Guided by the theory of latent pathogens， it is believed that the basic pathogenesis of adult-onset Still's disease is the latent pathogens in the deep yin level. The onset of the disease is fundamentally characterized by the deficiency of both qi and yin as the root， with dampness， heat， phlegm， and blood stasis as the branch， which triggered by intruding pathogens activate the latent pathogens in yin level. The treatment focuses on nourishing yin and dispersing heat as the key therapeutic method. It is proposed that clearing and resolving dampness-heat， expelling pathogens outward， dispersing the latent pathogens， reinforcing healthy qi and consolidating the root， boosting qi and nourishing yin as treatment idea. In clinic， Qinghao Biejia Decoction （青蒿鳖甲汤） could be used as the basic formula， and modified with characteristic herb pairs such as Qinghao （Artemisia annua） - Digupi （Lycium chinense） to enrich yin and clear heat， and enforce the power of clearing deficient heat； Biejia （Lawsonia inermis） - Xuchangqing （Vincetoxicum mukdenense） to enrich yin and activate blood， unblock the collaterals and dissipate masses； Duhuo （Angelica biserrata） - Mudanpi （Paeonia × suffruticosa） to dispel wind and activate blood， resolve dampness and unblock the collaterals， so as to clear and warm simultaneously， and regulate qi and blood at the same time； and Chuanshanlong （Dioscorea nipponica） - Difuzi （Bassia scoparia） to dissolve stasis and dispel phlegm， explore and dispel latent pathogens.

Objective:To discuss the clinical characteristics of autosomal recessive spinocerebellar ataxia type 16 patients caused by STUB1 gene mutation, in order to improve the clinical doctors′ understanding of the disease. Methods:The clinical manifestations, auxiliary examinations and genetic testing of 1 autosomal recessive spinocerebellar ataxia type 16 patient caused by STUB1 gene variants diagnosed in Qilu Hospital of Shandong University in May 2022 were collected, and the relevant literature was reviewed to summarize the clinical and genetic characteristics of this type of disease. Results:The proband was a 35-year-old male presenting with unsteady walk and dysarthria. Magnetic resonance imaging showed cerebellar atrophy. Next generation sequencing revealed compound heterozygous c.322dupG (p.Glu108Glyfs *4) and c.433A>C (p.Lys145Gln) variants in the STUB1 gene (according to the transcript NM_005861.4), and the c.322dupG (p.Glu108Glyfs *4) variant was a novel variant. Pedigree verification revealed the 2 variants were respectively inherited from the proband′s healthy parents. A total of 12 foreign literatures reported 32 autosomal recessive spinocerebellar ataxia type 16 patients. The main clinical manifestations were ataxia, dysarthria and tendon hyperreflexia. Besides, nystagmus, spasticity, action tremors, and myoclonus can be present. Magnetic resonance imaging predominantly showed cerebellar atrophy. Conclusions:The patient with autosomal recessive spinocerebellar ataxia type 16 caused by STUB1 gene variant is rare in China. The main clinical manifestation is cerebellar ataxia, and brain imaging reveals remarkable cerebellar atrophy. Genetic testing is helpful for definite diagnosis.

Objective To investigate whether levosimendan can inhibit the apoptosis of C2C12 cells induced by lipopolysaccharide(LPS)through the PTEN/Akt pathway.Methods C2C12 cells were randomly divided into four groups:blank control group,control group comprising cells treated with levosimendan only,LPS-treated group,and a group comprising cells pretreated with levosimendan for 24 h a subsequently treated with LPS for 48 h.The survival rate of C2C12 cells was determined via the CCK-8 method,and cell apoptosis was assessed via Hoechst 33342 staining.The mRNA and protein expression levels of PTEN/Akt pathway components were evaluated via RT-qPCR and Western blotting,respectively.C2C12 cells were also transfected with siRNA to knockdown the PTEN gene,and the effect on the protein expression of apoptotic pathway components was determined.Results Levosimendan increased the survival rate and decreased the apoptosis rate of C2C12 cells after LPS treatment.PTEN gene expression was inhibited by siRNA and the mRNA and protein levels of PTEN/Akt signaling pathway components changed correspondingly.Furthermore,the apoptosis rate of C2C12 cells decreased.Conclusion Levosimendan can inhibit LPS-induced C2C12 cell apoptosis via the PTEN/Akt pathway.

Objective Pulmonary oxygen poisoning resulting from hyperbaric oxygen,frequently occurs in specialized operations,without any current effective prevention or treatment measures.To elucidate the impact and mechanism of neostigmine(NEO)in combination with anisodamine(ANI)(neoscopolamine)on pulmonary oxygen toxicity.Methods The animal model of pulmonary oxygen poisoning was established.C57BL/6 mice were exposed to 2.5 ATA 99.9%oxygen for 6 h.The control group mice were injected with normal saline ip,while the treatment group mice received injections of ANI(25 mg/kg,ip)and NEO(50 μg/kg,ip).Lung tissues were collected and stained with HE to observe any pathological injuries after exposure.Evans blue stain was utilized to identify lung permeability,wet/dry lung ratio,and protein concentration in the bronchoalveolar lavage fluid(BALF)to assess the lung injury's severity.The modifications in inflammatory factors,oxidative stress indicators,and iron content in lung tissue were assessed.Results The results showed that the 2.5 ATA 99.9%oxygen-exposed group experienced a significant worsening of lung injury,as well as increased lung permeability,lung wet/dry ratio,and protein content in alveolar lavage fluid when compared to the control group.Moreover,mRNA levels of pro-inflammatory cytokines IL-1β,IL-6,TNF-α,and IFN-γ in the lung tissue of the model group were significantly elevated,while the levels of anti-inflammatory cytokines IL-4 and TGF-β were significantly reduced.The oxidative index MDA also significantly increased,while the antioxidant index GSH significantly decreased.Additionally,the expression of GPX4,a marker of ferroptosis,increased with an increase in iron content.Neoscopolamine treatment successfully reversed those effects.Conclusion The combined use of ANI and NEO had a protective effect on pulmonary oxygen poisoning.Neoscopolamine may inhibit inflammation and oxidative stress by activating the cholinergic anti-inflammatory pathway,thereby reducing the content of free iron in lung tissue and finally inhibiting cell ferroptosis.

Objective:To explore the efficacy and safety of restylane volyme cross-linked sodium hyaluronate gel injection via dual-plane technique for cheek depression and mild to moderate skin laxity in the mid-lower face.Methods:The data of patients with cheek concavity accompanied by mild to moderate skin laxity in the mid-lower face treated at Jinan MeiAo Plastic Surgery Hospital from February 2023 to January 2024 were retrospectively collected. The treatment was injection of cross-linked sodium hyaluronate gel via double-plane technique, with needle insertion points located 1-2 cm anterior to the tragus. After insertion, a 23 G blunt needle was used to fanwise inject the subcutaneous fat (superficial layer) and the subcutaneous (deep layer) fat compartments in the concave area of the cheek, and a suitable amount of subcutaneous injection was administered below the zygomatic arch to soften the prominent zygomatic arch and achieve natural smoothness of the filling area. The total volume injected per side ranged from 1.5 to 3.5 ml. The patient’s skin condition was closely observed during the injection process, followed by gentle compression after injection. Patient images were collected preoperatively, immediately postoperatively, and at 6 months postoperatively. Blind evaluator used the facial laxity rating scale (FLRS) and medicis midface volume scale (MMVS) to evaluate the improvement in facial laxity and fullness. A higher rating/score of the scale indicates greater laxity or worse fullness of the face, and a decrease of 1 grade/point postoperatively compared to preoperative status was considered effective, while a decrease of ≥2 grades/points was considered significantly effective. Patients used the global aesthetic improvement scale (GAIS) to self-assess the improvement in facial appearance before and after treatment, with a maximum score of 5 points indicating the most noticeable improvement. Patient satisfaction and effect durability were investigated using a self-made satisfaction scale. The occurrence of patient complications was recorded. Data were analyzed using SPSS 26.0 statistical software, with measurement data expressed as Mean±SD, and paired t-tests used for comparison of GAIS scores immediately postoperatively and at 6 months postoperatively within the same patient. Categorical data were presented as cases (%). Results:A total of 80 female patients aged 30 to 50 years were included, all of whom were followed up for over 6 months. The FLRS grades showed that compared with preoperative status, all patients immediately postoperatively were rated as effective (69 cases, 86.3%) or significantly effective (11 cases, 13.8%). Compared with immediately postoperatively, 74 cases (92.5%) had no change in rating at 6 months postoperatively, while 6 cases (7.5%) experienced a 1-grade increase, indicating a slight reduction in treatment efficacy. The MMVS scores of the right and left facial sides of patients showed that compared with preoperative status, all patients immediately postoperatively achieved effective (right side: 55 cases, 68.8%; left side: 69 cases, 86.2%) or significantly effective (right side: 25 cases, 31.2%; left side: 11 cases, 13.8%) improvement in facial fullness. Compared with immediately postoperatively, at 6 months postoperatively, right side of 70 cases (87.5%) and left side of 77 cases (96.2%) had no change in grading, the other 12 patients (13 sides) increased by 1 point, indicating that the treatment effect was slightly weakened. All patients believed that their facial appearance improved after treatment, with GAIS scores of 4.5±0.5 immediately after treatment, while of 4.4±0.5 at 6 months postoperatively, the difference was not statistically significant ( t=1.08, P=0.280). The satisfaction rate (very satisfied+ satisfied) immediately postoperatively was 97.5% (78/80). Seventy-two (90.0%) cases expressed willingness to undergo secondary treatment. At 6 months post-treatment, the satisfaction rate (very satisfied+ satisfied) with treatment improvement and maintenance was 98.8% (79/80). Sixty-eight (85.0%) cases believed the treatment improvement effect could be maintained for about 6 months. One patient experienced mild redness and slight swelling in the injection area immediately postoperatively, which subsided after icing. No other obvious adverse reaction occurred. Conclusion:The use of double-plane technique injection of cross-linked sodium hyaluronate gel can safely and effectively improve cheek concavity, alleviate mild to moderate skin laxity in the mid-lower face, and maintain treatment efficacy for approximately 6 months.

Objective:To explore the efficacy and safety of restylane volyme cross-linked sodium hyaluronate gel injection via dual-plane technique for cheek depression and mild to moderate skin laxity in the mid-lower face.Methods:The data of patients with cheek concavity accompanied by mild to moderate skin laxity in the mid-lower face treated at Jinan MeiAo Plastic Surgery Hospital from February 2023 to January 2024 were retrospectively collected. The treatment was injection of cross-linked sodium hyaluronate gel via double-plane technique, with needle insertion points located 1-2 cm anterior to the tragus. After insertion, a 23 G blunt needle was used to fanwise inject the subcutaneous fat (superficial layer) and the subcutaneous (deep layer) fat compartments in the concave area of the cheek, and a suitable amount of subcutaneous injection was administered below the zygomatic arch to soften the prominent zygomatic arch and achieve natural smoothness of the filling area. The total volume injected per side ranged from 1.5 to 3.5 ml. The patient’s skin condition was closely observed during the injection process, followed by gentle compression after injection. Patient images were collected preoperatively, immediately postoperatively, and at 6 months postoperatively. Blind evaluator used the facial laxity rating scale (FLRS) and medicis midface volume scale (MMVS) to evaluate the improvement in facial laxity and fullness. A higher rating/score of the scale indicates greater laxity or worse fullness of the face, and a decrease of 1 grade/point postoperatively compared to preoperative status was considered effective, while a decrease of ≥2 grades/points was considered significantly effective. Patients used the global aesthetic improvement scale (GAIS) to self-assess the improvement in facial appearance before and after treatment, with a maximum score of 5 points indicating the most noticeable improvement. Patient satisfaction and effect durability were investigated using a self-made satisfaction scale. The occurrence of patient complications was recorded. Data were analyzed using SPSS 26.0 statistical software, with measurement data expressed as Mean±SD, and paired t-tests used for comparison of GAIS scores immediately postoperatively and at 6 months postoperatively within the same patient. Categorical data were presented as cases (%). Results:A total of 80 female patients aged 30 to 50 years were included, all of whom were followed up for over 6 months. The FLRS grades showed that compared with preoperative status, all patients immediately postoperatively were rated as effective (69 cases, 86.3%) or significantly effective (11 cases, 13.8%). Compared with immediately postoperatively, 74 cases (92.5%) had no change in rating at 6 months postoperatively, while 6 cases (7.5%) experienced a 1-grade increase, indicating a slight reduction in treatment efficacy. The MMVS scores of the right and left facial sides of patients showed that compared with preoperative status, all patients immediately postoperatively achieved effective (right side: 55 cases, 68.8%; left side: 69 cases, 86.2%) or significantly effective (right side: 25 cases, 31.2%; left side: 11 cases, 13.8%) improvement in facial fullness. Compared with immediately postoperatively, at 6 months postoperatively, right side of 70 cases (87.5%) and left side of 77 cases (96.2%) had no change in grading, the other 12 patients (13 sides) increased by 1 point, indicating that the treatment effect was slightly weakened. All patients believed that their facial appearance improved after treatment, with GAIS scores of 4.5±0.5 immediately after treatment, while of 4.4±0.5 at 6 months postoperatively, the difference was not statistically significant ( t=1.08, P=0.280). The satisfaction rate (very satisfied+ satisfied) immediately postoperatively was 97.5% (78/80). Seventy-two (90.0%) cases expressed willingness to undergo secondary treatment. At 6 months post-treatment, the satisfaction rate (very satisfied+ satisfied) with treatment improvement and maintenance was 98.8% (79/80). Sixty-eight (85.0%) cases believed the treatment improvement effect could be maintained for about 6 months. One patient experienced mild redness and slight swelling in the injection area immediately postoperatively, which subsided after icing. No other obvious adverse reaction occurred. Conclusion:The use of double-plane technique injection of cross-linked sodium hyaluronate gel can safely and effectively improve cheek concavity, alleviate mild to moderate skin laxity in the mid-lower face, and maintain treatment efficacy for approximately 6 months.

Objective To study the occurrence of tinnitus in elderly population in the Chengqiao area of Chongming Island,Shanghai,and explore the influencing factors,so as to provide reference for prevention and treatment of tinnitus in special areas.Methods A combination of questionnaire surveys,scale assessments,and pure-tone audiometry test were employed in this study.The study involved 6 358 elderly individuals who underwent health examinations at the Chengqiao Town Community Health Service Center in Chongming,Shanghai,from June 2019 to December 2021.Single and multiple factor analysis methods were used to analyze the impact of 13 factors,including gender,age,hearing status,sleep quality,anxiety and depression status,history of alcohol consumption,smoking history,history of noise exposure,history of ototoxic drug use,hypertension,diabetes,hyperlipidemia,and coronary heart disease on tinnitus in the elderly population.Results ① Among the 6 358 elderly cases,there were 2 110 cases with tinnitus,and the incidence rate of tinnitus was 33.2％(2 110/6 358),and 1 712 cases were chronic tinnitus(81.1％),and 1 156 cases were bilateral tinnitus(54.8％).According to THI score,there were 1 012 patients(48％)were mild tinnitus,and 2 030 patients(96.2％)with average hearing threshold ≥25 dB HL.② Univariate analysis showed that age,hearing status,sleep quality,anxiety and depression,history of noise expo-sure,history of ototoxic drugs,and history of hypertension were related to the occurrence of tinnitus.Further bina-ry logistic regression analysis showed that increasing age(OR=1.10,95％CI 1.09～1.11,P＜0.001),hearing loss(OR=5.56,95％CI 4.31～7.18,P＜0.001),sleep disorder(OR=3.32,95％CI 2.82～3.91,P＜0.001),anxiety depression(OR=2.02,95％CI 1.71～2.39,P＜0.001),history of noise exposure(OR=3.67,95％CI 3.20～4.21,P＜0.001),history of ototoxic drugs(OR=2.20,95％CI 1.84～2.64,P＜0.001)and history of hy-pertension(OR=1.73,95％CI 1.53～1.95,P＜0.001)increased the risk of tinnitus.Conclusion The incidence of tinnitus in the elderly people in the Chengqiao area of Chongming is relatively high.Factors such as age,hearing status,sleep quality,anxiety and depression,history of noise exposure,history of ototoxic drugs,and history of hypertension are risk factors for the occurrence of tinnitus in the elderly population.

Three novel sesquiterpenoid heterodimers,designated as auckcostusolides A-C(1-3),were isolated from Aucklandia costus leaves.The structures of compounds 1-3 were elucidated through comprehensive spectroscopic analysis,with their absolute configurations established using a combination of X-ray single-crystal diffraction and electronic circular dichroism(ECD)calculations.Notably,compounds 1 and 2,despite sharing identical planar structures derived from two identical sesquiterpenoids,exhibited oppos-ite configurations at C-11 and C-8'.This configurational difference can be attributed to distinct Diels-Alder cycloaddition processes between the sesquiterpenoid monomers.Additionally,the cytotoxic effects of compounds 1-3 were evaluated against colorectal can-cer HCT116 cells,fibrosarcoma HT1080 cells,and hepatocellular carcinoma HepG2 cells.Compounds 1-3 induced cell death was characterized by endoplasmic reticulum(ER)swelling and cytoplasmic vacuolization,typical morphological changes associated with paraptosis.Mechanistic studies revealed that compounds 1 and 3 triggered paraptosis-like cell death through the accumulation of react-ive oxygen species(ROS),activation of ER stress,and stimulation of the MAPK signaling pathway.

Objective To observe the alterations in functional complexity of brain regions in autism spectrum disorder(ASD)patients and correlations with the predicted brain age.Methods Open brain resting-state functional MRI(rs-MRI)data of 93 ASD patients and 96 typically developing adolescents(healthy subjects)were downloaded.The functional complexity in brain regions were extracted with self-developed virtual digital brain software,and the alterations in functional complexity of brain regions in ASD patients and correlations with their ages were analyzed.Two networks were prospectively trained with data of 65 ASD patients and 67 healthy subjects as the training set to predict brain age,and the results were evaluated,and the predicting errors were compared using test set,i.e.the other 28 ASD patients and 29 healthy subjects.Results Compared to healthy subjects,on the basis of anatomical automatic labeling(AAL)atlas,ASD patients exhibited significantly reduced functional complexity based on Shannon entropy in the left precuneus,left cuneus and right parahippocampal gyrus.Conversely,functional complexity of ASD patients based on permutation entropy significantly increased in the left cuneus and right cerebellar Crus Ⅱ region.The left hippocampus showed reduced functional complexity based on Pearson correlation coefficient,while the left middle temporal gyrus showed increased functional complexity based on Pearson correlation coefficient.The functional complexity in brain regions of ASD patients were not closely correlated with ages(all|r|＜0.4).According to the trained fully connected network,the predicted brain ages of ASD patients and healthy subjects in test set were all lower than their physiological ages,but no significant difference was found between the prediction errors of ASD patients and healthy subjects(P=0.283).Conclusion Functional complexity changed in some brain region functions in ASD patients.The predicted brain ages of ASD patients based on the obtained fully connected network were on the low side,but not obviously affected by the alterations of functional complexity in brain regions.

Objective:To explore the correlation between subclavian artery stenosis disease (SASD) classification and posterior circulation ischemia.Methods:A retrospective study was performed; the clinical data, and Doppler vascular ultrasound and vascular imaging results of 81 SASD patients, admitted to Cerebrovascular Stenosis Diagnosis and Treatment Center, Second Affiliated Hospital of Qiqihar Medical College and Department of Neurology, Rocket Force Specialty Medical Center from May 2018 to August 2023, were collected. SASD was categorized into 2 types (single type and concurrent type) based on the presence or absence of other posterior circulation artery (basilar artery, vertebral artery, or subclavian artery distal segment) stenosis/occlusion, and into 3 groups (non-posterior circulation ischemia group, posterior circulation transient ischemic attack group and posterior circulation cerebral infarction group) based on the presence or absence of posterior circulation ischemia. Blood stealing pathways in different SASD classifications were analyzed, and correlation of SASD classification with posterior circulation ischemia was discussed.Results:Single-type SASD was noted in 44 patients (54.3%), mainly initiating blood stealing through the vertebral artery to the vertebral artery and then to the subclavian artery ( n=26); concurrent-type SASD was noted in 37 patients (45.7%), mainly initiating blood stealing through the occipital artery to the costocervical trunk and then to the subclavian artery ( n=10). Sixty-five patients (80.2%) were into the non-posterior circulation ischemia group, 4 (4.9%) into the posterior circulation transient ischemic attack group and 12 (14.8%) into the posterior circulation cerebral infarction group. Among the 44 patients with single-type SASD, 39 did not have posterior circulation ischemia, and 3 had posterior circulation cerebral infarction. Among the 37 patients with concurrent-type SASD, 26 did not have posterior circulation ischemia, and 9 had posterior circulation cerebral infarction. Conclusion:Initiation of blood stealing in SASD patients is related to SASD classification, and concurrent-type SASD patients trend to have posterior circulation ischemia.