The role of osteoblast(OB)autophagy in regulating bone metabolism is a research hotspot in the field of biomedicine.OB autophagy can regulate osteoporosis(OP)induced by aging,oxidative stress,estrogen deficiency,and glucocorticoids(GCs)by mediating factors such as run and cysteine rich domain containing Beclin-1 interacting protein(RUBCN),silent information regulator of transcription 1(SIRT1),and osteoprotegerin(OPG).OB autophagy can also regulate OP by activating notch receptor(Notch)and forkhead box protein O subfamily(FoxO),up-regulating the expression of osteogenic transcription factors(such as Runx2 and Osterix),and mediating the amp-activated protein kinase(AMPK),mammalian target of rapamycin complex(mTOR),Wnt,and c-Jun n terminal kinase(JNK)pathways to act on OB and osteoclast(OC)differentiation.Exercise is an important means of improving OP,and its molecular mechanism is closely related to the up-regulation of phosphatidylinositol 3 kinase(PI3K),adenosine monophosphate(AMP),tumor necrosis factor-alpha(TNF-α),and SIRT1 expression.These in turn activate key factors or pathways(including AMPK,mTOR,Wnt,PI3K/protein kinase B(Akt)/mTOR,and nuclear transcription factor-KB(NF-κB)),regulate the expression of downstream target genes(β-catenin,mTOR,FoxO3a and B cell lymphoma-2(Bcl-2))to up-regulate the expression of autophagy factors(Beclin-1,autophagy related genes(ATG),and microtubule-associated protein 1 light chain 3(LC3)),and promote OB autophagy to restore the dynamic balance in the body,thereby regulating bone formation and bone resorption and improving OP.The relationships among exercise,OB autophagy and OP,however,remain unclear and there is currently a lack of systematic reviews.Here we review and analyze the mechanism of OB autophagy in relation to exercise-induced improvements in OP,and provide a new theoretical basis and research ideas for the prevention and treatment of OP.

Objective:To investigate clinical characteristics and genetic variations in a case of self-improving collodion ichthyosis in the adult stage.Methods:An adult patient with clinically suspected self-improving collodion ichthyosis was collected from the Department of Dermatology, Henan Provincial People′s Hospital in April 2023. Clinical data were collected from the patient and her parents. Peripheral blood samples were obtained from them, and whole blood DNA was extracted. Whole-exome sequencing was performed to screen genetic variation sites, which were then verified by Sanger sequencing. The deleteriousness of the identified variants was assessed using pathogenicity analysis software.Results:The 54-year-old female patient presented with facial and neck flushing, mild dry skin on the trunk and limbs, sheepskin-like skin of the dorsal hand, and short fingers. Genetic testing identified two in-frame deletion mutations c.406_408del (p.E136del) and c.769_801del (p.H257_Q267del) in the non-repetitive region of the ALOX12B gene in the patient, which were inherited from her father and mother respectively. Bioinformatics analysis revealed that both genetic variations were deleterious pathogenic mutations.Conclusions:Two in-frame deletion mutations c.406_408del (p.E136del) and c.769_801del (p.H257_Q267del) were identified in the non-repetitive region of the ALOX12B gene in the patient with self-improving collodion ichthyosis, which may contribute to the clinical phenotype of the patient. The mutation c.769_801del had not been reported in literature.

OBJECTIVE To compare the efficacy and safety of dupilumab versus thalidomide in the treatment of refractory prurigo nodularis （PN） in adults. METHODS A retrospective analysis was conducted on the clinical data of 123 adult patients with refractory PN admitted to Wuhan First Hospital from May 2021 to June 2024. Among them， 63 patients who received dupilumab comprised the observation group and 60 patients who received thalidomide comprised the control group. Clinical efficacy indicators [Investigator Global Assessment （IGA） score， Pruritus Numerical Rating Scale （P-NRS） score， Patient-Oriented Eczema Measure （POEM） score， and Dermatology Life Quality Index （DLQI） score]， allergic biomarkers [eosinophil （EOS） count in peripheral blood and serum total immunoglobulin E （IgE） level]， psychological scores [Hospital Anxiety and Depression Scale （HADS）] before and after treatment， as well as the occurrence of adverse drug reaction during treatment， were compared between the two groups. RESULTS Before treatment， there were no statistically significant differences between the two groups in above clinical efficacy indicators， allergic biomarkers， or psychological scores （P＞0.05）. At 4， 8， 12 and 16 weeks after treatment， both groups showed significant decreases in IGA score （except for the control group 4 weeks after treatment）， IGA activity score （except for the control group 4 weeks after treatment）， P-NRS score， POEM score， DLQI score （except for the control group 4 weeks after treatment）， serum EOS count， and serum total IgE level compared with baseline （P＜0.05）； at 12 and 16 weeks after treatment， scores on both the HADS-anxiety subscale and HADS-depression subscale were also significantly lower than baseline in both groups （P＜0.05）； the observation group was significantly lower than the control group （P＜0.05）. The overall incidence of adverse events was 12.70% in the observation group， which was significantly lower than 28.33% in the control group （P＜0.05）. CONCLUSIONS Dupilumab treatment in adults with refractory PN demonstrates superior efficacy compared with thalidomide in improving skin lesions， relieving pruritus， reducing peripheral EOS counts and serum total IgE， and improving quality of life and psychological status， while showing a more favorable safety profile.

Objective:To investigate clinical characteristics and genetic variations in a case of self-improving collodion ichthyosis in the adult stage.Methods:An adult patient with clinically suspected self-improving collodion ichthyosis was collected from the Department of Dermatology, Henan Provincial People′s Hospital in April 2023. Clinical data were collected from the patient and her parents. Peripheral blood samples were obtained from them, and whole blood DNA was extracted. Whole-exome sequencing was performed to screen genetic variation sites, which were then verified by Sanger sequencing. The deleteriousness of the identified variants was assessed using pathogenicity analysis software.Results:The 54-year-old female patient presented with facial and neck flushing, mild dry skin on the trunk and limbs, sheepskin-like skin of the dorsal hand, and short fingers. Genetic testing identified two in-frame deletion mutations c.406_408del (p.E136del) and c.769_801del (p.H257_Q267del) in the non-repetitive region of the ALOX12B gene in the patient, which were inherited from her father and mother respectively. Bioinformatics analysis revealed that both genetic variations were deleterious pathogenic mutations.Conclusions:Two in-frame deletion mutations c.406_408del (p.E136del) and c.769_801del (p.H257_Q267del) were identified in the non-repetitive region of the ALOX12B gene in the patient with self-improving collodion ichthyosis, which may contribute to the clinical phenotype of the patient. The mutation c.769_801del had not been reported in literature.

OBJECTIVE: To explore the safety and effectiveness of the "talus home technique (THT) " in the surgery of pronation open ankle fractures (POAF). METHODS: A retrospective analysis was conducted on 14 patients with POAF admitted between January 2023 and December 2023 who met the selection criteria. There were 7 males and 7 females; age ranged from 26 to 58 years, with a median age of 53 years. Injury causes included 9 cases of traffic accident injury, 3 cases of fall from hight injury, and 2 cases of crush injury. There were 5 cases of type Ⅱ, 6 cases of type ⅢA, and 3 cases of type ⅢB according to Gustilo classification; and 6 cases of pronation-abduction grade Ⅲ and 8 cases of pronation-external rotation grade Ⅳ according to Lauge-Hansen classification. Emergency first-stage debridement of the ankle joint was performed, followed by second-stage open reduction and internal fixation surgery. The THT was used through a limited incision on the lateral malleolus to restore the height of the lateral malleolus, rotational alignment, and anatomical relationship of the distal tibiofibular syndesmosis (DTFS). Wound healing was observed postoperatively. At 4 months postoperatively, weight-bearing anteroposterior, lateral, and mortise view X-ray films and CT scans of both ankles were reviewed to measure the medial clear space (MCS), tibiofibular clear space (TFCS), distal fibular tip to lateral process of talus (DFTL), and anterior/posterior syndesmosis distances of DTFS, and the quality of reduction of ankle fractures was evaluated. Ankle joint function was assessed using the American Orthopedic Foot and Ankle Society (AOFAS) ankle-hindfoot score, and active dorsiflexion/plantar flexion range of motion were recorded at last follow-up. RESULTS: After second-stage internal fixation, 8 patients achieved wound healing by first intention, 1 case had skin edge necrosis, 2 cases had local skin necrosis, 1 case had extensive medial soft tissue defect, and 2 cases developed medial wound infection with sinus formation. All 14 patients were followed up 13-24 months (mean, 16.8 months). Postoperative X-ray films showed 1 case of delayed union of the lateral malleolus, which healed after bone grafting at 12 months; the remaining 13 cases achieved clinical union at 12-32 weeks (mean, 21.5 weeks). At 4 months postoperatively, X-ray films and CT examination showed no significant differences in MCS, TFCS, DFTL, and anterior/posterior syndesmosis distances of DTFS between the healthy and affected sides ( P>0.05), with no poor DTFS reduction. AOFAS ankle-hindfoot score ranged from 80 to 95, with an average of 87.7; ankle range of motion ranged from 10° to 25° (mean, 19.6°) in dorsiflexion and from 32° to 50° (mean, 41.2°) in plantar flexion. CONCLUSION THT is safe and effective in POAF surgery. It can restore lateral malleolar height and rotational alignment, enhance DTFS reduction quality, and obtain satisfactory short-term functional recovery of the ankle.
Humans ; Male ; Female ; Middle Aged ; Ankle Fractures/surgery* ; Adult ; Retrospective Studies ; Fracture Fixation, Internal/methods* ; Pronation ; Fractures, Open/surgery* ; Talus/surgery* ; Treatment Outcome ; Debridement/methods* ; Ankle Joint/surgery* ; Open Fracture Reduction/methods*

OBJECTIVE: To evaluate the safety and effectiveness of reducing posterior malleolar fractures via the modified Rammelt transfibular approach. METHODS: A retrospective analysis was conducted on 26 patients with ankle fractures who met the selection criteria and were admitted between September 2023 and May 2024. There were 13 males and 13 females, aged from 14 to 59 years (median, 43.5 years). Causes of injury included traffic accident (1 case), falls (7 cases), and sprains (18 cases). Time from injury to operation ranged from 1 to 13 days (mean, 3.9 days). According to the Lauge-Hansen classification, there were 5 supination-external rotation type Ⅲ fractures and 21 supination-external rotation type Ⅳ fractures. According to the Bartoníček classification for posterior malleolar fractures, there were 12 type Ⅱ fractures, 10 type Ⅲ fractures, and 4 type Ⅳ fractures. During operation, the fracture was exposed via the modified Rammelt transfibular approach; then, the fracture reduction was achieved under direct vision using techniques such as towel clip traction, posterolateral compression, and lifting with a posterior transverse periosteal elevator; finally, the fracture was fixed using anteroposterior cannulated screws or Kirschner wires. The incision healing was observed after operation. At 4 months after operation, X-ray film and CT were reviewed to evaluate the quality of fracture reduction. The medial clear space, tibiofibular clear space, and the anterior/posterior tibiofibular syndesmotic distances were measured. At last follow-up, the ankle function was assessed using the American Orthopaedic Foot & Ankle Society (AOFAS) score and the range of motion. RESULTS: The marginal necrosis occurred in 2 lateral malleolar incisions, and superficial infection occurred in 1 lateral malleolar incision; the remaining incisions healed by first intention. All 26 patients were followed up 13-21 months (mean, 15.6 months). X-ray films showed that fractures in 25 patients achieved clinical union within 3-8 months (mean, 5.4 months); 1 case had delayed union of the lateral malleolus. At 4 months after operation, no significant difference was found between the injured and healthy sides in the medial clear space, tibiofibular clear space, or the anterior/posterior tibiofibular syndesmotic distances ( P>0.05). No malreduction of the posterior malleolus or the tibiofibular syndesmosis occurred. At last follow-up, the AOFAS score ranged from 80 to 100 (mean, 91.9). The range of motion ranged from 17° to 22° (mean, 21.0°) in active ankle dorsiflexion and from 40° to 49° (mean, 44.6°) in plantar flexion. Internal fixator was removed in 12 patients at 1 year after operation, with no ankle instability occurring. Ankle joint degeneration was observed in 1 patient at last follow-up. CONCLUSION The modified Rammelt transfibular approach is a safe and reliable technique. It enables precise reduction under direct vision, improves the quality of reduction for the distal tibial articular surface and the tibiofibular syndesmosis, and provides satisfactory ankle functional recovery in short-term follow-up.
Humans ; Male ; Female ; Adult ; Ankle Fractures/diagnostic imaging* ; Middle Aged ; Retrospective Studies ; Fracture Fixation, Internal/instrumentation* ; Adolescent ; Treatment Outcome ; Young Adult ; Bone Screws ; Ankle Joint/surgery* ; Fibula/surgery* ; Range of Motion, Articular

A growing interest in the comprehensive pathogenic mechanisms of psychiatric disorders from the perspective of the microbiome has been witnessed in recent decades; the intrinsic link between microbiota and brain function through the microbiota-gut-brain axis or other pathways has gradually been realized. However, little research has focused on viruses-entities characterized by smaller dimensions, simpler structures, greater diversity, and more intricate interactions with their surrounding milieu compared to bacteria. To date, alterations in several populations of bacteriophages and viruses have been documented in both mouse models and patients with psychiatric disorders, including schizophrenia, major depressive disorder, autism spectrum disorder, and Alzheimer's disease, accompanied by metabolic disruptions that may directly or indirectly impact brain function. In addition, eukaryotic virus infection-mediated brain dysfunction provides insights into the psychiatric pathology involving viruses. Efforts towards virus-based diagnostic and therapeutic approaches have primarily been documented. However, limitations due to the lack of large-scale cohort studies, reliability, clinical applicability, and the unclear role of viruses in microbiota interactions pose a challenge for future studies. Nevertheless, it is conceivable that investigations into viruses herald a new era in the field of precise psychiatry.
Humans ; Mental Disorders/virology* ; Animals ; Brain/virology* ; Gastrointestinal Microbiome/physiology* ; Viruses ; Virus Diseases/complications*

The role of osteoblast(OB)autophagy in regulating bone metabolism is a research hotspot in the field of biomedicine.OB autophagy can regulate osteoporosis(OP)induced by aging,oxidative stress,estrogen deficiency,and glucocorticoids(GCs)by mediating factors such as run and cysteine rich domain containing Beclin-1 interacting protein(RUBCN),silent information regulator of transcription 1(SIRT1),and osteoprotegerin(OPG).OB autophagy can also regulate OP by activating notch receptor(Notch)and forkhead box protein O subfamily(FoxO),up-regulating the expression of osteogenic transcription factors(such as Runx2 and Osterix),and mediating the amp-activated protein kinase(AMPK),mammalian target of rapamycin complex(mTOR),Wnt,and c-Jun n terminal kinase(JNK)pathways to act on OB and osteoclast(OC)differentiation.Exercise is an important means of improving OP,and its molecular mechanism is closely related to the up-regulation of phosphatidylinositol 3 kinase(PI3K),adenosine monophosphate(AMP),tumor necrosis factor-alpha(TNF-α),and SIRT1 expression.These in turn activate key factors or pathways(including AMPK,mTOR,Wnt,PI3K/protein kinase B(Akt)/mTOR,and nuclear transcription factor-KB(NF-κB)),regulate the expression of downstream target genes(β-catenin,mTOR,FoxO3a and B cell lymphoma-2(Bcl-2))to up-regulate the expression of autophagy factors(Beclin-1,autophagy related genes(ATG),and microtubule-associated protein 1 light chain 3(LC3)),and promote OB autophagy to restore the dynamic balance in the body,thereby regulating bone formation and bone resorption and improving OP.The relationships among exercise,OB autophagy and OP,however,remain unclear and there is currently a lack of systematic reviews.Here we review and analyze the mechanism of OB autophagy in relation to exercise-induced improvements in OP,and provide a new theoretical basis and research ideas for the prevention and treatment of OP.

Objective To observe the value of clinical and CT radiomics features for predicting microsatellite instability-high(MSI-H)status of gastric cancer.Methods Totally 150 gastric cancer patients including 30 cases of MSI-H positive and 120 cases of MSI-H negative were enrolled and divided into training set(n=105)or validation set(n=45)at the ratio of 7∶3.Based on abdominal vein phase enhanced CT images,lesions radiomics features were extracted and screened,and radiomics scores(Radscore)was calculated.Clinical data and Radscores were compared between MSI-H positive and negative patients in training set and validation set.Based on clinical factors and Radscores being significant different between MSI-H positive and negative ones,clinical model,CT radiomics model and clinical-CT radiomics combination model were constructed,and their predictive value for MSI-H status of gastric cancer were observed.Results Significant differences of tumor location and Radscore were found between MSI-H positive and negative patients in both training and validation sets(all P＜0.05).The area under the curve(AUC)of clinical model,CT radiomics model and combination model for evaluating MSI-H status of gastric cancer in training set was 0.760,0.799 and 0.864,respectively,of that in validation set was 0.735,0.812 and 0.849,respectively.AUC of clinical-CT radiomics combination model was greater than that of the other 2 single models(all P＜0.05).Conclusion Clinical-CT radiomics combination model based on tumor location and Radscore could effectively predict MSI-H status of gastric cancer.