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.

ObjectiveTo understand the status of parasitic infection in the food sold on market in Qingpu District of Shanghai, and to provide an evidence for the development of prevention and control strategies for parasitic infection applicable to Qingpu District. MethodsAquatic products, meat products and other foodstuffs sold on online shops, at farm product markets, supermarkets/foodstores and restaurants were sampled in Qingpu District, Shanghai, during 2015‒2023, based on the administrative division of Qingpu District. The parasitic infection in the food samples were examined using pressing method and digestion for detecting metacercariae in freshwater products and pickled products, using dissection microscopy for Anisakis larvae in seawater products, Taenia cysticercus and Trichinella encysted larvae in meat products. ResultsA total of 1 079 samples of food products were examined during 2015‒2023, with a total parasite infection rate of 13.44%. The total parasite infection rate of freshwater fish products was 3.40% (16/471), and the difference of parasite infection rates between different freshwater fish species was statistically significant (χ²=229.609, P=0.001). The total infection rate of Clonorchis sinensis was 3.18% (15/471), which had been detected in Pseudorasbora parva, Cyprinidae rhodeus, and Carassius auratus, with a positive rate of 77.78% (7/9), 50.00% (5/10) and 3.90% (3/77), respectively. Metorchis orientalis was detected in in Pseudorasbora parva, with a positive rate of 33.33% (3/9). The positive rate of Gnathostoma spinigerum (third-stage larvae) was 0.81%. Paragonimus metacercariae were not detected in the freshwater shrimps and crabs. The infection rate of seawater fish products was 26.46%. The difference of parasite infection rate in seawater fishes was statistically significant (χ²=109.181, P=0.001). A total of 53 pork and beef samples were tested, none was detected with Trichinella larva cysts, Taenia solium metacercariae, and Taenia saginata metacercariae. The total infection rate of pickled yellow mud snail products was 58.11% (43/74). Paragonimus metacercariae was not detected in any of the pickled aquatic product samples. ConclusionThere are different degrees of parasitic infection in freshwater products, seawater products and pickled aquatic products in Qingpu District of Shanghai. The risk of parasite infection from raw or undercooked foods is high. Health education on healthy dietary practices such as throughly cooked food should be strengthened for local residents.

Objective To investigate the effect of FUNDC1 tyrosine phosphorylation site mutations on mitophagy in H9c2 myocardial cells by constructing tyrosine site mutant plasmids (Y11 and Y18) of the FUN14 domain-containing protein 1 (FUNDC1). Methods The mutant plasmids constructed by whole-gene synthesis were transfected into rat myocardial H9c2 cells and divided into five groups: empty plasmid group, FUNDC1 overexpression group, Y11 mutant group, Y18 mutant group, and Y11 combined with Y18 mutant group. The viability of H9c2 cells was assessed using the CCK-8 assay. Additionally, tetramethylrhodamine ethyl ester (TMRE) staining was utilized to detect mitochondrial membrane potential. The protein expression levels of FUNDC1, translocase of the outer mitochondrial membrane 20 (TOM20), and cytochrome c oxidase IV (COX IV) were detected by Western blot analysis. Confocal microscopy was used to evaluate transfection efficiency as well as the co-localization of mitochondria and lysosomes. Results The FUNDC1 overexpression, Y11, Y18, and Y11 combined with Y18 mutant plasmids were successfully constructed. After plasmid transfection, widespread GFP fluorescence expression was observed under confocal microscopy. Compared with the empty plasmid group, FUNDC1 protein expression levels were significantly increased in the FUNDC1 overexpression group, Y11 mutation group, Y18 mutation group, and Y11 combined with Y18 mutation group, while cell viability and mitochondrial membrane potential showed no significant changes. Compared to the empty plasmid group, cells transfected with Y18 and Y11 combined with Y18 mutant plasmids showed increased TOM20 and COX IV expression levels and decreased mitochondrial-lysosomal co-localization. Conclusion Transfection with FUNDC1 Y18 or Y11 combined with Y18 mutant plasmids inhibited mitophagy in H9c2 myocardial cells.
Animals ; Rats ; Mitophagy/genetics* ; Myocytes, Cardiac/cytology* ; Mitochondrial Proteins/metabolism* ; Mutation ; Phosphorylation ; Tyrosine/genetics* ; Cell Line ; Membrane Proteins/metabolism* ; Membrane Potential, Mitochondrial

This consensus will introduce the characteristics of fillers used in the surgical cavities of domestic nasal surgery patients based on relevant literature and expert opinions. It will also provide recommendations for the selection of cavity fillers for different nasal diseases, with chronic sinusitis as a representative example.
Humans ; Nasal Cavity/surgery* ; Nasal Surgical Procedures ; China ; Consensus ; Sinusitis/surgery* ; Dermal Fillers

Zishen Huoxue decoction (ZSHX) enhances cardiomyocyte viability following hypoxic stress; however, its upstream therapeutic targets remain unclear. Network pharmacology and RNA sequencing analyses revealed that ZSHX target genes were closely associated with mitophagy and apoptosis in the mitochondrial pathway. In vitro, ZSHX inhibited pathological mitochondrial fission following hypoxic stress, regulated FUN14 domain-containing protein 1 (FUNDC1)-related mitophagy, and increased the levels of mitophagy lysosomes and microtubule-associated protein 1 light chain 3 beta II (LC3II)/translocase of outer mitochondrial membrane 20 (TOM20) expression while inhibiting the over-activated mitochondrial unfolded protein response. Additionally, ZSHX regulated the stability of beta-tubulin through Sirtuin 5 (SIRT5) and could modulate FUNDC1-related synergistic mechanisms of mitophagy and unfolded protein response in the mitochondria (UPR^mt) via the SIRT5 and -β-tubulin axis. This targeting pathway may be crucial for cardiomyocytes to resist hypoxia. Collectively, these findings suggest that ZSHX can protect against cardiomyocyte injury via the SIRT5-β-tubulin axis, which may be associated with the synergistic protective mechanism of SIRT5-β-tubulin axis-related mitophagy and UPR^mt on cardiomyocytes.
Mitophagy/drug effects* ; Tubulin/genetics* ; Animals ; Myocytes, Cardiac/metabolism* ; Drugs, Chinese Herbal/pharmacology* ; Sirtuins/genetics* ; Unfolded Protein Response/drug effects* ; Myocardial Ischemia/genetics* ; Rats ; Humans ; Rats, Sprague-Dawley ; Apoptosis/drug effects* ; Male

[摘 要] 目的：探究包被蛋白复合体β1亚基（COPB1）在食管鳞状细胞癌（ESCC）中的表达，及其对ESCC细胞恶性生物学行为的影响、作用机制及临床意义。方法：采用2014～2018年间在河北医科大学第四医院生物样本库中82例ESCC组织及癌旁组织，常规培养正常食管鳞状上皮细胞HEEC和食管癌细胞KYSE-150、KYSE-170、Eca109、TE1、KYSE-30、KYSE-450，用转染试剂将pcDNA3.1-vector（空载体）、pcDNA3.1-COPB1载体，si-NC和si-COPB1转染至KYSE-150、TE1细胞中，记为NC、COPB1-OE、si-NC和si-COPB1组。用数据库数据分析COPB1 mRNA在泛癌组织中的表达及其表达与免疫细胞浸润的关系，qPCR法检测ESCC组织和细胞中COPB1、PIK3CB、CD68、CD163、CD206、ARG1、IL-10 mRNA水平表达情况，WB法检测ESCC组织和各组细胞中的COPB1、PI3K、CD68、CD163、CD206、p-AKT蛋白表达，克隆形成实验和MTS实验检测各组细胞的增殖能力，划痕愈合实验和Transwell实验检测各组细胞的迁移和侵袭能力，免疫组织化学染色（IHC）法检测ESCC组织中COPB1和CD206蛋白表达。以人单核细胞白血病细胞（THP-1）构建巨噬细胞模型，用佛波酯（PMA）和IL-3和IL-4和ESCC细胞上清液诱导巨噬细胞转型，用qPCR和WB法检测CD68和CD206m RNA和蛋白的表达。结果：COPB1在泛癌组织和ESCC组织中均呈高表达且与淋巴结转移和TNM分期有关联（均P < 0.01），COPB1高表达的ESCC患者总生存期短（P < 0.05），COPB1是潜在的ESCC的诊断标志物。COPB1在KYSE-150和TE1细胞中也呈高表达（均P < 0.05），过表达或敲减COPB1可明显抑制或促进KYSE-150和TE1细胞的增殖能力、迁移和侵袭能力（均P < 0.05）。COPB1表达变化诱导的差异表达基因主要富集于PI3K/AKT通路（均P < 0.001）, COPB1可促进PI3K/AKT通路的活化（P < 0.05），COPB1高表达可导致M2型巨噬细胞浸润增加（P < 0.05），COPB1高表达促进TAM/M2极化（P < 0.05）。结论：COPB1在ESCC组织中呈高表达，其可激活PI3K/AKT通路及调控肿瘤免疫微环境促进 ESCC发生发展，COPB1有望成为ESCC诊断和预后的生物标志物及治疗靶点。

ObjectiveTo identify the prototypical components and metabolites absorbed into blood and cerebrospinal fluid of Schisandrae Chinensis Fructus（SCF） based on sequential metabolism combined with liquid chromatography-mass spectrometry. MethodBlood and cerebrospinal fluid samples of integrated metabolism， intestinal metabolism and hepatic metabolism were collected from male SD rats after gavage and in situ intestinal perfusion administration， and ultra-performance liquid chromatography-quadrupole/electrostatic field orbitrap high-resolution mass spectrometry（UPLC Q-Exactive Orbitrap MS） was used to analyze and compare the differences in the spectra of SCF extract， blank plasma， administered plasma， blank cerebrospinal fluid and administered cerebrospinal fluid with ACQUITY UPLC BEH Shield RP18 column（2.1 mm×100 mm， 1.7 µm）， the mobile phase was acetonitrile（A）-0.1% formic acid aqueous solution（B） for gradient elution（0-7 min， 95%B； 7-12 min， 95%-35%B； 12-17 min， 35%-15%B； 17-20 min， 15%-12%B； 20-22 min， 12%-5%B； 22-23 min， 5%B； 23-25 min， 5%-95%B； 25-28 min， 95%B）. And heated electrospray ionization（HESI） was used with positive and negative ion modes， the scanning range was m/z 100-1 500. The prototypical constituents and their metabolites absorbed into blood and cerebrospinal fluid of SCF were identified according to the retention time， characteristic fragments， molecular formulae and the information of reference substances. ResultA total of 42 chemical components were identified in the extract of SCF， including lignans， flavonoids， amino acids， tannins， and others， of which lignans were the main ones. A total of 27 prototypical components and 14 metabolites were identified in plasma samples from different sites. A total of 15 prototypical components and 9 metabolites were identified in cerebrospinal fluid. The main metabolic reactions involved in the formation of metabolites were mainly demethylation， methylation， demethoxylation and hydroxylation. ConclusionThrough the systematic identification of the prototypical components and metabolites of SCF in rats， it provides data support for further better exploring the material basis of SCF in the treatment of central nervous system diseases.

Objective　To study the clinical and epidemiological characteristics of the monkeypox epidemic in Longgang District, Shenzhen, and conduct a comprehensive analysis and discussion to provide a reference for monkeypox epidemic prevention and control. Methods An epidemiological investigation was conducted on 16 monkeypox cases found in the medical institutions of Longgang District on June 2023. The distribution of cases, high-risk exposure characteristics (contact objects, methods, locations, etc.), incidence characteristics, and medical treatment situation were analyzed. Relevant discussions on epidemic prevention and control were further conducted in light of the actual situation and the problems encountered. Results The cases were all unmarried young men and men who have sex with men (MSM) population. The disease was transmitted from person to person through same-sex contact, with non-fixed sexual partners as the source of infection and exposure locations being relatively concealed, and the average incubation period was 8.42 days. Most cases were discovered through active seeking medical attention, accounting for 68.78% (11/16). Fever was the primary initial symptom accounting for 56.25% (9/16), with the main symptoms being a rash and fever, at 100% and 68.75% (11/16), respectively. Time from fever to rash onset was mainly 0-3 days, accounting for 90.91% (10/11). The eruption site involveed multiple different parts of the body, and there was no special order of eruption. The time interval from onset to seeking medical attention and from onset to discovery was similar, with 5.91 days and 5.94 days respectively. The majority of cases were HIV infected, accounting for 68.75% (11/16)。Conclusions The monkeypox epidemic is prevalent in MSM populations and is transmitted through male to male contact through human transmission. However, due to unstable sexual partners and concealed exposure locations, tracing the source is difficult, with an average incubation period of 8.42 days. The symptoms are mainly fever and rash, with a long time from onset to medical treatment. The initial manifestations are mild, leading to missed diagnoses on the first visit, resulting in difficulty in timely discovery and prevention of further cases. At the same time, investigating and handling the epidemic are challenging, making the prevention and control of the outbreak a difficult task.

Objective: To establish an optimized method for isolation and purification of microglia from aged rat brain tissue, and the phenotype of microglia was detected by flow cytometry. Methods: With young rats(3 months old) as control, the brain tissues of aged rats were immediately processed into single cell suspensions by mechanical dissociation and enzymatic digestion using type IV collagenase. Microglia were isolated on Percoll gradients(30%-37%-70%). The cells were stained with fluorescence-labeled antibodies and the phenotype of microglia was detected by flow cytometry. Results: This study developed a method that enzymatic digestion and mechanical dissociation combined with density gradient centrifugation. More single cells could be obtained by using this method. And the survival rate of cells was more than 90%. The flow cytometric analysis showed that the expression of M1 microglia marker CD86 and MHC Ⅱ increased(P<0.01), and the expression of M2 microglia marker CD200R increased(P<0.01) in aged rats compared with that in young rats. Conclusion The use of type IV collagenase and mechanical digestion combined with density gradient centrifugation is good for isolating and purifying microglia from adult and aged rat brain tissue.

Objective:To report the long-term outcomes of Chinese rectal cancer patients after adopting a Watch and Wait (W&W) strategy following neoadjuvant therapy (NAT).Methods:This multicenter, cross-sectional study was based on real-world data. The study cohort comprised rectal cancer patients who had achieved complete or near complete clinical responses (cCRs, near-cCRs) after NAT and were thereafter managed by a W&W approach, as well as a few patients who had achieved good responses after NAT and had then undergone local excision for confirmation of pathological complete response. All participants had been followed up for ≥2 years. Patients with distant metastases at baseline or who opted for observation while living with the tumor were excluded. Data of eligible patients were retrospectively collected from the Chinese Wait-and-Watch Data Collaboration Group database. These included baseline characteristics, type of NAT, pre-treatment imaging results, evaluation of post-NAT efficacy, salvage measures, and treatment outcomes. We herein report the long-term outcomes of Chinese rectal cancer patients after NAT and W&W and the differences between the cCR and near-cCR groups.Results:Clinical data of 318 rectal cancer patients who had undergone W&W for over 2 years and been followed up were collected from eight medical centers (Peking University Cancer Hospital, Fudan University Shanghai Cancer Center, Sun Yat-sen University Cancer Center, Shanghai Changhai Hospital, Peking Union Medical College Hospital, Liaoning Cancer Hospital, the First Hospital of Jilin University, and Yunnan Cancer Hospital.) The participants comprised 221 men (69.4%) and 107 women (30.6%) of median age 60 (26-86) years. The median distance between tumor and anal verge was 3.4 (0-10.4) cm. Of these patients, 291 and 27 had achieved cCR or near-cCR, respectively, after NAT. The median duration of follow-up was 48.4 (10.2-110.3) months. The 5-year cumulative overall survival rate was 92.4% (95%CI: 86.8%-95.7%), 5-year cumulative disease-specific survival (CSS) rate 96.6% (95%CI: 92.2%-98.5%), 5-year cumulative organ-preserving disease-free survival rate 86.6% (95%CI: 81.0%-90.7%), and 5-year organ preservation rate 85.3% (95%CI: 80.3%-89.1%). The overall 5-year local recurrence and distant metastasis rates were 18.5% (95%CI: 14.9%-20.8%) and 8.2% (95%CI: 5.4%-12.5%), respectively. Most local recurrences (82.1%, 46/56) occurred within 2 years, and 91.0% (51/56) occurred within 3 years, the median time to recurrence being 11.7 (2.5-66.6) months. Most (91.1%, 51/56) local recurrences occurred within the intestinal lumen. Distant metastases developed in 23 patients; 60.9% (14/23) occurred within 2 years and 73.9% (17/23) within 3 years, the median time to distant metastasis being 21.9 (2.6-90.3) months. Common sites included lung (15/23, 65.2%), liver (6/23, 26.1%), and bone (7/23, 30.4%) The metastases involved single organs in 17 patients and multiple organs in six. There were no significant differences in overall, cumulative disease-specific, or organ-preserving disease-free survival or rate of metastases between the two groups (all P>0.05). The 5-year local recurrence rate was higher in the near-cCR than in the cCR group (41.6% vs. 16.4%, P<0.01), with a lower organ preservation rate (69.2% vs. 88.0%, P<0.001). The success rates of salvage after local recurrence and distant metastasis were 82.1% (46/56) and 13.0% (3/23), respectively. Conclusion:Rectal cancer patients who achieve cCR or near-cCR after NAT and undergo W&W have favorable oncological outcomes and a high rate of organ preservation. Local recurrence and distant metastasis during W&W follow certain patterns, with a relatively high salvage rate for local recurrence. Our findings highlight the importance of close follow-up and timely intervention during the W&W process.