Otitis media is an infection of the middle ear mainly caused by bacteria, and current treatments rely heavily on antibiotics. However, the emergence of antibiotic-resistant bacterial strains seriously affects their efficacy. In our study, we found that extracellular vesicles (EVs) derived from human natural killer cells (NKs) inhibit the proliferation of both standard and levofloxacin (LVX)-resistant strains of Staphylococcus aureus in a dose-dependent manner. Moreover, compared to LVX, EVs were more effective at reducing effusion and rescuing hearing thresholds in animal models. For LVX-sensitive strains, EVs were significantly more effective in terms of curative time but not curative rate. For LVX-resistant strains, EVs were significantly more effective in terms of both curative rate and curative time when applied alone or applied jointly with LVX. In summary, we found that NK EVs are highly effective in treating otitis media, providing an alternative approach for treating this common disease.
Killer Cells, Natural/metabolism* ; Exosomes/metabolism* ; Animals ; Humans ; Otitis Media/therapy* ; Staphylococcus aureus/drug effects* ; Disease Models, Animal ; Anti-Bacterial Agents/pharmacology* ; Levofloxacin/pharmacology*

Objective:To investigate the influencing factors for early tumor recurrence and the efficacy of adjuvant chemotherapy in gallbladder carcinoma (GBC) patients after curative-intent resection.Methods:The retrospective case-control study was conducted. The clinicopathological data of 506 patients with GBC in 11 medical centers, including The First Affiliated Hospital of Xi'an Jiaotong University et al, from January 2016 to December 2020 were collected. There were 168 males and 338 females, aged (62±11)years. All patients underwent curative-intent resection of GBC, and they were divided into patients with and without early recurrence based on time to postoperative recurrence. Observation indicators: (1) treatment; (2) follow-up and survival of patients; (3) analysis of influencing factors for early tumor recurrence after curative-intent resection of GBC; (4) efficacy of postoperative adjuvant chemotherapy. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M(range). Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test. Comparison of ordinal data was conducted using the Mann-Whitney U test. Univariate analysis was conducted using the corresponding statistical methods based on data type. Multivariate analysis was conducted using the Logistic regression model with forward method. The Kaplan-Meier method was used to draw survival curve and calculate survival rate, and Log-Rank test was used for survival analysis. Results:(1) Treatment. Of 506 patients, there were 112 cases with postoperative adjuvant chemotherapy, and 394 cases without postopera-tive adjuvant chemotherapy. They underwent 5(range, 3-9)cycles of postoperative adjuvant chemo-therapy. (2) Follow-up and survival of patients. All 506 patients underwent postoperative follow-up, with the follow-up time of 55(range, 34-93)months. During the follow-up, there were 248 patients with tumor recurrence, including 158 cases of early recurrence and 90 cases of late recurrence, and there were 258 patients without tumor recurrence. Of 506 patients, 275 cases survived, and 231 cases died of multiple organ failure caused by tumor recurrence and metastasis. The postoperative recurr-ence-free survival time, overall survival time were 52(range,1-93)months, 62(range, 2-93)months. The 1-, 3-, 5-year disease-free survival rates and 1-, 3-, 5-year overall survival rates of the 506 pati-ents were 68.8%, 53.8%, 47.9% and 78.3%, 58.7%, 51.6%, respectively. Results of survival analysis showed that the median overall survival time of 158 patients with postoperative early recurrence and 348 patients without postoperative early recurrence (including 90 cases of late recurrence and 258 cases of no tumor recurrence) were 9(range, 2-73)months and unreached, showing a significant difference between them ( χ2=456.15, P<0.05). (3) Analysis of influencing factors for early tumor recurrence after curative-intent resection of GBC. Results of multivariate analysis showed that carcinoembryonic antigen (CEA) >5.0 μg/L, poorly differentiated tumor, liver invasion, and tumor N staging as stage N1-N2 were independent risk factors influencing early tumor recurrence after cura-tive-intent resection of GBC ( odds ratio=2.74, 6.20, 1.81, 2.93, 4.82, 95% confidence interval as 1.62-4.64, 1.82-21.12, 1.15-3.08, 1.68-5.09, 1.91-12.18, P<0.05), while postoperative adjuvant chemo-therapy was an independent protect factor ( odds ratio=0.39, 95% confidence interval as 0.21-0.71, P<0.05). (4) Efficacy of postoperative adjuvant chemotherapy. The median overall survival time of 394 patients without postoperative adjuvant chemotherapy and 112 patients with postoperative adjuvant chemotherapy were 57(range, 2-93)months and unreached, showing a significant differ-ence between them ( χ2=9.38, P<0.05). Of the 158 patients with postoperative early recurrence after curative-intent resection of GBC, 135 cases didn't receive adjuvant chemotherapy and 23 cases received adjuvant chemotherapy, with the overall survival time of 8(range, 2-73)months and 17(range, 8-61)months, respectively, showing a significant difference between them ( χ2=7.68, P<0.05). Conclusions:CEA >5.0 μg/L, poorly differentiated tumor, liver invasion, and tumor N staging as stage N1-N2 are independent risk factors influencing early tumor recurrence after curative-intent resection of GBC, while postoperative adjuvant chemotherapy is an independent protect factor. Postoperative adjuvant chemotherapy can prolong the overall survival time of patients with post-operative tumor early recurrence.

Objective:To observe the changes of 5-hydroxytryptamine (5-HT) level in myocardial tissue of pre-treatment mice with sepsis myocardial injury by electroacupuncture at Zusanli point, and to explore the protective effect and possible mechanism of electroacupuncture on myocardial injury in sepsis.Methods:Twenty male C57BL/6 mice were divided into control group (NC group), sepsis model group (LPS group), electroacupuncture group (EA group) and electroacupuncture + fluoxetine group (EA+FLU group) by random number table method, with 5 mice in each group. The myocardial injury model of sepsis was established by intraperitoneal injection of lipopolysaccharide (LPS) 10 g/L. The NC group was intraperitoneally injected with the same amount of normal saline. 3 days before mold making, EA group and EA+FLU group were electrocuted at Zusanli point on both sides for 15 minutes, once a day for 3 days. The EA+FLU group was intraperitoneally injected fluoxetine 1.4 g/L before electroacupuncture. After modeling, the cardiac histopathological changes were observed by hematoxylin-eosin (HE) staining. The serum levels of inflammatory cytokines interleukins (IL-6, IL-8), and tumor necrosis factor-α (TNF-α), the content of 5-HT in myocardial tissue, myocardial injury markers MB isoenzyme of creatine kinase (CK-MB), and cardiac troponin I (cTnI), and the levels of adenosine triphosphate (ATP) and lactic acid in myocardial tissue were detected. Quantitative polymerase chain reaction (qPCR) was used to detect the mRNA expressions of 5-hydroxytryptamine transporter (5-HTT), hexokinase 2 (HK2) and glucose transporter 4 (GLUT4) in myocardial tissue. GLUT4 expression in myocardial tissue was detected by immunofluorescence assay.Results:Compared with NC group, the serum levels of IL-6, IL-1β and TNF-α, myocardial 5-HT content, myocardial tissue injury markers CK-MB, cTnI in LPS group and EA+FLU group were significantly increased. Compared with LPS group, the above indexes in EA group were significantly decreased [IL-6 (ng/L): 443.03±156.16 vs. 19?843.75±0.00, IL-1β (ng/L): 75.72±10.60 vs. 894.66±350.88, TNF-α (ng/L): 46.17±4.71 vs. 533.01±170.58, 5-HT (μg/L): 161.19±5.96 vs. 244.74±14.38, CK-MB (ng/L): 468.21±12.46 vs. 662.02±22.54, cTnI (ng/L): 0.83±0.05 vs. 0.99±0.08, all P < 0.05]. Compared with NC group, the levels of ATP in myocardium of LPS group, EA group and EA+FLU group were significantly decreased, the levels of lactic acid in myocardium were significantly increased. Compared with LPS group, the level of ATP in myocardium of EA group was significantly increased, the level of lactic acid in myocardium was significantly decreased [ATP (mmol/L): 0.10±0.01 vs. 0.08±0.01, lactic acid (mmol/L): 56.03±1.07 vs. 72.45±4.32, both P < 0.05]. Compared with NC group, the mRNA expression of HK2 in myocardium of LPS group was significantly increased, and the mRNA expressions of GLUT4 and 5-HTT were significantly decreased. Compared with LPS group, the mRNA expression of HK2 in myocardium of EA group was significantly decreased, the mRNA expressions of GLUT4 and 5-HTT were significantly increased [HK2 mRNA (relative expression level): 0.73±0.19 vs. 1.82±0.57, GLUT4 mRNA (relative expression level): 1.00±0.33 vs. 0.47±0.18, 5-HTT mRNA (relative expression level): 1.18±0.31 vs. 0.38±0.15, all P < 0.05]. Compared with NC group, the fluorescence intensity of GLUT4 in LPS group and EA+FLU group were significantly decreased. Compared with LPS group, the fluorescence intensity of GLUT4 in EA group was significantly enhanced. Conclusions:Electroacupunctureat Zusanli can reduce the content of 5-HT in myocardial tissue of sepsis mice, and its regulatory mechanism may be related to the regulation of 5-HTT and GLUT4.

Objective:To explore the clinical value of a trinity strategy for the treatment of multiple orthopedic trauma.Methods:A retrospective case series study was conducted to analyze the clinical data of 1 267 patients with multiple orthopedic trauma admitted to Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine and the First Affiliated Hospital of Navy Medical University from June 2013 to May 2023, including 862 males and 405 females, aged 18-93 years [(55.2±19.8)years]. Associated injuries included hemorrhagic shock in 632 patients, traumatic wet lung in 274, cranial injuries in 135, abdominal and pelvic bleeding in 116, pneumothorax in 89, urinary injury in 13, and vesical rupture in 8. All the patients were treated with the trinity strategy and the treatment process was divided into the phases of first aid, remodeling, and rehabilitation. The first aid phase focused on stabilizing symptoms and saving lives; the remodeling phase centered on restoring the anatomical structure and alignment; the rehabilitation phase aimed for functional recovery through the integration of both Western and traditional Chinese medicine. The all-cause mortality within 30 days after surgery and fracture healing time were calculated; the excellent and good rates of Constant-Murley shoulder score, Mayo elbow score, Gartland-Werley wrist score, Harris hip score, Hospital for Special Surgery (HSS) knee score and the American Orthopedic Foot & Ankle Society (AOFAS) ankle-hindfoot score at the last follow-up and the overall excellent and good rate of all joint function scores were measured. The short form health survey (SF-36) scores were collected preoperatively and at 6 months postoperatively, including 8 aspects such as physical functioning, physical role, bodily pain, general health, vitality, social functioning, emotional role, and mental health. The incidence of postoperative complications was recorded.Results:All the patients were followed up for 6-18 months [(10.2±4.2)months]. The mortality rate during the acute phase (within 30 days after surgery) was 2.37% with 12 deaths due to hemorrhagic shock, 10 due to traumatic brain injury, 6 due to multiple organ dysfunction syndrome (MODS), and 2 due to pulmonary infection. The average fracture healing time averaged 3.8-18 months [(11.5±4.2)months], with 89.49% of the patients having bone union within 12 months after surgery, 8.93% having bone union within 18 months after surgery, and 1.58% undergoing reoperation. For the patients with internal fixation failure and nonunion, the average healing time was extended to (10.2±2.2)months and (13.7±3.3)months respectively. At the last follow-up, the excellent and good rates of Constant-Murley shoulder score, Mayo elbow score, Gartland-Werley wrist score, Harris hip score, HSS knee score, and AOFAS ankle-hindfoot score were 83.93%, 90.24%, 94.12%, 85.57%, 88.46%, and 92.31% respectively, with an overall excellent and good rate of 89.11%. At 6 months after surgery, the SF-36 scores of all the patients in the eight dimensions,including the physical functioning, physical role, bodily pain, general health, vitality, social functioning, emotional role, and mental health were (74.4±8.6)points, (44.7±14.4)points, (77.4±10.9)points, (68.4±18.2)points, (72.5±16.0)points, (76.8±8.7)points, (49.9±17.6)points, and (72.8±17.9)points, significantly improved compared with those before operation [(63.4±12.7)points, (30.9±17.4)points, (56.4±18.0)points, (55.4±24.7)points, (53.5±21.0)points, (55.8±24.3)points, (36.9±24.0)points, (58.8±21.6)points] ( P<0.01). Complications of different degrees occurred in 214 patients (16.89%), including lung infections in 118 patients (9.31%), lower extremity deep vein thrombosis in 50(3.95%), pressure injuries in 26(2.05%), internal fixation failure in 12(0.95%), and nonunion in 8(0.63%). Conclusions:The trinity strategy provides whole-process management, personalized treatment, and overall rehabilitation for multiple orthopedic trauma. It can decrease mortality, shorten fracture healing time, improve joint function and quality of life, and reduce the incidence of complications.

Objective To discover the best physical training way including frequency and intensity each day ,and to guide pa‐tients to get the best cure .Methods Totally 60 chicken ,which were randomly divided into 3 groups ,20 for each ,the deep flexor tendon of the third left toes were found ,repairing after cut them off .Flexor tendon proximal were found by making knees incision then indwelling long silk line .External fixation bandage were used .Their left toes were accepted physical training ,Training stand‐ards :6 pulling backs each time ,toe flexion 1/4 arc ,but less than 2 N .For group A ,exercised once a day ,twice a day for group B , three times a day for group C .Right ones were consider as control group weren′t processed after operation .28 days later ,tendon distance was recorded by using 2 N pulling forces at tendon proximal with aspiring balance .Gross specimen was observed and histo‐logical specimens using Tang Jinen classification method to classify adhesions ,and the dates were analyzed by statistics SPSS 19 .0 . Results Group A remaining of 18 ,rate of 5 .56% ,grade Ⅰ of 1 ,Ⅱ of 2 ,Ⅲ of 4 ;Ⅳ of 10 .Group B remaining of 17 ,rate of 5 .88% , grade Ⅰ of 12 ,Ⅱ of 2 ,Ⅲ of 1 ,Ⅳ of 1 .group C remaining of 16 ,15 toes broke again ,fracture rate was 93 .75 % ,grade Ⅰ of 1 ,con‐trol group were grade Ⅳ .Between group A and B there were no significant differences in degree of adhesion(P> 0 .05) .Group A and Cs′ differences were statistically tested (P< 0 .05) .So were group B and C (P< 0 .05) .The average sliding distance for group A was (3 .01 ± 1 .58) mm ,(6 .72 ± 2 .02) mm for group B ,group C only got one sample ,8 .60mm ,and it was out of statistics .Be‐tween group A and B ,difference resulting from its tendon sliding after statistical tests(P< 0 .05) .For fracture rate ,Group A and B no significant difference was found(α′ = 0 .012 5 ,PAB > α′) .Conclusion Physical training can reduce chicken′s tendon adhesion effectively .

ObjectiveTo explore the correlation between phosphatase of regenerating liver-3 (PRL-3) and portal vein tumor thrombus in hepatocellular carcinoma (HCC).MethodsClinical data of 248 patients with HCC undergoing hepatectomy in the First People's Hospital of Foshan between December 2003 and December 2008 were retrospectively analyzed. The informed consents of all patients were obtained and the local ethical committee approval had been received. Among the 248 patients, 193 were males and 55 were females with the age ranging from 18 to 75 years old and the median of 48 years old. Forty-ifve cases were complicated with portal vein tumor thrombus. The expression of PRL-3 in HCC and portal vein tumor thrombus were observed by immunohistochemistry. The correlation between the expression of PRL-3 and the clinicopathological parameters of HCC patients and its signiifcance in portal vein tumor thrombus formation were analyzed. The analysis on the correlation between the expression of PRL-3 and the clinicopathological parameters of HCC was conducted usingχ2 test and the analysis on the risk factors associated with portal vein tumor thrombus formation was conducted using Logistic regression analysis.ResultsThe positive expression rate of PRL-3 in HCC and portal vein tumor thrombus was 70% (174/249) and 98% (44/45) respectively, and the positive expression rate in portal vein tumor thrombus was signiifcantly higher than that in HCC (χ2=15.253,P<0.05). The positive expression of PRL-3 was associated with the serum AFP, tumor diameter, histological differentiation of tumor, portal vein tumor thrombus formation, tumor TNM staging and early recurrence (χ2=4.836, 7.186, 4.226, 5.357, 13.862, 10.824;P<0.05). The positive expression of PRL-3 was the risk factor for portal vein tumor thrombus formation (OR=2.674,P<0.05).ConclusionsPRL-3 expression increases in HCC portal vein tumor thrombus and positive expression of PRL-3 may be closely associated with the invasion and metastasis of HCC.

Objective To investigate the hospitalized patients incidence of nutritional risk and nutritional support in six departments (general surgery, thoracic surgery, gastroenterology, neurology, urology and respirology) in a middle hospital and in the medical/surgical departments in a small hospital, so provide reference for rational nutritional support for patients. Method Nutritional Risk Screening 2002 was used to assess the existence of nutritional risk and the necessity of nutritional support. Results The overall prevalence of the nutrition risk was 25% in the six departments in the middle hospital; more specifically, the prevalence of nutrition risk arranged from 18% to 31% in these six departments: 31% in the department of respiratory medicine, 29% in the department of neurology, 27% in the department of urology, 23% in the department of thoracicsurgery, 22% in the department of gastroenterology, and 18% in the department of general surgery. For those at nutritional risk, the nutritional support rate was 24%. For non-risky patients, 9% received nutritional support. The overall prevalence of nutrition risk was 18% in the small hospital; more specifically, the prevalence of nutrition risk was 29% in the department of internal medicine and 7% in the department of surgery. For those at nutritional risk, the nutritional support rate was 24%.For non-risky patients, the nutritional support rate was 4%. Conclusions Certain nutritional risk and malnutrition exist in inpatients in the middle and small hospitals in Shijiazhuang. The applications of parenteral and enteral nutritions still have some problems. It is of particular importance to further promote the application of evidence-based parenteral/enteral nutrition guidelines in middle and small hospitals to standardize the application of nutritional support.

OBJECTIVETo analyze the mutations in a pedigree with maternally inherited sensorineural hearing loss, and to investigate whether 235delC heterozygote mutation in gap junction protein beta 2 (GJB2) gene modulates the severity of hearing loss associated with the A1555G mitochondrial mutation.

METHODSThe PCR products were digested with the Alw26 I restriction enzyme, followed by direct sequencing to detect the mitochondrial mutations in 72 members of a core pedigree of an extensive family with matrilineal nonsyndromic deafness; 235delC mutation of the GJB2 gene was screened in this family by using the Apa I restriction enzyme and direct sequencing.

RESULTSThe A1555G mutation of the mitochondrial DNA was present in all 27 members of maternal line, out of them, 21 members had phenotype of deafness (77.8%), with a high penetrance. Only three maternal line members of 72 members possessed 235delC heterozygote mutations, and the three had different phenotypes.

CONCLUSIONThe A1555G homozygous mutation of mitochondrial DNA is the susceptive etiological factor of nonsyndromic deafness in this family, but in the study of this pedigree, the 235delC heterozygous mutation in GJB2 gene may not aggravate the symptoms of hearing loss associated with the A1555G mitochondrial mutation.

Base Sequence ; Connexin 26 ; Connexins ; genetics ; DNA Mutational Analysis ; DNA, Mitochondrial ; chemistry ; genetics ; Female ; Hearing Loss, Sensorineural ; genetics ; Heterozygote ; Humans ; Male ; Mutation ; Pedigree ; Polymerase Chain Reaction