OBJECTIVE: To explore the effectiveness of arthroscopic release of elbow joint assisted by medial small incision ulnar nerve release in the treatment of non-traumatic elbow stiffness. METHODS: The clinical data of 15 patients with non-traumatic elbow stiffness treated with arthroscopic release of elbow joint assisted by medial small incision ulnar nerve release between April 2019 and September 2023 were retrospectively analyzed. There were 6 males and 9 females with an average age of 46 years ranging from 34 to 56 years. The causes included rheumatoid arthritis in 3 cases, gouty arthritis in 2 cases, loose bodies in 3 cases, and elbow osteoarthritis in 7 cases. There were 4 cases with ulnar neuritis and 3 cases with synovial osteochondromatosis. The duration of elbow stiffness ranged from 6 to 18 months, with an average of 10 months. The operation time and intraoperative blood loss were recorded. The effectiveness was evaluated by visual analogue scale (VAS) score, range of elbow motion (maximum flexion, maximum extension, and total flexion and extension), Mayo score, and Hospital for Special Surgery (HSS) elbow score. RESULTS: The operation time was 60-90 minutes, with an average of 65 minutes, and the intraoperative blood loss was 40-100 mL, with an average of 62 mL. All patients were followed up 13-18 months, with an average of 14 months. There was no complication such as vascular and nerve injury, poor wound healing, collateral ligament injury, elbow joint space narrowing, osteophyte proliferation, or loose body formation around the joint. At last follow-up, the elbow range of motion (maximum flexion, maximum extension, and total flexion and extension), VAS score, and Mayo score significantly improved when compared with those before operation ( P<0.05). The HSS elbow score was 85-95, with an average of 92; 12 cases were excellent, 3 cases were good, and the excellent and good rate was 100%. CONCLUSION Arthroscopic release of elbow joint assisted by medial small incision ulnar nerve release is an effective way to treat non-traumatic elbow stiffness, which has the advantages of small trauma, short operation time, and good effectiveness. It can carry out early elbow rehabilitation training and significantly improve elbow function.
Humans ; Male ; Female ; Arthroscopy/methods* ; Adult ; Middle Aged ; Elbow Joint/physiopathology* ; Retrospective Studies ; Range of Motion, Articular ; Treatment Outcome ; Ulnar Nerve/surgery* ; Operative Time

In November 23, 2023, a patient with 9 digits traumatic crush injury by machine compression was emergently admitted to the Department of Hand and Microsurgery, Sichuan Modern Hospital. Emergency procedures included amputation the distal stumps and replantation of proximal phalanges of left ring and little fingers. Wounds in both hands were temporarily covered with bone cement. On December 4, 2023, reconstruction of 5 digits were performed. Digital defects were: Type Ⅲ defects of left index and middle fingers and right thumb and index fingers and Type IV defect of right middle finger. All 5 reconstructed digits survived. Subsequent refinements yielded favourable outcomes and all donor toes were preserved completely. At the 14-month follow-up, the reconstructed digits exhibited satisfactory appearance and length without difficulties in daily life and at work.

In November 23, 2023, a patient with 9 digits traumatic crush injury by machine compression was emergently admitted to the Department of Hand and Microsurgery, Sichuan Modern Hospital. Emergency procedures included amputation the distal stumps and replantation of proximal phalanges of left ring and little fingers. Wounds in both hands were temporarily covered with bone cement. On December 4, 2023, reconstruction of 5 digits were performed. Digital defects were: Type Ⅲ defects of left index and middle fingers and right thumb and index fingers and Type IV defect of right middle finger. All 5 reconstructed digits survived. Subsequent refinements yielded favourable outcomes and all donor toes were preserved completely. At the 14-month follow-up, the reconstructed digits exhibited satisfactory appearance and length without difficulties in daily life and at work.

Background Chronic excessive exposure to fluoride can cause damage to the central nervous system and a certain degree of learning and memory impairment. However, the associated mechanism is not yet clear and further exploration is needed. Objective Using 4D unlabelled quantitative proteomics techniques to explore differentially expressed proteins and their potential mechanisms of action in chronic excessive fluoride exposure induced brain injury. Methods Twenty-four SPF-grade adult SD rats, half male and half male, were selected and divided into a control group and a fluoride group by random number table method, with 12 rats in each group. Among them, the control group drank tap water (fluorine content<1 mg·L⁻¹), the fluoride group drank sodium fluoride solution (fluorine content 10 mg·L⁻¹), and both groups were fed with ordinary mouse feed (fluoride content<0.6 mg·kg⁻¹). After 180 d of feeding, the SD rats were weighed, and then part of the brain tissue was sampled for pathological examination by hematoxylin-eosin (HE) staining and Nissl staining. The rest of the brain tissue was frozen and stored at −80 ℃. Three brain tissue samples from each group were randomly selected for proteomics detection. Differentially expressed proteins were screened and subcellular localization analysis was performed, followed by Gene Ontology (GO) function analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, cluster analysis, and protein-protein interaction analysis. Finally, Western blotting was used to detect the expression levels of key proteins extracted from the brain tissue samples. Results After 180 d of feeding, the average weight of the rats in the fluoride group was significantly lower than that in the control group (P<0.05). The brain tissue stained with HE showed no significant morphological changes in the cerebral cortex of the fluoride treated rats, and neuron loss, irregular arrangement of neurons, eosinophilic changes, and cell body pyknosis were observed in the hippocampus. The Nissl staining results showed that the staining of neurons in the cerebral cortex and hippocampus of rats exposed to fluoride decreased (Nissl bodies decreased). The proteomics results showed that a total of 6927 proteins were identified. After screening, 206 differentially expressed proteins were obtained between the control group and the fluoride group, including 96 up-regulated proteins and 110 down-regulated proteins. The differential proteins were mainly located in cytoplasm (30.6%), nucleus (27.2%), mitochondria (13.6%), plasma membrane (13.6%), and extracellular domain (11.7%). The GO analysis results showed that differentially expressed proteins mainly participated in biological processes such as iron ion transport, regulation of dopamine neuron differentiation, and negative regulation of respiratory burst in inflammatory response, exercised molecular functions such as ferrous binding, iron oxidase activity, and cytokine activity, and were located in the smooth endoplasmic reticulum membrane, fixed components of the membrane, chloride channel complexes, and other cellular components. The KEGG significantly enriched pathways included biosynthesis of secondary metabolites, carbon metabolism, and microbial metabolism in diverse environments. The results of differential protein-protein interaction analysis showed that the highest connectivity was found in glucose-6-phosphate isomerase (Gpi). The expression level of Gpi in the brain tissue of the rats in the fluoride group was lower than that in the control group by Western blotting (P<0.05). Conclusion Multiple differentially expressed proteins are present in the brain tissue of rats with chronic fluorosis, and their functions are related to biosynthesis of secondary metabolites, carbon metabolism, and microbial metabolism in diverse environments; Gpi may be involved in cerebral neurological damage caused by chronic overdose fluoride exposure.

Objective:Through the investigation of the pathogenicity of COL4A4 heterozygous splicing mutations and the genotype-phenotype correlation in autosomal dominant Alport syndrome (ADAS), to better understand the impact of COL4A4 heterozygous splicing mutations on ADAS. Methods:The study was a case series analysis. Patients from 5 ADAS families with COL4A4 heterozygous splicing mutations detected by whole exome sequencing were recruited by three hospitals. In vivo transcriptional analysis and/or in vitro minigene splicing assay were conducted to determine the splicing patterns and assess the pathogenicity of COL4A4 heterozygous splicing mutations. Results:In the five ADAS pedigrees carrying COL4A4 heterozygous splicing mutations, four novel ADAS splicing patterns were described. In pedigree 1-4, most patients presented with continuous hematuria or/and microalbuminuria. Otherwise,the proband in pedigree 4 presented with macroalbuminuria and the proband in pedigree 1 had progressed to chronic kidney disease stage 2 at the age of 70 years old. In pedigree 5, all patients developed end-stage renal disease between 28 and 41 years old. c.735+3A>G detected in pedigree 1 and pedigree 2 and c.694-1G>C detected in pedigree 3 both led to exon 12 skipping in COL4A4, resulting in 42 nucleotides in-frame deletion (c.694_735del). c.2056+3A>G detected in pedigree 4 led to COL4A4 exon 26 skipping, which caused in-frame deletion of 69 nucleotides (c.1988_2056del). c.2716+5G>T detected in pedigree 5 led to a 360 nucleotides large in-frame deletion, including 100 bp sequence at the 3'end of exon 29,the whole sequence of exon 30 and 89 bp sequence at the 5'end of exon 31 (c.2446_2805del). Conclusions:Renal prognosis differs significantly for patients with small in-frame deletions versus large in-frame deletion splicing abnormalities. Determination of the pathogenicity and the splicing patterns of COL4A4 heterozygous splicing mutations using in vivo and in vitro transcriptional analysis may provide renal prognostic information.

Alzheimer’s disease （AD）is a common latent neurodegenerative disease ，which is characterized by cognitive impairment，loss of learning and memory function ，abnormal behavior and dementia. At present ，there is no specific drug to effectively prevent or reverse AD. Gardenia jasminoides is the dried and mature fruit of G. jasminoides J. Ellis ，a gardenia plant in Rubiaceae. Its chemical components mainly include iridoids ，triterpenoids，organic acids and volatile oils ，among which iridoids are the main active components of G. jasminoides . This paper summarizes the researches on the mechanism of iridoids from G. jasminoides against AD at home and abroad in recent years ，in order to provide reference for the development of new drugs against AD.

Abstract: To investigate the changes of cerebral blood flow(CBF) in patients with type 2 diabetes mellitus(T2 DM) and its correlation with cognitive function and olfactory impairment. Methods: Cognitive function assessment and smell identification test were performed on 83 patients with T2 DM and 62 healthy controls(HC). Three-dimensional pseudo-continuous arterial spin labeling(3 D-pcASL) head images were collected from the two groups. CBF values of the cerebral cortex were compared between the patients and HC after the postprocessing. Correlations between the CBF values and cognitive function assessment and between the CBF values and smell identification test scores were analyzed as well. Results: Compared to the HC, Chinese smell identification test(CSIT), montreal cognitive assessment(MoCA), digit span test(DST), verbal fluency test(VFT) scores were lower in T2 DM patients(P<0.05).The CBF of the bilateral middle frontal gyrus in T2 DM patients was higher than that in HC group(P<0.001). The CBF of the bilateral gyrus rectus and olfactory cortex in T2 DM patients was lower than that in HC group(P<0.001). Conclusion The cognitive and olfactory function of patients with T2 DM decreased. Patients with T2 DM have abnormal perfusion in the bilateral middle frontal gyrus, gyrus rectus and olfactory cortex, revealing that CBF changes in these brain regions may be one of the causes for cognitive impairment and olfactory dysfunction in T2 DM.

Anaplastic lymphoma kinase (ALK) fusions represent the second most common oncogenic driver mutation in non-small cell lung cancer (NSCLC). As the new class of 3rd generation of ALK tyrosine kinase inhibitor (TKI), lorlatinib has shown robust potency and brain-penetrant clinical activity against a wide spectrum of multiple resistance mutations within the ALK domain detected during crizotinib and 2nd generation ALK TKI treatment. Lorlatinib is generally well-tolerated with unique adverse drug reaction/adverse event, including hyperlipidemia and central nervous system effects, which are mostly mild to moderate severity and manageable through dosage modifications and/or standard medical intervention. For advanced NSCLC with ALK positivity, patients should be evaluated for baseline characteristics and pre-existing medication, informed of the potential toxicities, and periodically monitored to balance benefits and risks. Moreover, a multidisciplinary group of experts is essential to establish a comprehensive diagnostic and therapeutic strategy.
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Aminopyridines ; Carcinoma, Non-Small-Cell Lung/pathology* ; China ; Consensus ; Drug Resistance, Neoplasm/genetics* ; Drug-Related Side Effects and Adverse Reactions/drug therapy* ; Humans ; Lactams ; Lactams, Macrocyclic/adverse effects* ; Lung Neoplasms/pathology* ; Protein Kinase Inhibitors/adverse effects* ; Protein-Tyrosine Kinases/genetics* ; Pyrazoles

Objective:To explore the sex-based heterogeneity in demographic and pathological trends of lung cancer during the past 30 years.Methods:Patients with primary lung cancer who received surgical treatment in the Department of thoracic surgery, Shanghai Pulmonary Hospital Tongji University from 1989 to 2018 were retrospectively analyzed. The differences between male and female patients in age, smoking history, pathological stage and type were compared. Mann- Kendall trend test was performed for trend analysis. Results:A total of 58 433 patients were included in this study, encompassing 30 729(52.6%) men and 27 , 704(47.4%) women. Compared with male patients, female patients were younger(56.0 years old vs. 59.7 years old), and had a higher proportion of non-smokers(98.3% vs. 52.3%), stage Ⅰ lung cancers(60.6% vs. 49.3%), and adenocarcinoma(93.7% vs. 56.1%, all P-values <0.001). Trend analyses revealed that the proportion of female patients increased year by year, and surpassed males in 2015, with the current ratio of male to female being 1∶1.5. After 2013, the age of onset in females was getting younger, and the average age decreased from 58.7 years old to 54.7 years old( P=0.02). The decrease in the proportion of smoking patients was mainly reflected by male patients(from 68.5% to 31.1%, P<0.01). Stage Ⅰ lung cancers in male and females outnumbered advanced stage in 2012 and 2010, respectively, with a much higher proportion in female patients. Among male patients, adenocarcinoma has replaced squamous cell carcinoma as the most common pathological type since 2012, while in female patients adenocarcinoma remained the most common pathological type of lung cancer, and its proportion continued to increase reaching over 98%. Conclusion:A dramatic change in gender distribution was noticed during the past 30 years. Female patients became the primary population in surgically-treated lung cancers, with a trend of getting younger. The proportion of smokers and squamous cell carcinoma decreased significantly in male patients, and adenocarcinoma has become the most common pathological type of lung cancer. The proportion of stage Ⅰ lung cancers was on a dramatic rise, with the popularization of CT screening for lung cancer.

Objective: Taxifolin is a natural flavonoid compound that can be isolated from onions, grapes, oranges and grapefruit. It also acts as a medicine food homology with extraordinary antioxidant and anti-inflammatory activity. This study aims to explain the protective effects and potential mechanisms of taxifolin against inflammatory reaction. Methods: Levels of interleukin (IL)-6, IL-1β and intracellular reactive oxygen species (ROS) were assessed in different time after the treatment of taxifolin in RAW264.7 cells induced by lipopolysaccharide (LPS). Subsequently, the mRNA and protein levels of inducible nitric oxide synthase (iNOS), vascular endothelial growth factor (VEGF), cyclooxygenase (COX)-2, tumor necrosis factor (TNF)-α and the phosphorylation expression levels of the MAPK signal pathway were also evaluated. A silico analysis was used to explain the binding situation for the investigation of taxifolin and MAPK signal pathway. And then MAPK inhibitors were used to reveal the expression level of iNOS, VEGF, COX-2 and TNF-α in RAW264.7 cells. Results: It was demonstrated that cell inflammatory damage induced by LPS was significantly alleviated after the treatment of taxifolin. Then, the mRNA and protein levels of iNOS, VEGF, COX-2 and TNF-α were reduced and the phosphorylation expression levels of the MAPK signal pathway were down-regulated remarkably as well. In silico analysis, taxifolin could form a relatively stable combination with MAPK signal pathway. MAPK inhibitors showed increasing or decreasing effect in the mRNA levels of iNOS, VEGF, COX-2 and TNF-α, which suggesting that taxifolin down-regulated iNOS, VEGF, COX-2 and TNF-α expressions were not entirely through the MAPK pathway. Conclusion: This finding demonstrated that taxifolin improved the inflammatory responses that partly involved in the phosphorylation expression level of MAPK signal pathway in RAW264.7 cells exposed to acute stress.