Lianggesan was first recorded in Taiping Huimin Heji Jufang， which was composed of Rhei Radix et Rhizoma， Natrii Sulfas， Gardeniae Fructus， Forsythiae Fructus， Scutellariae Radix， Glycyrrhizae Radix et Rhizoma（GRR）， Menthae Haplocalycis Herba， Lophatheri Herba and Mel. It was clinically applied to treat fire-heat syndrome in the upper and middle Jiao， and the curative effect was positive. In this study， the bibliometric method was used to conduct a detailed textual research on the formula name， medicinal composition， dosage evolution， origin and processing， functional indications and other aspects of Lianggesan. Research revealed that Lianggesan has six other names， such as Lianqiao Yinzi， Lianqiao Jiedusan， Jufang Lianggesan， Jiegu Lianggesan， Hejian Lianggesan and Qingji Lianggesan. Based on the edition of Taiping Huimin Heji Jufang， an analysis of the evolution of its formula composition revealed that the missing Chinese medicines were predominantly bamboo leaves and honey， while the added Chinese medicines were primarily supplements introduced to address changes in disease manifestations. After textual research， the dosage for one dose of Lianggesan from Taiping Huimin Heji Jufang was as follows：826 g of Rhei Radix et Rhizoma， 826 g of Natrii Sulfas， 826 g of GRR， 413 g of Gardeniae Fructus， 413 g of Menthae Haplocalycis Herba， 413 g of Scutellariae Radix， and 1652 g of Forsythiae Fructus. Decocting method was as following：Grinding the Chinese medicines into coarse powder（2-4 mm）， taking 8.16 g per dose， adding 300 mL of water， along with 2 g of Lophatheri Herba and 5 g of Mel， and decocting to 140 mL. The residue was removed and taken warmly 30 min after meals. It was recommended to take it three times daily until improvement was achieved. The origins of the 9 Chinese medicines were consistent with the 2020 edition of Pharmacopoeia of the People's Republic of China. Except for GRR， which required single frying（stir-frying）， the remaining medicines were all raw products. The description of the function of this formula in ancient books was summarized as purging fire and promoting bowel movements， clearing heat from the upper body and purging the lower body， and the main syndromes included facial redness， tongue swelling， red eyes， etc. In modern applications， the formula is primarily used for respiratory and digestive system diseases， including acute lung injury， chronic obstructive pulmonary disease， herpetic angina and aphthous stomatitis， covering 142 types of diseases. In summary， this paper can provide a basis for further research and development of Lianggesan through the literature review and key information combing.

T-cell acute lymphoblastic leukemia (T-ALL) is a highly aggressive hematologic malignancy with a poor prognosis, despite advancements in treatment. Many patients struggle with relapse or refractory disease. Investigating the role of the super-enhancer (SE) regulated gene ubiquitin-specific protease 20 (USP20) in T-ALL could enhance targeted therapies and improve clinical outcomes. Analysis of histone H3 lysine 27 acetylation (H3K27ac) chromatin immunoprecipitation sequencing (ChIP-seq) data from six T-ALL cell lines and seven pediatric samples identified USP20 as an SE-regulated driver gene. Utilizing the Cancer Cell Line Encyclopedia (CCLE) and BloodSpot databases, it was found that USP20 is specifically highly expressed in T-ALL. Knocking down USP20 with short hairpin RNA (shRNA) increased apoptosis and inhibited proliferation in T-ALL cells. In vivo studies showed that USP20 knockdown reduced tumor growth and improved survival. The USP20 inhibitor GSK2643943A demonstrated similar anti-tumor effects. Mass spectrometry, RNA-Seq, and immunoprecipitation revealed that USP20 interacted with hypoxia-inducible factor 1 subunit alpha (HIF1A) and stabilized it by deubiquitination. Cleavage under targets and tagmentation (CUT&Tag) results indicated that USP20 co-localized with HIF1A, jointly modulating target genes in T-ALL. This study identifies USP20 as a therapeutic target in T-ALL and suggests GSK2643943A as a potential treatment strategy.

Retiform hemangioendothelioma (RH) is a rare vasogenic malignancy with a high local recurrence rate and rare distant metastasis. Hepatic RH in infants is extremely rare. Here we report a case of liver RH in a 7-month-old infant.

Objective:To investigate the alterations in brain dynamic functional network connectivity (dFNC) and their significance in Parkinson's disease (PD) patients with postural instability/gait difficulty (PIGD).Methods:Ninety PD patients admitted to Department of Neurology, First Affiliated Hospital of Nanjing Medical University from May 2016 to August 2019 were recruited, and 54 healthy controls matched with gender and age were chosen; their clinical data and resting-state functional MRI (rs-fMRI) data were collected. PD patients were divided into PD with PIGD (PD-PIGD) group ( n=49) and PD without PIGD (PD-non-PIGD) group ( n=41) according to Unified Parkinson's Disease Rating Scale (UPDRS) scores. Independent component analysis (ICA), sliding window method and k-means clustering were used to analyze the dFNC and compare among groups. Correlations of dFNC alterations with clinical scales were verified by partial correlation analysis. Results:Four repeated recurring functional connectivity states were identified, and PD-PIGD patients had high frequency in state 3 (44%) and state 2 (23%) of the low dFNC. In terms of dFNC time attributes, PD-PIGD patients had longer mean dwell time in state 3 than PD-non-PIGD patients and had lower number of transitions in state 3 than PD-non-PIGD patients and healthy controls, with significant differences ( P<0.05); PD-PIGD patients had significantly higher fractional windows and statistically longer mean dwell time in state 2 than healthy controls ( P<0.05). In terms of dFNC strengths, compared with healthy controls, PD-PIGD patients showed significantly decreased functional connectivity within default mode network (DMN, between medial superior frontal gyrus and precuneus) and auditory network (AN, between superior temporal gyrus and middle temporal gyrus), but significantly increased functional connectivity between sensorimotor network (SMN, supplementary motor area) and DMN (precuneus) in state 2 ( P<0.05, false discovery rate [FDR]-corrected). Partial correlation analysis indicated positive correlation between mean dwell time in state 3 and PIGD scores in PD-PIGD patients ( r=0.450, P=0.039). Conclusion:PD-PIGD patients exhibit specific dFNC, mainly characterized by low connectivity of the brain functional network and prolonged dwell time; local functional network domains often separate between DMN, AN and SMN networks and within the networks.

Background: Irritable bowel syndrome (IBS) is a functional bowel disorder (FBD). Objectives: To assess the therapeutic effects of paeoniflorin (PF) on IBS in rats.Method: Sixty male Sprague–Dawley rats were randomly divided into normal, model, positive drug, low-dose PF, medium-dose PF and high-dose PF groups (n = 10). After gavage for 2 consecutive weeks, the effect of PF on abdominal pain symptoms was assessed based on the abdominal withdrawal reflex (AWR) score, fecal water content and pathological changes in colon tissues. D-lactate, interleukin-1β (IL-1β), transforming growth factor-β (TGF-β) and tumor necrosis factor-α (TNF-α) were detected by enzyme-linked immunosorbent assay, and phosphorylated nuclear factor kappa B (p-NF-κB) p65 was detected by Western blotting. The abundance and diversity changes of intestinal flora were explored using 16S ribosomal RNA sequencing.Result: In PF groups, the mucosal morphology of colon tissues was intact, and the glands were arranged neatly and structured clearly, without obvious inflammatory cell infiltration.Compared with the model group, PF groups had significantly elevated pain threshold, and mRNA and protein levels of zonula occludens-1 (ZO-1) and occludin, decreased AWR score at 20 mmHg pressure, fecal water content, mRNA levels of IL-1β, TGF-β, and TNF-α, protein level of p-NF-κB p65 and level of serum D-lactate, and reduced levels of serum IL-1β, TGF-β, and TNF-α (p < 0.05, p < 0.01). PF groups had higher abundance of Lactobacillus, Akkermansia, Alistipes, and Bacteroides, but lower abundance of Desulfovibrio, Parasutterella, and Enterococcus than those of the model group. Conclusions PF exerts therapeutic effects on IBS in rats probably by regulating the intestinal flora, and then up-regulating the expressions of ZO-1 and occludin in colon tissue while down-regulating the levels of IL-1β, TGF-β, TNF-α, D-lactate and p-NF-κB p65.

Objective:To investigate the alterations of amplitude of low frequency fluctuation (ALFF) and functional connectivity (FC) in patients with Parkinson′s disease (PD) with apathy.Methods:From May 2016 to August 2019, PD patients and age-, gender-and education level-matched healthy controls (HC) in the First Affiliated Hospital of Nanjing Medical University were prospectively recruited. The clinical and resting-state functional MRI (rs-fMRI) data of PD patients and HC were analyzed. According to the Starkstein Apathy Scale (SAS) scores, PD patients were divided into PD with apathy (PD-A) group and PD without apathy (PD-NA) group. Rs-fMRI images were processed by DPABI based on MATLAB. ALFF values were calculated and the standard ALFF (zALFF) were obtained. ANOVA and Post-Hoc t test were performed to compare the differences in local brain activity among the three groups. The brain regions with significant different zALFF values were selected as the seeds to calculate the FC values of the whole brain. The associations between FC values and the SAS scores were performed using pearson correlation analyses. Results:A total of 75 PD patients (50 males, 25 females, aged from 44 to 88 years) and 41 HC (25 males, 16 females, aged from 54 to 72 years) were enrolled. There were 42 patients in the PD-A group and 33 patients in the PD-NA group. Significant differences were found in zALFF values among the PD-A, PD-NA and HC groups ( P<0.05). After Post-Hoc t test, compared with the HC group, zALFF values were significantly increased in the right middle frontal gyrus in the PD-A group ( P<0.05) and significantly decreased in the left precuneus in the PD-NA group; The zALFF values of the right middle frontal gyrus and left precuneus in the PD-A group were significantly higher than those in PD-NA group ( P<0.05). Brain regions with different zALFF values were used as seeds for whole-brain FC. Compared with PD-NA group, FC values between the right middle frontal gyrus and bilateral precuneus, left superior frontal gyrus and its medial side, left middle frontal gyrus, left angular, left anterior cingulate gyrus, left posterior cingulate gyrus, left parahippocampal gyrus were significantly decreased in the PD-A group ( P<0.05). Additionally, FC values of PD patients between the right middle frontal gyrus with the left precuneus, the left superior frontal gyrus and its medial side, and the left middle frontal gyrus were negatively correlated with SAS scores ( r=-0.31, -0.30 and -0.34, both P<0.05). Conclusion:PD-A and PD-NA patients have different brain functional activities and connections in the frontal lobe, parietal lobe and limbic system, suggesting that apathy in PD may be associated with the abnormal functional connections of the frontal-parietal cortical circuit and the frontal-limbic-striatal loop.

Objective:To evaluate and compare the efficacy and safety of ultra-rapid lispro insulin (URLi) and humalog lispro (HL) in the treatment of type 2 diabetes mellitus.Methods:This was an international multicenter, double-blind, randomized controlled study. From May 2019 to January 2021, a total of 481 patients with type 2 diabetes mellitus, who had been using insulin for at least 90 days and had poor glycemic control, were included. These patients were recruited from 34 research centers in China, including Shanghai Jiao Tong University School of Medicine Affiliated Sixth People′s Hospital. They were assigned to either the URLi group (319 patients) or the HL group (162 patients) using stratified blocked randomization. The primary endpoint was the change in hemoglobin A 1c (HbA 1c) relative to baseline after 26 weeks of treatment. Secondary endpoints included the proportion of patients who achieved HbA 1c<7.0% and ≤6.5% after 26 weeks of treatment, 1-h postprandial glucose (1hPG) or 2-h postprandial glucose (2hPG) excursions during a mixed meal tolerance test at week 26, as well as safety parameters. Continuous variables were compared using mixed model repeated measures or analysis of covariance, and categorical variables were compared using logistic regression or Fisher′s exact test. Results:Data based on the Chinese subgroup showed that there were no statistically significant differences between the URLi and HL groups in terms of male percentage [56.1% (179/319) vs. 56.2% (91/162); P=0.990], age [(59.5±8.4) vs. (59.6±9.3) years; P=0.839] and other baseline characteristics. Regarding the change in HbA 1c relative to baseline, the URLi group was non-inferior to the HL group (-0.59%±0.05% vs. -0.66%±0.06%; P=0.312). There were no statistically significant differences between the URLi and HL groups in proportion of patients who achieved HbA 1c<7.0% [47.3% (138/292) vs. 45.2% (70/155); P=0.907] and≤6.5% [27.7% (81/292) vs. 27.7% (43/155); P=0.816]. The excursions in 1hPG [(6.20±0.21) vs. (6.90±0.25) mmol/L; P=0.001] and 2hPG [(8.10±0.27) vs. (9.30±0.31) mmol/L; P<0.001] were lower in the URLi group than the HL group, with statistically significant differences. In terms of safety, there were no statistically significant differences in the percentage of subjects who reported treatment-emergent adverse events between the URLi and HL groups [49.8% (159/319) vs. 50.0% (81/162); P=1.000]. The event rate of nocturnal hypoglycemia was lower in the URLi group than the HL group, with statistically significant differences [(0.53±0.10) vs. (0.89±0.16) events per patient -year; P=0.040]. Conclusions:With good glycemic control, URLi showed non-inferiority for HbA 1c improvement versus HL and was superior to HL for postprandial glucose excursion control. Meanwhile the rate and incidence of nocturnal hypoglycemia were lower in the URLi group than the HL group.

Objective:To evaluate the status of T, B and NK lymphocytes in peripheral blood of patients with chronic hepatitis B virus(HBV) infection and low-level viremia after nucleos(t)ide analogue (NA) treatment and to provide ideas for solving low-level viremia.Methods:This retrospective study involved 344 patients with chronic HBV infection who had been treated with NAs. They were divided into two groups: low-level viremia group (LLV group) and complete virological response group (CVR group). Clinical data including basic information, biochemistry and coagulation test results, HBV DNA, peripheral blood lymphocyte counts, PD1 and CD28 expression by T lymphocytes, and perforin and granzyme B expression by NK lymphocytes were collected and compared between the two groups. Propensity matching analysis was performed to verify the accuracy of the results.Results:Among the 344 cases, 162 were in the LLV group and 182 in the CVR group. There were no significant differences in disease diagnosis, alanine aminotransferase (ALT), aspartate aminotransferase (AST) or albumin (ALB) level between the two groups ( P>0.05), but the differences in gender and age were statistically significant ( P<0.05). The differences in the counts and percentages of peripheral blood CD3 +, CD4 + and CD8 + T lymphocyte and CD4 + /CD8 + ratios between the two groups were not statistically significant ( P>0.05), but the expression of PD1 and CD28 by peripheral blood CD3 +, CD4 + and CD8 + T lymphocytes was higher in the LLV group than in the CVR group ( P<0.05). The count of peripheral blood CD19 + B lymphocytes in the LLV group was higher than that in the CVR group ( P>0.05), and the percentage of peripheral blood CD19 + B lymphocytes was also higher in the LLV group ( P<0.05). The count of peripheral blood CD16 + CD56 + NK lymphocytes and the expression of perforin in the LLV group were lower than those in the CVR group ( P>0.05). The percentage of peripheral blood CD16 + CD56 + NK lymphocytes and the expression of granzyme B in the LLV group were lower than those in the CVR group ( P<0.05). After propensity score matching, 108 cases in the LLV group and 108 cases in the CVR group showed no significant differences in basic information ( P>0.05); the percentage of CD4 + T lymphocytes and CD4 + /CD8 + ratio in peripheral blood T lymphocyte subsets were higher in the LLV group than in the CVR group, while the percentage of CD8 + lymphocytes was lower in the LLV group ( P<0.05); the expression of PD1 and CD28 by CD3 +, CD4 + and CD8 + T lymphocytes remained higher in the LLV group ( P<0.05); the differences in the counts and percentages of peripheral blood CD19 + B lymphocytes as well as CD16 + CD56 + NK lymphocytes between the two groups were not statistically significant ( P>0.05); no significant difference in the expression of perforin by CD16 + CD56 + NK lymphocytes was found between the two groups ( P>0.05), and the expression of granzyme B remained lower in the LLV group ( P<0.05). Conclusions:Abnormal number and function of T lymphocytes and decreased function of NK lymphocytes might be related to the development of LLV in patients with chronic HBV infection after treatment. Therefore, in addition to adjusting NAs, targeting of T and NK lymphocytes might also be a feasible measure for future LLV treatment.

Objectives:To construct a nomogram prediction model using common preoperative indicators for early weight loss (EWL) 1 year after laparoscopic sleeve gastrectomy (LSG).Methods:Relevant data of obese patients who had undergone LSG from January 2015 to May 2022 in Fujian Medical University Union Hospital and Quanzhou First Hospital Affiliated Fujian Medical University were analyzed. Patients with a history of major abdominal surgery, severe gastroesophageal reflux disease, pregnancy within 1 year after surgery, or who were lost to follow-up were excluded, resulting in a total of 200 patients in the study (190 from Fujian Medical University Union Hospital and 10 from Quanzhou First Hospital Affiliated Fujian Medical University). The participants were 51 men and 149 women of a mean age 29.9±8.2 years and a body mass index (BMI) 38.7±6.5 kg/m 2. All patients in this group underwent standardized LSG procedure. Achieving ideal weight (BMI≤25 kg/m 2) 1 year after LSG was defined as goal of EWL. Logistic regression analyses were performed to identify factors that independently influenced EWL. These factors were incorporated into the nomogram model. Receiver operating characteristic (ROC) curves (the larger the area under the curve [AUC], the better the predictive ability and accuracy of the model), likelihood ratio test (higher likelihood ratio indicates greater model homogeneity), decision curve analysis (higher net benefit indicates a better model), Akaike information criterion (AIC; smaller AIC indicates a better model), and Bayesian information criterion (BIC; smaller BIC indicates a better model) were used to validate the predictive ability of the column line diagram model. Results:In this study of 200 obese patients who underwent LSG surgery, 136 achieved EWL goal, whereas the remaining 64 did not. The rate of EWL goal achievement of the entire group was 68.0%. Compared with patients who did not achieve EWL goal, those who did had lower BMI, alanine transaminase, aspartate transaminase, triglycerides, and higher cholesterol. Additionally, the proportion of female was higher and the proportions of patients with fatty liver and hypertension lower in those who achieved EWL goal (all P<0.05). Univariate and multivariate logistic regression analysis revealed that preoperative BMI (OR=0.852, 95%CI: 0.796-0.912, P<0.001), alanine transaminase (OR=0.992, 95%CI: 0.985-0.999, P=0.024), presence of fatty liver (OR=0.185, 95%CI: 0.038-0.887, P=0.035) and hypertension (OR=0.374, 95%CI: 0.144-0.969, P=0.043) were independently associated with failure to achieve EWL goal. Cholesterol (OR=1.428, 95%CI: 1.052-1.939, P=0.022) was independently associated with achieving EWL goal. We used the above variables to establish an EWL nomogram model. ROC analysis, the likelihood ratio test, decision curve analysis, and AIC all revealed that the predictive value of the model was better than that of BMI alone (nomogram model vs. BMI: area under the curve 0.840 vs. 0.798, P=0.047; likelihood ratio: 58.785 vs. 36.565, AIC: 193.066 vs. 207.063, BIC: 212.856 vs. 213.660). Conclusion:Our predictive model is more accurate in predicting EWL after LSG compared with using BMI.

Objectives:To construct a nomogram prediction model using common preoperative indicators for early weight loss (EWL) 1 year after laparoscopic sleeve gastrectomy (LSG).Methods:Relevant data of obese patients who had undergone LSG from January 2015 to May 2022 in Fujian Medical University Union Hospital and Quanzhou First Hospital Affiliated Fujian Medical University were analyzed. Patients with a history of major abdominal surgery, severe gastroesophageal reflux disease, pregnancy within 1 year after surgery, or who were lost to follow-up were excluded, resulting in a total of 200 patients in the study (190 from Fujian Medical University Union Hospital and 10 from Quanzhou First Hospital Affiliated Fujian Medical University). The participants were 51 men and 149 women of a mean age 29.9±8.2 years and a body mass index (BMI) 38.7±6.5 kg/m 2. All patients in this group underwent standardized LSG procedure. Achieving ideal weight (BMI≤25 kg/m 2) 1 year after LSG was defined as goal of EWL. Logistic regression analyses were performed to identify factors that independently influenced EWL. These factors were incorporated into the nomogram model. Receiver operating characteristic (ROC) curves (the larger the area under the curve [AUC], the better the predictive ability and accuracy of the model), likelihood ratio test (higher likelihood ratio indicates greater model homogeneity), decision curve analysis (higher net benefit indicates a better model), Akaike information criterion (AIC; smaller AIC indicates a better model), and Bayesian information criterion (BIC; smaller BIC indicates a better model) were used to validate the predictive ability of the column line diagram model. Results:In this study of 200 obese patients who underwent LSG surgery, 136 achieved EWL goal, whereas the remaining 64 did not. The rate of EWL goal achievement of the entire group was 68.0%. Compared with patients who did not achieve EWL goal, those who did had lower BMI, alanine transaminase, aspartate transaminase, triglycerides, and higher cholesterol. Additionally, the proportion of female was higher and the proportions of patients with fatty liver and hypertension lower in those who achieved EWL goal (all P<0.05). Univariate and multivariate logistic regression analysis revealed that preoperative BMI (OR=0.852, 95%CI: 0.796-0.912, P<0.001), alanine transaminase (OR=0.992, 95%CI: 0.985-0.999, P=0.024), presence of fatty liver (OR=0.185, 95%CI: 0.038-0.887, P=0.035) and hypertension (OR=0.374, 95%CI: 0.144-0.969, P=0.043) were independently associated with failure to achieve EWL goal. Cholesterol (OR=1.428, 95%CI: 1.052-1.939, P=0.022) was independently associated with achieving EWL goal. We used the above variables to establish an EWL nomogram model. ROC analysis, the likelihood ratio test, decision curve analysis, and AIC all revealed that the predictive value of the model was better than that of BMI alone (nomogram model vs. BMI: area under the curve 0.840 vs. 0.798, P=0.047; likelihood ratio: 58.785 vs. 36.565, AIC: 193.066 vs. 207.063, BIC: 212.856 vs. 213.660). Conclusion:Our predictive model is more accurate in predicting EWL after LSG compared with using BMI.