BACKGROUND: To evaluate the efficacy and safety of the first cohort of people in China treated with a responsive neurostimulation system (Epilcure TM , GenLight MedTech, Hangzhou, China) for focal drug-resistant epilepsy in this study. METHODS: This multicenter, before-and-after self-controlled study was conducted across 8 centers from March 2022 to June 2023, involving patients with drug-resistant epilepsy who were undergoing responsive neurostimulation (RNS). The study was based on an ongoing multi-center, single-blind, randomized controlled study. Efficacy was assessed through metrics including median seizure count, seizure frequency reduction (SFR), and response rate. Multivariable linear regression analysis was conducted to explore the relationships of basic clinical factors and intracranial electrophysiological characteristics with SFR. The postoperative quality of life, cognitive function, depression, and anxiety were evaluated as well. RESULTS: The follow-up period for the 19 participants was 10.7 ± 3.4 months. Seizure counts decreased significantly 6 months after device activation, with median SFR of 48% at the 6th month (M6) and 58% at M12 ( P  <0.05). The average response rate after 13 months of treatment was 42%, with 21% ( n  = 4) of the participants achieving seizure freedom. Patients who have previously undergone resective surgery appear to achieve better therapeutic outcomes at M11, M12 and M13 ( β  <0, P  <0.05). No statistically significant differences were observed in patients' scores of quality of life, cognition, depression and anxiety following stimulation when compared to baseline measurements. No serious adverse events related to the devices were observed. CONCLUSIONS: The preliminary findings suggest that Epilcure TM exhibits promising therapeutic potential in reducing the frequency of epileptic seizures. However, to further validate its efficacy, larger-scale randomized controlled trials are required. REGISTRATION Chinese Clinical Trial Registry (No. ChiCTR2200055247).
Humans ; Female ; Male ; Drug Resistant Epilepsy/therapy* ; Adult ; Young Adult ; Middle Aged ; China ; Adolescent ; Treatment Outcome ; Quality of Life ; Single-Blind Method ; Seizures ; Electric Stimulation Therapy/methods*

Objective To investigate the predictive value of the combined tumor burden score (TBS) and platelet-albumin-bilirubin (PALBI) score model for postoperative tumor recurrence in liver transplant recipients with hepatocellular carcinoma (HCC). Methods The general information of 158 recipients diagnosed with HCC and underwent liver transplantation at the 900th Hospital of the Joint Logistics Support Force of the Chinese People's Liberation Army from 2008 to 2021 was collected. Lasso regression analysis combined with multivariate Cox regression analysis were used to identify independent risk factors for postoperative tumor recurrence after liver transplantation with HCC. A nomogram prediction model was constructed based on variables selected by Lasso regression analysis, and the predictive performance of the model was verified by calibration curve and clinical decision curve. The optimal cut-off values for postoperative tumor recurrence in liver transplant recipients with HCC were determined by receiver operating characteristic (ROC) curve, and Kaplan-Meier analysis was used to compare survival differences among different groups. Results Among the 158 liver transplant recipients with HCC, 82 experienced tumor recurrence, with a recurrence rate of 51.9% and a median tumor-free survival time of 10 (4, 25) months. Results of Lasso regression analysis and multivariate Cox regression analysis showed that alpha-fetoprotein (AFP) ≥400 ng/mL, TBS and PALBI score were all independent risk factors for postoperative tumor recurrence in liver transplant recipients with HCC (all P<0.05). The combined high TBS-high PALBI score showed the highest predictive value (hazard ratio 6.909, 95% confidence interval 3.067-15.563, P<0.001). A nomogram prediction model was constructed based on six variables selected by Lasso regression analysis. Calibration curve showed good consistency between the model's predicted results and the ideal curve. Decision curve analysis indicated that the nomogram prediction model provided the highest clinical benefit for predicting 1-year tumor-free survival after liver transplantation with HCC. Time-dependent ROC curves at 1, 3 and 5 years after surgery showed that TBS-PALBI model had good predictive performance, with no significant difference in area under the curve (AUC) compared with TBS-PALBI-AFP model. The optimal cut-off values for predicting postoperative tumor recurrence were determined by ROC curve, with a PALBI score cut-off of −2.334 and a TBS cut-off of 5.305. Recipients were divided into a low TBS-low PALBI score group (n=47) and a low/high TBS-low/high PALBI score group (at least one score was high) (n=111). Kaplan-Meier survival analysis showed that the low TBS-low PALBI score group had a higher tumor-free survival rate than the low/high TBS-low/high PALBI score group, with a significant difference (P<0.05). Conclusions TBS-PALBI model provides a novel, simple and effective tool for assessing the prognosis of liver transplant recipients with HCC. The nomogram model constructed based on this has significant advantages in predictive performance and may serve as a reference for guiding individualized treatment plans and improving clinical outcomes.

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.

Objective To investigate the role of pharmacists in smoking cessation abroad and foster the dissemination and initiation of smoking cessation services led by pharmacist. Methods A search and compiles information on the value of pharmacists in offering smoking cessation services were carried out through the PubMed and Scopus electronic databases and the evolution of supportive policies were analyzed. The feasibility and barriers to pharmacists providing these services were examined. Results The involvement of pharmacists in smoking cessation positively impacted public health and the economy. Endowing pharmacists with the authority to prescribe smoking cessation medications, providing training in this service, and bolstering their potential through interprofessional collaboration can effectively address the barriers to their role in smoking cessation. Conclusion It is advisable to consider integrating smoking cessation services led by pharmacist into healthcare and public health policy guidelines ,which could enhance the efficacy and sustainability of smoking cessation initiatives.

Objective To investigate the effect of Jisuikang formula-medicated serum for promoting spinal cord injury (SCI) repair in rats and explore the possible mechanism. Methods Thirty adult SD rats were randomized into sham-operated group, SCI (induced using a modified Allen method) model group, and Jisuikang formula-medicated serum treatment group. After the operations, the rats were treated with normal saline or Jisuikang by gavage on a daily basis for 14 days, and the changes in hindlimb motor function of the rats was assessed with Basso-Beattie-Bresnahan (BBB) scores and inclined-plate test. The injured spinal cord tissues were sampled from the SCI rat models for single-cell RNA sequencing, and bioinformatics analysis was performed to identify the target genes of Jisuikang, spinal cord injury and glycolysis. In the cell experiment, cultured astrocytes from neonatal SD rat cortex were treated with SOX2 alone or in combination with Jisuikang-medicated serum for 21 days, and the protein expressions of PKM2, p-PKM2 and YAP and colocalization of PKM2 and YAP in the cells were analyzed with Western blotting and immunofluorescence staining, respectively. Results The SCI rats with Jisuikang treatment showed significantly improved BBB scores and performance in inclined-plate test. At the injury site, high PKM2 expression was detected in various cell types. Bioinformatic analysis identified the HIPPO-YAP signaling pathway as the target pathway of Jisuikang. In cultured astrocytes, SOX2 combined with the mediated serum, as compared with SOX2 alone, significantly increased PKM2, p-PKM2 and YAP expressions and entry of phosphorylated PKM2 into the nucleus, and promoted PKM2 and YAP co-localization in the cells. Conclusion Jisuikang formula accelerates SCI repair in rats possibly by promoting aerobic glycolysis of the astrocytes via activating the PKM2/YAP axis to induce reprogramming of the astrocytes into neurons.

Objective To investigate the effect of Jisuikang formula-medicated serum for promoting spinal cord injury (SCI) repair in rats and explore the possible mechanism. Methods Thirty adult SD rats were randomized into sham-operated group, SCI (induced using a modified Allen method) model group, and Jisuikang formula-medicated serum treatment group. After the operations, the rats were treated with normal saline or Jisuikang by gavage on a daily basis for 14 days, and the changes in hindlimb motor function of the rats was assessed with Basso-Beattie-Bresnahan (BBB) scores and inclined-plate test. The injured spinal cord tissues were sampled from the SCI rat models for single-cell RNA sequencing, and bioinformatics analysis was performed to identify the target genes of Jisuikang, spinal cord injury and glycolysis. In the cell experiment, cultured astrocytes from neonatal SD rat cortex were treated with SOX2 alone or in combination with Jisuikang-medicated serum for 21 days, and the protein expressions of PKM2, p-PKM2 and YAP and colocalization of PKM2 and YAP in the cells were analyzed with Western blotting and immunofluorescence staining, respectively. Results The SCI rats with Jisuikang treatment showed significantly improved BBB scores and performance in inclined-plate test. At the injury site, high PKM2 expression was detected in various cell types. Bioinformatic analysis identified the HIPPO-YAP signaling pathway as the target pathway of Jisuikang. In cultured astrocytes, SOX2 combined with the mediated serum, as compared with SOX2 alone, significantly increased PKM2, p-PKM2 and YAP expressions and entry of phosphorylated PKM2 into the nucleus, and promoted PKM2 and YAP co-localization in the cells. Conclusion Jisuikang formula accelerates SCI repair in rats possibly by promoting aerobic glycolysis of the astrocytes via activating the PKM2/YAP axis to induce reprogramming of the astrocytes into neurons.

Objective:To explore the application value of 3.0T magnetic resonance imaging(MRI)combined with transvaginal ultrasound elastography technique in diagnosing uterine fibroids and adenomyosis.Methods:A retrospective analysis was performed on 56 patients with uterine fibroids and 41 patients with adenomyosis who admitted to Fengfeng General Hospital of North China Medical and Health Group from January 2021 to January 2022.MRI and transvaginal ultrasound elastography were respectively performed on all patients,and pathological diagnosis was taken as the"gold standard".The diagnostic results of MRI,transvaginal ultrasound elastography technique and their combination were compared,and the diagnostic situation of different examination methods were recorded.And then,the total coincidence rate was analyzed,and the sensitivity,specificity and accuracy were further calculated.Results:The totally diagnostic coincidence rate of MRI combined with transvaginal ultrasound elastography was 96.43% in detecting uterine fibroids,and that of MRI was 75.00%,and that of transvaginal ultrasonography was 80.36%.The differences of totally diagnostic coincidence rates among combined detection and single detection were significant(x2=10.500,7.049,P＜0.05).The totally diagnostic coincidence rate of MRI combined with transvaginal ultrasound elastography was 97.56% in detecting adenomyosis,which was significantly higher than that(78.05%)of MRI and that(78.05%)of transvaginal ultrasound elastography,and the differences were significant(x2=7.289,7.289,P＜0.05).The sensitivities of single MRI,single transvaginal ultrasound elastography and the combined detection of them were 71.74%,78.26% and 95.62% in detecting uterine fibroids,and the specificities of them were 90.00%,90.00% and 100.00%,and the accuracies of them were 75.00%,80.36% and 96.43%,respectively.The sensitivity and accuracy of the combined detection were significantly higher than those of single MRI detection(x2=5.029,10.500,P＜0.05),respectively.The accuracy of the combined detection was significantly higher than that of the single detection of vaginal ultrasonography(x2=7.049,P＜0.05).The sensitivities of single MRI,single transvaginal ultrasound elastography and the combined detection of them were 81.25%,78.73% and 96.88% in detecting adenomyosis,and the specificities of them were 66.67%,77.78% and 100.00%,and the accuracies of them were 78.05%,78.05% and 97.56%,respectively.The accuracy of the combined detection was significantly higher than that of single MRI detection(x2=7.289,P＜0.05),and the accuracy of the combined detection was significantly higher than that of single detection of vaginal ultrasonography(x2=7.289,P＜0.05).Conclusion:The diagnosis rate of MRI combined with transvaginal ultrasound elastography technique is higher for uterine fibroids and adenomyosis,which has better diagnostic value,and can provide reliable reference materials for clinicians in performing treatment.

Objective To investigate the expression and clinical significance of mismatch repair (MMR) protein,human epidermal growth factor receptor (HER)2 and Ki-67 in colorectal cancer.Methods The clini-cal data of 559 patients with colorectal cancer who underwent surgical treatment in the hospital from October 2017 to May 2022 were retrospectively analyzed.The expressions of MMR protein (MLH1,MSH2,PMS2, MSH6),HER2 and Ki-67 in colorectal cancer were detected by immunohistochemistry,and the relationship between them and the clinicopathological features of colorectal cancer was analyzed.Results Among the 559 patients with colorectal cancer,43 cases (7.7％) were deficient mismatch repair (dMMR),8 cases(1.4％) were HER2 +++,and 251 cases (44.9％) were Ki-67 +++.The expression rate of dMMR in the colorec-tal cancer patients with different age,tumor location,tumor maximum diameter,gross type,histological grade,lymph node metastasis and TNM stage was significantly different (P<0.05).The expression rate of HER2 ++/+++ in the patients with different gross types of colorectal cancer was statistically significant (P<0.05).The expression rate of Ki-67 +++ in the colorectal cancer patients with different histological types,histological grades,lymph node metastasis,distant metastasis and TNM staging was statistically signifi-cant (P<0.05).There was no correlation between MMR protein and the expression of HER2 and Ki-67 (P>0.05).Conclusion The expression of MMR proteins in colorectal cancer is closely related to its clinicopatho-logical features.