Local anesthetics (LAs), such as articaine (AT), exhibit limited efficacy in inflammatory environments, which constitutes a significant limitation in their clinical application within oral medicine. In our prior research, we developed AT-17, which demonstrated effective properties in chronic inflammatory conditions and appears to function as a novel oral LA that could address this challenge. In the present study, we further elucidated the beneficial effects of AT-17 in acute inflammation, particularly in oral acute inflammation, where mitochondrial-related apoptosis played a crucial role. Our findings indicated that AT-17 effectively inhibited lipopolysaccharide (LPS)-induced nerve cell apoptosis by ameliorating mitochondrial dysfunction in vitro. This process involved the inhibition of mitochondrial reactive oxygen species (mtROS) production and the subsequent activation of the NRF2 pathway. Most notably, improvements in mitochondria-related apoptosis were key contributors to AT-17's inhibition of voltage-gated sodium channels. Additionally, AT-17 was shown to reduce mtROS production in nerve cells through the Na⁺/NCLX/ETC signaling axis. In conclusion, we have developed a novel local anesthetic that exhibits pronounced anesthetic functionality under inflammatory conditions by enhancing mitochondria-related apoptosis. This advancement holds considerable promise for future drug development and deepening our understanding of the underlying mechanisms of action.

OBJECTIVE: To explore the epidemiological characteristics of knee osteoarthritis (KOA) among the elderly in the community, and its correlation with bone mass loss. METHODS: A cross-sectional study was conducted on elderly community population over 50 year old from 12 community health service centers in Zhejiang province. Their gender, age, body mass index (BMI), T value and KOA diagnosis were collected using face to face questionnaire survey. Univariate regression was used to analyze the influence of age, gender, BMI and bone loss on KOA. Logistic multivariate regression model was used to analyze the independent effect of bone mass loss on KOA. RESULTS: Among 4 173 subjects in this study, 1 710 of them were had a KOA. The prevalence rate was 40.9%. The mean age, the proportion of females and the mean BMI in KOA patients were (65.5±3.8) years old, 67.7%(1 158/1 710) and(24.59±1.28) kg·m^-2, respectively, which were significantly higher than (58.5±3.2) years old, 51.3%(1 263/2 463), and (23.48±1.25) kg·m^-2 in non-KOA subjects (P<0.001). In the population aged from 60 to 69 years old, the influence of osteopenia and osteoporosis on the prevalence of KOA was[OR=1.21, 95%CI(1.00, 1.46), P=0.053 2], [OR=1.42, 95%CI(1.14, 1.78), P=0.002 2]. The influence of male and female osteoporosis on the prevalence of KOA was [OR=1.52, 95%CI(1.16, 1.99), P=0.002 7] and [OR=1.87, 95%CI(1.51, 2.32), P<0.000 1], respectively. In the population of 24 kg·m^-2≤BMI<28 kg·m^-2, the influence of osteopenia and osteoporosis on the prevalence of KOA was [OR=1.47, 95%CI(1.21, 1.80), P=0.000 1], [OR=2.69, 95%CI(2.11, 3.42), P<0.000 1], respectively. After controlling the confounding factors of age, gender and BMI, compared with people with normal bone mass, the effect of osteopenia on the prevalence of KOA was [OR=1.34, 95%CI(1.08, 1.67), P=0.009 2], and the effect of osteoporosis on the prevalence of KOA was [OR=1.38, 95%CI(1.06, 1.79), P=0.017 9]. CONCLUSION Elderly overweight women are more likely to develop KOA. Bone mass loss is an independent risk factor for KOA, which will significantly increase the prevalence of KOA in people overweight or aged 60 to 69 years old.
Humans ; Female ; Male ; Aged ; Osteoarthritis, Knee/etiology* ; Middle Aged ; Cross-Sectional Studies ; Bone Density ; Aged, 80 and over ; Incidence ; Body Mass Index ; China/epidemiology* ; Osteoporosis/epidemiology*

Objective:To observe the efficacy and safety of polatuzumab vedotin(pola)combined with chemotherapy in the treatment of relapsed and refractory diffuse large B-cell lymphoma(R/R DLBCL).Methods:A total of 23 patients with R/R DLBCL treated at the First Affiliated Hospital of Zhejiang University and its Liangzhu Branch from April 2023 to March 2024 were retrospectively collected.All patients were treated with pola combined with chemotherapy regimens such as BR,R-GDP,R-CHOP,or other regimens.Results:All 23 patients were evaluable for efficacy,with 10 achieving complete response(CR),7 partial response(PR),3 stable disease(SD),and 3 progressive disease(PD).The most common adverse events included myelosuppression,fever,and pulmonary infection.No severe adverse events resulted in drug withdrawal.Conclusion:Pola combined with chemotherapy demonstrates promising efficacy and a favorable safety profile in the treatment of R/R DLBCL.

This study was aimed at identifying the pathogenic bacteria responsible for the death of a young tiger at the Fujian Meihua Mountain South China Tiger Breeding Research Institute.Tissue samples from the lungs,liver,and intestines of the deceased tiger were collected,and the bacteria were cultured inasterile environment.The bacterial strains were characterized according to their morphological and molecular biological properties,including assessment of virulence genes and antibiotic resistance genes,mouse lethality tests,and antibiotic susceptibility evaluations.A predominant bacterial strain isolated from the liver of the deceased tiger was identified as enterotoxigenic Escherichia coli(ETEC)strain Tiger22513F.Phylogenetic analysis of the 16S rRNA gene revealed that the Tiger22513F strain exhibited close genetic similarity to the reference strain ETEC(MF919609.1),with 99.9%nucleotide similarity,and resided on the same evolutionary branch.The Tiger22513F strain contained 11 antibiotic resistance genes(tetA,sul1,sul3,cmlA,floR,blaTEM,blaSHV,blaCMY-2,qnrA,qnrS,and qnrD)along with five virulence genes(VT1,fyuA,tsh,iucD,and ST).Mouse lethality tests indicated significant pathogenicity toward mice,affecting primarily the lungs,liver,and intestines.Antibiotic susceptibility testing demonstrated that this strain exhibited resistance to various classes of beta-lactam antibiotics,as well as quinolones and aminoglycosides.This investigation successfully isolated a multi-drug resistant enterotoxigenic Escherichia coli strain with pronounced pathogenicity from the liver of a deceased tiger;thus providing valuable scientific insights for clinical diagnosis,as well as prevention and control measures,against ETEC infections in South China tigers.

Objective:To observe the efficacy and safety of polatuzumab vedotin(pola)combined with chemotherapy in the treatment of relapsed and refractory diffuse large B-cell lymphoma(R/R DLBCL).Methods:A total of 23 patients with R/R DLBCL treated at the First Affiliated Hospital of Zhejiang University and its Liangzhu Branch from April 2023 to March 2024 were retrospectively collected.All patients were treated with pola combined with chemotherapy regimens such as BR,R-GDP,R-CHOP,or other regimens.Results:All 23 patients were evaluable for efficacy,with 10 achieving complete response(CR),7 partial response(PR),3 stable disease(SD),and 3 progressive disease(PD).The most common adverse events included myelosuppression,fever,and pulmonary infection.No severe adverse events resulted in drug withdrawal.Conclusion:Pola combined with chemotherapy demonstrates promising efficacy and a favorable safety profile in the treatment of R/R DLBCL.

Objective:To investigate the magnetic resonance imaging (MRI) features of non-midline atypical medulloblastoma (MB) in children and analyze the causes of misdiagnosis, so as to improve the understanding and diagnosis of MB.Methods:The clinical and imaging data of 12 cases with non-midline atypical MB confirmed by pathology in Hunan Children′s Hospital from September 2018 to August 2023 were retrospectively analyzed. 12 cases underwent MRI plain scan, 11 cases underwent enhanced scan, and 10 cases underwent diffusion weighted imaging (DWI) and magnetic sensitivity weighted imaging (SWI). The location, morphology, peritumoral edema, size, signal characteristics (cystic lesion or hemorrhage), diffusion and enhancement of the tumor were observed, and the causes of misdiagnosis were analyzed.Results:Among the 12 cases, 9 cases were single, 4 cases were located in the cerebellar hemisphere, 2 cases were in the cerebellopontine angle (CPA), 2 cases were in the brain stem and CPA, and 1 case was in the left parietal lobe. There were 3 cases of multiple lesions, 1 case was located in the right pontine arm and cerebellar hemisphere (2 masses), 1 case was multiple lesions in bilateral cerebellar hemisphere, and 1 case was multiple nodular lesions in the cerebellar vermis mass and left cerebellar hemisphere. 6 cases were irregular in shape and 6 cases were quasi-circular. There were 3 cases without cystic change and 9 cases with varying degrees of cystic change (5 with large cystic change and 4 with small cystic change). 3 cases of hemorrhage, no calcification, 10 cases of DWI showed varying degrees of limited diffusion; 11 cases of enhanced scanning showed mild to obvious enhancement; There were 2 cases without peritumoral edema and 10 cases with mild to moderate peritumoral edema. There were 11 cases with supratentorial hydrocephalus and interstitial cerebral edema, and 1 case without hydrocephalus. 5 cases complicated with subtonsillar hernia; 9 cases were misdiagnosed before operation. Among them, 3 cases were misdiagnosed as high-grade glioma, 3 as low-grade glioma (1 of which was diagnosed as hair-cell astrocytoma), 2 as ependymoma, and 1 as atypical teratoma/rhabdomyoma.Conclusions:The MRI manifestations of non-midline atypical MB in children are varied. Combined with the location of the disease, age and focal signal characteristics, non-midline atypical MB can be included in the diagnostic range after the exclusion diagnosis, which can improve the preoperative diagnosis accuracy of this disease.

This study was aimed at identifying the pathogenic bacteria responsible for the death of a young tiger at the Fujian Meihua Mountain South China Tiger Breeding Research Institute.Tissue samples from the lungs,liver,and intestines of the deceased tiger were collected,and the bacteria were cultured inasterile environment.The bacterial strains were characterized according to their morphological and molecular biological properties,including assessment of virulence genes and antibiotic resistance genes,mouse lethality tests,and antibiotic susceptibility evaluations.A predominant bacterial strain isolated from the liver of the deceased tiger was identified as enterotoxigenic Escherichia coli(ETEC)strain Tiger22513F.Phylogenetic analysis of the 16S rRNA gene revealed that the Tiger22513F strain exhibited close genetic similarity to the reference strain ETEC(MF919609.1),with 99.9%nucleotide similarity,and resided on the same evolutionary branch.The Tiger22513F strain contained 11 antibiotic resistance genes(tetA,sul1,sul3,cmlA,floR,blaTEM,blaSHV,blaCMY-2,qnrA,qnrS,and qnrD)along with five virulence genes(VT1,fyuA,tsh,iucD,and ST).Mouse lethality tests indicated significant pathogenicity toward mice,affecting primarily the lungs,liver,and intestines.Antibiotic susceptibility testing demonstrated that this strain exhibited resistance to various classes of beta-lactam antibiotics,as well as quinolones and aminoglycosides.This investigation successfully isolated a multi-drug resistant enterotoxigenic Escherichia coli strain with pronounced pathogenicity from the liver of a deceased tiger;thus providing valuable scientific insights for clinical diagnosis,as well as prevention and control measures,against ETEC infections in South China tigers.

Objective:To investigate the magnetic resonance imaging (MRI) features of non-midline atypical medulloblastoma (MB) in children and analyze the causes of misdiagnosis, so as to improve the understanding and diagnosis of MB.Methods:The clinical and imaging data of 12 cases with non-midline atypical MB confirmed by pathology in Hunan Children′s Hospital from September 2018 to August 2023 were retrospectively analyzed. 12 cases underwent MRI plain scan, 11 cases underwent enhanced scan, and 10 cases underwent diffusion weighted imaging (DWI) and magnetic sensitivity weighted imaging (SWI). The location, morphology, peritumoral edema, size, signal characteristics (cystic lesion or hemorrhage), diffusion and enhancement of the tumor were observed, and the causes of misdiagnosis were analyzed.Results:Among the 12 cases, 9 cases were single, 4 cases were located in the cerebellar hemisphere, 2 cases were in the cerebellopontine angle (CPA), 2 cases were in the brain stem and CPA, and 1 case was in the left parietal lobe. There were 3 cases of multiple lesions, 1 case was located in the right pontine arm and cerebellar hemisphere (2 masses), 1 case was multiple lesions in bilateral cerebellar hemisphere, and 1 case was multiple nodular lesions in the cerebellar vermis mass and left cerebellar hemisphere. 6 cases were irregular in shape and 6 cases were quasi-circular. There were 3 cases without cystic change and 9 cases with varying degrees of cystic change (5 with large cystic change and 4 with small cystic change). 3 cases of hemorrhage, no calcification, 10 cases of DWI showed varying degrees of limited diffusion; 11 cases of enhanced scanning showed mild to obvious enhancement; There were 2 cases without peritumoral edema and 10 cases with mild to moderate peritumoral edema. There were 11 cases with supratentorial hydrocephalus and interstitial cerebral edema, and 1 case without hydrocephalus. 5 cases complicated with subtonsillar hernia; 9 cases were misdiagnosed before operation. Among them, 3 cases were misdiagnosed as high-grade glioma, 3 as low-grade glioma (1 of which was diagnosed as hair-cell astrocytoma), 2 as ependymoma, and 1 as atypical teratoma/rhabdomyoma.Conclusions:The MRI manifestations of non-midline atypical MB in children are varied. Combined with the location of the disease, age and focal signal characteristics, non-midline atypical MB can be included in the diagnostic range after the exclusion diagnosis, which can improve the preoperative diagnosis accuracy of this disease.

Parabacteroides distasonis is a gram-negative bacterium initially isolated from a clinical specimen in the 1930s. The strain was re-classified to form the new genus Parabacteroides in 2006. P. distasonis can regulate intestinal barrier function and plays a key role in immune response and metabolic regulation of bodies. Traditional Chinese medicine(TCM) is closely related to the intestinal microbiota. Polysaccharides, saponins, and other ingredients of TCM can treat diseases by interacting with P. distasonis, but the specific mechanisms underlying these processes are still unclear, requiring further exploration. This study reviewed the roles and related mechanisms of P. distasonis in inflammatory-immune diseases, metabolic diseases, cardiovascular disease, neuropsychiatric diseases, cancer, and other diseases and summarized the relevant research results of TCM to prevent and treat diseases by regulating P. distasonis. This study provides a reference for subsequent exploration of P. distasonis and research on the interaction between TCM and intestinal microbiota.
Humans ; Gastrointestinal Microbiome/drug effects* ; Medicine, Chinese Traditional ; Animals ; Bacteroidetes ; Drugs, Chinese Herbal/pharmacology*

Glioma is the most common malignancy of the central nervous system, originating mainly from glial cells. Because of its highly aggressive nature, glioma has one of the highest rates of death among all types of cancer. Therefore, it is very important to develop new therapeutic approaches and drugs for glioma treatment. Instead of activate the telomerase, approximately 30% of glioma use alternative lenthening of telomere (ALT) to maintain telomere length. The mechanism of ALT development is poorly understood, however, some genetic mutations have been reported to induce the development of ALT glioma, such as ATRX, IDH1, p53, etc. The lack of ALT glioma cell lines and preclinical ALT glioma models has limited the mechanistic studies of ALT glioma. Therefore, this review listed ALT glioma cell lines that derived from primary culture or gene editing in the last decade, as well as the xenografted animal models established by ALT glioma cell lines, and discussed the role and significance these cell and animal models play in preclinical studies.