Osteoarthritis （OA） is a common chronic， highly prevalent， painful， and disabling degenerative joint disease. It has imposed a heavy burden on social healthcare and patients' psychology and economy due to its clinical symptoms such as impaired joint mobility and severe joint pain and the immature therapies. Studies have shown that OA is closely associated with articular cartilage dysfunction， synthesis and degradation disorders of chondrocyte extracellular matrix （ECM）， and joint inflammation. Moderate autophagy can restore the function of damaged chondrocytes， regulate chondrocyte apoptosis， and promote the synthesis and metabolism of ECM to alleviate the inflammation of joints and delay the onset and progression of OA. According to the clinical symptoms， OA can be classified into the category of impediment in traditional Chinese medicine. With the theories of holistic conception， treatment based on syndrome differentiation， and individualised diagnosis and treatment， traditional Chinese medicine has demonstrated definite effects in the treatment of OA in thousands of years of practice. Moreover， traditional Chinese medicine causes mild adverse reactions， and the patients have high tolerance and acceptance. This paper briefly explains the roles of autophagy and the related regulatory proteins， such as Unc-51-like autophagy-activated kinase 1 （ULK1）， Beclin-1， and microtubule-associated protein light chain 3 （LC3）， and details the latest research achievements in the prevention and control of OA by traditional Chinese medicines and its related markers via the regulation of autophagy， so as to provide a idea for the in-depth research in this field and the clinical application of traditional Chinese medicine in preventing and treating OA.

Objective:To investigate the efficacy of immune checkpoint inhibitor maintenance therapy after radical radiotherapy and chemotherapy for stage Ⅲ-ⅣA esophageal squamous cell carcinoma (ESCC) in the real world.Methods:The clinical data of 65 patients with stage Ⅲ-ⅣA ESCC treated by radical radiotherapy and chemotherapy from January 1, 2018 to December 31, 2022 in Hefei Cancer Hospital, Chinese Academy of Sciences were retrospectively analyzed. According to whether to undergo immune checkpoint inhibitor maintenance therapy after radical radiotherapy and chemotherapy, the patients were divided into a control group ( n=29) and an immune maintenance therapy group ( n=36) . The objective response rate (ORR) , progression-free survival (PFS) , and overall survival (OS) between the two groups were compared. Kaplan-Meier method was used to draw the survival curve accompanied with log-rank test. Cox regression model was used to conduct both univariate and multivariate analyses. Results:The ORR was 34.5% (10/29) in the control group and 61.1% (22/36) in the immune maintenance therapy group, with a statistically significant difference ( χ2=4.56, P=0.032) . The median PFS of control group and immune maintenance therapy group were 7.2 and 17.9 months, respectively, with a statistically significant difference ( χ2=7.86, P=0.005) . The median OS was 14.1 and 27.8 months, respectively, with a statistically significant difference ( χ2=5.40, P=0.020) . Univariate analysis showed that, objective response ( HR=0.09, 95% CI: 0.03-0.28, P<0.001) and immune maintenance therapy ( HR=0.38, 95% CI: 0.17-0.88, P=0.024) were the influential factors of OS in ESCC patients treaded by radical chemoradiotherapy in stage Ⅲ-ⅣA. Multivariate analysis showed that, objective response ( HR=0.09, 95% CI: 0.03-0.29, P<0.001) and immune maintenance therapy ( HR=0.40, 95% CI: 0.17-0.92, P=0.032) were the independent influencing factors for OS in ESCC patients treaded by radical chemoracial therapy in stage Ⅲ-ⅣA. The incidence of adverse reactions was 22.22% (8/36) in the immune maintenance therapy group and 10.34% (3/29) in the control group, with no statistically significant difference ( χ2=1.61, P=0.204) . All the adverse reactions were grade 1-2, and the symptoms were relieved after symptomatic treatment. Conclusion:Maintenance therapy with immune checkpoint inhibitors after radical chemoradiotherapy of stage Ⅲ-ⅣA ESCC can significantly improve the prognosis of patients with good safety.

Objective To explore the inhibitory effect of saikosonin a(SSa)on pentylenetetrazol-induced acute epilepsy seizures in a mouse model of depression and explore the mechanism mediating this effect.Methods Male C57BL/6J mouse models of depression was established by oral administration of corticosterone via drinking water for 3 weeks,and acute epileptic seizures were induced by intraperitoneal injection of a single dose of pentylenetetrazole.The effect of intraperitoneal injection of SSa prior to the treatment on depressive symptoms and epileptic seizures were assessed using behavioral tests,epileptic seizure grading and hippocampal morphology observation.ELISA was used to detect blood corticosterone levels of the mice,and RT-qPCR was performed to detect the pro-and anti-inflammatory factors.Microglia activation in the mice was observed using immunofluorescence staining.Results The mouse model of corticosterone-induced depression showed body weight loss and obvious depressive behaviors with significantly increased serum corticosterone level(all P<0.05).Compared with those with pentylenetetrazole-induced epilepsy alone,the epileptic mice with comorbid depression showed significantly shorter latency of epileptic seizures,increased number,grade and duration of of seizures,reduced Nissl bodies in hippocampal CA1 and CA3 neurons,increased number of Iba1-positive cells,and significantly enhanced hippocampal expressions of IL-1β,IL-10,TNF-α and IFN-γ.Pretreatment of the epileptic mice with SSa significantly prolonged the latency of epileptic seizures,reduced the number,duration,and severity of seizures,increased the number of Nissl bodies,decreased the number of Iba1-positive cells,and reduced the expression levels of IL-1β,IL-10,TNF-α,and IFN-γ in the hippocampus(P<0.05).Conclusion Depressive state aggravates epileptic seizures,increases microglia activation,and elevates inflammation levels.SSA treatment can alleviate acute epileptic seizures in mouse models of depression possibly by suppressing microglia activation-mediated inflammation.

Rheumatoid arthritis is a common clinical autoimmune disease characterized by persistent synovitis and pannus formation. In late stage， irreversible destruction and deformation of bone and joint may occur. In this paper， the authors believe that kidney deficiency and essence deficiency is the core mechanism of rheumatoid arthritis bone destruction， and its disease evolution law is summarized as "marrow reduction， flesh flaccid， collaterals blocked". On the basis of modern medical understanding of bone destruction in rheumatoid arthritis， it is considered that the mechanism in Chinese medicine of "marrow reduction， flesh flaccid， collaterals blocked" ultimately leads to bone destruction， is similar to that in the western medicine of abnormal differentiation of osteoclasts， high expression of nuclear factor-κB receptor activator of ligand， and abnormal expression of inflammatory factors. This point of view may provide a more comprehensive and scientific understanding of the key pathogenic mechanism of bone destruction in rheumatoid arthritis.

Objective:To explore the efficacy of consolidation chemotherapy after radical radiotherapy and chemotherapy in stage Ⅲ-ⅣA esophageal squamous cell carcinoma (ESCC) patients in the real world.Methods:The clinical data of 139 patients with stage Ⅲ-ⅣA ESCC who underwent radical radiotherapy and chemotherapy from January 1, 2018 to December 31, 2022 in Hefei Cancer Hospital, Chinese Academy of Sciences were retrospectively analyzed. Patients were divided into a control group ( n=85) and a consolidation chemotherapy group ( n=54) based on whether they underwent consolidation chemotherapy after radical radiotherapy and chemotherapy. The objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) between the two groups were compared. The Kaplan-Meier method was used to draw survival curves and log-rank tests were conducted. The Cox proportional risk model was used for univariate and multivariate analysis. Results:The ORR of the control group and the consolidation chemotherapy group were 44.71% (38/85) and 66.67% (36/54), respectively, with a statistically significant difference ( χ2=5.54, P=0.018) ; the DCR were 70.59% (60/85) and 87.04% (47/54), respectively, with a statistically significant difference ( χ2=5.04, P=0.025). The median PFS of the two groups of patients were 9.0 and 13.1 months, respectively, with a statistically significant difference ( χ2=12.74, P<0.001) ; the median OS were 15.0 and 20.6 months, respectively, with a statistically significant difference ( χ2=24.75, P<0.001). The median OS of ESCC patients in two subgroups of cT 3-4N 1-3M 0 were 16.0 and 30.8 months, respectively, with a statistically significant difference ( χ2=23.49, P<0.001). Univariate analysis showed that tumor length ( HR=1.57, 95% CI: 1.04-2.36, P=0.032), objective response ( HR=0.08, 95% CI: 0.04-0.17, P<0.001), and consolidation chemotherapy ( HR=0.32, 95% CI: 0.20-0.51, P<0.001) were all influencing factors for OS in ESCC patients undergoing radical radiotherapy and chemotherapy in stages Ⅲ-ⅣA. Multivariate analysis showed that tumor length ( HR=1.59, 95% CI: 1.05-2.43, P=0.030), objective response ( HR=0.05, 95% CI: 0.02-0.10, P<0.001), and consolidation chemotherapy ( HR=0.22, 95% CI: 0.13-0.36, P<0.001) were all independent influencing factors for OS in stage Ⅲ-ⅣA ESCC patients undergoing radiotherapy and chemotherapy. In terms of safety, the consolidation chemotherapy group experienced 7 adverse reactions mainly gastrointestinal reaction and leukopenia, including 5 cases of grade 1-2 and 2 cases of grade 3-4; 22 cases of adverse reactions occurred in the control group including 16 cases of grade 1-2 and 6 cases of grade 3-4 mainly including neutropenia, thrombocytopenia, anemia and digestive tract reaction. The incidence rates of adverse reactions in the two groups were 12.96% (7/54) and 25.88% (22/85), respectively, with no statistically significant difference ( χ2=3.34, P=0.068) . Conclusion:After radical radiotherapy and chemotherapy, consolidation chemotherapy can significantly improve the prognosis of stage Ⅲ-ⅣA ESCC patients, and the overall adverse reactions are controllable.

Objective To explore the inhibitory effect of saikosonin a(SSa)on pentylenetetrazol-induced acute epilepsy seizures in a mouse model of depression and explore the mechanism mediating this effect.Methods Male C57BL/6J mouse models of depression was established by oral administration of corticosterone via drinking water for 3 weeks,and acute epileptic seizures were induced by intraperitoneal injection of a single dose of pentylenetetrazole.The effect of intraperitoneal injection of SSa prior to the treatment on depressive symptoms and epileptic seizures were assessed using behavioral tests,epileptic seizure grading and hippocampal morphology observation.ELISA was used to detect blood corticosterone levels of the mice,and RT-qPCR was performed to detect the pro-and anti-inflammatory factors.Microglia activation in the mice was observed using immunofluorescence staining.Results The mouse model of corticosterone-induced depression showed body weight loss and obvious depressive behaviors with significantly increased serum corticosterone level(all P<0.05).Compared with those with pentylenetetrazole-induced epilepsy alone,the epileptic mice with comorbid depression showed significantly shorter latency of epileptic seizures,increased number,grade and duration of of seizures,reduced Nissl bodies in hippocampal CA1 and CA3 neurons,increased number of Iba1-positive cells,and significantly enhanced hippocampal expressions of IL-1β,IL-10,TNF-α and IFN-γ.Pretreatment of the epileptic mice with SSa significantly prolonged the latency of epileptic seizures,reduced the number,duration,and severity of seizures,increased the number of Nissl bodies,decreased the number of Iba1-positive cells,and reduced the expression levels of IL-1β,IL-10,TNF-α,and IFN-γ in the hippocampus(P<0.05).Conclusion Depressive state aggravates epileptic seizures,increases microglia activation,and elevates inflammation levels.SSA treatment can alleviate acute epileptic seizures in mouse models of depression possibly by suppressing microglia activation-mediated inflammation.

Mutations of the X-linked methyl-CpG-binding protein 2 (MECP2) gene in humans are responsible for most cases of Rett syndrome (RTT), an X-linked progressive neurological disorder. While genome-wide screens in clinical trials have revealed several putative RTT-associated mutations in MECP2, their causal relevance regarding the functional regulation of MeCP2 at the etiologic sites at the protein level requires more evidence. In this study, we demonstrated that MeCP2 was dynamically modified by O-linked-β-N-acetylglucosamine (O-GlcNAc) at threonine 203 (T203), an etiologic site in RTT patients. Disruption of the O-GlcNAcylation of MeCP2 specifically at T203 impaired dendrite development and spine maturation in cultured hippocampal neurons, and disrupted neuronal migration, dendritic spine morphogenesis, and caused dysfunction of synaptic transmission in the developing and juvenile mouse cerebral cortex. Mechanistically, genetic disruption of O-GlcNAcylation at T203 on MeCP2 decreased the neuronal activity-induced induction of Bdnf transcription. Our study highlights the critical role of MeCP2 T203 O-GlcNAcylation in neural development and synaptic transmission potentially via brain-derived neurotrophic factor.
Animals ; Humans ; Methyl-CpG-Binding Protein 2/metabolism* ; Mice ; Neurodevelopmental Disorders/genetics* ; Rett Syndrome/genetics* ; Synaptic Transmission ; Threonine

Objective:To explore the characteristics and influencing factors of blood carnitine metabolism in premature infants.Methods:A retrospective analysis of 37 037 neonates with negative results of genetic metabolic disease screening at Guangxi Newborn Disease Screening Center from 2018 to 2021, of which 34 517 normal full-term infants were the control group and 2 520 preterm infants were the research group.According to gestational age, the preterm infants were further divided into three groups: extremely preterm group( n=232), moderately preterm group( n=324)and late preterm group( n=1 964). According to birth weight, they were divided into three groups: very low birth weight group( n=188), low birth weight group( n=1 276)and normal birth weight group( n=1 056). According to blood collection time, they were divided into three groups: 3~7 days group( n=1 990), 8~14 days group( n=342) and 15~28 days group( n=188). Tandem mass spectrometry was used to detect the levels of 31 carnitines in dried blood spots and analyze the differences in the levels of metabolic indicators in each group. Results:Carnitine levels in preterm infants are most affected by gestational age.Adjusting the physiological and pathological conditions of premature infants and other related factors, grouped by gestational age, there were differences in the levels of 31 carnitines among the groups(all P<0.05), the smaller the gestational age, the greater the difference in carnitine levels; grouped by blood collection time, there were statistically significant differences in carnitine levels between preterm infants with different blood collection age groups and full-term 3~7 days groups(all P<0.05), and showing age-related; there are differences among 31 carnitines grouped by body weight(all P<0.05), the smaller the body weight, the greater the difference in carnitine levels.Combined with the analysis of gestational age, birth weight and blood collection date, 17 indicators including C0, C2, C3, C4, C6DC, C10, C10∶1, C12, C12∶1, C14, C14∶1, C14OH, C16, C16∶1, C18, C18∶1 and C18∶1OH are important biomarkers of carnitine metabolism in premature infants. Conclusion:Carnitine in premature newborns has different metabolic differences at different gestational ages, birth weights and blood collection ages, which provides a strong basis for establishing reference standards and interpretation of preterm infants in the laboratory in this region, and provides reasonable and effective early diagnosis and treatment for clinical practice.Meanwhile, it provides an optimized program for timely detection of carnitine deficiency and carnitine supplementation to improve nutrition of premature infants.

Osteoporotic thoracolumbar fracture in the elderly will seriously reduce their quality of life and life expectancy. For osteoporotic thoracolumbar fracture in the elderly, spinal reconstruction is necessary, which should comprehensively consider factors such as the physical condition, fracture type, clinical characteristics and osteoporosis degree. While there lacks relevant clinical norms or guidelines on selection of spinal reconstruction strategies. In order to standardize the concept of spinal reconstruction for osteoporotic thoracolumbar fracture in the elderly, based on the principles of scientificity, practicality and progressiveness, the authors formulated the Clinical guideline for spinal reconstruction of osteoporotic thoracolumbar fracture in elderly patients ( version 2022), in which suggestions based on evidence of evidence-based medicine were put forward upon 10 important issues related to the fracture classification, non-operative treatment strategies and surgical treatment strategies in spinal reconstruction after osteoporosis thoracolumbar fracture in the elderly, hoping to provide a reference for clinical treatment.

Objective:To investigate the value of CD4/CD8 ratio and total B lymphocytes before radiotherapy in predicting the occurrence of radiation pneumonitis (RP) in patients with esophageal cancer and lung cancer.Methods:The clinicopathological data of 28 patients with esophageal and 16 patients with lung cancer undergoing radiotherapy from April 2018 to March 2020 in Hefei Cancer Hospital, Chinese Academy of Sciences were retrospectively analyzed, and the patients were divided into RP group ( n=16) and non-RP group ( n=28) according to whether RP occurred during and after treatment. The CD4/CD8 ratio and total B lymphocytes before radiotherapy between the two groups, and the CD4/CD8 ratio and total B lymphocytes before and after radiotherapy in the RP group were compared. Receiver operating characteristic curve was used to analyze the value of CD4/CD8 ratio and total B lymphocytes before radiotherapy in predicting RP. Results:The CD4/CD8 ratio before radiotherapy in the RP group was significantly lower than that in the non-RP group (0.993±0.179 vs. 1.708±0.170), with a statistically significant difference ( t=2.706, P=0.009); the total B lymphocytes in the RP group was significantly lower than that in non-RP group [(4.409±0.823)% vs. (8.153±1.017)%], with a statistically significant difference ( t=0.986, P=0.015). The CD4/CD8 ratio in the RP group was lower than that before radiotherapy when RP occurred (0.785±0.167 vs. 0.993±0.179), with no statistically significant difference ( t=1.376, P=0.189). The total B lymphocytes in the RP group was lower than that before radiotherapy when RP occurred [(3.487±1.018)% vs. (4.409±0.823)%], with no statistically significant difference ( t=0.804, P=0.433). The critical values of CD4/CD8 ratio and total B lymphocytes predicted RP were 0.580 and 0.357, respectively. The areas under the curve (AUC) of CD4/CD8 for predicting RP was 0.802 (95% CI: 0.653-0.932), the sensitivity was 89.29%, and the specificity was 68.75%. The AUC of total B lymphocytes for predicting RP was 0.694 (95% CI: 0.483-0.814), the sensitivity was 85.71%, and the specificity was 50.00%. The AUC of the two combined diagnostic method for RP was 0.834 (95% CI: 0.697-0.932), the sensitivity and specificity were 81.25% and 89.29%. AUC of the two combined tests was significantly higher than that of the single test, with statistically significant differences ( Z=1.115, P=0.046; Z=1.992, P=0.026). Conclusion:The CD4/CD8 ratio and total B lymphocytes in the RP group are lower than those in the non-RP group. The CD4/CD8 ratio and total B lymphocytes in the serum are of great significance in predicting the occurrence of RP in patients with malignant tumors receiving chest radiotherapy.