OBJECTIVE To estimate the cost-effectiveness of penpulimab combined with chemotherapy versus chemotherapy alone in first-line treatment of advanced squamous non-small-cell lung cancer （sq-NSCLC）. METHODS From the perspective of Chinese health system， cost-utility analysis was used to evaluate the cost-effectiveness of penpulimab combined with chemotherapy （paclitaxel + carboplatin） versus chemotherapy （paclitaxel + carboplatin） in first-line treatment of sq-NSCLC. A three-health states Markov model was constructed with R packages， and clinical data used in the model were derived from the AK105-302 clinical trial. Costs and utilities were collected from the open-access database and published literature. The quality-adjusted life-years （QALY） was used as the utility index， and the willingness-to-pay （WTP） threshold was set at three times China’s per capita GDP in 2024， equivalent to 287 247 yuan/QALY. The cost-effectiveness of the schemes was evaluated by comparing the incremental cost- utility ratios （ICER） of the two schemes with the WTP threshold. One-way sensitivity analysis and probabilistic sensitivity analysis （PSA） were used to verify the stability of the basic analysis results. RESULTS Compared with chemotherapy， penpulimab combined with chemotherapy increased 0.73 QALY with an incremental cost of 150 681.93 yuan， and the ICER was 206 413.60 yuan/QALY. One-way sensitivity analysis showed that the utility of progression-free survival was the most sensitive factor on ICERs. At the WTP threshold of 3 times China’s per capita GDP， the economic probability of this scheme was 98.80%. At the WTP threshold of 1 times China’s per capita GDP， the probability of ICER being cost-effective was less than 0.01%. CONCLUSIONS For patients with advanced sq-NSCLC， penpulimab combined with chemotherapy is a cost-effective first-line treatment option when WTP threshold is 3 times China’s per capita GDP.

BACKGROUND: Several studies have demonstrated the occurrence of secondary tumors as a rare but significant complication of chimeric antigen receptor T (CAR-T) cell therapy, underscoring the need for a detailed investigation. Given the limited variety of secondary tumor types reported to date, a comprehensive characterization of the various secondary tumors arising after CAR-T therapy is essential to understand the associated risks and to define the role of the immune microenvironment in malignant transformation. This study aims to characterize the immune microenvironment of a newly identified secondary tumor post-CAR-T therapy, to clarify its pathogenesis and potential therapeutic targets. METHODS: In this study, the bone marrow (BM) samples were collected by aspiration from the primary and secondary tumors before and after CD19 CAR-T treatment. The CD45 + BM cells were enriched with human CD45 microbeads. The CD45 + cells were then sent for 10× genomics single-cell RNA sequencing (scRNA-seq) to identify cell populations. The Cell Ranger pipeline and CellChat were used for detailed analysis. RESULTS: In this study, a rare type of secondary chronic myelomonocytic leukemia (CMML) were reported in a patient with diffuse large B-cell lymphoma (DLBCL) who had previously received CD19 CAR-T therapy. The scRNA-seq analysis revealed increased inflammatory cytokines, chemokines, and an immunosuppressive state of monocytes/macrophages, which may impair cytotoxic activity in both T and natural killer (NK) cells in secondary CMML before treatment. In contrast, their cytotoxicity was restored in secondary CMML after treatment. CONCLUSIONS This finding delineates a previously unrecognized type of secondary tumor, CMML, after CAR-T therapy and provide a framework for defining the immune microenvironment of secondary tumor occurrence after CAR-T therapy. In addition, the results provide a rationale for targeting macrophages to improve treatment strategies for CMML treatment.
Humans ; Lymphoma, Large B-Cell, Diffuse/therapy* ; Tumor Microenvironment/genetics* ; Antigens, CD19/metabolism* ; Leukemia, Myelomonocytic, Chronic/genetics* ; Immunotherapy, Adoptive/adverse effects* ; Male ; Single-Cell Analysis/methods* ; Female ; Sequence Analysis, RNA/methods* ; Receptors, Chimeric Antigen ; Middle Aged

Objective To explore the value of dynamic ultrasound combined with 3.0T MRI for diagnosing and typing synovial plica of knee joint.Methods Dynamic ultrasound and 3.0T MRI data of 100 patients with suspected synovial plica of knee joint were retrospectively analyzed.Taking the results of arthroscopy as standards,the efficacy of dynamic ultrasound and 3.0T MRI alone and their combination for diagnosing synovial plica of knee joint were evaluated and compared.The length and thickness of synovial plica of knee joint measured with dynamic ultrasound,3.0T MRI alone and their combination were compared with those of arthroscopy,and the consistencies of the location and classification of synovial plica of knee joint with arthroscopy were analyzed.Results Synovial plica was detected in 70 cases,including 11 cases of supropatellar synovial plica,15 cases of infrapatellar synovial plica,medial patellar in 30 cases and lateral patellar synovial plica in 14 cases,among them type A,B,C and D were classified in 9,35,23 and 3 cases,respectively.No significant difference of sensitivity was found between dynamic ultrasound and 3.0T MRI alone for diagnosing synovial plica of knee joint(P＞0.05),which were both lower than that of their combination(both P＜0.05).The length and thickness of knee synovial plica measured with dynamic ultrasound and 3.0T MRI alone were lower than those measured with their combination and arthroscopy(all P＜0.05),and there was no significant difference between the results of their combination and arthroscopy(both P＞0.05).Dynamic ultrasound,3.0T MRI alone and their combination had high consistency of location(Kappa=0.755,0.826,0.897)and classification of knee synovial plica with those of arthroscopy(Kappa=0.721,0.744,0.860).Conclusion Dynamic ultrasound combined with 3.0T MRI was valuable for diagnosing and typing of synovial plica of knee joint.

Sex-determining region Y-related high-mobility group box 11(SOX11)was initially considered as one of the trans-acting factors supporting the differentiation of stem cells and the survival of neural precursors.However,in recent studies,it was found that SOX11 played an important role in the transcriptional regulation of the development,shaping and regeneration of neurons,and it was expected to be a target for the regeneration of injured nerves.This article reviews the physiological and pathophysiological functions of SOX11 in the central nervous system and its role in nerve regeneration.

Traumatic supraorbital fissure syndrome (TSOFS) is a symptom complex caused by nerve entrapment in the supraorbital fissure after skull base trauma. If the compressed cranial nerve in the supraorbital fissure is not decompressed surgically, ptosis, diplopia and eye movement disorder may exist for a long time and seriously affect the patients′ quality of life. Since its overall incidence is not high, it is not familiarized with the majority of neurosurgeons and some TSOFS may be complicated with skull base vascular injury. If the supraorbital fissure surgery is performed without treatment of vascular injury, it may cause massive hemorrhage, and disability and even life-threatening in severe cases. At present, there is no consensus or guideline on the diagnosis and treatment of TSOFS that can be referred to both domestically and internationally. To improve the understanding of TSOFS among clinical physicians and establish standardized diagnosis and treatment plans, the Skull Base Trauma Group of the Neurorepair Professional Committee of the Chinese Medical Doctor Association, Neurotrauma Group of the Neurosurgery Branch of the Chinese Medical Association, Neurotrauma Group of the Traumatology Branch of the Chinese Medical Association, and Editorial Committee of Chinese Journal of Trauma organized relevant experts to formulate Chinese expert consensus on the diagnosis and treatment of traumatic supraorbital fissure syndrome ( version 2024) based on evidence of evidence-based medicine and clinical experience of diagnosis and treatment. This consensus puts forward 12 recommendations on the diagnosis, classification, treatment, efficacy evaluation and follow-up of TSOFS, aiming to provide references for neurosurgeons from hospitals of all levels to standardize the diagnosis and treatment of TSOFS.

Objective:To evaluate the efficacy and safety of unilateral adrenalectomy for treating primary bilateral macronodular adrenal hyperplasia (PBMAH) of different clinical types.Methods:The clinical and biochemical data of 54 patients with PBMAH who underwent unilateral adrenalectomy from May 2008 to March 2023 were retrospectively collected. Preoperative CT images of all patients showed enlarged bilateral adrenal glands with multiple nodules of " fused masses". Mean preoperative blood cortisol concentration at 8am was (21.5±7.7)μg/dl, urinary free cortisol concentration was (442.6±300.4)μg/24h, and mean 8am ACTH concentration was (6.4±2.3)pg/ml. Postoperative symptoms, BMI, blood pressure, mass diameter, cortisol and ACTH concentration were recorded and analyzed.Results:Compared with ordinary laparoscopic surgery, robot-assisted surgery showed shorter operation time [(115.4±22.1)min vs.(95.0±19.8)min, P=0.045]; less blood loss [(118.2±57.0)ml vs. (125.6±45.3)ml, P=0.441] and shorter hospitalization time [(5.2±0.9)day vs. (6.4±1.2)day, P=0.279]. Compared with laparoscopic surgery, open surgery showed longer operation time [(134 34.5) min vs. (104.3±20.1) min, P=0.035]; more blood loss [(305.5±85.2) ml vs. (122.5±44.3) ml, P=0.012] and longer hospitalization time[(10.4±3.2)day vs. (5.7±1.0) day, P=0.020]. The average follow-up time was (23.7±11.7) months. Sixteen cases biochemically relapsed, and the average relapse-free time was (25.4±13.4) month. Mean postoperative systolic blood pressure was (131.1±16.8)mmHg ( P=0.001) while diastolic blood pressure decreased to (82.2±11.1)mmHg ( P=0.002). Postsurgical average blood cortisol concentration decreased to (10.2±4.0)μg/dl ( P<0.01), while urine cortisol concentration decreased to (106.6±43.4)μg/24h( P<0.01). Average ACTH concentration increased to (12.6±4.1)pg/ml( P=0.005). Recurrent patients had higher preoperative blood and urine cortisol concentration(24.7±8.2)μg/dl( P=0.046), (522.8±234.2)μg/24h( P=0.028), and all of them underwent contralateral adrenalectomy. Conclusions:Unilateral adrenalectomy is safe and effective for treatment of PBMAH while part of patients biochemically relapsed. Subclinical patients were observed no recurrent cases after surgery. Recurrent patients have higher preoperative blood and urine cortisol levels and should undertake contralateral adrenalectomy and supplement corticosteroids for whole life.

Objective:To explore the predictive value of the prognostic nutritional index (PNI) in concurrently infected patients with acute-on-chronic liver failure (ACLF).Methods:220 cases with ACLF diagnosed and treated at the First Affiliated Hospital of Xi'an Jiaotong University from January 2011 to December 2016 were selected. Patients were divided into an infection and non-infection group according to whether they had co-infections during the course of the disease. Clinical data differences were compared between the two groups of patients. Binary logistic regression analysis was used to screen out influencing factors related to co-infection. The receiver operating characteristic curve was used to evaluate the predictive value of PNI for ACLF co-infection. The measurement data between groups were compared using the independent sample t-test and the Mann-Whitney U rank sum test. The enumeration data were analyzed using the Fisher exact probability test or the Pearson χ2 test. The Pearson method was performed for correlation analysis. The independent risk factors for liver failure associated with co-infection were analyzed by multivariate logistic analysis. Results:There were statistically significant differences in ascites, hepatorenal syndrome, PNI score, and albumin between the infection and the non-infection group ( P ?

Objective To investigate the effects of B cell lymphoma factor-3(Bcl-3)on estrogen receptor α(ERα)signaling pathway and cell proliferation in breast cancer.Methods MCF-7 cells at the logarithmic growth stage were randomly divided into the siControl group and the siBcl-3#1 group.The cells were added with ControlsiRNA and siBcl-3#1siRNA,respectively,and transfected with LipofectamineTM 2000 for 5 hours.MCF-7 cells in the siControl group and siBcl-3#1 group were obtained after stable transfection for 48 hours.The expressions of Bcl-3,growth regulation by estrogen in breast cancer 1(GREB1),PDZ domain protein 1(PDZK1),and Erα target gene trefoil factor 1(TFF1)mRNA in MCF-7 cells were detected by quantitative real-time polymerase chain reaction.The expressions of Bcl-3 and ERα protein in MCF-7 cells were detected by Western blot assay,and the proliferation of MCF-7 cells was detected by cell counting kit-8.HEK293T cells were randomly divided into the Input group(positive control group),IP group(co-immunoprecipitation group),and IgG group(negative control group).After co-transfected with Bcl-3 and ERα plasmids for 48 hours,the cells were lysed with 100 μL co-immunoprecipitation(Co-IP)cell lysate on ice,and the supernatant was separated.In the Input group,90 μL supernatant was taken and added with 30 μL 4 × Loading buffer.In the IP group,450μL supernatant was taken and added with 40 μL protein A/G and 0.5 μL green fluorescent protein antibody.In the IgG group,450 μL supernatant was taken and added with 0.5 μL IgG and 30 μL protein A/G magnetic agarose beads.The binding effect of Bcl-3 and ERα was detected by Co-IP assay.MCF-7 cells at the logarithmic growth stage were selected,and the co-localization of Bcl-3 and ERα was detected by an immunofluorescence co-localization experiment.Results The relative expression levels of Bcl-3,GREB1,TFF1 and PDZK1 mRNA in MCF-7 cells in the si-Bcl-3#1 group were significantly lower than those in the siControl group(P＜0.05).The relative expression levels of Bcl-3 and ERα protein in MCF-7 cells in the si-Bcl-3#1 group were significantly lower than those in the siControl group(P＜0.05).There was no significant difference in the proliferation ability of MCF-7 cells between the si-Bcl-3#1 group and the siControl group at 0 h and 24 h after culture(P＞0.05).The proliferation ability of MCF-7 cells in the si-Bcl-3#1 group was significantly lower than that in the siControl group at 48 h and 72 h after culture(P＜0.05).The results of the Co-IP assay showed that there was interaction between Bcl-3 and ERα.The results of the immunofluorescence co-localization experiment showed that the co-localization of Bcl-3 and ERα existed.Conclusion Bcl-3 is highly expressed in breast cancer cells,which can enhance the conduction activity of the ERα signaling pathway and promote the proliferation of ERα positive breast cancer cells.

The erector spinae plane block(ESPB)technique proposed by Forero et al.has drawn increasing attention due to its reliable effects and fewer complications in simple and safe procedures.It has been successfully applied in anesthesia management during the perioperative period.This article mainly introduces the anatomical basis,possible mechanism of action,common operating methods,and clinical applications during the perioperative period of ESPB.Starting from the advantages,disadvantages,and complications of ESPB,it compares ESPB with other common thoracolumbar analgesic methods,providing better evidence support for the perioperative application and future development of ESPB.