Objective To investigate the influences of Lycium barbarum polysaccharide on apoptosis of corneal epithelial cells induced by hypertonicity through regulating adenosine monophosphate activated protein kinase(AMPK)/uncoordinated 51-like kinase 1(ULK1)autophagy pathway.Methods The ophthalmoxerosis cell model was established by osmotic pressure of 500 mOsm·L-1 on corneal epithelial cells.They were divided into model group,positive control group(0.3％sodium hyaluronate eye drops),inhibitor group(1 mg·mL-1 Lycium barbarum polysaccharide+10 μmol·L-1compound C),experimental-L,-H groups(0.5,1.0 mg·mL 1 Lycium barbarum polysaccharide),and normal cultured CRL-11135 cells were taken as blank group(no treatment was performed).Cell apoptosis was detected by flow cytometry.Autophagy was detected by MDC staining.Western blot was used to detect the expressions of p-AMPK/AMPK and p-ULK1/ULK1.Results The apoptosis rates of experimental-L,experimental-H,positive control,inhibitor,model and blank groups were(26.47±2.13)％,(13.68±2.21)％,(12.54±2.16)％,(18.73±2.12)％,(37.56±3.25)％and(6.35±2.14)％;the relative contents of autophagosomes were(59.63±8.14)％,(89.89±9.04)％,(90.31±9.13)％,(62.75±7.26)％,(43.11±6.45)％and(100.00±0.00)％;p-AMPK/AMPK were 0.45±0.07,0.64±0.08,0.66±0.06,0.53±0.04,0.34±0.05 and 0.87±0.06;p-ULKl/ULKl were 0.54±0.06,0.75±0.05,0.77±0.03,0.65±0.04,0.46±0.04 and 0.92±0.08,respectively.The above indexes in experimental-L,-H groups and positive control group were significantly different from those in model group(all P＜0.05);the above indexes in inhibitor group were significantly different from those in experimental-H group(all P＜0.05).Conclusion Lycium barbarum polysaccharide can inhibit the apoptosis of corneal epithelial cells induced by hypertonicity by activating the AMPK/ULK1 autophagy pathway.

Objective To investigate the distribution and antimicrobial resistance of bacterial isolates from blood samples in the hospitals participating in China Antimicrobial Surveillance Network (CHINET) from 2015 to 2021.Methods Bacterial strains isolated from blood samples were collected from 52 medical centers participating in CHINET from 2015 to 2021 for analysis of bacetrial distribution and antimicrobial resistance.Results A total of 153591 isolates were collected,48.8％ of which were gram-positive bacteria and 51.2％ were gram-negative bacteria.The top five bacterial strains were coagulase negative Staphylococcus (28.2％),Escherichia coli (20.7％),Klebsiella (13.7％),Enterococcus (7.2％),and Staphylococcus aureus (6.6％).Compard to female patients,male patients showed lower proportion of E.coli and higher proportions of other bacterial species in all the bacterial isolaets from blood samples.The proportions of Streptococcus pneumoniae and Salmonella in all the bacterial isolaets from blood samples were higher in children compared to adults.Enterobacterales species showed various resistance rates to antimicrobial agents.Overall,≥58.0％,≥36.8％ and ≥56.8％ of E.coli strains were resistant to cefotaxime,gentamicin and levofloxacin respectively over the 7-year period.However,less than 2.5％ of the E.coli strains were resistant to carbapenems.K.pneumoniae showed higher resistance rates to imipenem and meropenem than other Enterobacterales species.During the 7-year period,the prevalence of imipenem-resistant and meropenem-resistant K.pneumoniae increased from 21.4％ and 19.9％ in 2015 to 25.7％ and 26.6％ in 2021,respectively.However,carbapenems still maintained good antibacterial activity against other Enterobacterales,associaetd with lower resistance rates.In the 7-year period,Acinetobacter baumannii showed a dwonward trend in the resistance rates to imipenem and meropenem,but remained 72.9％ and 73.2％ respectively in 2021.The prevalence of imipenem-resistant and meropenem-resistant P.aeruginosa decreased from 26.7％ and 22.9％ in 2015 to 18.5％ and 14.7％ in 2021,respectively.The prevalence of PRSP was 1.5％ in the isolaets from adults and and 0.8％ in the isolates from children.Less than 3.0％ of the Enterococcus faecium and Enterococcus faecalis strains were resistant to vancomycin,teicolanin,or linezolid.The prevalence of methicillin-resistant S.aureus (MRSA) and coagulase negative Staphylococcus (MRCNS) was 32.1％ and 81.0％,respectively.The prevalence of MRSA was relatively stable,28.5％ in 2015 and 28.0％ in 2021.Conclusions Coagulase negative Staphylococcus,E.coli and K.pneumoniae were the main bacterial species isolated from blood samples in the hospitals participaing in the CHINET from 2015 to 2021.Significant sex and age differences were found in the distribution of bcterial isolates from blood samples.The overall resistance rates of the top bacetrial strains from blood samples to antimicrobial agents showed a downward trend.Ongoing surveillance of antimicrobial resistance for the isolates from blood samples is still essential for prescribing rational antimicrobial therapies and curbing bacterial resistance.

AIM To explore the ameliorative effects of Zigui Yichong Formula on mitochondrial energy metabolism in in vitro model of premature ovarian insufficiency (POI).METHODS A POI model in vitro was established in human ovarian granulosa cell KGN with acrolein ( ACR ) for the further intervention of serum containing Zigui Yichong Formula.The control group,the ACR group,the Zigui Yichong Formula group,the EX527 ( SIRT1 inhibitor) group and the EX527+Zigui Yichong Formula group were set up.The cells had their apoptosis rate detected by flow cytometry;their ROS level detected by DCFH-DA method;their mitochondria number detected by Mito-Trakine fluorescence labeling method;their oxidative phosphorylation level of mitochondria detected by Seahorse method;their ATP level detected by colorimetry;their copy number of mtDNA and mRNA expressions of SIRT1,PGC-1α,Nrf1 and TFAM detected by RT-qPCR;and their protein expressions of SIRT1,PGC-1α,Ac-PGC-1α,Nrf1 and TFAM detected by Western blot.RESULTS Compared with the control group,the ACR group displayed increased apoptosis rate and ROS level of KGN cells ( P<0.05,P<0.01 );decreased number of mitochondria and mtDNA copy number ( P<0.01 );decreased basic value of mitochondrial aerobic respiration,maximum respiration,reserve value and ATP level (P<0.05,P<0.01),decreased mRNA and protein expressions of SIRT1,PGC-1α,Nrf1 and TFAM ( P<0.05,P<0.01 );and increased protein expression of Ac-PGC-1α( P<0.01 ).Compared with the ACR group,the Zigui Yichong Formula group demonstrated improvement in terms of the aforementioned indices levels ( P<0.05,P<0.01).The combination use of Zigui Yichong Formula and EX527 reversed the effects of single use of Zigui Yichong Formula on KGN cells ( P<0.05,P<0.01).CONCLUSION Zigui Yichong Formula may improve the mitochondrial energy metabolism disorder induced by ACR in KGN cells by increasing mitochondrial biosynthesis via SIRT1/PGC-1α signaling pathway.

Objective To investigate the distribution and antimicrobial resistance of bacterial isolates from blood samples in the hospitals participating in China Antimicrobial Surveillance Network (CHINET) from 2015 to 2021.Methods Bacterial strains isolated from blood samples were collected from 52 medical centers participating in CHINET from 2015 to 2021 for analysis of bacetrial distribution and antimicrobial resistance.Results A total of 153591 isolates were collected,48.8％ of which were gram-positive bacteria and 51.2％ were gram-negative bacteria.The top five bacterial strains were coagulase negative Staphylococcus (28.2％),Escherichia coli (20.7％),Klebsiella (13.7％),Enterococcus (7.2％),and Staphylococcus aureus (6.6％).Compard to female patients,male patients showed lower proportion of E.coli and higher proportions of other bacterial species in all the bacterial isolaets from blood samples.The proportions of Streptococcus pneumoniae and Salmonella in all the bacterial isolaets from blood samples were higher in children compared to adults.Enterobacterales species showed various resistance rates to antimicrobial agents.Overall,≥58.0％,≥36.8％ and ≥56.8％ of E.coli strains were resistant to cefotaxime,gentamicin and levofloxacin respectively over the 7-year period.However,less than 2.5％ of the E.coli strains were resistant to carbapenems.K.pneumoniae showed higher resistance rates to imipenem and meropenem than other Enterobacterales species.During the 7-year period,the prevalence of imipenem-resistant and meropenem-resistant K.pneumoniae increased from 21.4％ and 19.9％ in 2015 to 25.7％ and 26.6％ in 2021,respectively.However,carbapenems still maintained good antibacterial activity against other Enterobacterales,associaetd with lower resistance rates.In the 7-year period,Acinetobacter baumannii showed a dwonward trend in the resistance rates to imipenem and meropenem,but remained 72.9％ and 73.2％ respectively in 2021.The prevalence of imipenem-resistant and meropenem-resistant P.aeruginosa decreased from 26.7％ and 22.9％ in 2015 to 18.5％ and 14.7％ in 2021,respectively.The prevalence of PRSP was 1.5％ in the isolaets from adults and and 0.8％ in the isolates from children.Less than 3.0％ of the Enterococcus faecium and Enterococcus faecalis strains were resistant to vancomycin,teicolanin,or linezolid.The prevalence of methicillin-resistant S.aureus (MRSA) and coagulase negative Staphylococcus (MRCNS) was 32.1％ and 81.0％,respectively.The prevalence of MRSA was relatively stable,28.5％ in 2015 and 28.0％ in 2021.Conclusions Coagulase negative Staphylococcus,E.coli and K.pneumoniae were the main bacterial species isolated from blood samples in the hospitals participaing in the CHINET from 2015 to 2021.Significant sex and age differences were found in the distribution of bcterial isolates from blood samples.The overall resistance rates of the top bacetrial strains from blood samples to antimicrobial agents showed a downward trend.Ongoing surveillance of antimicrobial resistance for the isolates from blood samples is still essential for prescribing rational antimicrobial therapies and curbing bacterial resistance.

AIM To explore the ameliorative effects of Zigui Yichong Formula on mitochondrial energy metabolism in in vitro model of premature ovarian insufficiency (POI).METHODS A POI model in vitro was established in human ovarian granulosa cell KGN with acrolein ( ACR ) for the further intervention of serum containing Zigui Yichong Formula.The control group,the ACR group,the Zigui Yichong Formula group,the EX527 ( SIRT1 inhibitor) group and the EX527+Zigui Yichong Formula group were set up.The cells had their apoptosis rate detected by flow cytometry;their ROS level detected by DCFH-DA method;their mitochondria number detected by Mito-Trakine fluorescence labeling method;their oxidative phosphorylation level of mitochondria detected by Seahorse method;their ATP level detected by colorimetry;their copy number of mtDNA and mRNA expressions of SIRT1,PGC-1α,Nrf1 and TFAM detected by RT-qPCR;and their protein expressions of SIRT1,PGC-1α,Ac-PGC-1α,Nrf1 and TFAM detected by Western blot.RESULTS Compared with the control group,the ACR group displayed increased apoptosis rate and ROS level of KGN cells ( P<0.05,P<0.01 );decreased number of mitochondria and mtDNA copy number ( P<0.01 );decreased basic value of mitochondrial aerobic respiration,maximum respiration,reserve value and ATP level (P<0.05,P<0.01),decreased mRNA and protein expressions of SIRT1,PGC-1α,Nrf1 and TFAM ( P<0.05,P<0.01 );and increased protein expression of Ac-PGC-1α( P<0.01 ).Compared with the ACR group,the Zigui Yichong Formula group demonstrated improvement in terms of the aforementioned indices levels ( P<0.05,P<0.01).The combination use of Zigui Yichong Formula and EX527 reversed the effects of single use of Zigui Yichong Formula on KGN cells ( P<0.05,P<0.01).CONCLUSION Zigui Yichong Formula may improve the mitochondrial energy metabolism disorder induced by ACR in KGN cells by increasing mitochondrial biosynthesis via SIRT1/PGC-1α signaling pathway.

Objective:To compare the clinical effects robot navigation assisted and conventional proximal femoral nail antirotation (PFNA) implantation and fixation in the treatment of elderly femoral trochanteric fractures.Methods:A total of 86 elderly patients with tuberosity fracture of the femur were admitted as research samples from January to March in 2022 in the Department of Trauma Orthopaedic, Xi′an Honghui Hospital Affiliated to Xi′an Jiaotong University, including 37 males and 49 females, who aged from 63 to 92 years, with an average age of (79.6 ± 6.9) years. All patients were treated with intramedullary nails (PFNA), 32 with dimensity robotic-assisted therapy (robot group) and 54 with traditional methods (conventional group). The length of incision, the number of intraoperative fluoroscopy, the amount of intraoperative blood loss, and the operation time were recorded. The occurrence of postoperative complications in the two groups was observed. The rate of excellent hip Harris score at 3 month after surgery was compared between the two groups. Measurement data with normal distribution were represented as mean ± standard deviation( ± s), and the comparison between groups was conducted using the t-test; the comparison of count data were represented as [ n(%)], and was conducted by Chi-square test or Fisher exact probability between groups. Results:All patients were followed up for 9 to 12 months, with an average of (10.6 ± 0.9) months. The incision length and tip apex distance (TAD) of the robot group were (3.40±0.82) cm and (21.85±1.44) mm, which were smaller than (4.82±0.75) cm and (26.83±1.75) mm in the conventional group ( P<0.05 for all). The number of intraoperative fluoroscopy and guide needle adjustment [(14.53±3.26) and 0 times] in the robot group were less than those in the conventional group [(20.67±4.84) and (2.83±1.42)] ( P<0.05). The intraoperative blood loss and drainage rate of the robot group were (87.03±9.41) and (46.40±8.91) mL, which were smaller than that of the conventional group [(110.00±12.52) and (69.62±10.22) mL] ( P<0.05). There was no significant difference in the number of days of hospitalization and operation time between the two groups ( P>0.05). The postoperative complication rate in the robot group was 9.4%, which was lower than that in conventional group (42.6%), and the difference was statistically significant ( χ2=11.88, P=0.036). The excellent rate of postoperative hip joint function in the robot group was 75.0%, and the conventional group was 66.7%, and there was no significant difference between the two groups ( χ2=0.66, P=0.416). Conclusion:Robot-assisted navigation downward PFNA surgery can have good clinical effect in the treatment of femoral tuberosity fracture in the elderly, which can reduce the number of surgical incisions and intraoperative fluoroscopy, and reduce the incidence of postoperative complications, which is helpful to achieve minimally invasive surgery and rapid recovery of elderly patients with femoral tuberosity fracture.

Objective: To examine the feasibility and surgical approach of removing type D trigeminal schwannoma through nasal cavity and nasal sinus under endoscope. Methods: Eleven patients with trigeminal schwannoma who were treated in the Department of Otorhinolaryngology, Qilu Hospital of Shandong University from December 2014 to August 2021 were analyzed retrospectively in this study. There were 7 males and 4 females, aged (47.5±13.5) years (range: 12 to 64 years). The neoplasm involved the pterygopalatine fossa, infratemporal fossa, ethmoidal sinus, sphenoid sinus, cavernous sinus, and middle cranial fossa. The size of tumors were between 1.6 cm×2.0 cm×2.0 cm and 5.7 cm×6.0 cm×6.0 cm. Under general anesthesia, the tumors were resected through the transpterygoid approach in 4 cases, through the prelacrimal recess approach in 4 cases, through the extended prelacrimal recess approach in 2 cases, and through the endoscopic medial maxillectomy approach in 1 case. The nasal endoscopy and imaging examination were conducted to detect whether neoplasm recurred or not, and the main clinical symptoms during follow-up. Results: All the surgical procedures were performed under endonasal endoscope, including Gross total resection in 10 patients. The tumor of a 12-year-old patient was not resected completely due to huge tumor size and limited operation space. One patient was accompanied by two other schwannomas located in the occipital region and the ipsilateral parotid gland region originating from the zygomatic branch of the facial nerve, both of which were removed concurrently. After tumor resection, the dura mater of middle cranial fossa was directly exposed in the nasal sinus in 2 cases, including 1 case accompanied by cerebrospinal fluid leakage which was reconstructed by a free mucosal flap obtained from the middle turbinate, the other case was packed by the autologous fat to protect the dura mater. The operation time was (M(IQR)) 180 (160) minutes (range: 120 to 485 minutes). No complications and deaths were observed. No recurrence was observed in the 10 patients with total tumor resection during a 58 (68) months' (range: 10 to 90 months) follow-up. No obvious change was observed in the facial appearance of all patients during the follow-up. Conclusion: Type D trigeminal schwannoma involving pterygopalatine fossa and infratemporal fossa can be removed safely through purely endoscopic endonasal approach by selecting the appropriate approach according to the size and involvement of the tumor.
Male ; Female ; Humans ; Child ; Retrospective Studies ; Endoscopy/methods* ; Nasal Cavity/surgery* ; Neurilemmoma/surgery* ; Cranial Nerve Neoplasms/surgery*

With the improved understanding of driver mutations in non-small cell lung cancer (NSCLC), expanding the targeted therapeutic options improved the survival and safety. However, responses to these agents are commonly temporary and incomplete. Moreover, even patients with the same oncogenic driver gene can respond diversely to the same agent. Furthermore, the therapeutic role of immune-checkpoint inhibitors (ICIs) in oncogene-driven NSCLC remains unclear. Therefore, this review aimed to classify the management of NSCLC with driver mutations based on the gene subtype, concomitant mutation, and dynamic alternation. Then, we provide an overview of the resistant mechanism of target therapy occurring in targeted alternations ("target-dependent resistance") and in the parallel and downstream pathways ("target-independent resistance"). Thirdly, we discuss the effectiveness of ICIs for NSCLC with driver mutations and the combined therapeutic approaches that might reverse the immunosuppressive tumor immune microenvironment. Finally, we listed the emerging treatment strategies for the new oncogenic alternations, and proposed the perspective of NSCLC with driver mutations. This review will guide clinicians to design tailored treatments for NSCLC with driver mutations.
Humans ; Carcinoma, Non-Small-Cell Lung/genetics* ; Lung Neoplasms/genetics* ; Mutation ; Tumor Microenvironment/genetics*

This study aims to investigate the effect and mechanism of hydnocarpin(HC) in treating triple negative breast cancer(TNBC). Cell counting kit-8(CCK-8), xCELLigence real-time cellular analysis(RTCA), and colony formation assay were employed to determine the effects of HC on the proliferation of two TNBC cell lines: MDA-MB-231 and MDA-MB-436. The effects of HC on the migration and invasion of TNBC cells were detected by high-content analysis, wound-healing assay, and Transwell assay. The changes in the epithelial-mesenchymal transition(EMT) and the expression of invasion-and migration-associated proteins [E-cadherin, vimentin, Snail, matrix metalloproteinase-2(MMP-2), and MMP-9] were detected by Western blot. Western blot and RT-qPCR were employed to determine the protein and mRNA levels of Yes-associated protein(YAP) and downstream targets(CTGF and Cyr61). TNBC cells were transfected with Flag-YAP for the overexpression of YAP, and the role of YAP as a key target for HC to inhibit TNBC malignant progression was examined by CCK-8 assay, Transwell assay, and wound-healing assay. The pathway of HC-induced YAP degradation was detected by the co-treatment of proteasome inhibitor with HC and ubiquitination assay. The binding of HC to YAP and the E3 ubiquitin ligase Ccr4-not transcription complex subunit 4(CNOT4) was detected by microscale thermophoresis(MST) assay and drug affinity responsive target stability(DARTS) assay. The results showed that HC significantly inhibited the proliferation, colony formation, invasion, and EMT of TNBC cells. HC down-regulated the protein and mRNA levels of CTGF and Cyr61. HC down-regulated the total protein level of YAP, while it had no effect on the mRNA level of YAP. The overexpression of YAP antagonized the inhibitory effects of HC on the proliferation, migration, and invasion of TNBC cells. HC promoted the degradation of YAP through the proteasome pathway and up-regulated the ubiquitination level of YAP. The results of MST and DARTS demonstrated direct binding between HC, YAP, and CNOT4. The above results indicated that HC inhibited the malignant progression of TNBC via CNOT4-mediated degradation and ubiquitination of YAP.
Humans ; Triple Negative Breast Neoplasms/metabolism* ; Matrix Metalloproteinase 2/metabolism* ; Cell Line, Tumor ; Cell Proliferation ; Cell Movement ; Ubiquitination ; RNA, Messenger/metabolism* ; Epithelial-Mesenchymal Transition ; Transcription Factors/metabolism*

Pulmonary blast injury has become the main type of trauma in modern warfare, characterized by externally mild injuries but internally severe injuries, rapid disease progression, and a high rate of early death. The injury is complicated in clinical practice, often with multiple and compound injuries. Currently, there is a lack of effective protective materials, accurate injury detection instrument and portable monitoring and transportation equipment, standardized clinical treatment guidelines in various medical centers, and evidence-based guidelines at home and abroad, resulting in a high mortality in clinlcal practice. Therefore, the Trauma Branch of Chinese Medical Association and the Editorial Committee of Chinese Journal of Trauma organized military and civilian experts in related fields such as thoracic surgery and traumatic surgery to jointly develop the Clinical treatment guideline for pulmonary blast injury ( version 2023) by combining evidence for effectiveness and clinical first-line treatment experience. This guideline provided 16 recommended opinions surrounding definition, characteristics, pre-hospital diagnosis and treatment, and in-hospital treatment of pulmonary blast injury, hoping to provide a basis for the clinical treatment in hospitals at different levels.