BACKGROUND:Studies have shown that mitochondrial apoptosis of alveolar epithelial cells plays an important role in the pathogenesis of pulmonary fibrosis,and Feibi prescription can attenuate pulmonary fibrosis and inhibit the transformation of extracellular mechanisms in mice with pulmonary fibrosis. OBJECTIVE:To investigate the mechanism of Feibi prescription on mitochondrial apoptpsis of alveolar epithelial cells in bleomycin induced pulmonary fibrosis mice. METHODS:Forty male C57BL/6 mice were randomly divided into blank control group,model group,pirfenidone group,and Feibi prescription group.There were 10 mice in each group.Except for the blank control group,the other three groups were intraperitoneally injected with bleomycin(7.5 mg/kg per day)for 10 continuous days to establish the model of pulmonary fibrosis.On day 1 after modeling,the mice in corresponding drug groups were intragastrically administered with pirfenidone(51.43 mg/kg per day)or Feibi prescription(12.86 mg/kg per day).Drug administration lasted for 28 days.Then,morphological changes of lung tissue in mice were observed by hematoxylin-eosin staining and Masson staining.The levels of interleukin-1,interleukin-6,interleukin-17,and interleukin-37 in the serum were detected by ELISA,and the expression of Bax,Bcl-2,Beclin-1,and Caspase3 in the lung tissue was detected by western blot assay. RESULTS AND CONCLUSION:Morphological observation of lung tissue showed that in the model group,the alveolar septum and alveolar lumen were infiltrated with a large number of inflammatory cells,and there were large clusters of fibrous foci;in the pirfenidone group,alveolar septa were thickened,with a small infiltration of inflammatory cells and the appearance of pulmonary fibrous foci;in the Feibi prescription group,the alveolar structure was widened,with a small amount of inflammatory cell infiltration,and the alveolar structure was almost not obviously damaged,with a small number of lung fibrous foci.Compared with the blank control group,the mass concentrations of interleukin-1,interleukin-6,interleukin-17,and interleukin-37 were significantly higher in the model group(P<0.01),while the levels were significantly lower in the two drug groups than the model group(P<0.01).Moreover,the mass concentrations of interleukin-1,interleukin-6,interleukin-17,and interleukin-37 in the Feibi prescription group were lower than those in the pirfenidone group.Compared with the blank control group,the expression of Bax and Caspase3 proteins in the lung tissue of mice was significantly higher in the model group,while the expression of Bax and Caspase3 proteins was significantly lower in the two drug groups than the model group.Compared with the blank control group,the expression of Bcl-2 and Beclin-1 proteins in the lung tissue of mice was significantly lower in the model group,while the expression of Bcl-2 and Beclin-1 proteins was significantly higher in the two drug groups than the model group.To conclude,Feibi prescription can reduce pulmonary fibrosis and its mechanism may be related to the downregulation of interleukin-1,interleukin-6,interleukin-17,and interleukin-37 levels.This prescription can also reduce the apoptosis of alveolar epithelial cells by regulating mitochondrial apoptosis-related proteins,Bax,Bcl-2,Beclin-1 and Caspase3.

ObjectiveThe controllability changes of structural brain network were explored based on the control and brain network theory in young smokers, this may reveal that the controllability indicators can serve as a powerful factor to predict the sleep status in young smokers. MethodsFifty young smokers and 51 healthy controls from Inner Mongolia University of Science and Technology were enrolled. Diffusion tensor imaging (DTI) was used to construct structural brain network based on fractional anisotropy (FA) weight matrix. According to the control and brain network theory, the average controllability and the modal controllability were calculated. Two-sample t-test was used to compare the differences between the groups and Pearson correlation analysis to examine the correlation between significant average controllability and modal controllability with Fagerström Test of Nicotine Dependence (FTND) in young smokers. The nodes with the controllability score in the top 10% were selected as the super-controllers. Finally, we used BP neural network to predict the Pittsburgh Sleep Quality Index (PSQI) in young smokers. ResultsThe average controllability of dorsolateral superior frontal gyrus, supplementary motor area, lenticular nucleus putamen, and lenticular nucleus pallidum, and the modal controllability of orbital inferior frontal gyrus, supplementary motor area, gyrus rectus, and posterior cingulate gyrus in the young smokers’ group, were all significantly different from those of the healthy controls group (P<0.05). The average controllability of the right supplementary motor area (SMA.R) in the young smokers group was positively correlated with FTND (r=0.393 0, P=0.004 8), while modal controllability was negatively correlated with FTND (r=-0.330 1, P=0.019 2). ConclusionThe controllability of structural brain network in young smokers is abnormal. which may serve as an indicator to predict sleep condition. It may provide the imaging evidence for evaluating the cognitive function impairment in young smokers.

ObjectiveThis study sought to investigate the impact of exosomes derived from LoVo cells (LoVo-Exos) in colorectal cancer (CRC) on tumor angiogenesis, as well as to elucidate the potential molecular mechanisms underlying their pro-angiogenic effects. MethodsLoVo-Exos were isolated via ultracentrifugation, and their internalization into recipient human umbilical vein endothelial cells (HUVECs) was visualized using confocal microscopy. The influence of LoVo-Exos on angiogenesis was assessed through an in vitro tube formation assay. Additionally, the pro-angiogenic effects of LoVo-Exos were evaluated in vivo using a matrix gluing assay in mice. To investigate the molecular mechanisms through which LoVo-Exos facilitate angiogenesis, Western blot analysis was employed to examine the transfer of pEGFR by LoVo-Exos into recipient cells. Both Western blot and ELISA were utilized to assess the expression levels of key signaling proteins within the EGFR-ERK pathway, as well as the expression of downstream angiogenic core molecules. Furthermore, the impact of EGFR knockdown and ERK inhibitor treatment on angiogenesis was evaluated, with subsequent analysis of the expression of downstream angiogenic core molecules following these interventions. ResultsConfocal microscopy demonstrated the internalization of LoVo-Exos into HUVECs. In vitro angiogenesis assays further indicated that LoVo-Exos significantly enhanced the formation of tubular structures in HUVECs. Additionally, macroscopic examination of subcutaneous matrix plug formation in mice revealed a substantial increase in vascular-like structures within the matrix plugs following the administration of LoVo-Exos, compared to the PBS control group. Hematoxylin and eosin (HE) staining revealed the presence of erythrocyte-filled microvessels within the matrix plugs combined with LoVo-Exos. Furthermore, immunohistochemical analysis demonstrated the expression of the endothelial cell marker CD31 in these matrix plugs. The presence of CD31-positive cells in the LoVo-Exos-treated matrix plugs was associated with a significant enhancement in the formation of luminal structures. These findings suggest that LoVo-Exos facilitate the in vivo development of vascular-like structures. Subsequent investigations demonstrated that LoVo-Exos facilitated the delivery of pEGFR to HUVEC, thereby enhancing angiogenesis. Conversely, LoVo-Exos with EGFR knockdown exhibited a diminished capacity to promote angiogenesis, an effect that was further attenuated by the ERK phosphorylation inhibitor U0126. Western blot analysis assessing the activation of the EGFR-ERK signaling pathway in HUVEC indicated that LoVo-Exos augmented angiogenesis through the activation of this pathway. Furthermore, analysis of the impact of LoVo-Exos on the expression of downstream angiogenic core molecules revealed an increase in interleukin-8 (IL-8) secretion in HUVEC. The enhancement observed was diminished in LoVo-Exos following EGFR knockdown, and this reduction was counteracted by the ERK phosphorylation inhibitor U0126. ConclusionThe underlying mechanism may involve the delivery of pEGFR in LoVo-Exos to HUVECs, leading to increased IL-8 secretion via the EGFR-ERK signaling pathway, thereby enhancing the angiogenic potential of HUVECs. This finding may offer new insights into the mechanisms underlying cancer metastasis.

Objective To observe the efficacy and safety of Morinda officinalis oligosaccharides in the continuation treatment of mild and moderate depression.Methods An open,single-arm,multi-center design was adopted in our study.Adult patients with mild and moderate depression who had received acute treatment of Morinda officinalis oligosaccharides were enrolled and continue to receive Morinda officinalis oligosaccharides capsules for 24 weeks,the dose remained unchanged during continuation treatment.The remission rate,recurrence rate,recurrence time,and the change from baseline to endpoint of Hamilton Depression Scale(HAMD),Hamilton Anxiety Scale(HAMA),Clinical Global Impression-Severity(CGI-S)and Arizona Sexual Experience Scale(ASEX)were evaluated.The incidence of treatment-related adverse events was reported.Results The scores of HAMD-17 at baseline and after treatment were 6.60±1.87 and 5.85±4.18,scores of HAMA were 6.36±3.02 and 4.93±3.09,scores of CGI-S were 1.49±0.56 and 1.29±0.81,scores of ASEX were 15.92±4.72 and 15.57±5.26,with significant difference(P＜0.05).After continuation treatment,the remission rate was 54.59％(202 cases/370 cases),and the recurrence rate was 6.49％(24 cases/370 cases),the recurrence time was(64.67±42.47)days.The incidence of treatment-related adverse events was 15.35％(64 cases/417 cases).Conclusion Morinda officinalis oligosaccharides capsules can be effectively used for the continuation treatment of mild and moderate depression,and are well tolerated and safe.

Objective:To investigate the factors related to hypothyroidism induced by programmed death(PD)-1 treatment in elderly patients with cancer.Methods:A total of 193 older patients(≥60 years old)with advanced solid tumors who received PD-1 treatment between January 2018 and January 2021 at the Department of Oncology of Xiangyang Central Hospital were included in this study.The patients were divided into two groups based on whether they were diagnosed with hypothyroidism after PD-1 treatment: the hypothyroidism group(36 cases)and the non-hypothyroidism group(157 cases).The clinical data of both groups, including age, gender, Eastern Cooperative Oncology Group performance status(ECOG PS), PD-1 inhibitors, thyroid function, and thyroid antibody, were compared to analyze the risk factors associated with hypothyroidism.Results:Among the 193 patients, 36(18.7%)were diagnosed with hypothyroidism.The study found no significant differences between the two groups in terms of age, gender, ECOG PS, tumor type, and PD-1 type(all P>0.05).However, significant differences were observed in the baseline levels of thyroid stimulating hormone(TSH)and thyroid antibody subgroups(both P<0.05).The results of multivariate Logistic regression analysis revealed that the presence of baseline anti-thyroid peroxidase antibody(TPOAb)( OR=20.256, 95% CI: 5.709-71.868, P<0.001), the presence of both baseline thyroglobulin antibody(TGAb)and TPOAb( OR=5.853, 95% CI: 1.475-23.227, P=0.012), and an increase in baseline TSH levels( OR=3.065, 95% CI: 1.049-8.959, P=0.041)were identified as risk factors for hypothyroidism induced by PD-1 treatment.On the other hand, there was no significant association between the presence of baseline TGAb and the occurrence of hypothyroidism( OR=1.373, 95% CI: 0.353-5.341, P=0.648). Conclusions:The incidence rate of hypothyroidism induced by PD-1 inhibitors is high among elderly patients with cancer.Additionally, the risk of hypothyroidism is higher in patients with elevated baseline TSH and positive TPOAb.Therefore, it is crucial to remain vigilant for the occurrence of hypothyroidism during PD-1 treatment.Timely diagnosis and treatment of hypothyroidism are necessary to minimize the incidence of adverse events.

Objective To explore the characteristics of blood lipid metabolism indicators and risk factors of prognosis in children with systemic lupus erythematosus (SLE). Methods A total of 54 children who were diagnosed with SLE and hospitalized in Chengdu Women and Children’ s Central Hospital from January 2013 to August 2022 were selected. Clinical data of all children were collected and blood lipid metabolism indicators and biochemical indicators were detected , and binary logistic regression was used to analyze the prognosis risk factors in children with SLE. Results Among the 47 cases (87.04%) had abnormal blood lipid metabolism at admission, and is mainly manifested as elevated levels of LDL-C, TG and TC and decreased level of HDL-C. The proportion of cardiovascular system damage, hematological system damage, urinary protein positivity, and SLEDAI-2000 score in the group with good prognosis were lower than those in the group with poor prognosis, while the proportion of dsDNA positivity was higher in the group with poor prognosis. Binary Logistic regression analysis showed that the cardiovascular system damage and positive urinary protein were risk factors for poor prognosis, with statistically significant differences (P<0.05). Conclusion Abnormal blood lipid metabolism is common in children with SLE, and cardiovascular system damage and positive urinary protein may increase the risk of poor prognosis in young children.

Objective To study the clinical manifestations,laboratory features,and labial gland pathological features in children with systemic lupus erythematosus(SLE)complicated by Sj?gren's syndrome(SS).Methods A retrospective analysis was conducted on 102 children with SLE who underwent labial gland biopsies at Renji Hospital,Shanghai Jiao Tong University School of Medicine from January 2013 to December 2022.The children were divided into two groups based on the presence of SS:the SLE with SS group(SLE-SS;60 children)and the SLE-only group(42 children).According to the focus score(FS)of the labial glands,children in the SLE-SS group were further subdivided into FS≥4 subgroup(26 children)and FS<4 subgroup(34 children).The clinical data of the groups were compared.Results Compared to the SLE-only group,children in the SLE-SS group had less skin and mucosal involvement,were more likely to have positive anti-SSA and anti-SSB antibodies,and had higher levels of rheumatoid factor(P<0.05).There was no significant difference in treatment protocols between the two groups(P>0.05).Compared to the FS<4 subgroup,the FS≥4 subgroup had more frequent musculoskeletal involvement(P<0.05),but there was no significant difference in SLE disease activity or other major organ involvement between the subgroups(P>0.05).Conclusions Children with SLE complicated by SS are less likely to have skin and mucous membrane involvement and exhibit specific serological characteristics.The SLE-SS children with an FS≥4 are more likely to experience musculoskeletal involvement.However,FS is not associated with disease activity or other significant organ damage.

Currently, there are practical and technical difficulties in the construction of clinical questions in the development of clinical practice guidelines. Clinicians or guideline developers seldom construct clinical questions based the actual case scenario, leading to some information loss between structured and actual clinical connotation. To overcome this challenge, we proposed a case-guided questions construction approach, and carried out case research and verification in the formulation of the guideline. We found that this method could more efficiently and scientifically assist the formulation of clinical questions, and provide reference for clinicians or guideline developers.

Objective:To establish a new classification system for distal clavicle fracture and evaluate its clinical effectiveness.Methods:A retrospective case series study was conducted to analyze the clinical data of 101 patients with distal clavicle fracture admitted to First Affiliated Hospital of Nanjing Medical University from January 2015 to March 2022, including 57 males and 44 females, aged 19-86 years [(53.8±14.0)years]. Before treatment, patients were routinely subjected to bilateral anteroposterior radiography of the shoulder joints to measure the length of the fractured fragments, coracoclavicular distance, and acromioclavicular distance. According to the correlation between the location of the fracture line and the insertion of the coracoclavicular ligament, distal clavicle fracture was divided into three types: type I, with the fracture line lateral to the coracoclavicular ligament region; type II, with the fracture line in the coracoclavicular ligament region; type III, with the fracture line medial to the coracoclavicular ligament region. According to the injury severity of the coracoclavicular ligament and acromioclavicular ligament, type I was further subdivided into type IA, IB, IC and ID, and type II fracture was further subdivided into type IIA, IIB, IIC, IID and IIE. All the 101 patients were classified and randomly reclassified at an interval of 3 months by 10 senior and 10 junior shoulder surgeons according to the new classification method. Kappa coefficients were used to evaluate the inter- and intra-observer consistency of the new classification. Fifty-two patients with stable fracture (types IA, IB, IIC, and IID) were treated non-surgically, while 49 patients with unstable fracture (types IC, ID, IIA, IIB, IIE, and III) were treated surgically, including 26 patients with anatomic coracoclavicular ligament reconstruction, 9 with locking plate fixation, 8 with clavicle hook plate fixation, 4 with anatomic coracoclavicular ligament reconstruction combined with locking plate fixation, and 2 with anatomic coracoclavicular ligament reconstruction combined with tension screw fixation. The patients were assessed using the visual analogue scale (VAS) and Constant-Murley shoulder score before treatment and at 3, 6, 12, and 18 months after treatment. The coracoclavicular distance and acromioclavicular distance on the anteroposterior radiographs of the healthy and affected shoulder joints were measured at 3, 6, 12, and 18 months after treatment, and fracture healing time and complications were observed.Results:The length of the fractured fragments was 12.9 (9.7, 17.6)mm in patients with type I fracture, 24.7 (21.8, 27.8)mm in patients with type II fracture, and 43.6 (41.2, 46.9)mm in patients with type III fracture ( P<0.01). There were no significant differences in the coracoclavicular distance and acromioclavicular distance of the affected and healthy shoulders among the patients with types IA, IB, IIC, IID, and III fracture ( P>0.05); For the patients with types IC, IIA, IIB and IIE fracture, the coracoclavicular distance of the affected shoulder was significantly increased compared with that of the healthy shoulder ( P<0.01), while there was no significant difference in the acromioclavicular distance of the affected and healthy shoulders ( P>0.05). Both of the inter- and intra-observer consistency of the new classification was good. The inter- and intra-observer Kappa values were 0.69 and 0.71 respectively among the senior shoulder surgeons, and 0.61 and 0.64 respectively among the junior shoulder surgeons. All the patients were followed up for 18-104 months [28(23, 32)months]. At 3, 6, 12 and 18 months after treatment, the VAS scores of non-surgical patients were 3(2, 3)points, 2(1, 2)points, 1(0, 1)points and 0(0, 1)points respectively, significantly decreased compared with 6(5, 6)points before treatment ( P<0.01); the VAS scores of surgical patients were 3(2, 3)points, 2(1, 2)points, 1(1, 1)points and 0(0, 1)points respectively, significantly decreased compared with 6(5, 7)points before treatment ( P<0.01); the Constant-Murley shoulder scores of non-surgical patients were (76.6±5.3)points, (84.3±5.0)points, (88.4±4.0)points and (91.9±3.8)points respectively, significantly higher than (42.7±5.2)points before treatment ( P<0.01); the Constant-Murley shoulder scores of surgical patients were (77.4±4.6)points, (84.4±4.7)points, (87.6±3.7)points and (91.7±4.0)points respectively, significantly higher than (42.8±5.3)points before treatment ( P<0.01). At 3, 6, 12 and 18 months after treatment, the coracoclavicular distance of the affected shoulder in non-surgical patients was not significantly different from that before treatment ( P>0.05), while the acromioclavicular distance of the affected shoulder in surgical patients was significantly reduced compared with that before treatment ( P<0.01). There were no significant differences in the coracoclavicular distance of the healthy shoulder or bilateral acromioclavicular distance in non-surgical and surgical patients at 3, 6, 12, and 18 months after treatment compared with those before treatment ( P>0.05). Fractures were healed within 12 months after treatment in all the patients, without dislocation or subluxation of the acromioclavicular joint, internal fixation failure or internal fixator breakage. Eight patients treated with clavicular hook plate fixation had shoulder pain associated with limited mobility after operation, and all underwent a second operation to remove the clavicular hook plate at 12 months after operation. Conclusions:The new classification system for distal clavicle fracture is established, which comprehensively considers the position of the fracture line, injury of the coracoclavicular and acromioclavicular ligaments, and fracture stability. The new classification system exhibits good inter- and intra- observer consistency, and the effectiveness of its preliminary clinical application is satisfactory.

BACKGROUND: Rheumatoid arthritis (RA), a chronic systemic autoimmune disease, is characterized by synovitis and progressive damage to the bone and cartilage of the joints, leading to disability and reduced quality of life. This study was a randomized clinical trial comparing the outcomes between withdrawal and dose reduction of tofacitinib in patients with RA who achieved sustained disease control. METHODS: The study was designed as a multicenter, open-label, randomized controlled trial. Eligible patients who were taking tofacitinib (5 mg twice daily) and had achieved sustained RA remission or low disease activity (disease activity score in 28 joints [DAS28] ≤3.2) for at least 3 months were enrolled at six centers in Shanghai, China. Patients were randomly assigned (1:1:1) to one of three treatment groups: continuation of tofacitinib (5 mg twice daily); reduction in tofacitinib dose (5 mg daily); and withdrawal of tofacitinib. Efficacy and safety were assessed up to 6 months. RESULTS: Overall, 122 eligible patients were enrolled, with 41 in the continuation group, 42 in the dose-reduction group, and 39 in the withdrawal group. After 6 months, the percentage of patients with a DAS28-erythrocyte sedimentation rate (ESR) of <3.2 was significantly lower in the withdrawal group than that in the reduction and continuation groups (20.5%, 64.3%, and 95.1%, respectively; P  < 0.0001 for both comparisons). The average flare-free time was 5.8 months for the continuation group, 4.7 months for the dose reduction group, and 2.4 months for the withdrawal group. CONCLUSION: Withdrawal of tofacitinib in patients with RA with stable disease control resulted in a rapid and significant loss of efficacy, while standard or reduced doses of tofacitinib maintained a favorable state. TRIAL REGISTRATION Chictr.org, ChiCTR2000039799.
Humans ; Quality of Life ; China ; Arthritis, Rheumatoid/drug therapy* ; Piperidines/therapeutic use* ; Treatment Outcome ; Antirheumatic Agents/therapeutic use* ; Pyrroles/therapeutic use*