BACKGROUND: Durvalumab after chemoradiotherapy (CRT) failed to bring survival benefits to patients with epidermal growth factor receptor ( EGFR ) mutations in PACIFIC study (evaluating durvalumab in patients with stage III, unresectable NSCLC who did not have disease progression after concurrent chemoradiotherapy). We aimed to explore whether locally advanced inoperable patients with EGFR mutations benefit from tyrosine kinase inhibitors (TKIs) and the optimal treatment regimen. METHODS: We searched the PubMed, Embase, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov databases from inception to December 31, 2022 and performed a meta-analysis based on a Bayesian framework, with progression-free survival (PFS) and overall survival (OS) as the primary endpoints. RESULTS: A total of 1156 patients were identified in 16 studies that included 6 treatment measures, including CRT, CRT followed by durvalumab (CRT-Durva), TKI monotherapy, radiotherapy combined with TKI (RT-TKI), CRT combined with TKI (CRT-TKI), and TKI combined with durvalumab (TKI-Durva). The PFS of patients treated with TKI-containing regimens was significantly longer than that of patients treated with TKI-free regimens (hazard ratio [HR] = 0.37, 95% confidence interval [CI], 0.20-0.66). The PFS of TKI monotherapy was significantly longer than that of CRT (HR = 0.66, 95% CI, 0.50-0.87) but shorter than RT-TKI (HR = 1.78, 95% CI, 1.17-2.67). Furthermore, the PFS of RT-TKI or CRT-TKI were both significantly longer than that of CRT or CRT-Durva. RT-TKI ranked first in the Bayesian ranking, with the longest OS (60.8 months, 95% CI = 37.2-84.3 months) and the longest PFS (21.5 months, 95% CI, 15.4-27.5 months) in integrated analysis. CONCLUSIONS: For unresectable stage III EGFR mutant NSCLC, RT and TKI are both essential. Based on the current evidence, RT-TKI brings a superior survival advantage, while CRT-TKI needs further estimation. Large randomized clinical trials are urgently needed to explore the appropriate application sequences of TKI, radiotherapy, and chemotherapy. REGISTRATION PROSPERO; https://www.crd.york.ac.uk/PROSPERO/ ; No. CRD42022298490.
Humans ; Carcinoma, Non-Small-Cell Lung/therapy* ; ErbB Receptors/genetics* ; Lung Neoplasms/drug therapy* ; Mutation/genetics* ; Protein Kinase Inhibitors/therapeutic use* ; Chemoradiotherapy ; Antibodies, Monoclonal/therapeutic use*

OBJECTIVE: To explore the clinical significance of circulating tumor DNA (ctDNA) in response evaluation and relapse monitoring for patients with primary mediastinal large B-cell lymphoma (PMBCL). METHODS: The clinical characteristics, efficacy and survival of 38 PMBCL patients in our hospital from January 2010 to April 2020 were retrospectively analyzed. The ctDNA monitoring was conducted by targeted next-generation sequencing (NGS). RESULTS: Among the 38 patients, 26 cases were female, and 32 cases were diagnosed with Ann Arbor stage I-II. The 5-year overall survival (OS) rate and progression-free survival (PFS) rate were 74.7% and 61.7%, respectively. Males and those with high aaIPI scores (3 points) had a relatively poor prognosis. The NGS results of 23 patients showed that STAT6 (65.2%), SOCS1 (56.5%), and TNFAIP3 (56.5%) were the most common mutated genes. Patients with stable disease (SD)/progressive disease (PD) exhibited enrichment in cell cycle, FoxO, and TNF signaling pathways. A total of 29 patients underwent end-of-treatment PET/CT (EOT PET/CT), and 16 of them received ctDNA monitoring with 12 negative. Among 6 patients with EOT PET/CT positive (Deauville 4), 4 underwent ctDNA monitoring, and 3 of them were negative, being still in continuous remission without any subsequent anti-tumor therapy. CONCLUSION CtDNA may be combined with PET/CT to assess efficacy, monitor relapse, and guide treatment of PMBCL.
Humans ; Circulating Tumor DNA/blood* ; Female ; Mediastinal Neoplasms ; Male ; Retrospective Studies ; High-Throughput Nucleotide Sequencing ; Prognosis ; Lymphoma, Large B-Cell, Diffuse/genetics* ; Middle Aged ; Adult ; Aged ; Neoplasm Recurrence, Local ; Mutation

Peripheral nerve injury (PNI) encompasses damage to nerves located outside the central nervous system, adversely affecting both motor and sensory functions. Although peripheral nerves possess an intrinsic capacity for self-repair, severe injuries frequently result in significant tissue loss and erroneous axonal junctions, thereby impeding complete recovery and potentially causing neuropathic pain. Various therapeutic strategies, including surgical interventions, biomaterials, and pharmacological agents, have been developed to enhance nerve repair processes. While preclinical studies in animal models have demonstrated the efficacy of certain pharmacological agents in promoting nerve regeneration and mitigating inflammation, only a limited number of these agents have been translated into clinical practice to expedite nerve regeneration. Chinese herb medicine (CHM) possesses a longstanding history in the treatment of various ailments and demonstrates potential efficacy in addressing PNI through its distinctive, cost-effective, and multifaceted methodologies. This review critically examines the advancements in the application of CHM for PNI treatment and nerve regeneration. In particular, we have summarized the most commonly employed and rigorously investigated CHM prescriptions, individual herbs, and natural products, elucidating their respective functions and underlying mechanisms in the context of PNI treatment. Furthermore, we have deliberated on the prospective development of CHM in both clinical practice and fundamental research.
Drugs, Chinese Herbal/pharmacology* ; Humans ; Peripheral Nerve Injuries/drug therapy* ; Animals ; Nerve Regeneration/drug effects* ; Medicine, Chinese Traditional

Objective:To explore the therapeutic efficacy and prognostic factors of induction therapy for secondary central nervous system lymphoma(SCNSL).Methods:Clinical data of patients diagnosed with SCNSL from 2010 to 2021 at Guangdong Provincial People's Hospital were retrospectively collected.A retrospective cohort study was performed on all and grouped patients to analyze the efficacy and survival.Multivariate logistic regression analysis was used to explore the adverse prognostic factors.Results:Thirty-seven diffuse large B-cell lymphoma patients with secondary central involvement were included in the research.Their 2-year overall survival(OS)rate was 46.01％and median survival time was 18.1 months.The 2-year OS rates of HD-MTX group and TMZ group were 34.3％and 61％,median survival time were 8.7 and 38.3 months,and median progression-free survival time were 8.1 and 47 months,respectively.Multivariate logistic regression analysis showed that age,sex,IPI,Ann Arbor stage were correlated with patient survival time.The median survival time of patients with CD79B,KMT2D,CXCR4.ERBB2,TBL1XR1,BTG2,MYC,MYD88,and PIM1 mutations was 8.2 months,which was lower than the overall level.Conclusion:HD-MTX combined with TMZ as the first-line strategy may improve patient prognosis,and early application of gene sequencing is beneficial for evaluating prognosis.

Objective To investigate the changes of coagulation,fibrinolysis and platelet indexes in ovarian cancer patients before and after neoadjuvant chemotherapy,and to analyze the risk relationship between relevant indexes before treatment and the effect of neoadjuvant chemotherapy(NACT).Methods Patients with ovarian cancer admitted to Xi'an Fengcheng Hospital,from March 2020 to March 2023 were included as the ovarian cancer group,and female patients who underwent physical examination in the same period were selected as the control group according to a 2∶1 ratio.Prothrombin time(PT),thrombin time(TT),activated partial thromboplastin time(APTT),fibrinogen(FIB),platelet distribution width(PDW),platelet hematocrit(PCT),platelet(PLT)and mean platelet volume(MPV)were compared between the two groups.The changes of these indexes were compared before and after NACT,at different clinical stages and before and after NACT with different efficacy effects.Moreover,they were divided into effective and ineffective groups according to their treatment efficacy.Logistic regression was used to explore the relationship between the parameters and NACT efficacy;receiver operating characteristic curve was drawn to predict the value of NACT efficacy.Results A total of 144 patients were included,with 96 cases in the ovarian cancer group and 48 in the control group.The FIB,PLT and MPV of patients in the ovarian cancer group were higher than those in the control group(P<0.05).The PT,TT,APTT,FIB and PLT of ovarian cancer patients after NACT were lower than those before NACT(P<0.05).FIB and PLT of stage Ⅱ patients were lower than those of stage Ⅲ before and after NACT,and the PT,TT,APTT,FIB and PLT of the effective group were lower than those of the ineffective group before and after NACT,and the PT,TT,APTT,FIB and PLT of the two groups after NACT were lower than those before NACT(P<0.05).Multivariate Logistic regression analysis indicated that high PT,TT,APTT,FIB and PLT before NACT were independent risk factors for NACT ineffectiveness(P<0.05).The area under the curve of PT,TT,APTT,FIB and PLT before NACT to predict the effect of NACT were 0.713(sensitivity of 80.95%,specificity of 69.33%),0.756(sensitivity of 71.43%,specificity of 82.67%)and 0.787(sensitivity of 76.19%,specificity of 70.67%),0.727(sensitivity of 71.43%,specificity of 84.00%),0.794(sensitivity of 80.95%,specificity of 76.00%),respectively.Conclusion Changes in coagulation and fibrinolytic function and platelet parameters in ovarian cancer patients after NACT are associated with clinical stages and NACT effect.High levels of PT,TT,APTT,FIB and PLT before NACT are important reasons affecting NACT effect.Constructing the risk prediction model of NACT efficacy in ovarian cancer patients based on the above five parameters can provide a reference for clinical practice.

Osteoarthritis(OA)is a chronic progressive osteoarthropathy in the elderly.Osteoclast activation plays a crucial role in the occurrence of subchondral bone loss in early OA.However,the specific mechanism of osteoclast differentiation in OA remains unclear.In our study,gene expression profiles related to OA disease progression and osteoclast activation were screened from the Gene Expression Omnibus(GEO)repository.GEO2R and Funrich analysis tools were employed to find differentially expressed genes(DEGs).Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses demonstrated that chemical carcinogenesis,reactive oxygen species(ROS),and response to oxidative stress were mainly involved in osteoclast differentiation in OA subchondral bone.Furthermore,fourteen DEGs that are associated with oxidative stress were identified.The first ranked differential gene,heme oxygenase 1(HMOX1),was selected for further validation.Related results showed that osteoclast activation in the pathogenesis of OA subchondral bone is accompanied by the downregulation of HMOX1.Carnosol was revealed to inhibit osteoclastogenesis by targeting HMOX1 and upregulating the expression of antioxidant protein in vitro.Meanwhile,carnosol was found to alleviate the severity of OA by inhibiting the activation of subchondral osteoclasts in vivo.Our research indicated that the activation of osteoclasts due to subchondral bone redox dysplasia may serve as a significant pathway for the advancement of OA.Targeting HMOX1 in subchondral osteoclasts may offer novel insights for the treatment of early OA.

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.

Adjuvant chemoradiotherapy,molecular targeted therapy,and immunotherapy are frequently employed to extend the survival of patients with advanced gastric cancer(GC).However,most of these treatments have toxic side effects,drug resistance,and limited improvements in survival and quality of life.Therefore,it is crucial to discover and develop new medications targeting GC that are highly effective and have minimal toxicity.In previous studies,the total terpene extract from the stem of Celastrus orbiculatus demonstrated anti-GC activity;however,the specific mechanism was unclear.Our research utilising co-immunoprecipitation-mass spectrometry(Co-IP-MS),polypyrimidine tract binding protein 1(ptbp1)clustered regularly interspaced short palindromic repeat-associated protein 9(Cas9)-knockout(KO)mouse model,tissue microarray,and functional experiments suggests that alpha actinin-4(ACTN4)could be a significant biomarker of GC.PTBP1 influences actin cytoskeleton restructuring in GC cells by interacting with ACTN4.Celastrus orbiculatus stem extract(COE)may directly target ACTN4 and affect the interaction between PTBP1 and ACTN4,thereby exerting anti-GC effects.

OBJECTIVE To evaluate the effectiveness， safety， economy， innovation， suitability and accessibility of recombinant Mycobacterium tuberculosis fusion protein （EC）， and to provide evidence for selecting skin detection methods for tuberculosis infection diagnosis and auxiliary diagnosis of tuberculosis. METHODS The effectiveness and safety of EC compared with purified protein derivative of tuberculin （TB-PPD） were analyzed by the method of systematic review. Cost minimization analysis， cost-effectiveness analysis and cost-utility analysis were used to evaluate the short-term economy of EC compared with TB-PPD， and cost-utility analysis was used to evaluate the long-term economy. The evaluation dimensions of innovation， suitability and accessibility were determined by systematic review and improved Delphi expert consultation， and the comprehensive score of EC and TB-PPD in each dimension were calculated by the weight of each indicator. RESULTS The scores of effectiveness， safety， economy， innovation and suitability of EC were all higher than those of TB-PPD. The affordability scores of the two drugs were consistent， while the availability score of EC was lower than those of TB-PPD. After considering dimensions and index weight， the scores of effectiveness， safety， economy， innovation， suitability， accessibility and the comprehensive score of EC were all higher than those of TB-PPD. CONCLUSIONS Compared with TB-PPD， EC performs better in all dimensions of effectiveness， safety， economy， innovation， suitability and accessibility. However， it is worth noting that EC should further improve its availability in the dimension of accessibility.

OBJECTIVE: To investigate the efficacy and safety of multiple-dose intravenous tranexamic acid (TXA) for reducing blood loss in complex tibial plateau fractures with open reduction internal fixation by a prospective randomized controlled trial. METHODS: A study was conducted on patients with Schatzker type Ⅳ-Ⅵ tibial plateau fractures admitted between August 2020 and December 2022. Among them, 88 patients met the selection criteria and were included in the study. They were randomly allocated into 3 groups, the control group (28 cases), single-dose TXA group (31 cases), and multiple-dose TXA group (29 cases), using a random number table method. There was no significant difference ( P>0.05) in terms of age, gender, body mass index, the Schatzker type and side of fracture, laboratory examinations [hemoglobin (Hb), activated partial thromboplastin time (APTT), prothrombin time (PT), fibrinogen (Fib), international normalized ratio (INR), D-dimer, and interleukin 6 (IL-6)], and preoperative blood volume. The control group received intravenous infusion of 100 mL saline at 15 minutes before operation and 3, 6, and 24 hours after the first administration. The single-dose TXA group received intravenous infusion of 1 g TXA (dissolved in 100 mL saline) at 15 minutes before operation, followed by an equal amount of saline at each time point after the first administration. The multiple-dose TXA group received intravenous infusion of 1 g TXA (dissolved in 100 mL saline) at each time point. The relevant indicators were recorded and compared between groups to evaluate the effectiveness and safety of TXA, including hospital stays, operation time, occurrence of infection; the occurrence of lower extremity deep vein thrombosis, intermuscular vein thrombosis, and pulmonary embolism at 1 week after operation; the lowest postoperative Hb value and Hb reduction rate, the difference (change value) between pre- and post-operative APTT, PT, Fib, and INR; D-dimer and IL-6 at 24 and 72 hours after operation; total blood loss, intraoperative blood loss, hidden blood loss, drainage flow during 48 hours after operation, and postoperative blood transfusion. RESULTS: ① TXA efficacy evaluation: the lowest Hb value in the control group was significantly lower than that in the other two groups ( P<0.05), and there was no significant difference between the single- and multiple-dose TXA groups ( P>0.05). The Hb reduction rate, total blood loss, intraoperative blood loss, drainage flow during 48 hours after operation, and hidden blood loss showed a gradual decrease trend in the control group, single-dose TXA group, and multiple-dose TXA group. And differences were significant ( P<0.05) in the Hb reduction rate and drainage flow during 48 hours after operation between groups, and the total blood loss and hidden blood loss between control group and other two groups. ② TXA safety evaluation: no lower extremity deep vein thrombosis or pulmonary embolism occurred in the three groups after operation, but 3, 4, and 2 cases of intermuscular vein thrombosis occurred in the control group, single-dose TXA group, and multiple-dose TXA group, respectively, and the differences in the incidences between groups were not significant ( P>0.05). There was no significant difference in the operation time between groups ( P>0.05). But the length of hospital stay was significantly longer in the control group than in the other groups ( P<0.05); there was no significant difference between the single- and multiple-dose TXA groups ( P>0.05). ③ Effect of TXA on blood coagulation and inflammatory response: the incisions of the 3 groups healed by first intention, and no infections occurred. The differences in the changes of APTT, PT, Fib, and INR between groups were not significant ( P>0.05). The D-dimer and IL-6 in the three groups showed a trend of first increasing and then decreasing over time, and there was a significant difference between different time points in the three groups ( P<0.05). At 24 and 72 hours after operation, there was no significant difference in D-dimer between groups ( P>0.05), while there was a significant difference in IL-6 between groups ( P<0.05). CONCLUSION Multiple intravenous applications of TXA can reduce perioperative blood loss and shorten hospital stays in patients undergoing open reduction and internal fixation of complex tibial plateau fractures, provide additional fibrinolysis control and ameliorate postoperative inflammatory response.
Humans ; Tranexamic Acid/therapeutic use* ; Blood Loss, Surgical/prevention & control* ; Interleukin-6 ; Prospective Studies ; Tibial Plateau Fractures ; Tibial Fractures/surgery* ; Thrombosis