BACKGROUND:Studies have reported that alendronate intake significantly increases bone mineral density in patients with osteoporosis. OBJECTIVE:To analyze and compare the changes in metabolites before and after alendronate intervention in ovariectomized rats by chromatography-mass spectrometry,and to further explore the specific mechanism and target of alendronate in the treatment of osteoporosis. METHODS:A total of 36 female Sprague-Dawley rats were randomly divided into model group,alendronate sodium group and sham operation group.The osteoporosis model was established by ovariectomy in the first two groups.Four weeks after modeling,the rats in the alendronate group were intragastrically given alendronate sodium,while those in the sham operation group and model group were given equal volume of normal saline.After 12 weeks of continuous gavage,the metabolites of the lumbar spine were analyzed by chromatography-mass spectrometry,and the common differential metabolites were obtained,which were analyzed by bioinformatics such as Kyoto Gene and Genome Encyclopedia pathway. RESULTS AND CONCLUSION:Totally 17 different metabolites were obtained in the three groups.The enrichment analysis of the Kyoto Encyclopedia of Genes and Genomes showed that alendronate sodium could regulate unsaturated fatty acid biosynthesis,linoleic acid metabolism and other pathways to protect ovariectomized rats.These results indicate that alendronate sodium may exert its anti-osteoporosis effect by interfering with unsaturated fatty acid bioanabolism and linoleic acid metabolism,so as to achieve the purpose of preventing osteoporosis

Objective:To establish contact dermatitis pruritus model and detect itch,anxiety and depression-like behaviors.To observe the activation of the medial prefrontal cortex(mPFC)neurons and provide morphological evi-dence for its involvement in the regulation of itch perception information.Methods:A model of contact dermatitis pruri-tus was constructed with diphenylcyclopyrenone(DCP)applied on the neck and back of the mouse,and the itch per-ception video tracking system was used to detect the scratching behavior.Open field and suspended tail behavioral ex-periments were conducted to explore the anxiety and depression-like behaviors of mice under contact dermatitis.The dis-tribution of c-Fos and p-ERK1/2 positive cells in the mPFC of contact dermatitis model mice was investigated by immu-nofluorescence staining.Results:The contact dermatitis pruritus model was successfully established,and the bouts of scratching in the contact dermatitis model group was significantly higher than that in the control group(P＜0.05).The results of open field test showed that the time and distances were significantly reduced in the central area of the contact dermatitis model group.The results of the tail suspension experiment suggested that the time of immobility increased sig-nificantly in the contact dermatitis model group(P＜0.05).There were more c-Fos positive and p-ERK1/2 positive cells in the mPFC compared with the control group(P＜0.05).Conclusion:Bouts of scratching were increased in the contact dermatitis group and the mice had anxiety and depression-like behaviors.In the contact dermatitis state,mPFC neurons were activated,providing morphological evidence for the involvement of mPFC neurons in contact dermatitis pruritus and accompanying affective disorders such as anxiety and depression.

Since the concept of mixed connective tissue disease was proposed，it remains controversial in its pathogenesis and diagnosis.Mixed connective tissue disease is generally recognized as a disease entity characterized by overlapping clinical features of systemic lupus erythematosus，systemic sclerosis，and polymyositis，as well as high titers of serum anti-U1 ribonucleoprotein antibody.Studies have shown that up to 1/4 of the patients have the disease at an early age，with the first symptoms of Raynaud's phenomenon and polyarthritis，and the disease has certain differences in clinical characteristics and diagnosis and treatment from adults.The disease may evolve into other connective tissue diseases in the later stage，so early diagnosis and treatment are of great significance to improve prognosis.This article elaborates on the epidemiology，pathogenesis，clinical manifestations，diagnosis and treatment of juvenile mixed connective tissue disease.

In March 2020, the outflow of age limited videos from ICU in Spain inspired us to rethink whether there is age discrimination in the allocation of scarce medical resources. This paper frist reflected on the problem of age discrimination caused by this phenomenon from four moral intuitions: the sacred view of life, the quality of life and values, public health ethics and Chinese culture, and then examined whether it is illegal from the legal level, finally pointed out the negative impact on the society, and put forward that taking age as the standard for the allocation of scarce medical resources is not suitable for China’s national conditions.

Objective:To isolate and identify SARS-CoV-2 epidemic strains and analyze the sequence characteristics of the virus strains following serial passages.Methods:Eleven nasopharyngeal swabs positive for SARS-CoV-2 antigen were collected from December 2022. Quantitative real-time PCR was used to detect SARS-CoV-2 nucleic acid, and positive specimens were inoculated onto Vero cells for virus isolation. The isolated strains were identified by Western blot and indirect immunofluorescence assay. The morphology of the isolated strains was observed using transmission electron microscopy. Nucleic acid was extracted from the isolates and passaged viruses for further sequencing and analysis.Results:All 11 specimens tested positive for SARS-CoV-2 using quantitative real-time PCR. SARS-CoV-2 strains were successfully isolated from seven specimens, and could be adaptively cultured, passaged, and expanded on Vero cells, achieving a peak titer exceeding 10 6.25 50% cell culture infectious dose (CCID 50)/ml. Western blot and indirect immunofluorescence results showed that the isolates could be specifically recognized by monoclonal antibodies and convalescent serum against SARS-CoV-2. Transmission electron microscopy revealed oval-shaped viral particles with diameters of approximately 100 nm. Next-generation sequencing of the viral isolates demonstrated a sequence homology greater than 99.50% with the Wuhan-Hu-1 reference strain (NC_045512) and 99.98% among the seven isolated strains, and all of the isolates belonged to the Omicron BF.7 variant. Sequence analysis after continuous passage and plaque purification of the BJ-NVSI-20230005 isolate showed that compared with passages 1-3, passages 4-6 had one nucleotide site mutation (C→T) in the ORF1ab gene and a deletion of 3 bp in the E gene, which resulted in a change from leucine to phenylalanine and the deletion of valine, respectively. Polymorphisms were observed in the sequences of plaque-purified clones. Conclusions:The seven successfully isolated SARS-CoV-2 strains all belong to the SARS-CoV-2 BF.7 variant, which is consistent with the prevalence trend in mainland China in December 2022.

Objective:To investigate the characteristics, process, and prognosis of esophageal stricture after circumferential endoscopic submucosal dissection (ESD), and to preliminarily analyze the prevention and treatment effects of simple dilation, stent placement, mucosal transplantation, and glucocorticoid (hereinafter referred to as hormone) application in esophageal stricture.Methods:From August 2017 to March 2022, at the First Affiliated Hospital of Zhengzhou University, the clinical and follow-up data of 55 patients who underwent circumferential ESD for early esophageal cancer and precancerous lesions were retrospectively analyzed. According to the prevention and treatment methods for esophageal stricture, the patients were divided into two groups: simple dilation group (23 cases) and combined dilation group (32 cases). The combined dilation group was divided into mucosal transplantation subgroup (9 cases), stent placement subgroup (14 cases), hormone application subgroup (7 cases), and bleomycin subgroup (2 cases, excluded from comparative analysis due to limited cases). Overall prognosis of patients was observed. Treatment efficacy, prognosis, and adverse events were compared among the simple dilation group, mucosal transplantation subgroup, stent placement subgroup, and hormone application subgroup. Independent samples t-test, chi-square test, and Fisher′s exact test were used for statistical analysis. Results:Among the 55 patients, the follow-up time was (894.1±417.7) days. Refractory esophageal stricture (total dilation times ≥ 5) occurred in 33 patients (60.0%). Fifty-two patients (94.5%) achieved clinical remission of the stricture. The total number of dilations was 5.8±4.0, and the average dysphagia-free period was (52.3±37.1) days. The dysphagia-free period of mucosal transplantation subgroup was longer than that of the simple dilation group, stent placement subgroup, and hormone application subgroup ((114.5±50.0) days vs. (40.9±20.0), (39.7±10.0), and (40.9±25.5) days, respectively), and the differences were statistically significant ( t=4.82, 3.77 and 3.14, P<0.001, =0.011, =0.009). There were no statistically significant differences between the simple dilation group and the mucosal transplantation subgroup, stent placement subgroup, and hormone application subgroup in the total number of dilations (6.8±4.8 vs. 3.0±2.5, 5.8±2.2, and 5.7±5.0), stricture remission rate (95.7%, 22/23 vs. 8/9, 13/14, and 7/7), and incidence of adverse events (17.4%, 4/23 vs. 5/9, 5/14, and 2/7; all P>0.05). Conclusions:Esophageal stricture formed after circumferential ESD shows the characteristics of recurrence and intractability. The over all number of dilations is high, and the average dysphagia-free period is short. Most patients can achieve clinical remission of the stricture after multiple times of endoscopic dilation treatment. However mucosal transplantation, stent placement, and hormone application cannot well intervene the natural process of esophageal stricture.

Objective:To evaluate the value of CT in preoperative assessment of tricuspid valve replacement with LuX-Valve.Methods:145 consecutive patients with severe tricuspid regurgitation from October 2020 to April 2021 were selected. The multi-slice spiral CT (256 slice and above) scans were used to measure related indicators. Then analyses were made to determine whether the patients were suitable for valves replacement and to select the appropriate valve model.Results:49 cases were excluded after CT measurements, including 8 cases because of the values of the valve annulus and the remaining 41 due to comprehensive indicators includes: valve annulus size and shape, fixation method and operational safety. A total of 96 TTVR operations were performed, of which 6 were treated with thoracic surgery, 1 had moderate valve regurgitation, and the rest had no or mild regurgitation or paravalvular leaks. The operations showed a high success rate of 92.7%. After comprehensive analysis, it was found that among the 89 successful tricuspid valve replacements with LuX-Valve, 26 cases had annulus models consistent with the measurements of the diameter from tricuspid annular circumferences, while the remaining 63 had valve models larger than the diameter measurements. The results indicate that the size of right atrium was statistically significant to the enlargement of the valve size.Conclusion:CT has important application value in the preoperative screening of TTVR. For non-radial force LuX-Valve, the annulus size is not the only decisive factor, and the valve model should be comprehensively judged considering all the measurement indicators.

In March 2020, the outflow of age limited videos from ICU in Spain inspired us to rethink whether there is age discrimination in the allocation of scarce medical resources. This paper frist reflected on the problem of age discrimination caused by this phenomenon from four moral intuitions: the sacred view of life, the quality of life and values, public health ethics and Chinese culture, and then examined whether it is illegal from the legal level, finally pointed out the negative impact on the society, and put forward that taking age as the standard for the allocation of scarce medical resources is not suitable for China’s national conditions.

Objective BAG3-related myopathy is a rare condition so far reported in twenty patients worldwide.The purpose of this study was to draw attention to this rare disease and to the fact that BAG3-related myopathy should be considered as a rare differential diagnosis of hypercapnia.Methods We report a sporadic case of a 14-year-old Chinese girl with a de novo p.Pro209Leu mutation in BAG3 and reviewed the literatures for reported cases related to this mutation.Results We described a 14-year-old Chinese girl who presented with gradually appearing symptoms of hypercapnia that required assisted ventilation.The muscle biopsy and the blood whole-exome sequencing results confirmed the diagnosis of myofibrillar myopathy with a de novo p.Pro209Leu mutation in BAG3.Totally twenty-one patients from twenty families with a confirmed diagnosis of BAG3-related myopathy were reported to date,including this patient and literature review.The male to female ratio was 11 :10 and most showed initial symptoms in the first decade of life.Most patients presented toe/clumsy walking or running as the onset symptom,followed by muscle weakness or atrophy.Creatine kinase levels were elevated in fourteen patients and were normal in three.Eighteen patients developed respiratory insufficiency during the disease course and thirteen (one could not tolerate non-invasive assisted ventilation) required non-invasive assisted ventilation for treatment.Except for one not reported,heart involvement was found in seventeen patients during the disease course and seven underwent heart transplantation.Z-disk streaming and aggregation could be observed in most of the patients' muscle histology.In the long-term follow-up,five patients died of cardiac or respiratory failure.Conclusion BAG3-associated myopathy is a rare type of myofibrillar myopathy.It should be considered as a rare differential diagnosis of hypercapnia.

The role of malate dehydrogenase 2 (MDH2) in tumors is double-sided,it has a cancerpromoting effect in some tumors and an inhibitory effect in other tumors.The function of MDH2 is related to energy metabolism,tumor resistance and its pseudo hypoxia.MDH2 plays an important role in the occurrence,development,invasion and metastasis of tumors.An in-depth understanding of the functional mechanism of MDH2 in tumors can provide new molecular targets for tumor intervention in the clinic.