This article presents a case study of a patient who visited the Geriatric Department of Peking Union Medical College Hospital due to "palpitations, shortness of breath for more than 2 years, limb weakness for 6 months, edema, and nocturnal dyspnea for 2 months". The patient exhibited decreased muscle strength in the limbs and involvement of swallowing and respiratory muscles, alongside complications of heart failure and various arrhythmias which were predominantly atrial. Laboratory tests revealed the presence of multiple autoantibodies and notably anti-mitochondrial antibodies. Following a comprehensive multidisciplinary evaluation, the patient was diagnosed with anti-mitochondrial antibody-associated inflammatory myopathy. Treatment involved a combination of glucocorticoids and immunosuppressants, along with resistance exercises for muscle strength and rehabilitation training for lung function, resulting in significant improvement of clinical symptoms. The case underscores the importance of collaborative multidisciplinary approaches in diagnosing and treating rare diseases in elderly patients, where careful consideration of clinical manifestations and subtle abnormal clinical data can lead to effective interventions.

Roxadustat is the world's first small molecule hypoxia-inducible factor prolyl hydroxylase inhibitor. Its adverse effect of causing hypothyroidism with low thyroid-stimulating hormone (TSH) is relatively rare and manifests subtly in elderly patients with multiple coexisting diseases. This article reports a case of an elderly patient with renal anemia who developed reversible low-TSH hypothyroidism after taking roxadustat for 12 days, with a significant decrease in thyroid hormone levels. After discontinuing roxadustat for 15 days, the thyroid hormone levels gradually returned to normal. Due to the worsening of renal anemia, the patient took roxadustat again, and 9 days later, the thyroid function-related indicators decreased upon re-examination, leading to the initiation of levothyroxine replacement therapy. In conjunction with relevant literature, this article analyzes the adverse reactions that occur during the oral administration of roxadustat in elderly patients with chronic kidney disease, aiming to provide reference for drug treatment of such patients.

To describe the history, current status and development trend of clinical pharmacist training in China.

ObjectiveTo observe the effectiveness and safety of modified Taohong Siwu Decoction （桃红四物汤） for patients of chronic heart failure with lower limb deep vein thrombosis in the chronic stage of blood stasis syndrome. MethodsA total of 120 patients of chronic heart failure with lower limb deep vein thrombosis in chronic stage of blood stasis syndrome were randomly divided into 60 cases each in control group and observation group. Both groups were given basic treatment of western medicine， and the observation group was additionally given modified Taohong Siwu Decoction （桃红四物汤） for oral administration， one dose per day. The treatment course for both groups lasted for 4 weeks. The total effective rate and the incidence of adverse reactions were compared between the two groups after treatment. Cardiac function indexes including left ventricular ejection fraction （LVEF）， and left ventricular end-systolic internal diameter （LVESd）， left ventricular end-diastolic internal diameter （LVEDd）， serological indexes including N-terminal natriuretic natriuretic peptide precursor （NT-proBNP）， high sensitivity C-reactive protein （hs-CRP） and vascular endothelial growth factor （VEGF）， score of traditional Chinese medicine （TCM） symptom including chest pain， swelling of the affected limb， fixed tenderness， and bruising， haemodynamics indicators including high cut whole blood viscosity， low cut whole blood viscosity， and erythrocyte pressure， and coagulation indices including activated partial thromboplastin time （APTT）， plasminogen time （PT）， and fibrinogen （FIB） levels were compared before and after treatment. ResultsDuring the study， 3 cases were excluded and 2 cases lost follow-up in the observation group， while 2 cases were excluded and 3 cases lost follow-up in the control group. A total of 110 patients completed the trial， 55 cases in each of the two groups. The total effective rate in the observation group was 92.73% （51/55）， which was significantly higher than that of the control group， 78.18% （43/55， P＜0.05）. Compared within group before treatment， LVEF， APTT and PT levels increased， LVESd， LVEDd， NT-proBNP， hs-CRP， VEGF， high cut whole blood viscosity， low cut whole blood viscosity， erythrocyte pressure volume and FIB levels decreased， chest pain， swelling of the affected limbs， stationary pressure pain and bruising score decreased in both groups after treatment， and the improvement of all above indexes was better in the observation group than that in control group （P＜0.05 or P＜0.01）. The incidence of adverse reactions was 7.27% （4/55） in the observation group and 21.82% （12/55） in the control group， and the incidence of adverse reactions in the observation group was significantly lower than that in the control group （P＜0.05）. ConclusionModified Taohong Siwu Decoction （桃红四物汤） as adjuvant treatment for patients of chronic heart failure with lower limb deep vein thrombosis in the chronic stage of blood stasis syndrome showed better clinical effectiveness when compared with western basic treatment， which can improve the clinical symptoms， cardiac function， haemodynamics， and coagulation， with good safety.

Objective: To investigate prevalence of hepatitis E virus (HEV) infection among voluntary blood donors in Dalian and provide evidence for enhancing blood screening strategies. Methods: A total of 3 277 blood donor samples collected between December 2023 and February 2024 at Dalian Blood Center underwent routine blood screening (ALT, HBsAg, anti-HCV, HIV Ag/Ab, anti-TP, and HBV/HCV/HIV NAT). Subsequently, HEV antigen (Ag) was detected using chemiluminescence immunoassay (CLIA). HEV-Ag reactive samples were further tested for HEV RNA, IgM and IgG antibodies. Blood donors with repeated reactive HEV Ag results were followed up to clarify the status of infection. Results: Among the 3 277 blood donor samples, 6 (0.18%) were repeatedly reactive for HEV Ag. However, supplemental testing for HEV RNA, anti-HEV IgM, and anti-HEV IgG on these samples yielded non-reactive results. One of these six blood donors was successfully followed up. On day 218 after the initial detection of HEV Ag reactivity, HEV Ag, HEV RNA, HEV IgM and IgG antibody were found to be non-reactive. Conclusion: The reaction rate for HEV antigen screening among voluntary blood donors in Dalian is low. CLIA method for detecting HEV antigen is easy to operate and cost-effective, but demonstrates some false reactivity. Improving the specificity of the assay and combining it with nucleic acid testing (NAT) would be valuable for implementing a selective HEV screening strategy for blood donors.

OBJECTIVE: An intelligent moxibustion instrument based on electromyography was designed to evaluate the real-time therapeutic effect of moxibustion. METHODS: Taking Shenshu (BL23) as the subject, surface electromyography (sEMG) at the center and equidistant points of Shenshu (BL23) were collected. The characteristic parameters, integrated electromyography (iEMG) and root mean square (RMS) were calculated before and after moxibustion. After analyzing the effect of moxibustion, a function algorithm for the end-of-moxibustion was obtained. Using this algorithm and combined with STM32 technology, the control system of moxibustion instrument and the upper computer software were designed to achieve the precise control during moxibustion delivery. Finally, the function, stability and safety of the moxibustion instrument were verified through clinical trials to ensure its effectiveness in practical application. RESULTS: During one cycle of moxibustion at the center of Shenshu (BL23), the iEMG of sEMG decreased over time, meaning the decrease in muscle fatigue degree, and after one cycle of moxibustion, it elevated over time, showing the increase in muscle fatigue degree. RMS increased by 1.90% before and after moxibustion at the equidistant points of Shenshu (BL23), and the system indicated the end of moxibustion when RMS increased by 0.15%, and decreased by 0.13% at the center of Shenshu (BL23). The intelligent moxibustion instrument designed based on this algorithm can realize the function of mild moxibustion, and the effect of moxibustion can be evaluated by the real-time monitoring of RMS changes through the upper computer. During the operation of moxibustion instrument, moxa stick was fixed stably, remained a safe distance of 3 cm to 4 cm away from the skin surface. When the length of moxa stick was less than 5 cm left after ignited and the skin temperature exceeded the preset safety threshold of 48 ℃, the system was alarmed automatically. CONCLUSION The intelligent moxibustion instrument designed in the research can effectively evaluate the effect of moxibustion, and ensure the safety and stability during moxibustion delivery.
Humans ; Moxibustion/methods* ; Electromyography/instrumentation* ; Adult ; Male ; Female ; Young Adult ; Acupuncture Points ; Algorithms ; Middle Aged

BACKGROUND: Immunosuppression is closely related to the pathogenesis of sepsis, but the underlying mechanisms have not yet been fully elucidated. In this study, we aimed to examine the role of the Sterile Alpha Motif, Src Homology 3 domain and nuclear localization signal 1 (SAMSN1) in sepsis and elucidate its potential molecular mechanism in sepsis induced immunosuppression. METHODS: RNA sequencing databases were used to validate SAMSN1 expression in sepsis. The impact of SAMSN1 on sepsis was verified using gene knockout mice. Flow cytometry was employed to delineate how SAMSN1 affects immunity in sepsis, focusing on immune cell types and T cell functions. Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9)-mediated gene editing in RAW264.7 macrophages enabled interrogation of SAMSN1 's regulatory effects on essential macrophage functions, including cell proliferation and phagocytic capacity. The mechanism of SAMSN1 in the interaction between macrophages and T cells was investigated using the RAW264.7 cell line and primary cell lines. RESULTS: SAMSN1 expression was significantly increased in patients with sepsis and was positively correlated with sepsis mortality. Genetic deletion of Samsn1 in murine sepsis model improved T cell survival, elevated T cell cytolytic activity, and activated T cell signaling transduction. Concurrently, Samsn1 knockout augmented macrophage proliferation capacity and phagocytic efficiency. In macrophage, SAMSN1 binds to Kelch-like epichlorohydrin-associated protein 1 (KEAP1), causing nuclear factor erythroid 2-related factor 2 (NRF2) to dissociate from the KEAP1-NRF2 complex and translocate into the nucleus. This promotes the transcription of the coinhibitory molecules CD48/CD86/carcinoembryonic antigen related cell adhesion molecule 1 (CEACAM1), which bind to their corresponding receptors natural killer cell receptor 2B4/CD152/T cell immunoglobulin and mucin domain-containing protein 3 (TIM3) on the surface of T cells, inducing T-cell exhaustion. CONCLUSIONS SAMSN1 deletion augmented adaptive T cell immunity and macrophage phagocytic-proliferative dual function. Furthermore, it mediates the KEAP1-NRF2 axis, which affects the expression of coinhibitory molecules on macrophages, leading to T-cell exhaustion. This novel immunosuppression mechanism potentially provides a candidate molecular target for sepsis immunotherapy.
Animals ; NF-E2-Related Factor 2/metabolism* ; Mice ; Macrophages/immunology* ; Sepsis/metabolism* ; Kelch-Like ECH-Associated Protein 1/genetics* ; T-Lymphocytes/immunology* ; Humans ; Signal Transduction/physiology* ; RAW 264.7 Cells ; Mice, Knockout ; Mice, Inbred C57BL ; Male ; Flow Cytometry ; T-Cell Exhaustion

Objective:To prepare hydroxyapatite(HA)coating on polyether ether ketone(PEEK)surface by magnetron sputtering technique and to study its biosafety.Methods:Sulfonated PEEK was used to increase the binding area and HA coating was constructed on it using magnetron sputtering technology.SEM and energy dispersive spectroscopy(EDAX)were used to detect the construction effect.Cell adhesion assay,cytoskeletal fluorescence staining and SEM validation were used to assess cytologrcal safety.In vivo safety tests were conducted in SD rats and golden hamsters.Results:HA coating with gradient morphology was successfully constructed on the PEEK surface using above technique.The coating promoted cell adhesion,extension and proliferation.No systemic toxicity and no sig-nificant influence in HE staining of the main infernal organs samples were observed.The coating alleviated the oral mucosal irritation caused by simple sulfonation to a certain extent.Conclusion:HA coating can be prepared stably with magnetron sputtering technology and can meet the biosafety needs for clinical applications.

Purpose To explore the application and clini-cal significance of molecular detection in cell block specimens of lung adenocarcinoma.Methods A total of 200 cell block spec-imens of lung adenocarcinoma were collected.Among them 49 specimens underwent multi-gene panel detection(including EG-FR,EML4-ALK,ROS1,KRAS,HER2,BRAF,RET,MET,NRAS,and PIK3CA),while 151 specimens underwent EGFR single-gene detection.In addition,97 specimens were tested for EML4-ALK fusion gene alterations using the Ventana method,and the results were compared with that by PCR detection.The mutation characteristics were summarized,and the cytological features of the mutations and fusions were observed.Results The positive rate of driver gene mutations in 49 cases of multi-gene panel detection was 65.31％,which indicated no statisti-cally significant difference from that of 99 lung adenocarcinoma tissue specimens(P＞0.05).The positive rates of ALK,ROS1,and RET fusion mutations were 4.08％,4.08％,and 2.04％,respectively,and the positive rates of EGFR,KRAS,HER2,MET,and BRAF mutations were 38.78％,6.12％,4.08％,4.08％,and 2.04％,respectively.The mutation rate of EGFR in 151 cases of single-gene detection was 54.97％,with a mutation rate of 42.86％in males and 67.57％in fe-males,showing a statistically significant difference between gen-ders(P＜0.05).Exon 19 deletion mutation(19-Del)and exon 21 point mutation(21-L858R)in the EGFR gene took the high-est proportions,accounting for 54.22％and 37.35％,respec-tively,significantly higher than other mutation types(P＜0.001).The positive rate of EML4-ALK fusion gene immuno-histochemistry(IHC)in 97 cytological paraffin-embedded speci-mens was 15.46％,among which 6 cases with weak positivity(+)showed negative results in molecular detection,and 9 ca-ses with diffuse positivity(+++)showed positive results in molec-ular detection.The results of immunohistochemistry were highly consistent with molecular detection in cases with diffuse strong positivity(Kappa=1).It was found from the cytological mor-phology of cases with gene alterations that KARS mutation carri-ers were born with unique characteristics,with tumor cells scat-tered or arranged in small clusters and more cytoplasmic vacu-oles were commonly seen.Conclusion Molecular detection in cytological specimens of lung adenocarcinoma is feasible with higher sensitivity.Multi-gene panel detection is superior to sin-gle-gene detection.Immunohistochemistry can be used for screening EML4-ALK fusion gene,and lung adenocarcinoma with KRAS mutation that exhibits distinct cytological morpholo-gy.

Objective:To investigate the clinicopathological characteristics of gastrointestinal tumors with SWI/SNF complex deficiency and to perform a prognostic analysis of the patients.Methods:Gastrointestinal tumor cases with SWI/SNF complex deficiency expression diagnosed at the Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, China from August 2021 to May 2023 were collected. Hematoxylin and eosin (HE) stained slides were reviewed, and immunohistochemical results were analyzed. Clinical and pathological information was recorded, and relevant literature was reviewed.Results:A total of 36 cases of gastrointestinal tumor with loss of SWI/SNF complex expression were identified, including 28 males (77.8%) and 8 females (22.2%). The average age at diagnosis was 70 years (range 48-85 years). Clinical staging showed 3 cases in stage Ⅰ (8.3%), 12 cases in stage Ⅱ (33.3%), 19 cases in stage Ⅲ (52.8%), and 2 cases in stage Ⅳ (5.6%). Complete or partial loss of ARID1A expression was observed in 20 cases (55.6%); complete or partial loss of SMARCA2 expression was observed in 24 cases (66.7%). SMARCA4 exhibited complete loss of expression in 4 cases (11.1%). Eleven cases (30.6%) showed concurrent complete or partial losses of both ARID1A and SMARCA2 expression. Twelve cases (33.3%) had mismatch repair protein deficiency, all of which were characterized by MLH1/PMS2 absence. Mismatch repair protein deficiency was associated with loss of ARID1A expression ( P<0.01). Patients with mismatch repair protein deficiency were also associated with earlier clinical stage and a lower risk of lymph node metastasis compared to the ones with intact mismatch repair proteins ( P<0.05). Conclusions:SWI/SNF complex deficiency in gastrointestinal tumors is associated with dedifferentiation and often accompanied by mismatch repair protein deficiency. Compared to the cases with intact mismatch repair proteins, the cases with defective mismatch repair protein have an earlier clinical stage and a lower risk of lymph node metastasis.