ObjectiveThis paper aims to use the digital muscle function assessment system Myoton PRO to assess the correlation between muscle tension，clinical characteristics， and traditional Chinese medicine（TCM） syndromes in patients with hepatolenticular degeneration ［also known as Wilson disease（WD）］. MethodsA total of 104 patients with WD accompanied by abnormal muscle tension（increased or decreased，hereinafter the same） who were hospitalized in the Brain Disease Centre of the First Affiliated Hospital of Anhui University of Chinese Medicine from April 2021 to November 2023 were selected，all of whom were subjected to TCM syndrome diagnosis and Myoton PRO for the measurement of F value of muscle tension，Goldstein， and UWDRS-N scales. The age of onset of the disease and disease duration were analyzed，and the differences and correlations of the above indexes in different TCM syndromes of WD were analyzed ResultsAmong the 104 patients with WD ，the phlegm and stasis syndrome was the most common（60 patients），followed by the damp-heat syndrome（33 patients），and the least common was the liver-kidney Yin deficiency syndrome（11 patients）. The F value of the phlegm and stasis syndrome group was higher than that of the liver-kidney Yin deficiency syndrome group and the damp-heat syndrome group（P<0.01）. The F value of the damp-heat syndrome group was higher than that of the liver-kidney Yin deficiency syndrome group（P<0.05），and the F value of the lower limbs of each group was higher than that of the upper limbs（P<0.01）. Goldstein and UWDRS-N scores of the patients in the phlegm and stasis syndrome group were higher than those in the damp-heat syndrome group and the liver-kidney Yin deficiency syndrome group（P<0.05）. There was no significant difference between the Goldstein and UWDRS-N scores of patients in the liver-kidney Yin deficiency syndrome group and the damp-heat syndrome group. Correlation analysis revealed that the age of onset and duration of the disease were positively correlated with the F values of the lower limbs（r=0.20，P<0.05，r=0.38，P<0.01）and had no significant correlation with those of the upper limbs. The F value levels of muscle tension of all limbs in the three groups of patients were positively correlated with the Goldstein and UWDRS-N scores（muscle tension of the upper limbs in the phlegm and stasis syndrome group，r=0.36，P<0.01，r=0.42，P<0.01. muscle tension of the lower limbs in the phlegm and stasis syndrome group，r=0.70，P<0.01，r=0.60，P<0.01. muscle tension of the upper limbs in the damp-heat syndrome group，r=0.64，P<0.01，r=0.53，P<0.01. muscle tension of the lower limbs in the damp-heat syndrome group，r=0.59，P<0.01，r=0.70，P<0.01. muscle tension of the upper limbs in the liver-kidney Yin deficiency syndrome group，r=0.70，P<0.01，r=0.74，P<0.01. muscle tension of the lower limbs in the liver-kidney Yin deficiency syndrome group，r=0.85，P<0.01，r=0.62，P<0.01）. Conlusion： The digital muscle function assessment system Myoton PRO can objectively evaluate the muscle tension level of patients with WD accompanied by abnormal muscle tension. This level has significant differences among different TCM syndromes and can evaluate the patient's condition to some extent.

ObjectiveTo investigate the incidence rate of sarcopenia in patients with Wilson’s disease （WD）-related liver cirrhosis， as well as the risk factors for sarcopenia and their impact on clinical outcomes. MethodsA total of 140 patients with WD-related liver cirrhosis who were treated in The First Affiliated Hospital of Anhui University of Chinese Medicine from January 2019 to June 2020， and according to the third lumbar skeletal muscle mass index （L3 SMI）， the patients were divided into sarcopenia group and non-sarcopenia group. Nutritional risk screening， anthropometric measurements， and blood biochemical tests were performed for the patients to identify the influencing factors for sarcopenia. The patients were followed up for 36 — 48 months， and survival status and complications were compared between the two groups. The independent-samples t test was used for comparison of normally distributed continuous data between two groups， and the chi-square test and the Mann-Whitney U rank sum test were used for comparison of categorical data between two groups. A binary Logistic regression analysis was used to investigate the influencing factors for sarcopenia， and univariate and multivariate Cox regression analyses were used to investigate the risk factors for the prognosis of patients with WD-related liver cirrhosis. The Kaplan-Meier survival curve was plotted， and the Log-rank test was used for comparison between groups. ResultsAmong the 140 patients with WD-related liver cirrhosis， 53 （37.9%） developed sarcopenia， with significantly lower body mass index （BMI） and L3 SMI than the patients without sarcopenia （t=10.550 and 3.982， both P<0.001）. The multivariate Logistic regression analysis showed that age （odds ratio ［OR］=2.243， 95% confidence interval ［CI］： 1.196 — 4.208， P=0.012）， sex （OR=0.450， 95%CI： 0.232 — 0.872， P=0.018）， BMI （OR=0.126， 95%CI： 0.089 — 0.294， P<0.001）， and hepatic encephalopathy （OR=8.367， 95%CI： 2.423 — 28.897， P<0.001） were the main influencing factors for sarcopenia in patients with WD-related liver cirrhosis. Compared with the non-sarcopenia group， the sarcopenia group had significantly higher mortality rate （χ²=6.158， P=0.019） and significantly higher incidence rates of infection （χ²=8.008， P=0.040）， recurrent abdominal/pleural efflux （χ²=17.742， P<0.001）， and hepatic encephalopathy （χ²=4.338， P=0.039）. The multivariate Cox regression analysis showed that sarcopenia （hazard ratio ［HR］=4.685， P=0.002） and hepatic encephalopathy （HR=19.156， P<0.001） were independent risk factors for death in patients with WD-related liver cirrhosis. The Kaplan-Meier survival curve analysis showed a significant reduction in survival rate in the patients with sarcopenia （P=0.003）. ConclusionSarcopenia is one of the manifestations of malnutrition in patients with WD-related liver cirrhosis， which increases the risk of mortality and other complications and has an adverse effect on prognosis. There is an increased risk of sarcopenia in male patients or patients with hepatic encephalopathy， a lower level of BMI or an older age.

Objective:Glaucoma is a multifactorial optic neuropathy with a high rate of irreversible visual loss,and its pathogenesis is complex and still unclear.Elevated intraocular pressure(IOP)is well recognized as the sole modifiable risk factor for the development of glaucoma in the majority of cases.This study aims to compare 2 different methods of inducing chronic ocular hypertension by circumlimbal suture or by laser burns in degree and lasting time of the IOP,different status of the retina and retinal ganglion cells(RGCs),and changes of the microstructure of neurons. Methods:The chronic ocular hypertension models were induced by 2 different ways.One kind of the models was built by unilateral circumlimbal suture(10/0)implantation(suture group),another kind of model was built by laser burns at trabecular meshwork and episcleral veins(laser group).The untreated contralateral eye served as the control group.Changes in IOP were observed and regularly monitored in the 2 groups of rats.HE staining was applied to observe the retinal and optic nerve pathology.Transmission electron microscope(TEM)was used to observe the mitochondrial morphology.RGCs were specifically labeled with Brn3b antibody and counted.The expression of caspase-3 was detected by Western blotting to clarify the apoptosis of RGCs. Results:Compared with the control group,IOP were significantly increased in the suture group and the laser group(both P<0.05).The suture group induced a 1.5-fold elevation of IOP,and sustained for 8 weeks.The laser group induced a 2-fold elevation of IOP for 12 weeks.Both methods could cause RGCs loss(both P<0.05),which were verified by pathology and immune staining of Brn3b.The expressions of caspase-3 were also increased(both P<0.05).The mitochondrial morphology became more fragment,which changed from long shape to round and small one under TEM in 2 models.For comparison,the pathology changes of retinal structure in suture group were not obviously than those in the laser group. Conclusion:Circumlimbal suture can build an effective model of chronic elevated IOP and induce glaucomatous pathologic changes similar to those in the laser photocoagulation,but the pathologic changes are milder than those in laser photocoagulation.Compare with translimbal laser photocoagulation,equipment and skill demand for circumlimbal suture is less.

Wilson's disease （WD） is a copper metabolism disorder caused by mutations in the ATP7B gene， with diverse phenotypes and complex pathogenesis. It is one of the few rare diseases that can achieve good clinical efficacy through standardized treatment. Since there are few systematic reviews of this disease， we summarize the pathogenesis and treatment methods of WD from traditional Chinese and western medicine by reviewing the literature related to WD. In western medicine， ATP7B gene mutation is considered as the root cause of WD， which affects copper transport and causes copper metabolism disorders. The excessive copper deposited in the body will result in oxidative stress， defects in mitochondrial function， and cell death. Western medicine treatment of WD relies mainly on drugs， and copper antagonists are the first choice in clinical practice， which are often combined with hepatoprotective and antioxidant therapy. Surgery is a common therapy for the patients with end-stage WD， and gene therapy provides an option for WD patients. According to the traditional Chinese medicine （TCM） theory， WD is rooted in constitutional deficiency and copper accumulation and triggered by dampness-heat accumulation or phlegm combined with stasis. The patient syndrome varies in different stages of the disease， and thus the treatment should be based on syndrome differentiation. The TCM treatment method of nourishing the liver and kidneys and warming the spleen and kidneys can address the root cause. The methods of clearing heat and drying dampness， resolving phlegm and dispelling stasis， and soothing liver and regulating qi movement can be adopted to treat symptoms. On the basis of syndrome differentiation， special prescriptions for the treatment of WD have been formulated， such as Gandou decoction， Gandouling， and Gandou Fumu decoction， which have been widely used in clinical practice. TCM and western medicine have their own advantages and shortcomings. The integrated Chinese and western medicine complementing with each other demonstrates great therapeutic potential. This paper summarizes the pathogenesis and treatment of WD with integrated Chinese and western medicine， aiming to provide a reference for the clinical diagnosis and treatment of this disease.

BACKGROUND:It was found that the ligands and receptors of Notch are both cell membrane surface proteins,which are important proteins to mediate intercellular communication,and the Notch signaling pathway plays a crucial regulatory role in the proliferation and differentiation of mesenchymal stem cells. OBJECTIVE:To review the regulatory mechanism of the Notch signaling pathway on the proliferation and differentiation of mesenchymal stem cells,summarize and clarify the research advance in how the Notch signaling pathway regulates the proliferation and differentiation of mesenchymal stem cells,and provide theoretical support for the future use of stem cells to treat various related diseases. METHODS:By using the computer,the first author searched the relevant studies involving Notch signaling pathway regulation of mesenchymal stem cell proliferation and differentiation on CNKI,Wanfang,VIP,PubMed,Web of Science,and Nature databases with Chinese search terms"mesenchymal stem cells,Notch,Notch signaling pathway,proliferation,differentiation"and the English search terms"mesenchymal stem cells,MSC,Notch,Notch signaling pathway,proliferation,differentiation".Part of the literature was searched in combination with the literature tracing method.Finally,87 articles were included in the review analysis. RESULTS AND CONCLUSION:(1)Notch signaling pathway is a conserved signaling pathway in multicellular organisms,which plays an important role in regulating cell differentiation,proliferation,apoptosis,and the cell cycle by mediating communication between neighboring cells through receptor-ligand binding.(2)Mesenchymal stem cells are a class of adult stem cells with self-proliferative and multi-directional differentiation potential,which can be regulated by external signaling pathways to affect their proliferation and differentiation.Notch signaling pathway,as one of them,when Notch ligands are activated,the Notch proteins will undergo two protein hydrolysis cleavages to release Notch intracellular structural domain NICD,which then enters the nucleus and thus promotes the transcription of target genes to regulate the proliferation and differentiation of mesenchymal stem cells from different sources,such as bone marrow,adipose,and umbilical cord.However,the specific mechanisms that regulate the proliferation and differentiation of mesenchymal stem cells from different tissue sources of the same species are different.(3)The Notch signaling pathway can regulate the differentiation of mesenchymal stem cells into different target cells,but due to different target cells,the expression levels of receptors or ligands in the Notch signaling pathway vary.(4)Clinical targeting of the Notch signaling pathway to promote mesenchymal stem cells for the treatment of various refractory diseases,such as aplastic anemia,severe joint injuries,ischemic strokes,and myocardial infarctions,has a promising application.(5)By exploring the Notch signaling pathway via regulating the expression levels of its receptors and ligands in bone marrow mesenchymal stem cells from rat,mouse,and human,it can be found that the Notch signaling pathway expression levels in the proliferation and differentiation of mesenchymal stem cells from different species origins are also different.(6)The role of mesenchymal stem cells in tissue engineering has been gradually highlighted due to their advantages of safety,low immune rejection,and wide therapeutic prospects.The Notch signaling pathway regulates the proliferation and differentiation of mesenchymal stem cells with a wide range of influencing factors,and subsequent studies should further optimize the influencing factor variables and explore the standardized studies of regulating the proliferation and differentiation of mesenchymal stem cells.

This study presents a case of a girl of three year and 4 month old with ataxia and severe sen-sorineural hearing loss for 2 years.In order to improve hearing,she was hospitalized in the PUMC Hospital.Ge-netic testing performed found compound heterozygous variants of c.1186C＞T(p.P396S)and c.1357C＞T(p.R453W)in TWNK gene.After a multidisciplinary discussion of the case,the team suspected mitochondrial DNA depletion syndrome type 7(hepatocerebral type).The patient has shown nervous system impairment in-volvement but no evidence of liver dysfunction.The efficacy of cochlear implantation is uncertain and general anesthesia if applied will accelerate the progress of encephalopathy and might lead to multiple organ failure.Unsure of the perioperative safety,the parents of the girl did not chose the option of hearing intervention tempo-rarily,but chose oral symptomatic supportive treatment with coenzyme Q10,folate,levocarnitine,and complex vitamins as recommended.

Objective:To investigate the recent epidemic trends and spatiotemporal distribution characteristics of gonorrhea in China, and to provide a reference for precise prevention and control of gonorrhea.Methods:Data on reported cases of gonorrhea in China (not including Hongkong, Macau and Taiwan regions of China) were collected from the Infectious Diseases Surveillance System of Chinese Disease Prevention and Control Information System from 2018 to 2023. The trends in reported incidence rates of gonorrhea in China were analyzed using the Joinpoint regression model. Global spatial autocorrelation analysis with the Moran's index and global G-statistic, as well as local spatial autocorrelation analysis, were employed to explore the clustering patterns and hotspot regions of gonorrhea at the county level. In the spatiotemporal scanning analysis, a Poisson distribution model was employed to identify clusters of gonorrhea cases.Results:The reported incidence rates of gonorrhea in China decreased from 9.59 per 100 000 in 2018 to 7.35 per 100 000 in 2023, with an average annual percent change of -4.9%, but this decreasing trend was not statistically significant ( P = 0.11). The reported incidence rates of gonorrhea at the county level in China exhibited a significant positive global spatial autocorrelation, with the global Moran's indices ranging from 0.39 to 0.60 (all P < 0.001) ; the Getis-Ord general G test statistic Z (G) values were all greater than 1.96, indicating a high-value clustering pattern of gonorrhea cases. The local spatial autocorrelation analysis showed that hotspot regions were predominantly distributed in southeastern coastal areas and southwestern China. A total of 70 clusters were identified through the spatiotemporal scanning analysis, and mainly located in southeastern coastal areas and southwestern China. Conclusions:In recent 6 years, the overall reported incidence rates of gonorrhea in China showed a fluctuating decline; there was a significant spatiotemporal clustering characteristic with regard to gonorrhea epidemic at the county level in China, and the hotspot regions were basically consistent with the spatiotemporal clusters, which were mainly distributed in southeastern coastal areas and southwestern China. Further investigation into the causes and precise prevention and control measures are needed.

  Objective  Mohr-Tranebjaerg syndrome (MTS) is a rare X-linked neurodegenerative disorder which usually involving hearing impairment, gradual dystonia, and other symptoms. In this study, we perform analyzed the genetic makeup of a family with this rare Mohr-Tranebjaerg syndrome.  Methods  We collected the clinical data of the family, did the whole exome sequencing on the proband Ⅲ6 with a rare mutation, and verified the mutation in another affected family member Ⅲ5 and unaffected members Ⅰ1, Ⅰ2, Ⅱ1, Ⅱ5, Ⅱ7, Ⅱ8, Ⅲ7.  Results  The patients in the family all showed early-onset deafness. More than a couple of affected male members have dystonia with/without mental disorders. Genetic testing results showed the proband Ⅲ6 had a c.133-2delA in TIMM8A (NM_ 004085.3, DDP1), highly likely pathogenic(LP). This variation was detected in affected Ⅲ5 as well as the unaffected females Ⅰ1, Ⅱ5, Ⅱ7.  Conclusions  MTS caused by the rare TIMM8A mutation, the molecular etiology of the family with this rare disease, is highly consistent with the clinical manifestations and segregation. Other than the deafness, other symptoms varied among the affected family members. Genetic diagnosis for such X-linked diseases can also identify female heterozygotes. Genetic and reproduction counseling can help families in the family planning.

Objective To investigate the clinical efficacy and related adverse reactions of the combination of camrelizumab with anlotinib as the third-line therapy on advanced non-small cell lung cancer. Methods We retrospectively analyzed the clinical data of 84 patients with advanced non-small cell lung cancer after second-line treatment. According to different treatment methods, 44 patients who received camrelizumab combined with anlotinib were included in the observation group, and 40 patients who received anlotinib alone were included in the control group. The PFS, ORR, DCR and incidence of adverse reactions were analyzed and compared between the two groups. Results The median PFS of the observation group was longer than that of the control group (7.0 vs. 5.6 months, P=0.001). No statistically significant difference was observed in ORR, DCR, the incidence of adverse reactions or the incidence of adverse reactions above grade 3 between two groups (all P > 0.05). Conclusion The clinical efficacy of camrelizumab combined with anlotinib as third-line therapy on advanced non-small cell lung cancer is better than anlotinib alone, and the safety is good.

OBJECTIVE To explore the improvement mechanism of Modified sanhuang ointment on anal ulcers and swelling model rats. METHODS The anal ulcer model of the rat was induced by using glacial acetic acid； the effects of Modified sanhuang ointment low-dose， medium-dose and high-dose groups （185， 370， 740 mg/kg）， western medicine positive control group （Compound carraghenates cream， 1 g/kg） and TCM positive control group （Mayinglong shexiang zhichuang ointments， 1 g/kg） on body weight， area of anal ulcer， grade of anal ulcer were investigated. The other groups of rats were used to induce rectal swelling models with croton oil； the effects of Modified sanhuang ointment low-dose， medium-dose and high-dose groups （185， 370， 740 mg/kg）， western medicine positive control group （Compound carraghenates cream， 1 g/kg） and TCM positive control group （Mayinglong shexiang zhichuang ointments， 1 g/kg） on the rate of rectal and anal swelling， serum contents of inflammatory factors [interleukin 2 （IL-2）， IL-4， tumor necrosis factor （TNF-α）]， pathological morphology of rectal tissue， the expression of transient receptor potential channel V1 （TRPV1） and substance P in rectal tissue and rectal vascular permeability were investigated. RESULTS In Modified sanhuang ointment， the increase in body weight was enhanced， and the area of anal ulcers， as well as the grade of anal ulcers in rats with anal ulcer models， were reduced to varying degrees； rectal tissue damage in rectal swelling model rats was improved； the rate of rectal and anal swelling， the serum contents of inflammatory factors， the expressions of TRPV1 and substance P in rectal tissue， and rectal vascular permeability were all decreased （P＜0.05 or P＜0.01）. The effect of Modified sanhuang ointment was better than that of western medicine positive control and TCM positive control.Modified sanhuang ointment can improve anal ulcers and swelling in rats by reducing the release of inflammatory factors， inhibiting the expression of TRPV1 and substance P.