Objective To investigate the protective effects of secretomes released by three-dimensional cultured mesenchymal stem cells(MSCs)on neurons subjected to seawater immersion(SW)and stretch injury(SI),and to provide new insights into neuronal repair following SW combined with traumatic brain injury(TBI).Methods MSCs were cultured using the hanging drop method,and the conditioned medium(CM)containing MSCs secretomes was collected.A cellular model combining SW with SI was established using mouse hippocampal neuronal cells(HT22 cells).HT22 cells were randomly assigned to five groups:control,SI,SI+SW,SI+CM,and SI+SW+CM groups.Cell viability was assessed using the CCK-8 assay,apoptosis rate was measured by flow cytometry,cell migration ability was evaluated by scratch assay,and the expression levels of apoptosis-related proteins Bcl-2 and Bcl-2-associated protein(Bax),and ferroptosis-related proteins long-chain acyl-CoA synthetase 4(ACSL4)and cyclooxygenase-2(COX-2)were detected by Western blotting.Results Immersion in 15%seawater for 12 h significantly decreased HT22 cell viability(P<0.05).The CCK-8 assay indicated that cell viability in both the SI and SI+SW groups was significantly lower than that in control group after 12 h of treatment(P<0.05).Treatment with CM containing MSCs secretomes significantly increased cell viability in SI+CM group compared to SI group(P<0.0001),and in SI+SW+CM group compared to SI+SW group(P<0.001).Flow cytometry results revealed that the apoptosis rate in SI and SI+SW groups was significantly higher than that in control group(P<0.05 or P<0.001),while in SI+CM group was lower than that in SI group(P<0.05),and in SI+SW+CM group was lower than that in SI+SW group(P<0.05).Western blotting showed that compared to control group,SI and SI+SW groups exhibited reduced Bcl-2 expression level(P<0.01 or P<0.0001)and increased expression levels of Bax,ACSL4,and COX-2(P<0.01 or P<0.0001).Compared to SI group,the SI+CM group displayed increased Bcl-2 expression level(P<0.05)and decreased expression levels of Bax,ACSL4,and COX-2(P<0.05).Compared to SI+SW group,SI+SW+CM group exhibited increased Bcl-2 expression level(P<0.01)and decreased expression levels of Bax,ACSL4,and COX-2(P<0.01 or P<0.001).Scratch assay results demonstrated that at both 12 h and 24 h,the cell migration rate in SI and SI+SW groups was significantly lower than that in control group(P<0.01 or P<0.0001),while the migration rate in SI+CM group was significantly higher than that in SI group(P<0.0001 or P<0.01),and the migration rate in SI+SW+CM group was significantly higher than that in SI+SW group(P<0.0001).Conclusion Secretomes derived from MSCs cultured using the hanging drop method can alleviate neuronal damage caused by SW and TBI,potentially offering a therapeutic approach for SW combined with TBI.

Objective To analyze medication rules of traditional Chinese medicine in the treatment of thyroid nodules based on real-world data mining technology. Methods Chinese medicine prescriptions for patients with thyroid nodules as clinical first diagnosis in the Department of Thyroid and Breast Surgery in Qingdao Hospital of Traditional Chinese Medicine from August 2018 to August 2023 were collected, and the Traditional Chinese Medicine Inheritance Assistant Platform (V3.0) was used to analyze the medication rules. Results A total of 1 206 traditional Chinese medicine prescriptions for the treatment of thyroid nodules were screened, involving 291 traditional Chinese medicines; the top five most frequently used drugs were Fritillaria thunbergii, Prunella vulgaris, Bupleurum chinense, Poria cocos, and Pinellia ternata; the main function of drugs were clearing heat, tonifying deficiency, resolving phlegm, activating blood circulation, and regulating qi; the main property of the drugs was cold, the main tastes of drugs were bitter, sweet and spicy, and the meridians involved were mainly the lung, liver and spleen meridians; association rule analysis identified 17 high-frequency drug combinations, with Fritillaria thunbergii-Prunella vulgaris as the most frequently occurring drug pair; among the 16 association rules, Radix Scrophulariae-Fritillaria thunbergii and Rhizoma Cyperi-Bupleurum chinense had the highest confidence level; clustering analysis found 6 core drug combinations. Conclusion The main idea of clinical treatment of thyroid nodules in traditional Chinese medicine is to resolve phlegm and reduce nodules, promote qi circulation and blood circulation, and nourish qi and blood; the common herbal combination of Fritillaria thunbergii and Prunella vulgaris is used to clear heat, resolve phlegm, and reduce nodules, and the basic formula for resolving scrofula is based on Xiaoluo Pills, which resolves phlegm, softens hardened nodules, and reduces nodules.

Objective To establish antemortem and postmortem injury models in nude mice,observe the morphological changes of the wounds and the changes of the microbial communities in the wounds at different time points after the injury,and analyze the differences between antemortem and postmor-tem wounds.Methods Abdominal injury models were established in 48 BALB/c nude mice,which were classified into antemortem injury,4 h and 72 h postmortem injury groups,and the gross manifesta-tions and histopathological changes were observed on days 1,3,5,8,11 and 15 after injury.The mi-crobial communities in the wounds were analyzed by 16S rRNA sequencing technology.QIIME 2 soft-ware was used to calculate Shannon and Observed species indices.The Kruskal-Wallis test was used to determine statistical differences in α-diversity between groups.Jaccard similarity coefficients were calculated by using R v4.3.0 software and applied to the principal co-ordinates analysis to demonstrate inter-sample differences.Permutational multivariate analysis of variance(PERMANOVA)was used to analyze the differences between groups in the composition of bacterial colonies,and R2 values were calculated.Results On days 8,11 and 15 after injury,the antemortem and postmortem injuries could not be differentiated by morphological examination;the Shannon index and Observed species index were statistically different between the antemortem injury group and the 72 h postmortem injury group;the Jaccard similarity coefficient of the microbial community was statistically different between the an-temortem injury group and the 72 h postmortem injury group.The PERMANOVA R2 value gradually increased with the extension of time(0.22-0.61).Conclusion Through the analysis of the wound mi-crobial community,the microbial composition of wounds at different time points can be identified and compared,which provides a new perspective and method for the differentiation of antemortem injuries from postmortem injuries,with good application prospects.

The fatality rate of liver failure caused by fatal amanita poisoning is high, and there are no effective antidote drugs in China. On July 30, 2020, the department of infectious diseases and liver diseases of the First People's Hospital of Yunnan Province admitted a 67-year-old female patient with liver failure caused by fatal amanita poisoning. The patient went to the emergency department for treatment due to abdominal pain, vomiting and diarrhea after eating 350-400 g of amanita mushroom for 2 days, accompanied by fatigue for 1 day. There was no abnormality in physical examination. Laboratory indexes: alanine aminotransferase (ALT) 4 798 U/L, aspartate aminotransferase (AST) 10 030 U/L, activated partial thromboplastin time (APTT) 57.5 s, prothrombin time (PT) 72.1 s, international normalized ratio (INR) 8.66, prothrombinactivity (PA) 10%. Based on the patient's medical history, clinical manifestations and laboratory data, the diagnosis was amanita peptide mushroom poisoning and acute liver failure. According to the mechanism of amanita toxin poisoning as enterohepatic circulation, endoscopic retrograde cholangiopancreatography and ultrasound-guided gallbladder puncture and drainage for drainage of bile to discharge toxins were performed to interrupt the enterohepatic circulation of toxins. However, both methods failed, so open cholecystostomy was performed. Because the patient's coagulation function was very poor, artificial hepatic plasma exchange was given to improve coagulation function before open cholecystostomy, and eventually bile was drained successfully. After a total of 19 days of comprehensive medical treatment, the patient was cured and discharged from the hospital, and no sequelae was found after 1 year of follow-up. For such patients, early identification of the disease is required, and blocking the enterohepatic circulation of toxins as soon as possible according to the characteristics and toxicological mechanism of toxins may be the key treatment for rescuing patients with liver failure poisoned by amanita toxin, and it is necessary to combine comprehensive treatments such as active fluid replacement and blood purification to further improve the survival rate.

Objective: To investigate the surgical indications and perioperative clinical outcomes of pelvic exenteration (PE) for locally advanced, recurrent pelvic malignancies and complex pelvic fistulas. Methods: This was a descriptive study.The indications for performing PE were: (1) locally advanced, recurrent pelvic malignancy or complex pelvic fistula diagnosed preoperatively by imaging and pathological examination of a biopsy; (2)preoperative agreement by a multi-disciplinary team that non-surgical and conventional surgical treatment had failed and PE was required; and (3) findings on intraoperative exploration confirming this conclusion.Contraindications to this surgical procedure comprised cardiac and respiratory dysfunction, poor nutritional status,and mental state too poor to tolerate the procedure.Clinical data of 141 patients who met the above criteria, had undergone PE in the Sixth Affiliated Hospital of Sun Yat-sen University from January 2018 to September 2022, had complete perioperative clinical data, and had given written informed consent to the procedure were collected,and the operation,relevant perioperative variables, postoperative pathological findings (curative resection), and early postoperative complications were analyzed. Results: Of the 141 included patients, 43 (30.5%) had primary malignancies, 61 (43.3%) recurrent malignancies, 28 (19.9%) complex fistulas after radical resection of malignancies,and nine (6.4%)complex fistulas caused by benign disease. There were 79 cases (56.0%) of gastrointestinal tumors, 30 cases (21.3%) of reproductive tumors, 16 cases (11.3%) of urinary tumors, and 7 cases (5.0%) of other tumors such mesenchymal tissue tumors. Among the 104 patients with primary and recurrent malignancies, 15 patients with severe complications of pelvic perineum of advanced tumors were planned to undergo palliative PE surgery for symptom relief after preoperative assessment of multidisciplinary team; the other 89 patients were evaluated for radical PE surgery. All surgeries were successfully completed. Total PE was performed on 73 patients (51.8%),anterior PE on 22 (15.6%),and posterior PE in 46 (32.6%). The median operative time was 576 (453,679) minutes, median intraoperative blood loss 500 (200, 1 200) ml, and median hospital stay 17 (13.0,30.5)days.There were no intraoperative deaths. Of the 89 patients evaluated for radical PE surgery, the radical R0 resection was achieved in 64 (71.9%) of them, R1 resection in 23 (25.8%), and R2 resection in two (2.2%). One or more postoperative complications occurred in 85 cases (60.3%), 32 (22.7%)of which were Clavien-Dindo grade III and above.One patient (0.7%)died during the perioperative period. Conclusion: PE is a valid option for treating locally advanced or recurrent pelvic malignancies and complex pelvic fistulas.
Humans ; Pelvic Exenteration/methods* ; Pelvic Neoplasms/surgery* ; Retrospective Studies ; Neoplasm Recurrence, Local/surgery* ; Postoperative Complications

Objective: This cross-sectional investigation aimed to determine the incidence, clinical characteristics, prognosis, and related risk factors of olfactory and gustatory dysfunctions related to infection with the SARS-CoV-2 Omicron strain in mainland China. Methods: Data of patients with SARS-CoV-2 from December 28, 2022, to February 21, 2023, were collected through online and offline questionnaires from 45 tertiary hospitals and one center for disease control and prevention in mainland China. The questionnaire included demographic information, previous health history, smoking and alcohol drinking, SARS-CoV-2 vaccination, olfactory and gustatory function before and after infection, other symptoms after infection, as well as the duration and improvement of olfactory and gustatory dysfunction. The self-reported olfactory and gustatory functions of patients were evaluated using the Olfactory VAS scale and Gustatory VAS scale. Results: A total of 35 566 valid questionnaires were obtained, revealing a high incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain (67.75%). Females(χ2=367.013, P<0.001) and young people(χ2=120.210, P<0.001) were more likely to develop these dysfunctions. Gender(OR=1.564, 95%CI: 1.487-1.645), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), oral health status (OR=0.881, 95%CI: 0.839-0.926), smoking history (OR=1.152, 95%CI=1.080-1.229), and drinking history (OR=0.854, 95%CI: 0.785-0.928) were correlated with the occurrence of olfactory and taste dysfunctions related to SARS-CoV-2(above P<0.001). 44.62% (4 391/9 840) of the patients who had not recovered their sense of smell and taste also suffered from nasal congestion, runny nose, and 32.62% (3 210/9 840) suffered from dry mouth and sore throat. The improvement of olfactory and taste functions was correlated with the persistence of accompanying symptoms(χ2=10.873, P=0.001). The average score of olfactory and taste VAS scale was 8.41 and 8.51 respectively before SARS-CoV-2 infection, but decreased to3.69 and 4.29 respectively after SARS-CoV-2 infection, and recovered to 5.83and 6.55 respectively at the time of the survey. The median duration of olfactory and gustatory dysfunctions was 15 days and 12 days, respectively, with 0.5% (121/24 096) of patients experiencing these dysfunctions for more than 28 days. The overall self-reported improvement rate of smell and taste dysfunctions was 59.16% (14 256/24 096). Gender(OR=0.893, 95%CI: 0.839-0.951), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), history of head and facial trauma(OR=1.180, 95%CI: 1.036-1.344, P=0.013), nose (OR=1.104, 95%CI: 1.042-1.171, P=0.001) and oral (OR=1.162, 95%CI: 1.096-1.233) health status, smoking history(OR=0.765, 95%CI: 0.709-0.825), and the persistence of accompanying symptoms (OR=0.359, 95%CI: 0.332-0.388) were correlated with the recovery of olfactory and taste dysfunctions related to SARS-CoV-2 (above P<0.001 except for the indicated values). Conclusion: The incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain is high in mainland China, with females and young people more likely to develop these dysfunctions. Active and effective intervention measures may be required for cases that persist for a long time. The recovery of olfactory and taste functions is influenced by several factors, including gender, SARS-CoV-2 vaccination status, history of head and facial trauma, nasal and oral health status, smoking history, and persistence of accompanying symptoms.
Female ; Humans ; Adolescent ; SARS-CoV-2 ; Smell ; COVID-19/complications* ; Cross-Sectional Studies ; COVID-19 Vaccines ; Incidence ; Olfaction Disorders/etiology* ; Taste Disorders/etiology* ; Prognosis

BACKGROUND: Coronavirus disease 2019 (Covid-19) remains a serious health threat worldwide. We aimed to investigate whether low molecular weight heparin (LMWH) can promote organ function recovery in moderate Covid-19 pneumonia patients. METHODS: We initiated an LMWH protocol in Covid-19 patients with increased D-dimer, body mass index >30 kg/m2 or a history of diabetes from January 18, 2020 at Shanghai Public Health Clinical Center. In this retrospective study, we assigned moderate Covid- 19 pneumonia patients admitted between January 18th and April 18, 2020 receiving the LMWH protocol to the LMWH group. Moderate patients who met the inclusion criteria but did not receive LMWH protocol were included in the control group by 1:2 propensity score matching. General clinical information, indicators for renal function, arterial blood gas analyses, arterial blood lactic acid content (mmol/L), and coagulation indexes at 0 day, 3 days, 7 days, and 11 days after admission were recorded and compared between the two groups. RESULTS: There were 41 patients in the LMWH group and 82 patients in the control group. General information in both groups were similar. Compared to the control group, the arterial blood lactic acid content (mmol/L) at day 11 (1.3 [1.1, 1.7] vs. 1.2 [0.9, 1.3], P = 0.016) was reduced in the LMWH group. The estimated glomerular filtration rate (eGFR) in the LMWH group was higher than that in the control group at day 7 (108.54 [89.11, 128.17] vs. 116.85 [103.39, 133.47], P = 0.039) and day 11 (113.74 [94.49, 126.34] vs. 128.31 [112.75, 144, 12], P  = 0.003). The serum creatinine levels (Scr) in the LMWH group were lower than that in the control group at day 7 (62.13 [51.47, 77.64] vs. 55.49 [49.50, 65.75], P = 0.038) and day 11 (63.35 [50.17, 75.73] vs. 51.62 [44.62, 61.24], P = 0.005). CONCLUSIONS: LMWH treatment can reduce arterial blood lactic acid levels and improve eGFR in moderate Covid-19 pneumonia patients. Randomized controlled trials are warranted to further investigate this issue. TRIAL REGISTRATION ChiCTR.org.cn, ChiCTR2000034796.
COVID-19 ; China ; Glomerular Filtration Rate ; Heparin, Low-Molecular-Weight/therapeutic use* ; Humans ; Lactic Acid ; Retrospective Studies

Objective: To compare clinical and laboratory features between JAK2 exon12 and JAK2 V617F mutated polycythemia vera (PV) . Method: We collected data from 570 consecutive newly-diagnosed subjects with PV and JAK2 mutation, and compared clinical and laboratory features between patients with JAK2 exon12 and JAK2 V617F mutation. Results: 543 (95.3%) subjects harboured JAK2 V617F mutation (JAK2 V617F cohort) , 24 (4.2%) harboured JAK2 exon12 mutations (JAK2 exon12 cohort) , and 3 (0.5%) harboured JAK2 exon12 and JAK2 V617F mutations. The mutations in JAK2 exon12 including deletion (n=10, 37.0%) , deletion accompanied insertion (n=10, 37.0%) , and missense mutations (n=7, 25.9%) . Comparing with JAK2 V617F cohort, subjects in JAK2 exon12 cohort were younger [median age 50 (20-73) years versus 59 (25-91) years, P=0.040], had higher RBC counts [8.19 (5.88-10.94) ×10(12)/L versus 7.14 (4.11-10.64) ×10(12)/L, P<0.001] and hematocrit [64.1% (53.7-79.0%) versus 59.6% (47.2%-77.1%) , P=0.001], but lower WBC counts [8.29 (3.2-18.99) ×10(9)/L versus 12.91 (3.24-38.3) ×10(9)/L, P<0.001], platelet counts [313 (83-1433) ×10(9)/L versus 470 (61-2169) ×10(9)/L, P<0.001] and epoetin [0.70 (0.06-3.27) versus 1.14 (0.01-10.16) IU/L, P=0.002] levels. We reviewed bone marrow histology at diagnosis in 20 subjects with each type of mutation matched for age and sex. Subjects with JAK2 exon12 mutations had fewer loose megakaryocyte cluster (40% versus 80%, P=0.022) compared with subjects with JAK2 V617F. The median follow-ups were 30 months (range 4-83) and 37 months (range 1-84) for cohorts with JAK2 V617F and JAK2 exon12, respectively. There was no difference in overall survival (P=0.422) and thrombosis-free survival (P=0.900) . Conclusions: Compared with patients with JAK2 V617F mutation, patients with JAK2 exon12 mutation were younger, and had more obvious erythrocytosis and less loose cluster of megakaryocytes.
Adult ; Aged ; Aged, 80 and over ; Bone Marrow/pathology* ; Exons ; Humans ; Janus Kinase 2/genetics* ; Middle Aged ; Mutation ; Mutation, Missense ; Polycythemia Vera/genetics* ; Young Adult

Objectives: To analyze the causes of a foodborne outbreak in rural areas of Xinjiang between April 2 and April 5 in 2016. Methods: Cases and the relevant background information were obtained by consulting outpatient records of local health centers and regional people's hospitals and interviewing doctors and residents. All samples were collected by the laboratory test through epidemiological and food hygiene investigations. The χ² test (Fisher's exact probability method) was used to compare differences in incidence rates. Molecular typing, virulence genes and single nucleotide polymorphisms (SNPS) were analyzed by using Pulsed Field Gel Electrophoresis (PFGE) and Whole Genome Sequencing (WGS). Results: A total of 142 cases were found in this study, with incidence rate at 5.7‰ (142/24 979). Among all cases, the main symptoms were nausea (94%), vomiting (92%) and abdominal pain (67%), and the incubation period was about 2 h (1-7.5 h). There were 16 Staphylococcus aureus isolates identified and all of them could produce A+C+E mixed enterotoxin. PFGE showed 100% homology. WGS further revealed that there were 9 and 1 strains contained by Sequence Type 1 (ST1) and ST5405, respectively. All ST1 strains were in the same clade on the genome tree. Among these, 7 strains shared close proximity (74 SNPs) and 2 strains shared close relationships as well (127 SNPs). The S. aureus isolates that caused the outbreak were introduced by a mutant isolate from the milk supply station. Conclusions: This foodborne outbreak was mainly caused by Staphylococcus aureus contamination.
Disease Outbreaks ; Electrophoresis, Gel, Pulsed-Field ; Foodborne Diseases/epidemiology* ; Humans ; Staphylococcus aureus/genetics*