Anti-CD20 monoclonal antibodies for the treatment of refractory nephrotic syndrome （RNS） in children. The first- generation rituximab is the most widely used in clinical practice； it shows definite efficacy in children with RNS， is recommended by guidelines， particularly for achieving a high remission rate in minimal change nephrosis， and can significantly reduce the cumulative use of glucocorticoids and immunosuppressants. The second-generation ofatumumab has potential as an alternative treatment for patients who are intolerant or resistant to rituximab， while the third-generation obinutuzumab has shown efficacy in complex cases such as rituximab resistance or post-transplant recurrence. However， there is still controversy regarding the optimization of rituximab treatment dosage and whether ofatumumab and obinutuzumab offer greater advantages than rituximab for the treatment of RNS in children. The most common adverse reaction induced by anti-CD20 monoclonal antibodies is infusion reactions， and long-term adverse events mainly include increased risks of sustained immunosuppression and infections. Rituximab has significant economic advantages for the treatment of RNS， but additional pharmacoeconomic research based on China’s healthcare environment is needed to evaluate the cost-effectiveness of ofatumumab and obinutuzumab in this population. Given that the current use of ofatumumab and obinutuzumab in this field is considered off-label use， clinical application should only proceed after a rigorous evaluation of the patient’s benefits and risks.

OBJECTIVE: To investigate the effect and mechanism of Hyssopus cuspidatus Boriss. extract (HCE) in ovalbumin (OVA)-induced allergic asthma. METHODS: Components identification of HCE was conducted using ultra performance liquid chromatography-quadrupole-time of flight-mass spectrometry. Mice were sensitized with OVA to establish asthmatic model, and dexamethasone was used as positive control. Respiratory reactivity, white cells counting in bronchoalveolar lavage fluid and peripheral blood, cytokine level measurement in serum and lung tissue, and histologic examination were performed to evaluate the therapeutic effect of HCE on asthma. Network pharmacology approach was used for mechanism prediction. Western blotting and untargeted lipidomics method were applied for mechanism validation. RESULTS: Fifty-two compounds were identified in HCE, predominantly terpenoids and flavonoids. HCE markedly reduced airway resistance, the eosinophil infiltration in lung tissues, and the levels of immunoglobulin E, interleukin-4, interleukin-5, and interleukin-13. Network pharmacology analysis suggested phosphatidylinositol 3-kinases (PI3K), c-Jun N-terminal kinase (JNK), and p38 Mitogen-activated protein kinase (p38 MAPK) may be key proteins of HCE in the treatment of allergic asthma. Western blot results indicated that the levels of phosphorylated PI3K, JNK, and P38 were downregulated in HCE-treated group. Moreover, HCE significantly upregulated the levels of ceramide and sphingomyelin and downregulated the level of phosphatidylcholine. CONCLUSION HCE inhibited allergic asthma via PI3K/JNK/P38 signaling pathway and lipid homeostasis regulation.

Osteoporosis is a prevalent skeletal condition characterized by reduced bone mass and strength, leading to increased fragility. Buqi-Tongluo (BQTL) decoction, a traditional Chinese medicine (TCM) prescription, has yet to be fully evaluated for its potential in treating bone diseases such as osteoporosis. To investigate the mechanism by which BQTL decoction inhibits osteoclast differentiation in vitro and validate these findings through in vivo experiments. We employed MTS assays to assess the potential proliferative or toxic effects of BQTL on bone marrow macrophages (BMMs) at various concentrations. TRAcP experiments were conducted to examine BQTL's impact on osteoclast differentiation. RT-PCR and Western blot analyses were utilized to evaluate the relative expression levels of osteoclast-specific genes and proteins under BQTL stimulation. Finally, in vivo experiments were performed using an osteoporosis model to further validate the in vitro findings. This study revealed that BQTL suppressed receptor activator of NF-κB ligand (RANKL)-induced osteoclastogenesis and osteoclast resorption activity in vitro in a dose-dependent manner without observable cytotoxicity. The inhibitory effects of BQTL on osteoclast formation and function were attributed to the downregulation of NFATc1 and c-fos activity, primarily through attenuation of the MAPK, NF-κB, and Calcineurin signaling pathways. BQTL's inhibitory capacity was further examined in vivo using an ovariectomized (OVX) rat model, demonstrating a strong protective effect against bone loss. BQTL may serve as an effective therapeutic TCM for the treatment of postmenopausal osteoporosis and the alleviation of bone loss induced by estrogen deficiency and related conditions.
Animals ; NFATC Transcription Factors/genetics* ; Drugs, Chinese Herbal/pharmacology* ; Ovariectomy ; Osteoclasts/metabolism* ; Female ; Osteogenesis/drug effects* ; Rats, Sprague-Dawley ; Rats ; NF-kappa B/genetics* ; Osteoporosis/genetics* ; Signal Transduction/drug effects* ; Bone Resorption/genetics* ; Cell Differentiation/drug effects* ; Humans ; RANK Ligand/metabolism* ; Mitogen-Activated Protein Kinases/genetics* ; Transcription Factors

Surgery is an important treatment for the anterior mediastinal disease. With the rapid development of minimally invasive techniques, complete resection of the lesion in most patients with thymic disease can be achieved through thoracoscopic surgery. Practice has proved that the three-port resection of anterior mediastinal thymus disease via the subxiphoid approach is an ideal surgical method for the treatment of anterior mediastinal thymic tumors at present, which has strong popularization and popularity and can benefit the patients. The procedure focuses primarily on the anterior and upper mediastinum and can thoroughly expose the anatomy of the mediastinum and both sides, with minimal intraoperative bleeding, high safety, minimal trauma and postoperative pain, and a short hospital stay. It has clear advantages over conventional thoracic open-heart surgery and transversal resection. However, the surgical approach and field of view, and intraoperative precautions of this procedure are completely different from those of previous thoracoscopic procedures, and from the subxiphoid single-port approach adopted by other centers. Based on 10 years of surgical experience at our center, a modular mode of surgical operation has been developed and its procedure has been standardized. This paper will share and discuss relevant operational points and experiences.

Objective:To retrospectively compare the clinical efficacy of percutaneous vertebroplasty and biopsy by unilateral and bilateral pedicle approaches for the treatment of vertebral metastasis.Methods:From June 2020 to July 2022, a total of 82 patients with vertebral metastasis underwent percutaneous vertebroplasty and biopsy treated in Linyi Cancer Hospital were enrolled, 39 patients with 57 vertebral bodies were performed by unilateral pedicle approach (unilateral group) and 43 patients with 52 vertebral bodies were performed by bilateral pedicle approaches (bilateral group), used bone cement filling vertebral bodies after biopsy. The clinical efficacy and the positive rate of biopsy were compared between the two groups.Results:Both groups experienced significant pain relief in the Visual Analog Scale (VAS) score and improvement in the Oswestry Disability Index (ODI) score after operation ( P<0.05), but there were no significant differences between the two groups ( P>0.05). The operative time for a single vertebra, volume of bone cement in unilateral group were less than those in the bilateral group:(44.81 ± 13.01) min vs. (31.84 ± 11.87) min, (4.87 ± 0.92) ml vs. (4.18 ± 0.90) ml, there were significant differences ( P<0.05). There were no significant differences in the incidence of bone cement leakage and the positive rate of biopsy between both groups ( P>0.05). Conclusions:Percutaneous vertebroplasty and biopsy by unilateral and bilateral pedicle approaches are significant improvement for symptoms and functions of patients with vertebral metastasis. The clinical efficacy and the positive rate of biopsy are similar. But the former has easier operation procedure, shorter operative time and less volume of bone cement.

Objective:The aim of the present study was to re-evaluate the diagnostic value and optimal cutoff point of captopril challenge test (CCT) in diagnosis of primary aldosteronism (PA).Methods:This is a retrospective study. All patients with a high risk for PA underwent screening test, and then proceeded to CCT and fludrocortisone suppression test (FST) on different days. The FST was used as a reference standard for PA. The plasma renin concentration (PRC) and plasma aldosterone concentration (PAC) were measured with an automated chemiluminescence immunoassay. Random number method was performed in the patients with unilateral primary aldosteronism (UPA), in order to make the proportion of the analyzed UPA in PA was 35%. Receiver operating characteristic (ROC) analyses were performed to compare diagnostic accuracy.Results:A total of 543 patients with 400 PA patients and 143 essential hypertension (EH) patients were enrolled. The diagnostic value of post-CCT PAC was significantly higher than that of the post-CCT plasma aldosterone-renin ratio (ARR), and that of the PAC suppression percentage, respectively. The area under the ROC curve (AUC ROC) was 0.86 (0.83, 0.89) for PAC, 0.78 (0.74, 0.82) for ARR, and 0.62 (0.56, 0.67) for the PAC suppression percentage (all P<0.01), respectively. The optimal cutoff point of post-CCT PAC for PA was 110 ng/L, in which the sensitivity and specificity were 73.25% and 79.02%, respectively. The diagnostic efficiency of post-CCT PAC was not improved either in combination with PAC suppression percentage or in combination with post-CCT ARR. Conclusions:CCT is a useful test for the confirmation of PA. PAC level of 110 ng/L at 2 h after 50 mg of captopril is recommended as an optimal cutoff point for the diagnosis of PA.

Objective:To investigate the clinicopathological features, diagnosis, differential diagnosis and treatment of nodal marginal zone lymphoma (NMZL) with elevated monoclonal IgM.Methods:The clinical data of one NMZL patient with elevated monoclonal IgM treated at Yancheng No.1 People's Hospital in July 2020 were retrospectively analyzed, and the related literature was analyzed.Results:The patient was a 57-year-old female and the main clinical manifestations were fatigue and bone pain in left rib. Serum immunofixation electrophoresis showed IgM-κ type M proteinemia, bone marrow cytology showed a few plasmacytoid lymphocytes, bone marrow biopsy and immunohistochemistry showed B-cell non-Hodgkin lymphoma, bone marrow genetic testing showed MYD88 L265p and CXCR4 were both negative, postoperative pathology result of retroperitoneal lymph node biopsy was marginal zone lymphoma (mature small B type, prone to NMZL),and immunohistochemistry results: CD3, CD5, CD138, κ, λ, CD10, Cyclin D1 were negative, CD20, Pax-5, CD23 (FDC), bcl-2 were positive; Ki-67 positive index < 5%. The final diagnosis was NMZL with elevated monoclonal IgM. Partial remission was achieved after 8 cycles of reduced-dose CHOP regimen; thalidomide was used in the maintenance treatment, the disease condition was stable until August in 2021 and the follow-up was continuing.Conclusions:NMZL with elevated monoclonal IgM is relatively rare. Its diagnosis should be differentiated from Waldenstr?m macroglobulinemia and other inert B-cell lymphomas. Currently, there is no standard treatment and following the principle of individualized treatment can improve the prognosis of patients.

Objective:To investigate the expression of Toll-like receptor 8 (TLR8) in diffuse large B-cell lymphoma (DLBCL) and its correlation with clinicopathological characteristics and prognosis of patients.Methods:The data in the Oncomine database was used to analyze the difference of TLR8 mRNA expression between DLBCL tumor tissues and normal lymphocytes, and the result was verified in two independent subsets GSE 25638 and GSE 32018 of the NCBI-GEO database. The OSDLBCL online survival analysis tool was used to analyze the correlation of TLR8 mRNA relative expression level with overall survival (OS) and progression-free survival (PFS) of DLBCL patients. Gene ontology bioprocess (GO_BP) enrichment analysis was performed by using GSEA software. The correlation of TLR8 mRNA expression with tumor immune cell infiltration degree and immune checkpoint-related molecule expression was analyzed by TIMER online tool website. A total of 53 DLBCL patients who underwent lymph node biopsy in Yancheng No. 1 People's Hospital from June 2020 to June 2021 were selected. Immunohistochemistry was used to detect the expression of TLR8 protein, and its relationship with the clinicopathological characteristics of patients was analyzed.Results:The analysis result of data from Oncomine and GEO databases showed that the relative expression levels of TLR8 mRNA in tumor tissues of patients with DLBCL or activated B cell-like DLCBL were higher than those in normal lymphocytes (all P < 0.001). The results of OSDLBCL online survival analysis indicated that the OS ( P = 0.020) and PFS ( P = 0.004) in DLBCL patients with high TLR8 mRNA expression were worse than those in patients with low TLR8 mRNA expression. The level of TLR8 was related to the abnormal function of immune response, cytokine metabolism and DNA damage monitoring; the result of TIMER online analysis showed that the expression level of TLR8 mRNA was positively related to the degree of neutrophil infiltration ( r = 0.78, P < 0.001) and the expression of immunosuppressive molecules [HAVCR2 ( r = 0.85, P < 0.001), LAG3 ( r = 0.63, P < 0.001), CD274 ( r = 0.77, P < 0.001), TIGIT ( r = 0.32, P = 0.037), and C10ORF54 ( r = 0.34, P = 0.029)]. Among 53 DLBCL patients, 29 patients (54.7%) had low expression of TLR8 protein and 24 patients (45.3%) had high expression of TLR8 protein. There were statistical differences in the expressions of TLR8 protein in DLBCL patients with different serum lactate dehydrogenase and β 2-microglobulin levels (both P < 0.05). Conclusions:TLR8 is highly expressed in DLBCL patients, and TLR8 may be a prognostic marker of DLBCL.

Objective:To discuss the effect of Xiaoqinglong decoction on vascular endothelin (ET) in rats pulmonary hypertension (PAH) model based on the Jiebiaokuoluo method.Methods:Sixty male SD rats were randomly divided into six groups: control group, PAH model group, positive drug group, and Xiaoqinglong decoction in the high-dose, medium-dose and low-dose groups, 10 rats in each group. The control group did not receive any treatment. The remaining groups were kept in low-pressure oxygen tanks, injections of lipopolysaccharide (LPS) at 200 μL on day 1 and day 14, respectively. The rats were smoked twice a day from day 2 to day 30 (except day 14) at 4 hours intervals. The rats were placed in a low-temperature environment for 1 hour per day, and were put into cold water to swim (for 2 weeks), while the rats were given a cold diet. After modeling, the control group and the PAH model group were given equal volumes of normal saline; the positive drug group was given bosentan (100 mg/kg); Xiaoqinglong decoction 15, 10 and 5 g/kg was given, respectively, in the high, medium and low dose groups; once daily for 30 days. The mean pulmonary artery pressure (mPAP) and right ventricle systolic pressure (RVSP) were then measured with right heart catheterization and the right ventricle hypertrophy index (RVHI) was assessed; ET-1 and nitric oxide (NO) levels were determined by radioimmunoassay.Results:Compared with the control group, the levels of mPAP, RVSP, RVHI and ET-1 were significantly increased in the PAH model group [mPAP (mmHg, 1 mmHg≈0.133 kPa): 33.20±1.04 vs. 13.20±1.03, RVSP (mmHg): 62.40±1.54 vs. 24.20±1.02, RVHI: 42.90±2.51 vs. 25.40±2.01, ET-1 (ng/L): 100.80±20.34 vs. 81.50±13.84, all P < 0.05], while NO levels were significantly decreased (mmol/L: 23.20±1.81 vs. 31.70±1.49, P < 0.05). Compared with the PAH model group, the levels of mPAP, RVSP, RVHI and ET-1 in the positive drug group and high, medium, low dose groups of Xiaoqinglong decoction were significantly decreased [mPAP (mmHg): 25.50±0.84, 26.90±0.74, 27.10±1.19, 29.10±0.75 vs. 33.20±1.04, RVSP (mmHg): 54.40±5.14, 50.10±1.67, 53.10±1.05, 56.60±1.07 vs. 62.40±1.54, RVHI: 41.10±1.19, 31.20±1.67, 31.30±1.89, 40.30±1.88 vs. 42.90±2.51, ET-1 (ng/L): 70.70±7.89, 69.90±2.92, 71.70±4.32, 73.90±5.19 vs. 100.80±20.34, all P < 0.05], while NO levels were significantly increased (mmol/L: 32.50±2.06, 34.70±1.16, 32.70±1.33, 30.10±1.19 vs. 23.20±1.81, all P < 0.05), and with the increased dose of Xiaoqinglong decoction, the change was more obvious, and the effect was better in the high-dose group. Conclusion:Xiaoqinglong decoction can reduce rats PAH by regulating ET-1 and NO levels in a dose-dependent manner.

Objective:To study the genomic sequence of Coxsackievirus A8 (CV-A8) associated with hand, foot and mouth disease (HFMD) from 2013 to 2018 in China and to analyze the genetic evolution of each coding region of the full-length genome.Methods:The genome sequences of 11 CV-A8 strains isolated from patients with HFMD in different regions of China from 2013 to 2018 were determined. Sequence alignment and genetic evolution analysis were performed by Sequencher 5.0 and MEGA 7.0 software, etc.Results:Sequence alignment showed that the genome length of 11 CV-A8 strains ranged from 7 393 bp to 7 400 bp. There was no base insertion or deletion in the coding region compared with the prototype strain, but there were individual base insertion or deletion in the non-coding region. The nucleotide and amino acid similarities in the VP1 region of 11 CV-A8 strains were 78.3%-98.6% and 92.6%-99.7%, respectively, and the nucleotide and amino acid sequences identities with the CV-A8 prototype strain were 78.3%-98.2% and 92.6%-99.7%, respectively. Based on the phylogenetic analysis of VP1 region sequences, the CV-A8 can be divided into five genotypes: A, B, C, D and E. The 11 CV-A8 strains in this study belonged to genotypes C (1 strain), D (2 strains) and E (8 strains). The nucleotide and amino acid similarities of 11 CV-A8 full-length genomes were 81.3%-98.8% and 95.9%-99.5%, respectively. The phylogenetic tree of the P2 region showed that the eight E genotypes CV-A8 had the closest evolutionary distance with CV-A4, CV-A14, and CV-A16. The phylogenetic tree of the P3 region showed that the eight E genotypes CV-A8 had a close evolutionary distance with CV-A5, CV-A16, CV-A14 and CV-A4.Conclusions:The 11 CV-A8 stains in this study showed significant intra-genotype diversity in capsid region and recombinant diversity in non-capsid region which indicated that CV-A8 quasispecies were still undergoing dynamics variation. CV-A8 may become an important pathogen of HFMD and the monitoring of CV-A8 needs to be further strengthened.