ObjectiveTo investigate the clinical efficacy and safety of Yanling Yishou prescription combined with aerobic exercise in the intervention of heart and spleen deficiency syndrome in middle-aged white-collar workers with "stress-induced aging". MethodsA randomized， controlled， and open-label trial was conducted involving 156 patients with stress-induced aging and heart and spleen deficiency syndrome who were recruited from the Affiliated Hospital of Nanjing University of Chinese Medicine. Participants were randomly assigned via a central randomization system into an intervention group and a control group， with 78 cases in each group. The intervention group received Yanling Yishou prescription combined with a standard aerobic exercise protocol， while the control group received the standard aerobic exercise protocol only. The composition of Yanling Yishou prescription was derived from Qinggong Medical Records： 10 g Ziziphi Spinosae Semen， 10 g Codonopsis Radix， 10 g Astragali Radix， 10 g Paeoniae Radix Alba， 10 g Angelicae Sinensis Radix， 10 g Rehmanniae Radix， 10 g Atractylodis Macrocephalae Rhizoma， 10 g Poria， and 3 g Glycyrrhizae Radix et Rhizoma， decocted in water and administered 2 hours after breakfast and dinner， respectively. The aerobic exercise protocol was prescriptionted according to the 2017 guidelines of the American College of Sports Medicine， consisting of a 5-minute warm-up， a progressively increasing exercise stage （starting at 5 minutes and increasing by 1-2 minutes daily up to a maximum of 20 minutes）， and a 10-minute cool-down. Both groups were treated for 28 days and followed up for 35 days. Outcome measures included Checklist Individual Strength （CIS）， sleep quality indicators （ total sleep time， light sleep， and deep sleep）， traditional Chinese medicine （TCM） symptom scores for heart and spleen deficiency syndrome， Hospital Anxiety and Depression Scale （HADS）， physical function score from the SF-36 scale （SF-36 PF）， Pain Visual Analog Scale （Pain VAS）， and vital signs. ResultsCompared with baseline， the intervention group showed a significantly greater reduction in CIS scores and improvement in sleep quality （P<0.05， P<0.01）， while the control group showed no significant changes. Post-treatment comparisons between groups revealed that the intervention group achieved significantly better outcomes in fatigue reduction and sleep improvement （P<0.05， P<0.01）. In terms of TCM syndrome scores， the intervention group showed significant improvements in fatigue， frequent awakening， vivid dreaming， poor appetite， palpitations， and loose stools （P<0.05， P<0.01）， while the control group showed no significant improvement in poor appetite， palpitations， or loose stools. After treatment， the intervention group showed significantly better improvements in fatigue， frequent awakening， vivid dreaming， and palpitations compared to the control group （P<0.05， P<0.01）. No significant differences were observed between the two groups in SF-36 PF， HADS， and Pain VAS scores before and after treatments. No serious adverse events occurred in either group during the study period. ConclusionYanling Yishou prescription combined with aerobic exercise can alleviate symptoms such as fatigue， frequent awakening， vivid dreaming， and palpitations， improve sleep quality， and alleviate heart and spleen deficiency symptoms， thereby improving the quality of life in middle-aged white-collar workers with stress-induced aging.

Objective:To investigate the current situation of the use of transjugular intrahepatic portosystemic shunt (TIPS) for portal hypertension, which should aid the development of TIPS in China.Methods:The China Portal Hypertension Alliance (CHESS) initiated this study that comprehensively investigated the basic situation of TIPS for portal hypertension in China through network research. The survey included the following: the number of surgical cases, main indications, the development of Early-TIPS, TIPS for portal vein cavernous transformation, collateral circulation embolization, intraoperative portal pressure gradient measurement, commonly used stent types, conventional anticoagulation and time, postoperative follow-up, obstacles, and the application of domestic instruments.Results:According to the survey, a total of 13 527 TIPS operations were carried out in 545 hospitals participating in the survey in 2021, and 94.1% of the hospital had the habit of routine follow-up after TIPS. Most hospitals believed that the main indications of TIPS were the control of acute bleeding (42.6%) and the prevention of rebleeding (40.7%). 48.1% of the teams carried out early or priority TIPS, 53.0% of the teams carried out TIPS for the cavernous transformation of the portal vein, and 81.0% chose routine embolization of collateral circulation during operation. Most of them used coils and biological glue as embolic materials, and 78.5% of the team routinely performed intraoperative portal pressure gradient measurements. In selecting TIPS stents, 57.1% of the hospitals woulel choose Viator-specific stents, 57.2% woulel choose conventional anticoagulation after TIPS, and the duration of anticoagulation was between 3-6 months (55.4%). The limitation of TIPS surgery was mainly due to cost (72.3%) and insufficient understanding of doctors in related departments (77.4%). Most teams accepted the domestic instruments used in TIPS (92.7%).Conclusions:This survey shows that TIPS treatment is an essential part of treating portal hypertension in China. The total number of TIPS cases is far from that of patients with portal hypertension. In the future, it is still necessary to popularize TIPS technology and further standardize surgical indications, routine operations, and instrument application.

Objective:To explore the risk factors of bortezomib-related peripheral neuropathy (BIPN) and the clinical and electrophysiological characteristics of patients in treatment of multiple myeloma (MM).Methods:The clinical data of 71 newly diagnosed MM patients treated with BD (bortezomib + dexamethasone) regimen in Yancheng First People's Hospital from March 2016 to December 2019 were retrospectively analyzed. The bone marrow morphology, immunology, cytogenetics, molecular biology (MICM), routine electrophysiological examination before and after treatment were performed. All patients were divided into the peripheral neuropathy (PN) group and the non-PN group according to the presence or not of BIPN, and the clinicopathological differences of both groups were also compared; a binary logistic regression model was used to analyze the factors affecting the occurrence of PN. The electrophysiological characteristics were summarized and fluorescence in situ hybridization (FISH) was used to detect karyotype of BIPN patients.Results:Among 71 MM patients, there were 40 cases (56.3%) of PN and 31 cases (43.7%) of non-PN. The proportion of patients at international staging system (ISS) staging Ⅲ, and the levels of IgA, IgG, IgM, serum creatinine, β 2-microglobulin (β 2-MG) in the PN group were higher than those in the non-PN group, and hemoglobin (Hb) level in the PN group was lower than that in the non-PN group, and the differences were statistically significant (both P < 0.05). Binary logistic regression analysis showed that increased IgA ( OR = 1.151, 95% CI 1.012-1.309, P = 0.033), increased IgG ( OR = 1.055, 95% CI 1.000~1.112, P = 0.049), increased IgM ( OR = 1.010, 95% CI 1.001-1.018, P = 0.022), increased serum creatinine ( OR = 1.037, 95% CI 1.011~1.065, P = 0.005), increased β 2-MG ( OR = 1.564, 95% CI 1.039-2.354, P = 0.032) were risk factors for BIPN. Among 40 patients with BIPN, 33 cases (82.5%) of sensory nerve conduction velocity (SCV) were abnormal, 23 cases (57.5%) of motor nerve conduction velocity (MCV) were abnormal; 31 cases (77.5%) showed demyelination damage, 9 cases (22.5%) had axonal damage. Among 40 patients with BIPN, 24 cases underwent FISH detection, including 19 cases (79.2%) with chromosomal mutations, of which 12 cases (50.0%) were mixed subtype abnormal. Conclusions:MM patients with high levels of β 2-MG, IgA, IgG, IgM and serum creatinine are more prone to PN when treated with bortezomib. The electrophysiology of patients with BIPN is mainly characterized by demyelination of sensory nerves.

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 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 evaluate the survival outcomes of radiotherapy in patients with newly-diagnosed metastatic head and neck squamous cell carcinoma (HNSCC) based on data from the Surveillance, Epidemiology and End Results (SEER) database.Methods:A total of 1226 patients newly-diagnosed with metastatic HNSCC between 2010 and 2015 were selected from the SEER database. There were 762 patients (62.1%) in the radiotherapy group and 464 patients (37.9%) in the non-radiotherapy group. Kaplan-Meier method was used to calculate the cancer-specific survival (CSS) and overall survival (OS). The effect of radiotherapy on survival was assessed by Cox multivariate regression and Propensity score-matched analyses (PSM). According to the results of multivariate analysis, the patients were further divided into low-, intermediate- and high-risk groups, and the effect of radiotherapy on survival was analyzed in different risk groups.Results:The median CSS and OS time of the whole group was 11.0 months and 10.0 months, respectively. For patients in the radiotherapy group and non-radiotherapy group, the median CSS time was 13.0 months and 6.0 months, and the median OS time was 12.0 months and 6.0 months, respectively. Multivariate analysis showed that age (CSS, P=0.045;OS, P=0.002), primary tumor site (CSS, P=0.021;OS, P<0.001), T stage (CSS, P=0.001;OS, P=0.002), N stage (CSS, P=0.002;OS, P<0.001), number of metastatic organs (CSS, P<0.001;OS, P<0.001), surgery (CSS, P<0.001;OS, P<0.001), radiotherapy (CSS, P<0.001;OS, P<0.001), and chemotherapy (CSS, P<0.001;OS, P<0.001)were the independent prognostic factors. After PSM, patients with and without radiotherapy in the low-,intermediate-,and high-risk groups, the 3-year CSS rates were 62.5% vs 23.5%( P=0.008), 22.4% vs 15.7%( P=0.001)and 10.5% vs 9.6%( P=0.203), respectively; the 3-year OS were 58.0% vs 20.8%( P=0.002), 19.8% vs 12.7%( P=0.001)and 7.0% vs 6.1%( P=0.166), respectively. Conclusion:Radiotherapy significantly improves CSS and OS in the low- and intermediate-risk groups, but patients in the high-risk group do not benefit from radiotherapy.

Objective:To investigate the familial inheritances, clinical features, treatments and outcomes of familial Waldenstrom macroglobulinemia (WM) patients.Methods:The clinical manifestations, laboratory examinations, diagnosis and treatments, and follow-up data of 6 familial WM patients who were admitted to Yancheng No.1 People's Hospital from June 2002 to July 2019 were retrospectively analyzed, and the literature was reviewed.Results:Among 6 WM patients, 4 patients had dizziness and fatigue at the onset, 1 patient had recurrent low-grade fever and abnormal sweating as the first manifestations, 1 patient was hospitalized due to pulmonary infection, and WM was found later. Two brothers of the patients were diagnosed with WM, another 2 brothers of the patients had IgM-type monoclonal gammopathy of undetermined significance (MGUS) during the physical examination. All the 6 patients were middle-aged/elderly men, with a median age of 63 years old (51-70 years old). The median follow-up time were 71.5 months (4-217 months), and by the end of the follow-up (June 2020), 2 cases died of pulmonary infection, and 1 of them developed acute myeloid leukemia; the other 4 cases were in regular chemotherapy. Two IgM-MGUS patients were followed up without symptoms.Conclusions:WM patients have familial aggregation, and their clinical manifestations are highly heterogeneous. Patients with family history may have poor prognosis. It is necessary to strengthen the awareness of WM and family history screening.

Objective:To evaluate the role of extracellular signal-regulated kinase 1/2 (ERK1/2)/cyclic adenosine monophosphate response element-binding protein (CREB)/brain-derived neurotrophic factor (BDNF) signaling pathway in dexmedetomidine-induced inhibition of propofol-caused apoptosis in isolated hippocampal neurons of fetal rats.Methods:Pregnant Sprague-Dawley rats at 16 days of gestation were sacrificed, and the fetal rats were taken out, and hippocampal neurons of fetal rats were obtained and primarily cultured in vitro for 7 days.The neurons were divided into 9 groups ( n=12 each) using a random number table method: control group (group C), fat emulsion group (group I), dimethyl sulfoxide (DMSO) group, dexmedetomidine group (group D), propofol group (group P), propofol plus dexmedetomidine group (group PD), PD98059 plus propofol plus dexmedetomidine group (group PDP), MH89 plus propofol plus dexmedetomidine group (group HDP), and KG501 plus propofol plus dexmedetomidine group (group KDP). Group C received no treatment.In group I, 20% fat emulsion was added, and the neurons were incubated for 30 min, and 0.25% DMSO was added in group DMSO, and the neurons were incubated for 30 min.Dexmedetomidine at a final concentration of 10 μmol/L was added, and the neurons were incubated for 30 min in group D. Propofol at a final concentration of 100 μmol/L was added, and the neurons were incubated for 3 h in group P. In group PD, dexmedetomidine at a final concentration of 10 μmol/L was added, the neurons were incubated for 30 min, propofol at a final concentration of 100 μmol/L was added, and the neurons were incubated for 3 h. In PDP, HDP and KDP groups, 25 μmol PD98059 (p-ERK1/2 inhibitor), 10 μmol H89 (p-CREB inhibitor) and 25 μmol KG501 (CREB inhibitor) were added, respectively, the neurons were incubated for 30 min, dexmedetomidine at a final concentration of 10 μmol/L was added, the neurons were incubated for 30 min, and propofol at a final concentration of 100 μmol/L was added, and the neurons were incubated for 3 h. The cell ultrastructure was observed with the transmission electron microscope, the apoptosis in neurons was detected by flow cytometry, the expression of ERK1/2, CREB and BDNF mRNA was detected by quantitative real-time polymerase chain reaction, and the expression of p-ERK1/2, CREB, p-CREB, BDNF and cleaved caspase-3 was detected by Western blot. Results:Compared with group C, the apoptosis rate was significantly increased, the expression of p-ERK1/2 and p-CREB was down-regulated, and the expression of cleaved caspase-3 was up-regulated in P, PD, PDP, HDP and KDP groups, and the expression of BDNF was significantly down-regulated in P, PDP, HDP and KDP groups ( P<0.05). Compared with group P, the apoptosis rate was significantly decreased, the expression of p-ERK1/2, p-CREB and BDNF was up-regulated, and the expression of cleaved caspase-3 was down-regulated in group PD ( P<0.05). Compared with group PD, the apoptosis rate was significantly increased, the expression of p-ERK1/2, p-CREB and BDNF was down-regulated, and the expression of cleaved caspase-3 was up-regulated in PDP, HDP and KDP groups ( P<0.05). Conclusion:The ERK1/2/CREB/BDNF signaling pathway is involved in dexmedetomidine-induced inhibition of propofol-caused apoptosis in isolated hippocampal neurons of fetal rats.

Objective:To detect IgG and neutralizing antibodies response to SARS-CoV-2 vaccine by comparing enzyme-linked immunosorbent assay (ELISA), commercial magnetic particle chemiluminescence assay(CLIA) and neutralization test(NT).Methods:ELISA, CLIA and NT were used to detect 143 healthy people before and after 28 days immunization with 2 doses of SARS-CoV-2 vaccine, and calculate the positive conversion rate, quantitative results and analysis the consistency of the three methods.Results:The positive conversion rate of SARS-CoV-2 vaccine antibody detected by ELISA, CLIA and NT were respectively 97.9%, 98.6% and 85.3%. The geometric mean of the highest dilution of the serum quantitatively detected by ELISA was 586.6; The mean of CLIA S/CO value was 11.26; The geometric mean titer of the NT was 7.6. The correlation coefficient between ELISA, CLIA and NT were respectively 0.69( P<0.01) and 0.65( P<0.01), and the correlation coefficient between ELISA and CLIA was 0.79( P<0.01). Conclusions:The three methods all detected high levels of antibodies response to SARS-CoV-2 vaccine immunization. ELISA and CLIA are more consistent to detect IgG antibody, and have a good correlation with the quantitative detection results of the NT.

Objective:To assess the efficacy and toxicity of chemoradiotherapy in the treatment of early stage extranodal nasal-type NK/T-cell lymphoma (ENKTCL).Methods:Retrospective review was conducted for 174 patients with pathological proved early stage ENKTCL who were treated in the Department of Radiation Oncology, Peking University Cancer Hospital & Institute. The Kaplan-Meier survival analysis was adopted to calculate the local-regional control (LRC), overall survival (OS), and progression free survival (PFS), and the Log-rank test COX regression model were applied to univariate and multivariate analyses.Results:The patients in this study included 102 and 72 patients diagnosed with Ann Arbor stage-Ⅰ and stage-Ⅱ, respectively. Among them, two patients received radiotherapy alone and 172 patients were treated with combined chemoradiotherapy. The overall response rate of all the patients was 94.2%, with a complete response (CR) rate of 87.9% (153). Furthermore, the rates of 5-year OS, PFS, and LRC were 87.3%, 83.1%, and 91.9%, respectively. The most common toxicities during the chemotherapy and radiotherapy included myelosuppression and oral mucositis, with grade ≥ 3 myelosuppression and grade ≥ 3 oral mucositis accounting for 62.1% and 10.9% of all patients, respectively. As shown by multivariate analysis, the adverse prognostic factors for OS included age > 60, B symptoms, and stage Ⅱ, while the adverse prognostic factors for PFS included age > 60 and stage Ⅱ. Meanwhile, the PFS rate was significantly improved by increasing the radiation dose (≥ 50 Gy vs.<50 Gy), and the 5-year PFS rates of the two groups were 83.5% and 76.5%, respectively [hazard ratio ( HR) 0.374; 95% CI, 0.169-0.826; P=0.015]. Conclusions:A good therapeutic effect can be achieved for early stage NK/T-cell lymphoma and the toxicities after combined chemoradiotherapy can be tolerated.