Hematologic malignancies, including leukemia, lymphoma, and multiple myeloma, are hazardous diseases characterized by the uncontrolled proliferation of cancer cells. Dysregulated cell cycle resulting from genetic and epigenetic abnormalities constitutes one of the central events. Importantly, cyclin-dependent kinases (CDKs), complexed with their functional partner cyclins, play dominating roles in cell cycle control. Yet, efforts in translating CDK inhibitors into clinical benefits have demonstrated disappointing outcomes. Recently, mounting evidence highlights the emerging significance of WEE1 G2 checkpoint kinase (WEE1) to modulate CDK activity, and correspondingly, a variety of therapeutic inhibitors have been developed to achieve clinical benefits. Thus, WEE1 may become a promising target to modulate the abnormal cell cycle. However, its function in hematologic diseases remains poorly elucidated. In this review, focusing on hematologic malignancies, we describe the biological structure of WEE1, emphasize the latest reported function of WEE1 in the carcinogenesis, progression, as well as prognosis, and finally summarize the therapeutic strategies by targeting WEE1.
Humans ; Protein-Tyrosine Kinases/physiology* ; Hematologic Neoplasms/drug therapy* ; Cell Cycle Proteins/antagonists & inhibitors* ; Nuclear Proteins/antagonists & inhibitors* ; Cyclin-Dependent Kinases ; Molecular Targeted Therapy ; Animals

Hepatocellular carcinoma (HCC) expresses abundant glycolytic enzymes and displays comprehensive glucose metabolism reprogramming. Aldolase A (ALDOA) plays a prominent role in glycolysis; however, little is known about its role in HCC development. In the present study, we aim to explore how ALDOA is involved in HCC proliferation. HCC proliferation was markedly suppressed both in vitro and in vivo following ALDOA knockout, which is consistent with ALDOA overexpression encouraging HCC proliferation. Mechanistically, ALDOA knockout partially limits the glycolytic flux in HCC cells. Meanwhile, ALDOA translocated to nuclei and directly interacted with c-Jun to facilitate its Thr93 phosphorylation by P21-activated protein kinase; ALDOA knockout markedly diminished c-Jun Thr93 phosphorylation and then dampened c-Jun transcription function. A crucial site Y364 mutation in ALDOA disrupted its interaction with c-Jun, and Y364S ALDOA expression failed to rescue cell proliferation in ALDOA deletion cells. In HCC patients, the expression level of ALDOA was correlated with the phosphorylation level of c-Jun (Thr93) and poor prognosis. Remarkably, hepatic ALDOA was significantly upregulated in the promotion and progression stages of diethylnitrosamine-induced HCC models, and the knockdown of A ldoa strikingly decreased HCC development in vivo. Our study demonstrated that ALDOA is a vital driver for HCC development by activating c-Jun-mediated oncogene transcription, opening additional avenues for anti-cancer therapies.

BACKGROUND: The use of inserted sham acupuncture as a placebo in randomized controlled trials (RCTs) is controversial, because it may produce specific effects that cause an underestimation of the effect of acupuncture treatment. OBJECTIVE: This systematic survey investigates the magnitude of insert-specific effects of sham acupuncture and whether they affect the estimation of acupuncture treatment effects. SEARCH STRATEGY: PubMed, Embase and Cochrane Central Register of Controlled Trials were searched to identify acupuncture RCTs from their inception until December 2022. INCLUSION CRITERIA: RCTs that evaluated the effects of acupuncture compared to sham acupuncture and no treatment. DATA EXTRACTION AND ANALYSIS: The total effect measured for an acupuncture treatment group in RCTs were divided into three components, including the natural history and/or regression to the mean effect (controlled for no-treatment group), the placebo effect, and the specific effect of acupuncture. The first two constituted the contextual effect of acupuncture, which is mimicked by a sham acupuncture treatment group. The proportion of acupuncture total effect size was considered to be 1. The proportion of natural history and/or regression to the mean effect (PNE) and proportional contextual effect (PCE) of included RCTs were pooled using meta-analyses with a random-effect model. The proportion of acupuncture placebo effect was the difference between PCE and PNE in RCTs with non-inserted sham acupuncture. The proportion of insert-specific effect of sham acupuncture (PIES) was obtained by subtracting the proportion of acupuncture placebo effect and PNE from PCE in RCTs with inserted sham acupuncture. The impact of PIES on the estimation of acupuncture's treatment effect was evaluated by quantifying the percentage of RCTs that the effect of outcome changed from no statistical difference to statistical difference after removing PIES in the included studies, and the impact of PIES was externally validated in other acupuncture RCTs with an inserted sham acupuncture group that were not used to calculate PIES. RESULTS: This analysis included 32 studies with 5492 patients. The overall PNE was 0.335 (95% confidence interval [CI], 0.255-0.415) and the PCE of acupuncture was 0.639 (95% CI, 0.567-0.710) of acupuncture's total effect. The proportional contribution of the placebo effect to acupuncture's total effect was 0.191, and the PIES was 0.189. When we modeled the exclusion of the insert-specific effect of sham acupuncture, the acupuncture treatment effect changed from no difference to a significant difference in 45.45% of the included RCTs, and in 40.91% of the external validated RCTs. CONCLUSION The insert-specific effect of sham acupuncture in RCTs represents 18.90% of acupuncture's total effect and significantly affects the evaluation of the acupuncture treatment effect. More than 40% of RCTs that used inserted sham acupuncture would draw different conclusions if the PIES had been controlled for. Considering the impact of the insert-specific effect of sham acupuncture, caution should be taken when using inserted sham acupuncture placebos in RCTs. Please cite this article as: Luo XC, Liu JL, Yao MH, Chen YM, Fan AY, Liang FR, Zhao JP, Zhao L, Zhou X, Zhong XY, Yang JH, Li B, Zhang Y, Sun X, Li L. Specific effect of inserted sham acupuncture and its impact on the estimation of acupuncture treatment effect in randomized controlled trials: A systematic survey. J Integr Med. 2025; 23(6):630-640.
Acupuncture Therapy/methods* ; Humans ; Randomized Controlled Trials as Topic ; Placebo Effect ; Placebos ; Treatment Outcome

Objective To explore the effectiveness of an integrated laparoscopic simulation training course (best essential surgical technique training, BEST) in enhancing laparoscopic peritoneal suturing techniques in surgical residents.Methods As an integrated two-stage program, the BEST course applied basic laparoscopic training system with simple molds in phase Ⅰ training, and then adopted advanced laparoscopic training system, 3D Laparoscope and ex-vivo animal models in phase Ⅱ training. The laparoscopic suturing techniques were practiced in phase Ⅱ training. From August 2021 to July 2024, surgical residents in the second year of the national standardized training program were divided into pilot and control groups based on whether they had undergone the BEST course. Two cases of laparoscopic peritoneal suture were performed by the surgical residents under supervision in the department of gastrointestinal surgery. The operative time, quality of suture, and independent completion rate were compared between the two groups.Results A total of 33 surgical residents (19 in pilot group and 14 in control group) were included in this study, and a total of 66 cases of laparoscopic peritoneal suture were performed (38 in pilot group and 28 in control group). The operative time was significantly shorter in pilot group than that in control group (15.7 min vs. 17.5 min, P=0.025). The quality of suture was significantly better in pilot group compared to control group (P=0.023). In pilot group, all peritoneal sutures were performed by residents independently, whereas in control group, 3 cases (10.7%) were assisted by the supervisor, and the independent completion rate was different significantly (P=0.039).Conclusions The BEST course can help improve surgical residents′ laparoscopic peritoneal suturing techniques and could be promoted in the national standardized training program for surgical residents.

Objective:To screen out the differentially expressed genes(DEGs)in multiple primary lung cancers(MPLCs)using bioinformatics methods,and to analyze their biological functions and their influence in the prognosis of lung adenocarcinoma.Methods:Single-cell transcriptome sequencing data(GSE200972)was downloaded from the Gene Expression Omnibus(GEO)database.After preliminary data processing with R software,the Seurat R package was used for data processing,cell clustering,and annotation.The clusterProfiler R package was used for Gene Set Enrichment Analysis(GSEA).The STRING database and Cytoscape software were employed to construct the protein-protein interaction(PPI)network and to screen out the key genes(Hub genes).The gene expression levels in the lung adenocarcinoma database were analyzed using Gene Expression Profiling Interactive Analysis(GEPIA)database.Real-time fluorescence quantitative PCR(RT-qPCR)method was used to detect the gene expression in tumor tissue of A549 xenograft mice and lung tissue of normal mice.Kaplan-Meier Plotter was used for prognosis analysis.Results:Seven cell types were identified from cell clustering analysis,which were epithelial cells,endothelial cells,fibroblasts,T cells and natural killer(NK)cells,B cells,myeloid cells,and mast cells.A total of 14 605 DEGs were screened out between tumor epithelial cells and normal epithelial cells.The GSEA results revealed four activated pathways in tumor samples[myelocytomatosis oncogene(MYC)pathway,P53 pathway,oxidative phosphorylation pathway and glycolysis pathway]and one inhibited pathway[tumor necrosis factor-α(TNF-α)and nuclear factor kappa B(NF-κB)pathway].The Hub genes identified from PPI network included CXC motif chemokine ligand 8(CXCL8),glyceraldehyde-3-phosphate dehydrogenase(GAPDH),CXC motif chemokine receptor 4(CXCR4),kirsten rat sarcoma viral proto-oncogene(KRAS),CXC motif chemokine ligand 1(CXCL1),C-C motif chemokine ligand 2(CCL2),mucin 1(MUC1),and secreted phosphoprotein 1(SPP1).The GEPIA database analysis and animal experiments showed that the expression levels of SPP1 mRNA in non-small cell lung cancer tissue were increased compared with normal lung tissue(P＜0.01).The Kaplan-Meier survival analysis indicated that the patients with high expression level of SPP1 had shorter overall survival(OS)than those with low expression level(P＜0.01).Conclusion:There are activation of oncogene-related pathways and activation of tumor suppressor pathway antagonizing tumor progression in MPLCs.Moreover,elevated expression of SPP1 in non-small cell lung cancer may indicate a relatively poor prognosis.

Objective:To analyze the safety and efficacy of ultrasound-guided percutaneous thermal ablation treatment for multiple T1N0M0 papillary thyroid carcinoma(PTC)with over 5 years follow-up.Methods:From January 2014 to January 2019,a retrospective analysis was conducted on patients with multiple T1N0M0 PTC who underwent ultrasound-guided thermal ablation.Patients with bilateral or unilateral lobes with isthmus PTC were enrolled in this study and were followed up at 1,3,6,12,24,36,48,and 60 months after ablation.The clinical data,ultrasound characteristics and ablation parameters of recurrent and non-recurrent patients were compared,and the efficacy and influencing factors of thermal ablation for multiple T1N0M0 PTC were analyzed.Results:After over 5 years follow-up,a total of 11 patients(16.18％)relapsed,57 patients(83.82％)did not re-lapse.No lymph node and distant metastasis were found.No significant correlation was detected between the recurrence and clinical features,ultrasound findings and ablation parameters(P＞0.05).Among the patients with recurrence,1 patient underwent observation,2 patients underwent total thyroidectomy,and the other 8 patients successfully underwent secondary ablation,all of which had no obvious adverse reactions.Conclusion:The ablation of multiple PTC in T1N0M0 stage is safe and effective,with a recurrence rate of 16.18％over 5 years follow-up,and ablation has no effect on second treatment for recurrent patients.

Objective:To evaluate the effect of ultrasound-guided adductor canal block with bupivacaine liposome on analgesia in elderly patients undergoing total knee arthroplasty.Methods:This was a prospective study. Sixty American Society of Anesthesiologists Physical Status classification Ⅱ or Ⅲ patients, regardless of gender, aged 65-83 yr, weighing 50-80 kg, scheduled for elective unilateral total knee arthroplasty under subarachnoid anesthesia from April 2023 to January 2024 in Zhengzhou Orthopaedic Hospital, were divided into 2 groups ( n=30 each) using a random number table method: bupivacaine liposome group (LB group) and ropivacaine group (R group). Ultrasound-guided adductor canal block was performed at 30 min before subarachnoid anesthesia, bupivacaine liposome diluent 20 ml (133 mg) was injected in LB group, and 0.5% ropivacaine 20 ml was injected in R group. Patient-controlled intravenous analgesia was performed after operation, and tramadol was used for rescue analgesia when the visual analogue scale (VAS) score ≥3. VAS scores at rest and during activity were recorded at 8, 12, 24, 48 and 72 h after surgery. The time to the first pressing analgesia pump and rescue analgesia were recorded within 72 h after surgery. The quadriceps muscle strength was measured at 1 day before surgery and 12, 24, 48 and 72 h after surgery. The knee joint range of motion was assessed at 1 day before surgery and 24, 48 and 72 h after surgery. Patient′s satisfaction with analgesia was recorded at 72 h after surgery. The adverse reactions within 72 h after surgery were also recorded. Results:Compared with R group, VAS scores at rest and during activity were significantly decreased at 12, 24, 48 and 72 h after surgery, the time to the first pressing analgesia pump was prolonged, the rate of rescue analgesia after surgery was decreased, the score for the patient′s satisfaction with analgesia was increased, the knee joint range of motion was increased ( P<0.05), and no significant change was found in the quadriceps muscle strength and incidence of adverse reactions in LB group ( P>0.05). Conclusions:Ultrasound-guided adductor canal block with bupivacaine liposome provides better analgesia than ropivacaine in elderly patients undergoing total knee arthroplasty.

Hormonal receptor positive human epidermal receptor 2 negative (HR⁺/HER2^-) is the commonest molecular subtype of breast cancer (BC). Patients with HR⁺/HER2^- BC may manifest clinically a late recurrence whose BC metastasizes 10-15 years post-operatively. We report one case who presented with pulmonary mass in upper lobe of lung and Horner syndrome 16 years after BC surgery. FDG PET/CT suggested pulmonary malignancy but could not differentiate between primary or metastatic cancer when invasive biopsy was quite risky. Novel ¹⁸F-FES PET/CT facilitated the non-invasive functional diagnosis of estrogen-receptor positive (ER+) pulmonary metastasis of BC, and the patient experienced partial response (PR) after CDK4/6 inhibitor and aromatase inhibitor as endocrine therapy. This article reviews the diagnosis and treatment process of this case, to provide guidance for non-invasive global evaluation of ER status among metastatic HR⁺/HER2^- BC patients with ¹⁸F-FES PET/CT.

To promote the conservation and utilization of the germplasm resources and provide a basis for the breeding of new varieties of Murraya paniculata, this study analyzed the genetic diversity of the germplasm resources and developed the molecular identity(ID) card of M. paniculata. Multiple fluorescence PCR-capillary electrophoresis was performed for 65 germplasm accessions of M. paniculata based on 9 SSR markers identified from the M. paniculata genome, and the molecular weights and alleles of the amplified bands were analyzed. According to the banding patterns of the 9 SSR primers, this study analyzed the genetic diversity of each germplasm accession of M. paniculata and developed molecular ID cards for the test samples. The results showed that 9 pairs of SSR primers detected 78 alleles, with an average of 8.67 alleles. The observed and expected heterozygosity was 0.338-0.831(average of 0.601) and 0.413-0.853(average of 0.721), respectively. The Shannon's information index varied within the range of 0.880-1.994, with an average of 1.41. The polymorphic information content was within the range of 0.391-0.835, with an average of 0.696, which indicated rich genetic diversity. When the genetic identity was 0.347, the 65 germplasm accessions were classified into 5 groups. Based on the results, this study employed the 5 SSR primers with higher polymorphisms to develop the molecular ID cards for the germplasm resources of M. paniculata and created QR code ID cards for the 49 core germplasm accessions preserved in the Yunfu germplasm nursery, laying a foundation for the new variety breeding, production, utilization, and traceability of M. paniculata.
Microsatellite Repeats ; DNA, Plant/genetics* ; Murraya/classification* ; Genetic Variation ; Alleles ; Polymerase Chain Reaction ; Polymorphism, Genetic

Objective To analyze the characteristics of drug resistance in patients with disseminated pulmonary tuberculosis,and provide references for the clinical development of individualized treatment plans.Methods A retrospective analysis was conducted on 71 hospitalized patients with disseminated pulmonary tuberculosis treated at the Beijing Chest Hospital,Capital Medical University from January 2015 to January 2024.The susceptibility of Mycobacterium tuberculosis from these patients to 16 anti-tuberculosis drugs was detected using the microplate method for mycobacterial drug susceptibility testing.The study analyzed the culture results of Mycobacterium tuberculosis,drug susceptibility test results,initial treatment or re-treatment status,drug resistance,and differences in drug resistance types between initial and re-treated patients.Results Among the 71 patients with disseminated pulmonary tuberculosis,there were 51 males(71.8%),and 58 cases(81.7%)of acute disseminated pulmonary tuberculosis,with an overall drug resistance rate to 16 anti-tuberculosis drugs of 38.0%.There was no statistically significant difference in the total drug resistance rate between re-treated patients and those undergoing initial treatment[52.2%(12/23)vs.31.3%(15/48),P=0.089].The top 7 drugs to which patients were resistant were streptomycin(Sm)and isoniazid(INH)with 13 cases each(18.3%),rifapentine(Rft)and isoniazid aminosalicylate(Pa)with 10 cases each(14.1%),rifampicin(RFP),rifabutin(Rfb),and capreomycin(Cm)with 9 cases each(12.7%).The top 6 drugs to which initially treated patients were resistant were Cm with 6 cases(12.5%),Sm with 5 cases(10.4%),Pa with 4 cases(8.3%),INH,clarithromycin(Clr),and p-aminosalicylic acid(PAS)with 3 cases each(6.3%).The top 7 drugs to which re-treated patients were resistant were INH with 10 cases(43.5%),Sm,RFP,and Rft with 8 cases each(34.8%),Rfb with 7 cases(30.4%),Pa and levofloxacin(Lfx)with 6 cases each(26.1%).The overall mono-resistance rate,poly-drug resistance rate,and multidrug-resistant rate to 16 anti-tuberculosis drugs were 9.9%,7.0%,and 11.3%,respectively;all mono-resistance patients were initially treated;there was no statistically significant difference in the poly-drug resistance rate between re-treated and initially treated patients(13.0%vs.4.2%,P=0.591),but the multidrug-resistant rate was significantly higher in re-treated patients(30.4%vs.2.1%,P=0.002).Conclusion Drug resistance in disseminated pulmonary tuberculosis is severe.Clinical physicians can develop personalized anti-tuberculosis treatment plans based on drug susceptibility test results.