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

Traumatic brain injury(TBI)is mostly caused by motor vehicle traffic accidents or competitive sports,with high mortality and disability.TBI mainly includes primary injury and secondary injury.Primary injuries were caused directly by external forces.Secondary injuries include brain edema,excitotoxic effect of neuron cells,oxidative stress and neuroinflammation,etc.Effective intervention of secondary injury not only helps to improve the prognosis of patients with TBI,but also reduces the risk of Parkinson's disease and other neurodegenerative diseases related to TBI.Autophagy is one of approaches to regulate homeostasis in cells,and autophagy dysfunction has been found in several neurodegenerative diseases and TBI.It is speculated that autophagy dysfunction may play an important role in TBI and explain why patients with TBI have higher risk of neurodegenerative disease.Discovering the role of autophagy in the pathological mechanism of TBI may provide new targets for TBI clinical treatment and cognitive impairment prevention in patients with TBI.

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.

BackgroundFluvoxamine is increasingly used in the treatment for depressive disorder in adolescents. However， little research has been done on the effect of fluvoxamine on lipid metabolism， and the disordered lipid metabolism would cause severe harm to the health of patients and affect relevant prognosis. ObjectiveTo analyze the effect of fluvoxamine on lipid metabolism in adolescent patients with depressive disorder and to investigate the safety of fluvoxamine treatment. MethodsFrom June 2022 to June 2023， 60 adolescent patients with depressive disorder were involved， who met the diagnostic criteria of International Classification of Diseases， tenth edition （ICD-10） and received inpatient treatments in Shanxi Mental Health Center. These cases were randomly divided into study group （receiving fluvoxamine treatment） and control group （receiving sertraline treatment） with 30 cases in each group. The treatment period was 4 weeks. At baseline as well as 2 weeks and 4 weeks after treatment， both groups' indexes of fasting lipid metabolism were measured， including serum total cholesterol （TC）， triglycerides （TG）， high-density lipoprotein （HDL） and low-density lipoprotein （LDL）， and Hamilton Depression Scale-17 item （HAMD-17） was adopted. The levels of lipid metabolism indexes and HAMD-17 score were compared between the two groups at different follow-up time points. ResultsFor HAMD-17 score， the time effect was statistically significant （F=849.687， P<0.01）， while the inter-group effect and interaction effect was not statistically significant （F=0.033， 1.760， P>0.05）. For TC levels， the inter-group effect was not statistically significant （F=1.461， P=0.232）， but the time effect and interaction effect were statistically significant （F=13.129， 5.029， P<0.05 or 0.01）. The time effect and the inter-group effect of TG level were not statistically significant （F=0.825， 0.185， P>0.05）， but the interaction effect was statistically significant （F=7.577， P=0.004）. For HDL levels， the time effect， inter-group effect and interaction effect were not statistically significant （F=1.079， 0.160， 1.877， P>0.05）. For LDL levels， there was no statistical significance in the inter-group effect （F=0.019， P=0.891）， while statistical significance was observed in both time effect and interaction effect （F=6.721， 9.075， P<0.01）. ConclusionFluvoxamine and sertraline have curative effectiveness of same level on adolescent depression disorder， and short-term application of fluvoxamine has little effect on lipid metabolism indexes of patients. ［www.chictr.org.cn number： ChiCTR2300074129］

Purpose: To determine the non-contrast computer tomography imaging features of pyonephrosis and evaluate the predictive value of Hounsfield units (HUs) in different hydronephrotic region slices. Materials and Methods: We retrospectively reviewed data from patients with hydronephrosis who had renal-ureteral calculi. All patients were categorized into pyonephrosis and simple hydronephrosis groups. Baseline characteristics, the mean HU values in the maximal hydronephrotic region (uHU) slice, and the range of uHU in different slices (△uHU) were compared between the two groups. Univariate and multivariate analyses were performed to identify risk factors for pyonephrosis. Results: Among the 181 patients enrolled in the current study, 71 patients (39.2%) were diagnosed with pyonephrosis. The mean dilated pelvis surface areas were comparable between patients with pyonephrosis and simple hydronephrosis (822.61 ㎟ vs.877.23 ㎟ , p=0.722). Collecting system debris (p=0.022), a higher uHU (p=0.038), and a higher △uHU (p<0.001) were identified as independent risk factors for pyonephrosis based on multivariate analysis. The △uHU sensitivity and specificity were 88.7% and 86.4%, respectively, at a cutoff value of 6.56 (p<0.001), whereas the sensitivity and specificity for detecting pyonephrosis at a uHU cutoff value of 7.96 was 50.7% and 70.9%, respectively (p=0.003). Conclusions Non-contrast computer tomography was shown to accurately distinguish simple hydronephrosis from pyonephrosis in patients with obstructive uropathy. Evaluation of the △uHU in different slices may be more reliable than the uHU acquired from a single slice in predicting pyonephrosis.

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.

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.

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.