Triple-negative breast cancer (TNBC) remains a refractory subtype of breast cancer due to its resistance to various therapeutic strategies. In this study, we introduce a "brake-release and accelerator-pressing" approach to engineer a microneedle patch embedded with copper-doped Prussian blue nanoparticles (Cu-PB) and the ferroptosis inducer sorafenib (SRF) for raised chemodynamic (CDT)/photothermal (PTT) combination therapy against TNBC. Upon transdermal insertion, the dissolving microneedles swiftly disintegrate and facilitate the release of SRF. Under gentle external light exposure, copper ions (Cu²⁺) and iron ions (Fe³⁺) were liberated from Cu-PB. The direct chelation of Cu²⁺ and the indirect suppression by SRF, collectively attenuate glutathione peroxidase 4 (GPX4) enzymatic function, destabilizing the cellular redox equilibrium (referred to as the "brake-release" strategy). The release of Cu²⁺ and Fe³⁺ ions instigates a Fenton/Fenton-like reaction within tumor cells, further yielding hydroxyl radicals and elevating reactive oxygen species (ROS) concentrations (referred to as the "accelerator-pressing" strategy). This overwhelming ROS accumulation, coupled with the impaired clearance of resultant lipid peroxides (LPO), ultimately triggers a robust ferroptosis cell death response. In summary, this study presents an innovative combinatorial therapeutic strategy based on dual-ferroptosis induction for TNBC, implying a promising therapeutic platform for developing ferroptosis-centered treatments for this aggressive breast cancer subtype.

Objective:To observe the effect of warming needle therapy combined with Tuina(Chinese therapeutic massage)on the clinical symptoms and anxiety state of patients with cervical vertigo accompanied by anxiety. Methods:Seventy patients with cervical vertigo accompanied by anxiety state were divided into an observation group and a control group using the random number table method,with 35 patients in each group.In addition to disease education,the observation group was treated with warming needle therapy and Tuina 3 times a week,and the control group was treated with betahistine mesylate tablets orally 3 times a day.Both groups were treated for 4 weeks.The changes in the scores of the evaluation scale for cervical vertigo(ESCV),self-rating anxiety scale(SAS),and Hamilton anxiety rating scale(HAMA)were compared between the two groups after treatment. Results:One case in the observation group dropped out due to failure to cooperate with the treatment during the study.In the treatment group,the total effective rate and the cured plus markedly effective rate were 94.1%and 50.0%,respectively,and 88.6%and 8.6%in the control group,respectively;the differences between the two groups were statistically significant(P<0.05).After treatment,the ESCV,SAS,and HAMA scores of both groups decreased significantly compared with those before treatment(P<0.01),and the scores of the observation group were lower than those of the control group(P<0.01 or P<0.05). Conclusion:Warming needle therapy combined with Tuina can significantly improve the clinical symptoms of patients with cervical vertigo accompanied by anxiety state.

To construct a hybrid decision-making model that integrates knowledge-driven and data-driven approaches, and to apply it to the etiological diagnosis of ventricular tachycardia (VT).

Objective:To investigate the perioperative impact of closure of mesenteric fissure in laparoscopic right hemicolectomy.Methods:The prospective randomized controlled trial was conducted. The clinical data of 320 patients who underwent laparoscopic right hemicolectomy in 11 medical centers, including The First Affiliated Hospital of China Medical University et al, from November 2022 to August 2023 were selected. Based on block randomization, patients were alloca-ted into the mesenteric fissure non-closure group and the mesenteric fissure closure group. Observa-tion indicators: (1) grouping of the enrolled patients; (2) intraoperative conditions; (3) postopera-tive conditions. Measurement data with skewed distribution were represented as M( Q1, Q3) and com-parison between groups was conducted using the Mann-Whitney U test. Count data were represen-ted as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test or Fisher's exact probability. Comparison of ordinal data was conducted using the rank sum test. Comparison of visual analog scores was analyzed using generalized estimating equations. Results:(1) Grouping of the enrolled patients. A total of 320 patients with colon cancer were screened for eligibility, including 156 males and 164 females, aged 68(59,73)years. All the 320 patients were allocated into the mesenteric fissure non-closure group with 164 cases and the mesenteric fissure closure group with 156 cases. There was no significant difference in the age, body mass index, American Society of Anesthesiologist score, maximum tumor diameter, anastomosis location, anastomosis method, surgical approach, range of lymph node dissection, tumor staging between the two groups ( P>0.05) and there was a significant difference in the sex between them ( P<0.05). (2) Intraoperative conditions. There was no significant difference between the mesenteric fissure closure group and the mesenteric fissure non-closure group in the volume of intraoperative blood loss, operation time, conversion to laparotomy, intraoperative complication ( P>0.05). Three patients in the mesenteric fissure non-closure group were converted to laparotomy. One patient in the mesenteric fissure closure group was converted to laparotomy, and 2 cases with intraoperative complication were mesenteric hematoma. (3) Postoperative conditions. There was no significant difference between the mesenteric fissure non-closure group and the mesenteric fissure closure group in the overall postoperative complications ( χ2=0.28, P>0.05). There was no significant difference in the occurrence of postoperative intestinal obstruction, abdominal distension, ascites, pleural effusion, gastric paralysis, anastomotic bleeding, anastomotic leakage, or surgical wound infection between the two groups ( P>0.05). There was no significant difference between the two groups in the reoperation, postoperative gastric tube replacement. There was no significant differ-ence in time to postoperative first flatus, time to postoperative initial liquid food intake, time to post-operative resumption of bowel movements, duration of postoperative hospital stay, total hospital expenses between the two groups ( Z=-0.01, 0.43, 1.04, -0.54, -0.36, P>0.05). One patient in the mesenteric fissure non-closure group received reoperation. No perioperative internal hernia or death occurred in either group. The visual analog score decreased with time in both groups. There was no significant difference in the visual analog score between the mesenteric fissure closure group and the mesenteric fissure non-closure group [ β=-0.20(-0.53,0.13), P>0.05]. Conclusion:Compared with closure of mesenteric fissure, non-closure of mesenteric fissure during laparoscopic right hemi-colectomy dose not increase perioperative complications or postoperative management risk.

Objective:To investigate the prognostic value of the combined preoperative albumin-globulin score (AGS) and skeletal muscle index (SMI), referred to as the CAS classification, in predicting postoperative outcomes in patients with pancreatic cancer.Methods:The clinical data from 265 patients who underwent surgical treatment and were pathologically confirmed to have pancreatic cancer at the Affiliated Hospital of Qingdao University between January 2012 and December 2022 were retrospectively analyzed. Patients were randomly divided into a training group ( n=184) and a validation group ( n=81) in a 7∶3 ratio. Patients' age, gender, body mass index (BMI), smoking history, alcohol consumption history, previous history of metabolic diseases, AGS, SMI, and CAS classifications within 7 days before surgery, preoperative upper abdominal CT imaging features, presence of vascular and neural invasion, and lymph node metastasis were recorded. Patients with AGS grade 0 were classified into the low AGS group ( n=48), while those with AGS grades 1 and 2 were classified into the high AGS group ( n=136). The optimal cutoff value for SMI was determined using X-tile software: male patients with SMI>42.6 cm 2/m 2 or female patients with SMI>37.8 cm 2/m 2 were categorized into the high SMI group ( n=125), while those below these thresholds were categorized into the low SMI group ( n=59). Patients with AGS grade 0 and SMI>42.6 cm 2/m 2 for males or >37.8 cm 2/m 2 for females were classified into the CAS grade 1 group (n=32). Patients with AGS grades 1 or 2 and SMI ≤42.6 cm 2/m 2 for males or ≤37.8 cm 2/m 2 for females were classified into the CAS grade 3 group ( n=43). The remaining patients were classified into the CAS grade 2 group ( n=109). Clinical characteristics were compared across these groups. Cumulative survival rates were estimated using the Kaplan-Meier method, and survival curves were plotted to analyze the relationship between AGS, SMI, and CAS classifications and overall survival after pancreatic cancer surgery. Differences among groups were assessed using the Log-Rank test. Receiver operating characteristic curves (ROC) were plotted, and the area under the curve (AUC) was calculated to evaluate the predictive efficacy of AGS, SMI, and CAS on postoperative survival. Results:Compared to the high AGS group, the low AGS group exhibited higher SMI values [(46.17±9.63) cm 2/m 2vs (44.11±7.43) cm 2/m 2], and a lower incidence of lymph node metastasis (16 vs 66, 33.3% vs 48.5%). The mortality rate in the low AGS group was 50.0%(24/48), significantly lower than the 70.6% (96/136) observed in the high AGS group, with a median overall survival of 22.08 months (95% CI 16.87-29.62) longer than 13.1 months (95% CI 8.84-18.82) in high AGS group. Compared to the low SMI group, the high SMI group had a lower prevalence of metabolic diseases (26.4% vs 44.1%). The mortality rate in the low SMI group was 78.0% (46/59), higher than the 58.4% (73/125) in the high SMI group, with a median overall survival of 12.97 months (95% CI 9.37-18.20) obviously shorter than 16.20 months (95% CI 10.7-24.12) in high SMI group. Lymph node metastasis rate for CAS grade 1, 2, and 3 was 34.4% ( n=11), 44.0% ( n=48), and 62.8% ( n=27), respectively, with corresponding mortality rate of 34.3% (11/32), 67.9% (74/109), and 79.1% (34/43), and median overall survival time of 25.55 months (95% CI 19.49-30.07), 14.10 months (95% CI 10.22-19.14), and 12.5 months (95% CI 8.53-18.00), respectively. All the differences were statistically significant (all P value <0.05). Kaplan-Meier survival analyses demonstrated that patients in the low AGS group had significantly longer overall survival than those in the high AGS group in both the training and validation cohorts. Similarly, patients in the high SMI group had longer overall survival compared to those in the low SMI group. Notably, patients in CAS grade 1 exhibited the longest overall survival, whereas those in CAS grade 3 had the shortest. ROC curve analysis revealed that the AUC for CAS classification was superior in the training cohort (0.649) compared to AGS (0.588) and SMI (0.593), and in the validation cohort (0.644) compared to AGS (0.587) and SMI (0.577). Conclusions:CAS classification could effectively predict postoperative prognosis in pancreatic cancer patients, with higher CAS grades correlating with poorer outcomes.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in tertiary hospitals in major regions of China in 2022.Methods Clinical isolates from 58 hospitals in China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2022 Clinical &Laboratory Standards Institute(CLSI)breakpoints.Results A total of 318 013 clinical isolates were collected from January 1,2022 to December 31,2022,of which 29.5％were gram-positive and 70.5％were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species(excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi)was 28.3％,76.7％and 77.9％,respectively.Overall,94.0％of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 90.8％of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis showed significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 94.2％in the isolates from children and 95.7％in the isolates from adults.The resistance rate to carbapenems was lower than 13.1％in most Enterobacterales species except for Klebsiella,21.7％-23.1％of which were resistant to carbapenems.Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.1％to 13.3％.The prevalence of meropenem-resistant strains decreased from 23.5％in 2019 to 18.0％in 2022 in Pseudomonas aeruginosa,and decreased from 79.0％in 2019 to 72.5％in 2022 in Acinetobacter baumannii.Conclusions The resistance of clinical isolates to the commonly used antimicrobial agents is still increasing in tertiary hospitals.However,the prevalence of important carbapenem-resistant organisms such as carbapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a downward trend in recent years.This finding suggests that the strategy of combining antimicrobial resistance surveillance with multidisciplinary concerted action works well in curbing the spread of resistant bacteria.

Objective To investigate the therapeutic effects of Isaria felina derived from Cordyceps sinensis combined with cyclophosphamide(CTX)in hepatoma H22 tumor-bearing mice.Methods An H22 tumor-bearing mouse model was established and mice were divided randomly into a normal control group(NC group,distilled water),model control group(MC group,distilled water),positive control group(CTX group,25 mg/kg),Isaria felina group(IF group,400 mg/kg),and combined administration group(IF+CTX group,IF 400 mg/kg+CTX 25 mg/kg),with 5 mice in each group.Distilled water and IF were administered by gavage,and CTX was administered by intraperitoneal injection.The administration cycle was 10 days.At the end of the experiment,the mean tumor volume and weight,tumor inhibition rate,q value,and immune organ index were calculated,and routine blood indexes and cytokine levels were determined.Histopathological changes in tumor tissues were observed by HE staining.Results The tumor volume and mass were significantly lower in mice in each treatment group compared with those in mice in the MC group(P＜0.05).The tumor inhibition rates in the CTX,IF,and IF+CTX groups were 49.3%,34.2%,and 72.8%,respectively,and the q value was 1.09.The numbers of white blood cells,Lymph,and platelets were significantly higher in the IF+CTX group than in the CTX group(P＜0.05).The spleen index was significantly higher in the MC group compared with that in the NC group,and significantly lower in the IF+CTX group compared with that in the MC group(P＜0.05).Serum interferon-γ levels were significantly lower in the MC group than in the NC group,and were significantly higher in the IF and IF+CTX groups compared with those in the MC and CTX groups(P＜0.05).Pathologically,tumor cells in the MC group grew well and were numerous and closely arranged,while cells in the CTX,IF,and IF+CTX groups were arranged loosely,with focal necrosis and nuclear pyknosis of necrotic cells in many places.Conclusions The combination of IF and CTX has an additive anti-tumor effect on H22 tumor-bearing mice,which can alleviate immunosuppression and have an immunomodulatory function.

In order to achieve the purpose of rapid detection of duck astrovirus type 1(DAstV-1),specific primers were designed based on the conservative region of ORF1a which belonged to DAstV-1(WF1202 strain).A real-time fluorescent quantitative PCR(qPCR)detective method for DAstV-1 was established.Clinical samples were detected by the qPCR method and the positive samples were used for virus isolation and identification.Results showed that the detection limit of the established method was 4.64×103 copies/μL,which was 10 times higher than the normal RT-PCR method.In addition,no cross-reactions were found with other common infectious disease pathogens in poultry,indicating that the qPCR method had good specificity.What's more,the coef-ficient of variations(Cv)in intra-and inter-assays were 0.85％-2.85％and 0.21％-2.94％,re-spectively,both less than 3％,indicating that the qPCR method had a good repeatability.Using this method,35 tissue samples from different duck farms in 10 provinces from 2020 to 2022 were detected for DAstV-1.Results showed that the positive rate was 25.71％(9/35),and the coinci-dence rate was 94.29％when compared with the normal RT-PCR method.A positive sample ran-domly taken for the virus isolation through duck embryo passage,and the allantoic fluid was col-lected and then was verified by the qPCR method and inoculated with 1-day-old healthy ducklings for the animal regression experiment.The infected ducklings suffered from transient disease but did not die.The liver tissues were all positive with DAstV-1 when detected by qPCR.Meanwhile,autopsy showed that there were slight changes in the livers,and the histopathological observation showed that the liver cells were steatosis.These findings indicated that the isolated DAstV-1 strain had weak pathogenicity and might be a low virulent strain.To sum up,the qPCR detection method of DAstV-1 was successfully established in this work,and could provide technical support for clini-cal diagnosis,isolation and identification,and molecular epidemiology monitoring of DAstV-1.

In order to establish a rapid,specific and sensitive detection method for Streptococcus equi subspecies zooepidemicus(SEZ)and to understand the infection status of SEZ in horses ente-ring China,specific primers were designed and synthesized based on the conserved gene comB of standard strain SEZ(ATCC 43079)in this work.Then,the pMD19-T-comB recombinant plasmid was constructed and used as a standard positive template.After that,the fluorescence-based quantitative PCR(qPCR)detection method based on SYBR Green Ⅰ dye was established.Totally,477 equine entry serum samples from 6 countries,including Netherlands,Belgium,Japan,Germa-ny,Argentina and New Zealand,during 2018 to 2023,were randomly selected and detected for SEZ by the qPCR method.Results showed that the established qPCR method had specific amplification for only SEZ,which illustrated a good specificity.Sensitivity test of the method showed that the limited detection amount was 4.58 X101 copies/μL.And the repeatability test showed that the coef-ficient of variation of intra-batch repeatability was less than 0.5％,while the inter-batch repeat-ability was less than 3.0％,which indicated good repeatability and high stability.Retrospective a-nalysis showed that totally 11 of 477 positive samples were detected,with a relatively low positive rate of 2.31％(11/477).Among them,all the 40 samples from Netherlands in 2018 were negative(0/40).In the samples of 2019,one positive was detected from Belgium(1/20),while all other 36 samples which form Japan and Germany were negative.In the samples of 2021,three samples(3/34)from Japan and one sample(1/20)from Argentina were positive,and all the other 40 samples from the Netherlands were negative.In the samples of 2022,76 samples from Netherlands were all negative.While in the 2023,5(5/126)of 126 samples from Netherlands and one(1/88)of 88 from New Zealand were found positive with SEZ.To summarize,The SYBR Green Ⅰ qPCR method for the diagnosis of SEZ was successfully established,and it could provide necessary technical support for the rapid quarantine of China's entry-exit and port departments,as well as the epidemiological investigation of the disease.

Objective:To explore the efficacy of secondary targeted percutaneous vertebroplasty (PVP) for the treatment of refracture of injured vertebrae after vertebral augmentation for osteoporotic vertebral compression fracture (OVCF).Methods:A retrospective case series study was performed on the clinical data of 25 patients with refracture of injured vertebrae after vertebral augmentation for OVCF admitted to Honghui Hospital, Xi′an Jiaotong University from January 2019 to January 2022, including 10 males and 15 females, aged 62-86 years [(73.8±5.2)years]. The fractured segments involved T 10 in 1 patient, T 11 in 2, T 12 in 10, L 1 in 10 and L 2 in 2. All the patients were treated with secondary targeted PVP. The operation time and the amount of bone cement injected were recorded. The visual analogue scale (VAS) of lower back, Oswestry disability index (ODI), vertebral body index (VBI) and kyphotic angle (KA) were compared before surgery, at 1 day, 6 months after surgery and at the last follow-up. Odom criteria were used to evaluate the efficacy of the surgical procedure at the last follow-up. The intraoperative bone cement leakage and new vertebrae fracture during follow-up were observed. Results:All the patients were followed up for 23-59 months [(36.8±7.6)months]. The operation time was 35-60 minutes [(42.6±5.2)minutes], with the amount of bone cement injected for 3-5 ml [(3.6±0.8)ml]. The VAS scores of lower back at 1 day, 6 months after surgery and at the last follow-up were 3.1(2.0, 4.0)points, 1.7(1.0, 2.0)points and 0.6(0.0, 1.0)points respectively, significantly lower than 7.6(7.0, 9.0)points before surgery ( P<0.01), and a statistically singnificant decrease was found over follow-up time ( P<0.01). The ODI values at 1 day, 6 months after surgery and at the last follow-up were (49.5±5.9)%, (28.5±4.6)% and (19.2±4.8)% respectively, significantly lower than (78.8±6.8)% before surgery ( P<0.01), and a statistically singnificant decrease was found over follow-up time ( P<0.01). The VBI values at 1 day, 6 months after surgery and at the last follow-up were (76.6±4.5)%, (76.3±4.0)% and (76.1±3.8)% respectively, significantly higher than (58.9±5.8)% before surgery ( P<0.01), while there were no significant differences among those at 1 day, 6 months after surgery and at the last follow-up ( P>0.05). The KA values at 1 day, 6 months after surgery and at the last follow-up were (12.4±2.7)°, (12.6±2.5)° and (12.8±2.9)° respectively, significantly lower than (20.8±3.6)° before surgery ( P<0.01), while there were no significant differences among those at 1 day, 6 months after surgery and at the last follow-up ( P>0.05). According to the Odom criteria, 20 patients were rated excellent and 5 good at the last follow-up, with an excellent and good rate of 100%. Intraoperative asymptomatic bone cement leakage occurred in 3 patients (12%), including 2 with intervertebral leakage and 1 with lateral vertebral leakage. No adjacent vertebral body or other vertebral fracture was observed during the follow-up. Conclusions:For patients with refracture of injured vertebrae after vertebral augmentation for OVCF, the secondary targeted PVP has advantages of attenuation of the lower back pain, improvement of the quality of life, restoration of the height of refractured vertebrae, correction of the local kyphosis, and a low incidence of complications.