Age-related macular degeneration(AMD)is a critical ophthalmic condition characterized by substantial vis-ual impairment.Retinal neuroinflammation is one of the fundamental pathophysiological features of AMD.The NOD-like re-ceptor protein 3(NLRP3)inflammasome plays a crucial role in regulating neuroinflammation.It has been demonstrated that the activation of NLRP3 inflammasome is closely correlated with mitochondrial dysfunction,the increased production of reactive oxygen species(ROS),and the anomalous expulsion of mitochondrial DNA in the progression of AMD.There-fore,inhibitors targeting the NLRP3 inflammasome may become a new approach with great potential for AMD treatment.This article rigorously examines the role of mitochondrial impairment and NLRP3 inflammasome signaling in the pathogene-sis of AMD,highlighting current research advancements and prospective trajectories in this evolving field.

Objective:To compare the effects of tele-rehabilitation delivered via a WeChat mim-program with traditional outpatient-home combined rehabilitation for non-specific neck pain patients.Method:Individuals with non-specific neck pain were recruited from the Rehabilitation Medicine Department of West China Hospital between January 2021 and August 2021,were randomly assigned to either tele-rehabili-tation treatment group(TRG)or outpatient-home combined rehabilitation group.Both groups received compre-hensive exercise therapy at home or in the clinic for 4 weeks.Assessments were conducted at baseline,4 weeks,and 8 weeks post-intervention,using the Neck Disability Index(NDI),Numeric Pain Rating Scale(NPRS),and Pain Self-efficacy Questionnaire(PSEQ).Result:A total of 60 patients completed the intervention,with 30 in each group.There were no significant de-mographic differences between groups.At the 4-week mark,both groups showed significant improvements in NDI,NPRS and PSEQ scores compared to baseline,but no significant differences were found between groups.By the 8th week,the tele-rehabilitation group showed further improvements in all three metrics,with NDI and NPRS scores significantly better than those of the outpatient-home combined rehabilitation group.Conclusion:Both remote and outpatient-home combined comprehensive exercise therapies demonstrate short-term effects on non-specific neck pain.However,tele-rehabilitation exhibited more sustained improvements,sug-gesting that it holds promise for further clinical application.

Objective:To compare the effects of tele-rehabilitation delivered via a WeChat mim-program with traditional outpatient-home combined rehabilitation for non-specific neck pain patients.Method:Individuals with non-specific neck pain were recruited from the Rehabilitation Medicine Department of West China Hospital between January 2021 and August 2021,were randomly assigned to either tele-rehabili-tation treatment group(TRG)or outpatient-home combined rehabilitation group.Both groups received compre-hensive exercise therapy at home or in the clinic for 4 weeks.Assessments were conducted at baseline,4 weeks,and 8 weeks post-intervention,using the Neck Disability Index(NDI),Numeric Pain Rating Scale(NPRS),and Pain Self-efficacy Questionnaire(PSEQ).Result:A total of 60 patients completed the intervention,with 30 in each group.There were no significant de-mographic differences between groups.At the 4-week mark,both groups showed significant improvements in NDI,NPRS and PSEQ scores compared to baseline,but no significant differences were found between groups.By the 8th week,the tele-rehabilitation group showed further improvements in all three metrics,with NDI and NPRS scores significantly better than those of the outpatient-home combined rehabilitation group.Conclusion:Both remote and outpatient-home combined comprehensive exercise therapies demonstrate short-term effects on non-specific neck pain.However,tele-rehabilitation exhibited more sustained improvements,sug-gesting that it holds promise for further clinical application.

Age-related macular degeneration(AMD)is a critical ophthalmic condition characterized by substantial vis-ual impairment.Retinal neuroinflammation is one of the fundamental pathophysiological features of AMD.The NOD-like re-ceptor protein 3(NLRP3)inflammasome plays a crucial role in regulating neuroinflammation.It has been demonstrated that the activation of NLRP3 inflammasome is closely correlated with mitochondrial dysfunction,the increased production of reactive oxygen species(ROS),and the anomalous expulsion of mitochondrial DNA in the progression of AMD.There-fore,inhibitors targeting the NLRP3 inflammasome may become a new approach with great potential for AMD treatment.This article rigorously examines the role of mitochondrial impairment and NLRP3 inflammasome signaling in the pathogene-sis of AMD,highlighting current research advancements and prospective trajectories in this evolving field.

BACKGROUND:Anterior cruciate ligament injury tends to lead to secondary meniscus injury and osteoarthritis.At present,there are few studies on the mechanics of meniscus and articular cartilage injury caused by anterior cruciate ligament injury. OBJECTIVE:To study the effect of partial rupture of the anterior cruciate ligament on the stress of medial and lateral meniscus and articular cartilage of knee joint by finite element analysis. METHODS:The CT and MRI images of the knee joint of a healthy volunteer were selected,and the scan data were imported into Mimics,Geomagic and SolidWorks software.After registration and fusion,four kinds of three-dimensional knee joint models were established:models of intact anterior cruciate ligament,rupture of the posterior external tract of anterior cruciate ligament,rupture of the anterior internal tract of anterior cruciate ligament,and absence of anterior cruciate ligament.Finally,data were imported into Ansys software to apply four different modes of loads to the knee joint:Longitudinal loads of 750 N were applied to the top of the femur;longitudinal load of 750 N to the top of the femur and forward thrust of 134 N behind tibia;a longitudinal load of 750 N and a varus moment of 10 Nm were applied to the top of the femur to simulate genu varus;750 N longitudinal load and 4 Nm internal rotation moment were applied to the proximal end of the femur to simulate knee internal rotation.The finite element analysis of biomechanical stress changes of the meniscus and articular cartilage of the knee joint was carried out. RESULTS AND CONCLUSION:(1)In the straight position of the knee joint,when the anterior medial tract of the anterior cruciate ligament was broken and the anterior cruciate ligament was missing under longitudinal loads of 750 N at the top of the femur,the total stress and peak value of meniscus increased significantly,but the stress distribution of the meniscus and the stress of articular cartilage did not change significantly.In longitudinal load of 750 N to the top of the femur and forward thrust of 134 N behind tibia,the fracture of the anterior internal tract of the anterior cruciate ligament increased the tibia forward,the compressive stress of posterior angle of the meniscus increased,and the stress of the articular cartilage did not change significantly.During simulating genu varus,the posterior angular stress of the lateral meniscus decreased,the stress of the medial meniscus increased,and the stress of articular cartilage slightly decreased when anterior cruciate ligament injuries were complete.When the anterior internal tract of the anterior cruciate ligament was broken or absent under knee internal rotation,the equivalent stress peak value of femoral cartilage and tibia cartilage shifted from medial cartilage to lateral cartilage,and the stress peak value of meniscus increased significantly.At this time,the anterior internal tract of the anterior cruciate ligament played a leading role in the rotational stability of the knee joint.(2)These results indicate that the risk of secondary meniscus injury in patients with anterior and medial anterior cruciate ligament band rupture was much higher than that in patients with posterior and external anterior cruciate ligament band rupture when the knee was in the upright standing position,varus and pronation,and there was no significant difference in the impact on articular cartilage.

BACKGROUND:The incidence of medial collateral ligament injuries in the knee joint is easy to lead to secondary meniscus and cartilage damage,and long-term chronic damage can lead to the occurrence of osteoarthritis.At present,there are few studies on the mechanics of meniscus and articular cartilage injury caused by medial collateral ligament rupture. OBJECTIVE:To investigate the effect of different degrees of medial collateral ligament injury on the biomechanics of meniscus and cartilage of knee joint. METHODS:The CT and MRI examinations of the knee joint of a healthy volunteer were performed to obtain the image data.The scanning data were imported into Mimics,Geomagic,and Solidworks software in turn.After registration and fusion,a 3D model of normal knee joint was established.On this basis,models of medial collateral ligament injury in different degrees of knee joint were simulated,which were divided into four groups,including:(1)medial collateral ligament was intact;(2)deep medial collateral ligament fracture;(3)superficial medial collateral ligament fracture;(4)complete rupture of medial collateral ligament.Finally,Ansys software was introduced to apply three modes of loads to the knee joint:(1)10 N·m valvaration torque was applied to the top of the femur.(2)A 4 N·m internal torque was applied to the top of the femur.(3)A 4 N·m external torque was applied to the top of the femur.The effects of four groups of models on knee biomechanics under different loads were analyzed. RESULTS AND CONCLUSION:(1)In the extension position of the knee joint,when a 10 N·m valgus torque was applied to the knee joint,the overall stress of the posterolateral meniscus increased with different degrees of medial collateral ligament injuries,while the stress of the articular cartilage did not change significantly.The peak stress of the posterolateral meniscus increased significantly with superficial medial collateral ligament rupture.(2)In the knee extension position,when a 4 N·m internal rotation torque was applied to the knee joint,the overall stress of the medial and lateral meniscus increased after different degrees of medial collateral ligament injury.When superficial medial collateral ligament rupture occurred,the peak stress of the meniscus shifted from the anterior horn of the medial meniscus to the anterior horn of the lateral meniscus.(3)In the knee extension position,applying a 4 N·m external rotation torque to the knee joint,the peak stress of the posterolateral meniscus increased more significantly than that of the medial meniscus,and the stress of the articular cartilage changed less.(4)These results show that the risk of meniscus injury secondary to superficial medial collateral ligament rupture is much higher than that of deep medial collateral ligament rupture when the knee is in extension,and the lateral meniscus is more vulnerable to injury than the medial meniscus.Both superficial medial collateral ligament and deep medial collateral ligament play an important role in the rotational stability of the knee joint.

Objective:To compare the differences in the prevalence of mild micro-hepatic encephalopathy (MHE) among patients with cirrhosis by using the psychometric hepatic encephalopathy score (PHES) and the Stroop smartphone application (Encephal App) test.Methods:This prospective, multi-center, real-world study was initiated by the National Clinical Medical Research Center for Infectious Diseases and the Portal Hypertension Alliance and registered with International ClinicalTrials.gov (NCT05140837). 354 cases of cirrhosis were enrolled in 19 hospitals across the country. PHES (including digital connection tests A and B, digital symbol tests, trajectory drawing tests, and serial management tests) and the Stroop test were conducted in all of them. PHES was differentiated using standard diagnostic criteria established by the two studies in China and South Korea. The Stroop test was evaluated based on the criteria of the research and development team. The impact of different diagnostic standards or methods on the incidence of MHE in patients with cirrhosis was analyzed. Data between groups were differentiated using the t-test, Mann-Whitney U test, and χ2 test. A kappa test was used to compare the consistency between groups. Results:After PHES, the prevalence of MHE among 354 cases of cirrhosis was 78.53% and 15.25%, respectively, based on Chinese research standards and Korean research normal value standards. However, the prevalence of MHE was 56.78% based on the Stroop test, and the differences in pairwise comparisons among the three groups were statistically significant (kappa = -0.064, P < 0.001). Stratified analysis revealed that the MHE prevalence in three groups of patients with Child-Pugh classes A, B, and C was 74.14%, 83.33%, and 88.24%, respectively, according to the normal value standards of Chinese researchers, while the MHE prevalence rates in three groups of patients with Child-Pugh classes A, B, and C were 8.29%, 23.53%, and 38.24%, respectively, according to the normal value standards of Korean researchers. Furthermore, the prevalence rates of MHE in the three groups of patients with Child-Pugh grades A, B, and C were 52.68%, 58.82%, and 73.53%, respectively, according to the Stroop test standard. However, among the results of each diagnostic standard, the prevalence of MHE showed an increasing trend with an increasing Child-Pugh grade. Further comparison demonstrated that the scores obtained by the number connection test A and the number symbol test were consistent according to the normal value standards of the two studies in China and South Korea ( Z = -0.982, -1.702; P = 0.326, 0.089), while the other three sub-tests had significant differences ( P < 0.001). Conclusion:The prevalence rate of MHE in the cirrhotic population is high, but the prevalence of MHE obtained by using different diagnostic criteria or methods varies greatly. Therefore, in line with the current changes in demographics and disease spectrum, it is necessary to enroll a larger sample size of a healthy population as a control. Moreover, the establishment of more reliable diagnostic scoring criteria will serve as a basis for obtaining accurate MHE incidence and formulating diagnosis and treatment strategies in cirrhotic populations.

Objective:To investigate the diagnostic accuracy of serological indicators and evaluate the diagnostic value of a new established combined serological model on identifying the minimal hepatic encephalopathy (MHE) in patients with compensated cirrhosis.Methods:This prospective multicenter study enrolled 263 compensated cirrhotic patients from 23 hospitals in 15 provinces, autonomous regions and municipalities of China between October 2021 and August 2022. Clinical data and laboratory test results were collected, and the model for end-stage liver disease (MELD) score was calculated. Ammonia level was corrected to the upper limit of normal (AMM-ULN) by the baseline blood ammonia measurements/upper limit of the normal reference value. MHE was diagnosed by combined abnormal number connection test-A and abnormal digit symbol test as suggested by Guidelines on the management of hepatic encephalopathy in cirrhosis. The patients were randomly divided (7∶3) into training set ( n=185) and validation set ( n=78) based on caret package of R language. Logistic regression was used to establish a combined model of MHE diagnosis. The diagnostic performance was evaluated by the area under the curve (AUC) of receiver operating characteristic curve, Hosmer-Lemeshow test and calibration curve. The internal verification was carried out by the Bootstrap method ( n=200). AUC comparisons were achieved using the Delong test. Results:In the training set, prevalence of MHE was 37.8% (70/185). There were statistically significant differences in AMM-ULN, albumin, platelet, alkaline phosphatase, international normalized ratio, MELD score and education between non-MHE group and MHE group (all P<0.05). Multivariate Logistic regression analysis showed that AMM-ULN [odds ratio ( OR)=1.78, 95% confidence interval ( CI) 1.05-3.14, P=0.038] and MELD score ( OR=1.11, 95% CI 1.04-1.20, P=0.002) were independent risk factors for MHE, and the AUC for predicting MHE were 0.663, 0.625, respectively. Compared with the use of blood AMM-ULN and MELD score alone, the AUC of the combined model of AMM-ULN, MELD score and education exhibited better predictive performance in determining the presence of MHE was 0.755, the specificity and sensitivity was 85.2% and 55.7%, respectively. Hosmer-Lemeshow test and calibration curve showed that the model had good calibration ( P=0.733). The AUC for internal validation of the combined model for diagnosing MHE was 0.752. In the validation set, the AUC of the combined model for diagnosing MHE was 0.794, and Hosmer-Lemeshow test showed good calibration ( P=0.841). Conclusion:Use of the combined model including AMM-ULN, MELD score and education could improve the predictive efficiency of MHE among patients with compensated cirrhosis.

Nucleos(t)ide analogues (NAs), which are widely used as the first-line anti-hepatitis B virus (HBV) drugs in clinical practice, can effectively inhibit the replication of HBV DNA, significantly slow down disease progression in chronic hepatitis B (CHB) patients, and reduce the development of end-stage liver diseases such as liver failure and liver cancer. However, for some CHB patients receiving first-line NAs for 48 weeks or longer, serum HBV DNA is still persistently or intermittently higher than the lower detection of limit of sensitive nucleic acid detection reagents. After discussion by the authors, low-level viremia (LLV) is defined as follows: persistent LLV refers to the condition in which CHB patients, who receive entecavir, tenofovir disoproxil fumarate, or tenofovir alafenamide fumarate for ≥48 weeks, test positive for HBV DNA by two consecutive detections with sensitive quantitative PCR, with an interval of 3-6 months, but have an HBV DNA level of ＜2000 IU/ml; intermittent LLV refers to the condition in which patients test positive for HBV DNA intermittently by at least three consecutive detections with sensitive quantitative PCR, with an interval of 3-6 months, but have an HBV DNA level of ＜2000 IU/ml. For the diagnosis of LLV, the issues of poor compliance and drug-resistant mutations should be excluded. LLV might be associated with the increased risk of progression to liver fibrosis or hepatocellular carcinoma in patients with liver cirrhosis under NA treatment, but there are still controversies over whether the original treatment regimen with NAs should be changed after the onset of LLV. This article summarizes the incidence rate of LLV under NA treatment and the influence of LLV on prognosis and analyzes the possible mechanisms of the osnet of LLV, so as to provide a reference for the management of LLV in patients treated with NAs.

Objective To analyze the pathologically confirmed pulmonary Actinomycosis in the 11 patients in focusing on clinical features and mis-diagnostic reasons so as to improve physicians' awareness of this rare disease and reduce the misdiagnosis.Methods We retrospectively reviewed the medical records of 11 cases with pathologically confirmed pulmonary Actinomycosis during January 2003-August 2015.The clinical data and main causes of misdiagnosis in these cases were collected and analyzed.Results The study included 11 patients with a mean age of(53.0 ± 11.6.0)years.Among the 11 cases,8 (72.7 ％) patients had complications,6 (54.5 ％) were current or ex-smokers.Main clinical manifestations of 11 cases were cough(11/11,100.0 ％),sputum(11/11,100.0 ％),hemoptysis (7/11,63.6％),chest pain(6/11,54.5％)and fever(3/11,27.3％).Ten patients presented with one lobe of lung lesions,including 4 patients in the lower lobe and 3 in the upper lobe of the left lung,2 in the upper lobe and 1 in the lower lobe of the right lung.While,the remained one case presented with lesion locating in right main bronchus.Iconography often presented as pulmonary mass shadow,consolidation shadow,spicule sign,lobulation sign,hilar and/or mediastinal lymphadenopathy and pleural effusion.Vacuolar lesions were observed in some of the focuses.Flexible bronchoscopy was performed in 8 (72.7％)patients.Among them,7 patients showed mucosal swelling and congestion,luminal occlusion with purulence secretion,2 cases with polypoid neoplasm.Initial misdiagnosis rate were 100％ (11/11),among which 7 cases were misdiagnosed as lung cancer,2 cases as fungus infection,and 1 case as pulmonary tuberculosis and 1 case as pneumonia,respectively.All patients were definitely diagnosed by biopsy finding an evidence of hyphae of Actinomycosis in lung tissue specimens.The definitive diagnosis was made by CT-guided percutaneous lung biopsy in 4 cases,by transbronchial lung biopsy (TBLB)in 5 cases and by thoracotomy or video-assisted thoracoscopic surgery(VATS) in 1 case respectively.Actinomycosis in most patients was cured with high-dose penicillin administration over a prolonged period.Conclusions The diagnosis of pulmonary Actinomycosis remains challenging via its non-specific clinical symptoms and iconography features,and the presence of comorbidity may further increase the difficulty and complexity of diagnosis,leading to delaying-or mistaking-diagnosis.Obtaining positively pathological specimens is diagnostic key.Transbronchial lung biopsy through a bronchoscope and CT-guided percutaneous needle biopsy are the priority methods.