Abnormal activation of the Janus kinase/signal transducer and activator of transcription （JAK/STAT） signaling pathway is involved in the pathogenesis of diffuse large B-cell lymphoma （DLBCL）. In recent years， inhibitors targeting JAK2 and STAT3 have emerged as promising therapeutic candidates in DLBCL. This review summarizes the efficacy and safety profiles of JAK2 inhibitors （e.g.， ruxolitinib） and STAT3 inhibitors （direct small-molecule inhibitors， the antisense oligonucleotide， and proteolysis targeting chimeras， etc.） in preclinical models and clinical trials. Accumulating evidence indicates that JAK2 and STAT3 inhibitors exhibit antitumor activity and are generally well tolerated in a subset of DLBCL patients. Meanwhile， the development of novel drug delivery systems has significantly enhanced the stability， bioavailability， and targeting ability of the compounds. Furthermore， JAK2 and STAT3 inhibitors may exhibit synergistic effects when combined with other therapy strategies （such as combinations with B-cell receptor signaling pathway inhibitors， immunomodulators， or other targeted drugs）. However， current clinical applications are still in their early stages. Future research should concentrate on precision treatment strategies based on the genetic subtyping of DLBCL， and further refine the delivery systems for inhibitors as well as combination drug regimens to improve clinical outcomes.

Objective:To investigate the predictive value of controlling nutritional status (CONUT) score in the prognosis of patients with advanced diffuse large B-cell lymphoma (DLBCL).Methods:A retrospective case series study was performed. The clinical data of 654 patients newly diagnosed with advanced DLBCL diagnosed in 7 medical centers in Huaihai Lymphoma Working Group from October 2009 to January 2022 were retrospectively collected. All the patients received rituximab-based immune chemotherapy regimens. The patients were randomly assigned to the training set (458 cases) and the validation set (196 cases) in a 7:3 ratio. The clinicopathological data of patients were collected, and the CONUT score was calculated based on albumin, lymphocyte count, and total cholesterol. The optimal critical value of CONUT scote was determined by using MaxStat method. Kaplan-Meier method was used to draw survival curves; Cox proportional hazards model was used to make univariate analysis and multivariate analysis on the factors influencing overall survival (OS). The efficacy of CONUT score in combination with the International prognostic index (IPI) and an enhanced IPI (NCCN-IPI) in predicting OS was evaluated by using receiver operating characteristic (ROC) curves.Results:The median follow-up time of 654 patients was 38.1 months (95% CI: 35.3 months- 40.9 months), and the 5-year OS rate was 49.2%. According to the MaxStat method, the optimal critical value for CONUT score was determined to be 6 points. All the patients were classified into the normal nutritional status group (CONUT score ≤ 6 points, 489 cases) and the poor nutritional status group (CONUT score > 6 points, 165 cases). The results of the multivariate analysis showed that CONUT score > 6 points, male, lactate dehydrogenase >240 U/L, high white blood cell count, low hemoglobin level and age > 60 years were independent risk factors for OS of patients with advanced DLBCL (all P < 0.05). Patients in the poor nutritional status group (CONUT score > 6 points) had worse OS compared with that in the normal nutritional status group in the overall cohort of advanced DLBCL. Subgroup analysis revealed that among patients with Eastern Cooperative Oncology Group-performance status (ECOG PS) score < 2 points, IPI low-intermediate risk, IPI intermediate-high risk, NCCN-IPI low-intermediate risk, and NCCN-IPI intermediate-high risk, the patients in the poor nutritional status group (CONUT score > 6 points) had worse OS compared with that in the normal nutritional status group (CONUT score ≤ 6 points) (all P < 0.05). Conclusions:CONUT score has a certain value in the assessment of the prognosis of patients with advanced DLBCL, and its predictive efficacy is further improved when combined with IPI and NCCN-IPI.

Objective To investigate the mechanism of inducing macrophage polarization induced by acupoint effect of electroacupuncture to promote the repair of acute skeletal muscle injury.Methods 45 SD rats were randomly divided into blank group,model group,electroacupuncture group(EA group),sodium chrominate group (DSCG group) and electroacupuncture+sodium chrominate group (hereinafter referred to as EA+DSCG group),with 9 rats in each group. The rats in the EA group and the EA+DSCG group were subjected to EA intervention at the right "Chengshan" (BL57) and "Yanglingquan"(GB34),with a frequency of 2 Hz/100 Hz. The gait changes of rats were recorded by animal gait analyzer. The morphological changes of the right gastrocnemius were observed by HE staining. The changes of mast cell aggregation and degranulation in local skin muscles of "chengshan" point were observed by toluidine blue staining. The expressions of Pax7,MyoD and skin mast cells and 5-HT in the right gastrocnemius were detected by immunofluorescence method. The positive expressions of CD68 and CD206 in right gastrocnemius macrophage was observed by immunohistochemical staining.Results Compared with blank group,the wiggle time of the right hind leg in model group and DSCG group increased,stride length decreased,HE staining showed inflammatory cell infiltration,myocyte enlargement,degeneration and necrosis. The degranulation rate of local skin mast cells in "Chengshan" (BL57) area increased,and the expressions of mast cell tryptase,5-HT,Pax7,MyoD,CD68 and CD206 increased (P<0.05). Compared with model group,the wiggle time of the right hind leg in EA group and EA+DSCG group decreased,stride length increased,HE staining showed that inflammatory cell infiltration was reduced,muscle cells were uniform in size and arranged neatly. Mast cell degranulation rate increased significantly in EA group,and the expressions of mast cell tryptase,5-HT,Pax7,MyoD and CD206 increased (P<0.05),while CD68 expression decreased (P<0.05). Compared with EA+DSCG group,the degranulation rate of mast cells and the expressions of mast cell tryptase,5-HT,Pax7,MyoD and CD206 increased (P<0.05),while CD68 expression decreased in EA group (P<0.05). Conclusion EA "Chengshan" (BL57) and "Yanglingquan" (GB34) can stimulate acupuncture points to locally induce mast cell degranulation,promote the polarization of macrophages,and then activate muscle satellite cells to play the regulatory process of repairing skeletal muscle injury.

Objective:To analyze the effect of traditional Chinese medicine fasting therapy on atherogenic index of plasma and metabolic indices in patients with metabolic syndrome.Methods:A case-control study was conducted on 90 patients with metabolic syndrome who were treated at Wenzhou Traditional Chinese Medicine Hospital between June 2021 and June 2023. The patients were divided into two groups with 45 patients in each group using a random number table method. The control group was given a normal diet, while the observation group underwent traditional Chinese medicine fasting therapy. Blood lipid indexes, atherogenic index of plasma, Homeostasis Model Assessment of Insulin Resistance index, anthropometric indices, and oxidative stress response were compared between the two groups.Results:After treatment, the levels of low-density lipoprotein cholesterol, total cholesterol, and triglyceride in the observation group were (2.11 ± 0.26) mmol/L, (4.31 ± 0.26) mmol/L, and (1.39 ± 0.26) mmol/L, respectively. They were significantly lower than those in the control group [(2.95 ± 0.34) mmol/L, (5.24 ± 0.33) mmol/L, (2.68 ± 0.41) mmol/L, t = 13.16, 14.85, 17.82, all P < 0.05]. After treatment, the level of high-density lipoprotein cholesterol was significantly higher in the observation group than in the control group [(1.18 ± 0.09) mmol/L vs. (1.03 ± 0.04) mmol/L, t = 10.21, P < 0.001]. After treatment, atherogenic index of plasma and Homeostasis Model Assessment of Insulin Resistance index in the observation group were (0.10 ± 0.04) and (5.12 ± 0.42), respectively in the observation group. They were significantly lower than those in the control group [(0.28 ± 0.10), (5.80 ± 0.67), t = 11.21, 5.76, both P < 0.001]. After treatment, waist circumference, hip circumference, and visceral adiposity index in the observation group were (91.05 ± 4.26) cm, (98.16 ± 5.06) cm, and (3.94 ± 0.52), respectively. They were significantly lower than those in the control group [(95.55 ± 9.87) cm, (102.64 ± 9.84) cm, (5.66 ± 1.04), t = 2.80, 2.71, 9.92, all P < 0.05). After treatment, the level of superoxide dismutase in the observation group was significantly higher than that in the control group [(101.52 ± 13.52) U/mL vs. (80.01 ± 6.82) U/mL, t = 9.52, P < 0.001]. After treatment, the level of malondialdehyde in the observation group was significantly lower than that in the control group [(4.41±0.35) nmol/L vs. (6.26 ± 0.61) nmol/L, t = 17.64, P < 0.001). Conclusion:Traditional Chinese medicine fasting therapy can effectively reduce the atherogenic index of plasma, blood lipid level, waist circumference, hip circumference, and visceral adiposity index in patients with metabolic syndrome. It also reduces oxidative stress reactions and is highly effective.

Objective To investigate the expression level of piR-35296 in clear cell renal cell carcinoma (ccRCC) and its pathological significance, as well as its effect on ccRCC cell proliferation. Methods Surgical resection specimens and clinicopathological data from 67 ccRCC patients were collected. Differential expression profiles of piRNAs in ccRCC were detected using piRNA microarray analysis, and validated by real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The effect of piR-35296 on the proliferative activity of ccRCC cells was examined by CCK-8 assay. Bioinformatic analysis predicted TAB2 as a potential downstream target gene of piR-35296; qRT-PCR was performed to detect theinfluence of piR-35296 overexpression or knockdown on TAB2 expression levels. Rescue experiments were conducted to verify the regulation of TAB2 by piR-35296 and its impact on ccRCC cell proliferation. The effect of piR-35296 knockdown on the growth of subcutaneous tumors in experimental nude mice was analyzed, and Ki-67 immunohistochemical staining was used to validate the influence of piR-35296 on ccRCC cell proliferation. Results Both piRNA expression profiling and qRT-PCR revealed an elevated expression level of piR-35296 in ccRCC (P < 0.05). The expression of piR-35296 was closely associated with tumor size and differentiation degree in ccRCC patients (χ²=3.984, 3.974, P < 0.05). CCK-8 proliferation assays demonstrated that piR-35296 overexpression enhanced the proliferative activity of ccRCC cells, whereas its downregulation inhibited cell proliferation (P < 0.05). qRT-PCR experiments showed that TAB2 expression was upregulated after piR-35296 overexpression and downregulated upon piR-35296 knockdown (P < 0.05). Rescue experiments indicated that piR-35296 promoted TAB2 mRNA and its protein expression in ccRCC cells, thereby stimulating cell proliferation; TAB2 downregulation inhibited ccRCC cell proliferation. In experimental nude mice, piR-35296 knockdown reduced the mass andvolume of subcutaneous tumors (P < 0.05). Immunohistochemical staining for Ki-67 revealed a decreased percentage of Ki-67-positive cells after piR-35296 downregulation, suggesting reduced cell proliferation capacity (P < 0.05). Conclusion The piR-35296 serves as a novel oncogenic growth promoter in ccRCC. By elevating TAB2 expression, piR-35296 promotes the proliferative growth of ccRCC cells.

Objective To study the correlations between thrombin indexes,related clinical features and prognosis of patients with spontaneous intracerebral hemorrhage.Methods Ninety-two patients with spontaneous intracerebral hemorrhage admitted to our hospital from January 2019 to January 2022 were enrolled.According to the results of modified Rankin scale(mRS)3 months after discharge,the patients were divided into good prognosis group(mRS≤2,n=65)and poor prognosis group(mRS>2,n=27).Clinical data were collected,including gender,age,body mass index(BMI),smoking,alcohol consumption,hypertension,diabetes mellitus,hyperlipidemia,National Institutes of Health Stroke Scale(NIHSS)score at admission,hematoma volume,and hematoma location.Endogenous thrombin potential(ETP),thrombin peak height(TPH)and thrombin peak time of the 2 groups were detected.Receiver operating characteristic(ROC)curve was used to analyze the value of age,NIHSS score,ETP,TPH,thrombin peak time and hematoma volume in predicting poor prognosis of patients with spontaneous intracerebral hemorrhage.Multivariate logistic regression was used to analyze the risk factors of poor prognosis in patients with spontaneous intracerebral hemorrhage.Results Age,NIHSS score,thrombin peak time,and hematoma volume in the good prognosis group were significantly lower than those in the poor prognosis group(P<0.05),while ETP,TPH and the proportion of patients with cerebellar hematoma in the good prognosis group were significantly higher than those in the poor prognosis group(P<0.05).There were no significant differences in gender composition,BMI,smoking,alcohol consumption,hypertension,diabetes mellitus,hyperlipidemia,cerebral lobe,basal ganglia or the number of brain stem hematoma between the 2 groups(P>0.05).ROC analysis proved that age,NIHSS score,ETP,TPH,thrombin peak time,and hematoma volume could predict the poor prognosis of patients with spontaneous intracerebral hemorrhage,and the areas under the curve were 0.598,0.848,0.859,0.862,0.797,and 0.852,respectively(P<0.05).Multiple logistic regression analysis confirmed that age≥59.040 years old,NIHSS score≥8.195,ETP≤420.510 nmol/(L·min),TPH≤87.395 nmol/L,thrombin peak time≥13.285 min,hematoma volume≥12.705 ml and hematoma located outside the cerebellum were risk factors for poor prognosis in patients with spontaneous intracerebral hemorrhage(P<0.05).Conclusion Age,NIHSS score,ETP,TPH,thrombin peak time,hematoma volume,and hematoma location are correlated with poor prognosis of patients with spontaneous intracerebral hemorrhage,which can provide reference for the clinical prognosis of patients with cerebral hemorrhage.

OBJECTIVE: To explore the risk factors of acute respiratory distress syndrome (ARDS) in patients with sepsis and to construct a risk nomogram model. METHODS: The clinical data of 234 sepsis patients admitted to the intensive care unit (ICU) of Tianjin Hospital from January 2019 to May 2022 were retrospectively analyzed. The patients were divided into non-ARDS group (156 cases) and ARDS group (78 cases) according to the presence or absence of ARDS. The gender, age, hypertension, diabetes, coronary heart disease, smoking history, history of alcoholism, temperature, respiratory rate (RR), mean arterial pressure (MAP), pulmonary infection, white blood cell count (WBC), hemoglobin (Hb), platelet count (PLT), prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (FIB), D-dimer, oxygenation index (PaO₂/FiO₂), lactic acid (Lac), procalcitonin (PCT), brain natriuretic peptide (BNP), albumin (ALB), blood urea nitrogen (BUN), serum creatinine (SCr), acute physiology and chronic health evaluation II (APACHE II), sequential organ failure assessment (SOFA) were compared between the two groups. Univariate and multivariate Logistic regression were used to analyze the risk factors of sepsis related ARDS. Based on the screened independent risk factors, a nomogram prediction model was constructed, and Bootstrap method was used for internal verification. The receiver operator characteristic curve (ROC curve) was drawn, and the area under the ROC curve (AUC) was calculated to verify the prediction and accuracy of the model. RESULTS: There were no significant differences in gender, age, hypertension, diabetes, coronary heart disease, smoking history, alcoholism history, temperature, WBC, Hb, PLT, PT, APTT, FIB, PCT, BNP and SCr between the two groups. There were significant differences in RR, MAP, pulmonary infection, D-dimer, PaO₂/FiO₂, Lac, ALB, BUN, APACHE II score and SOFA score (all P < 0.05). Multivariate Logistic regression analysis showed that increased RR, low MAP, pulmonary infection, high Lac and high APACHE II score were independent risk factors for sepsis related ARDS [RR: odds ratio (OR) = 1.167, 95% confidence interval (95%CI) was 1.019-1.336; MAP: OR = 0.962, 95%CI was 0.932-0.994; pulmonary infection: OR = 0.428, 95%CI was 0.189-0.966; Lac: OR = 1.684, 95%CI was 1.036-2.735; APACHE II score: OR = 1.577, 95%CI was 1.202-2.067; all P < 0.05]. Based on the above independent risk factors, a risk nomograph model was established to predict sepsis related ARDS (accuracy was 81.62%, sensitivity was 66.67%, specificity was 89.10%). The predicted values were basically consistent with the measured values, and the AUC was 0.866 (95%CI was 0.819-0.914). CONCLUSIONS Increased RR, low MAP, pulmonary infection, high Lac and high APACHE II score are independent risk factors for sepsis related ARDS. Establishment of a risk nomograph model based on these factors may guide to predict the risk of ARDS in sepsis patients.
Humans ; Retrospective Studies ; Alcoholism ; Prognosis ; Respiratory Distress Syndrome ; Pneumonia ; Sepsis ; Intensive Care Units ; Procalcitonin ; Fibrinogen ; ROC Curve

Objective:To explore the prognostic value of lymphocyte subsets in adult hemophagocytic syndrome (HPS).Methods:A total of 172 adult HPS patients diagnosed in 8 medical centers from January 2013 to August 2020 were selected for the study, of whom 87 were male (50.6%, 87/172), and 85 were female (49.4%, 85/172), with 68 survivors and 104 deaths. The clinical data were summarized, and variables such as lymphocyte subsets, immunoglobulin characteristics and fibrinogen were retrospectively analyzed, and the correlation between the mentioned variables and patient prognosis was analyzed. The optimal cut-off values of continuous variables were calculated by MaxStat, and the prognostic factors of HPS patients were screened based on the Cox proportional hazard regression model.Results:The median age of HPS patients was 56 (42, 66) years old, and the 5-year cumulative survival rate was 37.4% (37.4/100). The median age, platelet and albumin were 48 (27, 63) years, 84×10 9/L and 32.3 g/L in the survival group, and 59 years, 45.5×10 9/L, and 27.3 g/L in the death group, respectively. The differences between the two groups was statistically significant ( Z=?3.368, P=0.001; Z=?3.156, P=0.002; Z=?3.431, P=0.001). Patients with differentiated cluster 8+(CD8+)<11.1%, CD3+<64.9%, CD4+>51%, and CD4/CD8 ratio>2.18 had poor prognosis (χ 2=7.498, P=0.023; χ 2=4.169, P=0.041; χ 2=4.316, P=0.038; χ 2=9.372, P=0.002). Multivariable analysis showed that CD4/CD8 ratio, age, fibrinogen and hemoglobin were independent prognostic factors in HPS patients ( HR=2.435, P=0.027; HR=5.790, P<0.001; HR=0.432, P=0.018; HR=0.427, P=0.018). Conclusion:Peripheral blood lymphocyte subsets can be used to evaluate the prognosis of patients with HPS; CD4/CD8 ratio, age, fibrinogen, and hemoglobin are independent prognostic factors in HPS patients.

Objective To discuss the clinicopathological characteristics of cervical cancer patients with lymphatic metastasis, to evaluate lymph node metastasis in cervical cancer patients by combining pelvic MRI enlarged lymph nodes and SCC-Ag, and to analyze the prognostic value of the model. Methods We retrospectively analyzed the data of 124 patients with cervical cancer. The predictive model was established based on the result. Results The depth of interstitial infiltration, serum SCC-Ag change value before and after treatment, lymph node enlargement showed by pelvic MRI, D2-40 and Ki67 were independent risk factors for lymph node metastasis of cervical cancer (P < 0.05). The prediction model of lymph node metastasis: L=the serum SCC-Ag change value+7.127×lymph node enlargement showed by pelvic MRI+5.386×D2-40+5.135×the depth of interstitial infiltration+19.457×Ki67; the sensitivity was 78.6% and specificity was 79.2%. Conclusion The cervical cancer patients with L≥20.8261 should be noticed. Doctors should give them individualized neoadjuvant treatment, and ensure adequate surgical scope. The above lymphatic prediction model has predictive value for preoperative lymph node metastasis.

Background::Urticaria is a common skin disease characterized by episodes of wheals, and it has a negative effect on patients’ quality of life. Large-scale population-based epidemiological studies of urticaria are scarce in China. The aim of this survey was to determine the prevalence, clinical forms, and risk factors of urticaria in the Chinese population.Methods::This survey was conducted in 35 cities from 31 provinces, autonomous regions, and municipalities of China. Two to three communities in each city were selected in this investigation. Participants completed questionnaires and received dermatological examinations. We analyzed the prevalence, clinical forms, and risk factors of urticaria.Results::In total, 44,875 questionnaires were distributed and 41,041 valid questionnaires were collected (17,563 male and 23,478 female participants). The lifetime prevalence of urticaria was 7.30%, with 8.26% in female and 6.34% in male individuals ( P < 0.05). The point prevalence of urticaria was 0.75%, with 0.79% in female and 0.71% in male individuals ( P < 0.05). Concomitant angioedema was found in 6.16% of patients. Adults had a higher prevalence of urticaria than adolescents and children. Living in urban areas, exposure to pollutants, an anxious or depressed psychological status, a personal and family history of allergy, thyroid diseases, and Helicobacter pylori infection were associated with a higher prevalence of urticaria. Smoking was correlated with a reduced risk of urticaria. Conclusion::This study demonstrated that the lifetime prevalence of urticaria was 7.30% and the point prevalence was 0.75% in the Chinese population; women had a higher prevalence of urticaria than men. Various factors were correlated with urticaria.