistic regression model showed that GA/ALB was an independ-ent risk factor for CHD patients with occurrence of HF.Subgroup analysis also confirmed the stability of GA/ALB in predicting the occurrence of HF in CHD patients.Conclusion GA/ALB is an independent risk factor for the occurrence of HF in CHD patients,and monitoring GA/ALB levels provides predictive value for the oc-currence of HF in these patients.
3.Pharmacy practice of clinical pharmacists involved in the treatment of a case of bullous pemphigoid and pulmonary aspergillosis combined with disseminated Nocardia farcinica infection
Tiying DENG ; Min LIN ; Zhimin HU ; Liang ZOU ; Zhihong WU ; Jianmin LIU ; Lei HUANG
China Pharmacy 2024;35(16):2038-2043
OBJECTIVE To provide a reference for the adjustment of antibacterial drug regimens, identification of adverse reactions, and personalized pharmaceutical care for patients with bullous pemphigoid and pulmonary aspergillosis combined with disseminated Nocardia farcinica infection. METHODS Clinical pharmacists participated in the entire treatment process of a patient with bullous pemphigoid and pulmonary aspergillosis combined with disseminated N. farcinica infection. Evidence-based medicine was used to assist in the selection of an initial combined drug regimen against nocardiosis, and timely communication with the microbiology laboratory to provide early antimicrobial susceptibility data. When the patient exhibited epilepsy, the suspected drugs were identified, and it was reminded that imipenem-cilastatin sodium could affect the efficacy of valproic acid. It was suggested to replace valproic acid with levetiracetam for anti-epileptic treatment and to discontinue imipenem-cilastatin sodium. During treatment, it was recommended to monitor the blood concentrations of voriconazole and linezolid, and assist in adjusting the dosage promptly based on the monitoring results. RESULTS The physicians accepted the recommendations of the clinical pharmacists. The patient’s condition improved, and they were discharged with medication. CONCLUSIONS Based on evidence-based medical evidence, antimicrobial susceptibility test results, and blood concentration monitoring data, clinical pharmacists assist clinicians in selecting a sensitive anti-infective regimen for the patient, identifying adverse reactions, adjusting the treatment regimen and providing full-course medication monitoring to ensure the safety and efficacy of clinical drug therapy.
4.A synthetic minority oversampling technique-based early warning model of postoperative biliary leakage after resection for hepatocellular carcinoma
Chinese Journal of Hepatobiliary Surgery 2024;30(2):93-98
Objective:To analyze the influencing factors of postoperative bile leakage in laparoscopic liver lobectomy for hepatocellular carcinoma (HCC), and to create and validate an early warning model of postoperative bile leakage based on the synthetic minority oversampling technique (SMOTE).Methods:Clinical data of 120 patients with HCC undergoing laparoscopic lobectomy in Xiaolan People's Hospital of Zhongshan City from January 2016 to January 2022 were retrospectively analyzed, including 72 males and 48 females, aged (58.6±6.7) years old. The patients were divided into two groups according to the occurrence of bile leakage within 30 days after surgery: bile leakage group ( n=32) and non-bile leakage group ( n=88). Clinical data such as lesion size, remnant liver volume, intraoperative blood loss, and serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were collected. The positive sample size in the original dataset was expanded according to the SMOTE algorithm, and the SMOTE risk warning model (P 2) was established based on the new dataset. The predictive efficacy of the model was accessed using the receiver operating characteristic (ROC) curve and the area under the curve (AUC). Results:The incidence of postoperative bile leakage was 26.67%(32/120) in the patients. Lesion size, preoperative cholangitis, remnant liver volume, intraoperative blood loss, serum level of ALT and AST differs between the groups (all P<0.05). The sample size of the bile leakage group was expanded to 96 cases by the SMOTE algorithm, and then the sample size ratio of the two groups would be close to 1. Subsequent re-fitting of the expanded data based on the SMOTE algorithm showed that a lesion size of ≥5 cm, preoperative cholangitis, increased intraoperative hemorrhage, elevated ALT and AST were independent risk factors for postoperative bile leakage in patients with HCC (all P<0.05), while a larger remnant liver volume was a protective factor for postoperative bile leakage ( P<0.05). An early warning model P 2 was established based on the above factors. The Hosmer-Lemeshow test showed that the model fitting was good ( P=0.842, coefficient of determination R2=0.647). The sensitivity and specificity of the model for predicting postopera-tive bile leakage was 93.75% and 82.95%, respectively, with an AUC of 0.955 (95% CI: 0.901-0.985). Conclusion:Lesion size, preoperative cholangitis, remnant liver volume, intraoperative blood loss, serum levels of ALT and AST were associated with postoperative bile leakage after surgery for HCC. The early warning model of postoperative bile leakage based on the SMOTE algorithm has a high predictive efficacy.
5.Scientific, transparent and applicable rankings of Chinese pathological guidelines and consensus published in the medical journals in 2022
Xiaohua SHI ; Shixian WANG ; Zhe WANG ; Jian WANG ; Zhihong ZHANG ; Yueping LIU ; Hongying ZHANG ; Hongwen GAO ; Xiaoyan ZHOU ; Qiu RAO ; Li LIANG ; Xiaohong YAO ; Dongge LIU ; Zhiyong LIANG
Chinese Journal of Pathology 2024;53(6):528-534
The STAR tool was used to evaluate and analyze the science, transparency, and applicability of Chinese pathology guidelines and consensus published in medical journals in 2022. There were a total of 18 pathology guidelines and consensuses published in 2022, including 1 guideline and 17 consensuses. The results showed that the guideline score was 21.83 points, lower than the overall guideline average (43.4 points). Consensus ratings scored an average of 27.87 points, on par with the overall consensus level (28.3 points). Areas that scored above the overall level were "conflict of interest" and "working groups", while areas that scored below the overall level were "proposals", "funding", "evidence", "consensus approaches" and "accessibility". To sum up, the formulation of pathology guidelines and consensuses in 2022 is not standardized, and the evidence retrieval process, evidence evaluation methods and grading criteria for recommendations on clinical issues are not provided in the formulation process; the process and method for reaching consensus are not provided, the plan is lacking, and registration is not carried out. It is therefore suggested that guidelines/consensus makers in the field of pathology should attach importance to evidence-based medical evidence, strictly follow guideline formulation methods and processes, further improve the scientific, applicable and transparent guidelines/consensuses in the field, and better provide support for clinicians and patients.
6.HBsAg trajectory and key watersheds towards functional cure of hepatitis B
Xieer LIANG ; Zhihong LIU ; Yongyin LI ; Rong FAN ; Jinlin HOU
Chinese Journal of Hepatology 2024;32(11):961-964
Chronic hepatitis B virus (HBV) infection remains a pivotal global public health concern. Attaining a functional cure for hepatitis B continues to be a hot and difficult issue that requires immediate attention in clinical practice. There are currently nucleos(t)ide analogues (NAs) that can persistently suppress HBV DNA; however, the functional cure rate of pegylated interferon alfa (PEG-IFN-α) alone or in combination with NAs has not yet met clinical needs. The research and development on novel mechanisms for HBV antiviral drugs, especially small nucleic acid drugs, has brought breakthroughs to the functional cure of hepatitis B. The functional cure trajectory mapping and its prediction model can guide the selection of clinical treatment strategies based on the longitudinal data for HBsAg at various time intervals. The personalized management of hepatitis B patients can be optimized by utilizing varying HBsAg levels as a key watershed to aid in the screening of subjects in clinical trials.
7.Influence of ankle acupuncture on cognitive impairment caused by sevoflurane in elderly rats and expression of hippocampal phosphorylated phospholipase Cγ
Weiya KANG ; Xinggai XU ; Tao HE ; Zhihong CHENG ; Liang ZHAO
Chinese Journal of Anesthesiology 2024;44(5):564-567
Objective:To evaluate the influence of ankle acupuncture on the cognitive impairment caused by sevoflurane in elderly rats and the expression of hippocampal phosphorylated phospholipase Cγ (p-PLCγ).Methods:Fifteen SPF-grade healthy male Sprague-Dawley rats, aged 18 months, weighing 530-600 g, were allocated into 3 groups ( n=5 each) using a random number table method: sham surgery group (S group), cognitive dysfunction group (CD group) and ankle acupuncture group (A group). The cognitive dysfunction model was prepared by inhaling the mixture of 3% sevoflurane and air, with ankle acupuncture applied to the right hind limb 1-3 region for 30 min prior to anesthesia in A group. S group received sham stimulation. Two days later, the cognitive function was assessed using the Morris water maze test. The rats were subsequently sacrificed and hippocampal tissues were collected for microscopic examination of the pathological changes (using HE staining and Nissl staining) and for determination of the expression of p-PLCγ, phosphorylated calcium/calmodulin-dependent protein kinase Ⅱ (p-CaMKⅡ) and phosphorylated inositol-1, 4, 5-trisphosphate receptor (p-IP3R). Results:Compared with S group, the escape latency was significantly prolonged, the number of crossing the original platform quadrant was reduced, and the expression of p-PLCγ, p-CaMKII and p-IP3R was up-regulated in CD group and A group ( P<0.05). Compared with CD group, the escape latency was significantly shortened, the number of crossing the original platform quadrant was increased, and the expression of p-PLCγ, p-CaMKII and p-IP3R was down-regulated in A group ( P<0.05). The pathological changes were significantly reduced in A group compared with CD group. Conclusions:Ankle acupuncture can ameliorate cognitive dysfunction induced by sevoflurane in elderly rats, and the mechanism is related to inhibition of hippocampal p-PLCγ expression.
8.A case report of cirrhosis complicated with spontaneous spinal cord hemorrhage and literature review
Liang XIANG ; Zhihong ZHAO ; Zhiqun MAO
Chinese Journal of Neurology 2023;56(7):796-799
A case of cirrhosis with spontaneous spinal cord hemorrhage is reported. The patient was a 57-year-old male, whose main clinical symptoms were acute onset, sudden progressive decline of lower limb muscle strength, and incontinence. Magnetic resonance imaging+magnetic resonance angiography+susceptibility-weighted imaging of thoracic spinal cord showed that thin strip like equal and slightly high signal could be seen in the spinal cord of T 1WI sequence, a few low signal foci could be seen in the corresponding part of T 2WI sequence, and there was no obvious change in enhanced scanning. Obvious long strip like low signal foci were shown in the spinal cord of susceptibility-weighted imaging, and the range was significantly larger than that of T 2WI sequence. Spinal cord hemorrhage was diagnosed before operation, and no obvious improvement was found after drug treatment. Spontaneous spinal cord hemorrhage was diagnosed after surgical incision.
9.Thoughts on expert opinion on expanding antiviral therapy for chronic hepatitis B
Zhihong LIU ; Xieer LIANG ; Jinlin HOU
Journal of Clinical Hepatology 2023;39(1):14-21
Expanding antiviral therapy is currently the new trend for the diagnosis and treatment of chronic hepatitis B, and related research evidence should be studied and discussed. Reducing the threshold of alanine aminotransferase (ALT) for initiating antiviral therapy is one of the most important changes during the expansion of antiviral therapy. Chronic hepatitis B patients with a low-level increase in ALT or a high normal level of ALT still have a higher risk of liver cancer and thus require further intervention. At present, nucleos(t)ide analogues show a certain clinical effect in some patients in terms of virological inhibition and improvement in fibrosis, while reducing ALT threshold places higher requirements for biochemical response after treatment. In addition, although the mechanism and definition of low-level viremia (LLV) after treatment remain unclear, further intervention of LLV is an important strategy for optimizing patient management in clinical practice. Switch to another potent nucleos(t)ide analogue may improve the virologic response rate of patients with LLV, and nucleos(t)ide analogues combined with interferon or other new targeted drugs will be an important research direction for the treatment of LLV in the future.
10.Real-world Study of Medication Characteristics and Clinical Efficacy of Tenghuang Jiangu Tablets in Treatment of Knee Osteoarthritis in Remission Stage
Zhihong FU ; Shuwen LI ; Ruihan LI ; Yan JIA ; Ruizheng ZHU ; Xiangyu LI ; Zhi LIANG ; Shuai GAO ; Zhuoyun WU ; Lin CHEN ; Weiheng CHEN
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(6):120-127
ObjectiveTo explore the medication characteristics and clinical efficacy of the Tenghuang Jiangu tablets in the treatment of knee osteoarthritis (KOA) in the remission stage in the real world,providing references for rational clinical use of this prescription. MethodBased on the "registration system of KOA treated with Tenghuang Jiangu tablets",2 439 KOA cases in the remission stage were analyzed by SPSS 25.0,IBM SPSS Modeler18.0,and Apriori algorithm. To be specific,the age,body mass index (BMI),and course of treatment were described in the form of x̄±s. The information on gender,K-L grade,daily dose,and frequency of drug use was described by frequency analysis. The number of cases,course of treatment,daily dose,and drug use frequency of the single-use group and the combined-use group were described by frequency analysis,and the combination of drugs was described by frequency analysis and Apriori algorithm. Mann-Whitney U test was employed to compare the scores of Visual Analogue Scale (VAS),Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC),pain,stiffness,and joint function between the single-use group and the combined-use group. ResultThe results of clinical treatment showed that 2 439 patients with KOA in the remission stage were treated with Tenghuang Jiangu tablets,with 1 432 (58.71%) in the single-use group and 1 007 (41.29%) in the combined-use group. The average daily dose of Tenghuang Jiangu tablets was (3.90±1.44) g,and the majority of the patients were at grade Ⅱ (54.47%). The daily average daily dose of Tenghuang Jiangu tablets in the single-use group was (3.64±1.35) g,which was lower than that in the combined-use group [(4.26±1.48) g,P<0.05]. In the combined use,the top three western medicines were glucosamine (270 times,14.68%),sodium hyaluronate (126 times,6.85%),and imrecoxib (116 times,6.31%),and the top three Chinese medicines were Huoxuezhitong capsules/tablets/ointments (31 times,1.69%),Biqi capsules (25 times,1.36%),and Maizhiling (23 times,1.25%). As for the overall clinical efficacy,the VAS score was (5.13±0.93) score before treatment and (2.22±1.18) score after treatment (P<0.05),with an overall average decrease of (2.91±1.14) score, and the average decrease in the single-use group was (2.76±1.43) score, which was lower than that in the combined-use group [(3.12±1.36) score,(P<0.01)]. The WOMAC score was (31.05±11.84) score before treatment and (13.55±9.91) score after treatment (P<0.05). The overall average decrease was (17.50±11.79) score, and the average decrease in the single-use group and combined-use group was (16.39±11.14) score and (19.08±12.50) score,respectively (P<0.01). The patients with KOA>grade Ⅱ accounted for 91.34%(1 308/1 432) and 93.55%(942/1 007) in the single-use group and combined-use group,respectively (χ2=80.026,P<0.05). A total of 43.37%(621/1 432) of the patients in the single-use group had other complications,lower than that in the combined-use group [54.92%(553/1 432),(χ2=20.087,P<0.01)]. ConclusionMore than half of the patients with KOA in the remission stage are treated with Tenghuang Jiangu tablets alone,and the combination therapy is mainly applied in patients with severe conditions or other complications. In relieving knee joint pain and improving joint stiffness and joint function,both the Tenghuang Jiangu tablets alone and the combination therapy are effective.

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