[Saikosaponin a alleviates pentylenetetrazol-induced acute epileptic seizures in mouse models of depression by suppressing microglia activation-mediated inflammation].

OBJECTIVE: To explore the inhibitory effect of saikosonin a (SSa) on pentylenetetrazol-induced acute epilepsy seizures in a mouse model of depression and explore the mechanism mediating this effect. METHODS: Male C57BL/6J mouse models of depression was established by oral administration of corticosterone via drinking water for 3 weeks, and acute epileptic seizures were induced by intraperitoneal injection of a single dose of pentylenetetrazole. The effect of intraperitoneal injection of SSa prior to the treatment on depressive symptoms and epileptic seizures were assessed using behavioral tests, epileptic seizure grading and hippocampal morphology observation. ELISA was used to detect blood corticosterone levels of the mice, and RTqPCR was performed to detect the pro- and anti-inflammatory factors. Microglia activation in the mice was observed using immunofluorescence staining. RESULTS: The mouse model of corticosterone-induced depression showed body weight loss and obvious depressive behaviors with significantly increased serum corticosterone level (all P < 0.05). Compared with those with pentylenetetrazole-induced epilepsy alone, the epileptic mice with comorbid depression showed significantly shorter latency of epileptic seizures, increased number, grade and duration of of seizures, reduced Nissl bodies in hippocampal CA1 and CA3 neurons, increased number of Iba1-positive cells, and significantly enhanced hippocampal expressions of IL-1ß, IL-10, TNF-α and IFN-γ. Pretreatment of the epileptic mice with SSa significantly prolonged the latency of epileptic seizures, reduced the number, duration, and severity of seizures, increased the number of Nissl bodies, decreased the number of Iba1-positive cells, and reduced the expression levels of IL-1ß, IL-10, TNF-α, and IFN-γ in the hippocampus (P < 0.05). CONCLUSION: Depressive state aggravates epileptic seizures, increases microglia activation, and elevates inflammation levels. SSA treatment can alleviate acute epileptic seizures in mouse models of depression possibly by suppressing microglia activation-mediated inflammation.

Validation of metastasis-free survival as a surrogate endpoint for overall survival in localized prostate cancer in the era of docetaxel for castration-resistant prostate cancer.

BACKGROUND: Prior work from the Intermediate Clinical Endpoints in Cancer of the Prostate (ICECaP) consortium (ICECaP-1) demonstrated that metastasis-free survival (MFS) is a valid surrogate for overall survival (OS) in localized prostate cancer (PCa). This was based on data from patients treated predominantly before 2004, prior to docetaxel being available for the treatment of metastatic castrate-resistant prostate cancer (mCRPC). We sought to validate surrogacy in a more contemporary era (ICECaP-2) with greater availability of docetaxel and other systemic therapies for mCRPC. PATIENTS AND METHODS: Eligible trials for ICECaP-2 were those providing individual patient data (IPD) after publication of ICECaP-1 and evaluating adjuvant/salvage therapy for localized PCa, and which collected MFS and OS data. MFS was defined as distant metastases or death from any cause, and OS was defined as death from any cause. Surrogacy was evaluated using a meta-analytic two-stage validation model, with an R2 ≥ 0.7 defined a priori as clinically relevant. RESULTS: A total of 15 164 IPD from 14 trials were included in ICECaP-2, with 70% of patients treated after 2004. The median follow-up was 8.3 years and the median postmetastasis survival was 3.1 years in ICECaP-2, compared with 1.9 years in ICECaP-1. For surrogacy condition 1, Kendall's tau was 0.92 for MFS with OS at the patient level, and R2 from weighted linear regression (WLR) of 8-year OS on 5-year MFS was 0.73 (95% confidence interval 0.53-0.82) at the trial level. For condition 2, R2 was 0.83 (95% confidence interval 0.64-0.89) from WLR of log[hazard ratio (HR)]-OS on log(HR)-MFS. The surrogate threshold effect on OS was an HR(MFS) of 0.81. CONCLUSIONS: MFS remained a valid surrogate for OS in a more contemporary era, where patients had greater access to docetaxel and other systemic therapies for mCRPC. This supports the use of MFS as the primary outcome measure for ongoing adjuvant trials in localized PCa.

[Long-term follow-up of humanized and murine CD19 CAR-T-cell therapy for B-cell acute lymphoblastic leukemia].

Objective: Murine CD19 chimeric antigen receptor T-cell (CAR-T) products have been approved for the treatment of refractory/relapsed (R/R) B-cell acute lymphocytic leukemia (B-ALL) ; moreover, humanized products are also undergoing clinical trials. This study aimed to explore the differences in safety and short- and long-term follow-up efficacy between humanized and murine CD19 CAR-T-cells for treating relapsed and refractory B-ALL. Methods: Clinical data of 80 patients with R/R B-ALL treated with CD19-targeted CAR-T-cells at the Union Hospital of Tongji Medical College of Huazhong University of Science and Technology between May 2016 and March 2023 were analyzed, which included 31 patients with murine CAR-T and 49 with humanized products. Results: The proportion of patients with cytokine-release syndrome (CRS) in the murine and humanized groups was 63.1% and 65.3%, respectively. Moreover, a higher proportion of patients suffered from severe CRS in the murine group than in the humanized CAR-T group (19.4% vs 8.2%, P=0.174). Furthermore, one patient per group died of grade 5 CRS. The incidence of grade 1-2 immune effector cell-associated neurotoxicity syndrome (ICANS) was 12.9% and 6.1%, respectively; severe ICANS were not observed. Among patients receiving murine CAR-T-cells, an overall response (OR) was observed in 74.2%. Conversely, the OR rate of patients receiving humanized CAR-T-cells was 87.8%. During the median follow-up time of 10.5 months, the median recurrence-free survival (RFS) of patients with murine CAR-T-cells was 12 months, which was as long as that of patients with humanized CAR-T-cells. The median overall survival (OS) were not reached in both groups. Of the 45 patients with a bone marrow burden over 20% at baseline, humanized CAR-T therapy was associated with a significantly improved RFS (43.25% vs 33.33%, P=0.027). Bridging transplantation was an independent factor in prolonging OS (χ(2)=8.017, P=0.005) and PFS (χ(2)=6.584, P=0.010). Common risk factors, such as age, high proportion of bone marrow blasts, and BCR-ABL fusion gene expression, had no significant effect on patients' long-term follow-up outcomes. Three patients reached complete remission after reinfusion of humanized CAR-T-cells. However, one patient relapsed one month after his second infusion of murine CAR-T-cells. Conclusions: The results indicate that humanized CAR-T therapy showed durable efficacy in patients with a higher tumor burden in the bone marrow without any influence on safety. Moreover, it could overcome immunogenicity-induced CAR-T resistance, providing treatment options for patients who were not treated successfully with CAR-T therapies.

[Effects of miniature free groin perforator flaps in repairing small wounds on hands].

Objective: To investigate the effects of miniature free groin perforator flaps in repairing small wounds on hands. Methods: The retrospective observational study was conducted. Fifteen patients with 16 small wounds on hands were admitted to Tongren Hospital of Wuhan University & Wuhan Third Hospital from July 2020 to October 2022, including 12 males and 3 females, aged 19 to 56 years. The size of skin and soft tissue defect was 2.0 cm×1.5 cm to 6.0 cm×3.0 cm after debridement. According to size and shape of the wounds, 13 single-lobe perforator flaps and 2 bilobed perforator flaps were designed in the groin region, with the flap size of 4.5 cm×2.5 cm to 7.5 cm×3.5 cm. According to the condition of the recipient area, the arteries and veins at the pedicle of the flap were anastomosed to the arteries and veins of the recipient area respectively. The wounds in the donor area of the flap was closed by layered and tension-reducing suture. The thickness of the flap was measured during operation. The survival of the flap was observed, and the complications in the donor and recipient areas were recorded after operation. The appearance and texture of the flap were observed during follow-up. At the last follow-up, the sensory recovery of the affected hand was evaluated, the function of the affected hand was evaluated according to the trial standard of the upper limb partial function evaluation of the Hand Surgery Society of the Chinese Medical Association, the scar in the donor and recipient areas were observed, and the satisfaction of patients for the curative effects was inquired. Results: The thickness of the flap was ranged from 0.3 to 1.0 cm, with an average thickness of 0.6 cm. After operation, 11 single-lobe flaps and 2 bilobed flaps survived well; in the left 2 single-lobe flaps, one flap had venous crisis but returned to normal after removing stitches to reduce tension and bloodletting of flaps, while the other one flap had a little necrosis on tip but healed after dressing change. No complications occurred in donor and recipient areas. During follow-up of 8 to 35 months after operation, the flaps had good elasticity and soft texture; 8 flaps were slightly bloated and were trimmed 3 to 8 months after operation, while the appearances of the other flaps were good. At the last follow-up, all flaps recovered protective feeling; the function of the affected hand was evaluated as excellent in 10 cases, good in 4 cases, and fair in 1 case; only linear scar remained in the donor and recipient areas; the patients were satisfied with the appearance and function recovery of the affected hand. Conclusions: The miniature free groin perforator flaps in repairing small wounds on hands have the advantages of high survival rate of flaps, hidden flap donor area, little damage, few complications, good repair effect, etc., showing clinical application value. It is recommended for repairing non-functional wounds on hands.

[Influence of muscle energy technology combined with Maitland joint mobilization surgery on the elbow joint flexion function in patients with deep burn of elbow joint].

Objective: To investigate the influence of muscle energy technology (MET) combined with Maitland joint mobilization surgery on the elbow joint flexion function in patients with deep burn of elbow joint. Methods: A retrospective controlled clinical trial was conducted. From January 2020 to January 2022, 53 patients with elbow joint flexion dysfunction after deep burns who met the inclusion criteria were treated in Tongren Hospital of Wuhan University & Wuhan Third Hospital, including 32 males and 21 females, aged (37±12) years. According to the treatment method used, the patients were divided into conventional treatment alone group (15 cases), conventional treatment+joint mobilization surgery group (18 cases), and conventional treatment+joint mobilization surgery+MET group (20 cases). Before treatment and 2 months after treatment, the patient's elbow joint range of motion was measured using a protractor, the Mayo elbow joint function score was used to evaluate elbow joint function, a portable muscle strength tester was used to measure elbow extensor muscle strength, and visual analogue scale was used to evaluate pain degree. Data were statistically analyzed with one-way analysis of variance, least significant difference test, paired sample t test, Kruskal-Wallis H test, Wilcoxon signed rank-sum test, chi-square test, Fisher's exact probability test, and Bonferroni correction. Results: After two months of treatment, the elbow joint range of motion and elbow joint function scores of patients in conventional treatment+joint mobilization surgery group and conventional treatment+joint mobilization surgery+MET group ((103±12)° and 60 (50, 66), (131±14)° and 73 (65, 80)) were significantly larger and higher than those in conventional treatment alone group ((77±15)° and 45 (35, 50), P values all <0.05), respectively. The elbow joint range of motion and elbow joint function scores of patients in conventional treatment+joint mobilization surgery+MET group were significantly larger and higher than those in conventional treatment+joint mobilization surgery group (P values all <0.05), respectively. After two months of treatment, the elbow extensor muscle strength and pain score of patients in conventional treatment+joint mobilization surgery+MET group were respectively significantly larger and lower than those in conventional treatment alone group and conventional treatment+joint mobilization surgery group (P values all <0.05). The elbow extensor muscle strength and pain score of patients in conventional treatment+joint mobilization surgery group were similar to those in conventional treatment alone group (P>0.05). The elbow joint range of motion and elbow extensor muscle strength (with t values of 9.37, 25.54, 28.71, 6.70, 7.20, and 7.01, respectively, P<0.05), elbow joint function scores and pain scores (with Z values of 3.15, 3.63, 3.93, 3.30, 3.52, and 3.84, respectively, P<0.05) of patients in conventional treatment alone group, conventional treatment+joint mobilization surgery group, and conventional treatment+joint mobilization surgery+MET group after two months of treatment were significantly improved compared with those before treatment. Conclusions: The combination of MET and Maitland joint mobilization surgery can effectively improve elbow joint range of motion, elbow joint function, elbow extensor muscle strength, and pain of patients with deep elbow joint burns, therefore it is worthy of promotion.

[Pan-cancer analysis of ubiquitin-specific protease 7 and its expression changes in the carcinogenesis of scar ulcer].

Objective: To explore the biological role and clinical significance of ubiquitin-specific protease 7 (USP7) in the carcinogenesis of scar ulcer. Methods: A retrospective observational study combined with bioinformatics analysis was used. The RNA expression profile data of USP7 in tumor and/or its corresponding paracancular normal tissue were obtained from The Cancer Genome Atlas (TCGA) database and the Gene Expression Omnibus database, and the RNA sequencing data were transformed by log2. The variations of USP7 gene were analyzed by cBioPortal database. The USP7 mRNA expression in tumor and adjacent normal tissue in TCGA database were obtained by using the "Gene_DE" module in TIMER 2.0 database. The survival rates of patients with high and low USP7 expression in cutaneous melanoma (SKCM), cervical squamous cell carcinoma (CESC), lung squamous cell carcinoma (LUSC), and head and neck squamous cell carcinoma (HNSC) were analyzed using the Gene Expression Profile Interactive Analysis 2 (GEPIA2) database, and the Kaplan-Meier survival curves were drawn. Sangerbox database was used to analyze the correlation of USP7 expression in pan-cancer with microsatellite instability (MSI) or tumor mutation burden (TMB) pan-cancer. Through the "correlation analysis" module in the GEPIA2 database, the correlation of USP7 expression in pan-cancer with the expression levels of five DNA mismatch repair genes (MLH1, MSH2, MSH6, PMS2, and EPCAM) and three essential DNA methyltransferases (DNMT)--DNMT1, DNMT3A, and DNMT3B were evaluated. The USP7 expression in CESC, HNSC, LUSC, and SKCM and its correlation with infiltration of immune cells (B cells, CD4+ T cells, CD8+ T cells, neutrophils, macrophages, and dendritic cells) were analyzed by the "Immune-Gene" module in TIMER 2.0 database. The "Similar Genes Detection" module of GEPIA2 database was used to obtain the top 100 protein sets with similar expression patterns to USP7. Intersection analysis was performed between the aforementioned protein sets and the top 50 protein sets that were directly physically bound to USP7 obtained by using the STRING database. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analysis were performed for the two protein sets mentioned above using the DAVID database. The samples of normal skin, hypertrophic scar, scar ulcer, and scar carcinoma with corresponding clinicopathologic features were collected from the Department of Pathology of Tongren Hospital of Wuhan University & Wuhan Third Hospital from October 2018 to October 2022, and the USP7 expression in tissue was detected by immunohistochemical method, with the number of samples of 6. Data were statistically analyzed with Log-rank test, one-way analysis of variance, and Bonferroni test. Results: In pan-cancer, the main gene variations of USP7 were mutation and amplification, and the top 3 tumors with the highest variation frequency (>6%) were bladder urothelial carcinoma, SKCM, and endometrial carcinoma. The main mutation of USP7 gene in pan-cancer was missense mutation. In SKCM with the highest mutation frequency, the main type of mutation was missense mutation in USP7_ICP0_bdg domain. USP7 mRNA expression in breast invasive carcinoma, bile duct carcinoma, colon carcinoma, esophageal carcinoma, HNSC, renal chromophobe cell carcinoma, hepatocellular carcinoma, lung adenocarcinoma, LUSC, prostate carcinoma, and gastric carcinoma was significantly higher than that in corresponding paracancer normal tissue (P<0.05). USP7 mRNA expression in glioblastoma multiforme, renal clear cell carcinoma, renal papillary cell carcinoma, and thyroid carcinoma was significantly lower than that in corresponding paracancular normal tissue (P<0.05). In addition, USP7 mRNA expression in SKCM metastases was much higher than that in primary tumor tissue (P<0.05). Survival curves showed no significant difference in survival rate between patients with high USP7 expression and patients with low USP7 expression in CESC, HNSC, LUSC, and SKCM (Log-rank P>0.05, with hazard ratios of 1.00, 0.99, 1.00, and 1.30, respectively). USP7 expression in colon cancer, colorectal cancer, thymic cancer, and thyroid cancer was negatively correlated with TMB (with Pearson correlation coefficients of -0.26, -0.19, -0.19, and 0.11, respectively, P<0.05). USP7 expression in glioma, CESC, lung adenocarcinoma, mixed renal carcinoma, and LUSC was positively correlated with MSI expression (with Pearson correlation coefficients of 0.22, 0.14, 0.15, 0.08, and 0.14, respectively, P<0.05), and USP7 expression in colon cancer, colorectal cancer, invasive breast cancer, prostate cancer, HNSC, thyroid cancer, and diffuse large B-cell lymphoma were significantly negatively correlated with MSI expression (with Pearson correlation coefficients of -0.31, -0.27, -0.13, -0.19, -0.16, -0.18, and -0.53, respectively, P<0.05). The expression of USP7 in CESC was positively correlated with that of both MSH2 and MSH6 (with Spearman correlation coefficients of 0.51 and 0.44, respectively, P<0.05), and the expression of USP7 in HNSC was positively correlated with the expression of EPCAM, MLH1, MSH2, MSH6, and PMS2 (with Spearman correlation coefficients of 0.39, 0.14, 0.49, 0.54, and 0.41, respectively, P<0.05), and the expression of USP7 in LUSC was positively correlated with the expression of EPCAM, MSH2, MSH6, and PMS2 (with Spearman correlation coefficients of 0.20, 0.36, 0.40, and 0.34, respectively, P<0.05), and the expression of USP7 in SKCM was positively correlated with the expression of EPCAM, MLH1, MSH2, MSH6, and PMS2 (with Spearman correlation coefficients of 0.11, 0.33, 0.42, 0.55, and 0.34, respectively, P<0.05). The expression of USP7 in CESC, HNSC, LUSC, and SKCM was significantly positively correlated with the expression of DNMT1, DNMT3A, and DNMT3B (with Spearman correlation coefficients of 0.42, 0.34, 0.22, 0.45, 0.52, 0.22, 0.36, 0.36, 0.22, 0.38, 0.46, and 0.21, respectively, P<0.05). The expression of USP7 in CESC, HNSC, LUSC, and SKCM was positively correlated with CD4+ T cell infiltration (with Partial correlation coefficients of 0.14, 0.22, 0.13, and 0.16, respectively, P<0.05). Being similar to the pattern of USP7 expression and ranked among top 100 protein sets, the top 5 proteins were C16orf72, BCLAF1, UBN, GSPT1, ERI2 (with Spearman correlation coefficients of 0.83, 0.74, 0.73, and 0.72, respectively, all P values<0.05). The top 50 protein sets that directly physically bind to USP7 overlapped with the aforementioned protein set by only one protein, thyroid hormone receptor interaction factor 12. KEGG enrichment analysis showed that USP7 related genes were involved in cell cycle, spliceosome, cell senescence, and p53 signal pathway. GO enrichment analysis showed that USP7 related genes were involved in transcriptional regulation, protein ubiquitination, DNA repair, and cytoplasmic pattern recognition receptor signal pathways. Analysis of clinical samples showed that USP7 expression was significantly higher in hypertrophic scars (0.35±0.05), scar ulcers (0.43±0.04), and scar cancers (0.61±0.03) than in normal skin (0.18±0.04), P<0.05. Conclusions: USP7 may be a clinical biomarker for the progression of cicatricial ulcer cancer.

[Treatment methods of upper limbs with destructive electric burns and its clinical efficacy].

Objective: To investigate the treatment methods of upper limbs with destructive electric burns and its clinical efficacy. Methods: A retrospective observational study was conducted. From July 2014 to December 2020, 20 male patients with destructive electric burns in upper limbs who met the inclusion criteria were admitted to Tongren Hospital of Wuhan University & Wuhan Third Hospital, aged from 21 to 57 years, of whom 7 patients underwent emergency surgery, and a total of 20 affected limbs were treated with limb salvage. The necrotic bone was resected in 5 affected limbs, the residual hand and wrist at the distal end of left affected limb was replanted to the residual end of the right forearm in one patient in a cross heterotopic way, and short reduction and replantation after osteotomy were performed for two affected limbs with distal ulnar and radial necrosis. After thorough debridement, the area of wound proposed to be repaired by tissue flap was from 12 cm×7 cm to 58 cm×13 cm. According to the size and distribution of wound, the wounds of 2 affected limbs were repaired by transplantation of pedicled latissimus dorsi myocutaneous flap and free groin flap with vascular anastomosis. The wounds of the remaining 17 affected limbs were repaired with the transplantation of free latissimus dorsi myocutaneous flap, anterolateral thigh flaps, and paraumbilical perforator flap, with 10 affected limbs with larger wounds being jointly transplanted with the groin flap or the paraumbilical perforator flap on the other side. The total grafted tissue flap area was 20 cm×8 cm to 52 cm×20 cm. During tissue flap transplantation, according to the length of blood vessel defect in the affected limb, the distal artery of the affected limb was bridged with the distal part of flap vascular pedicle, undamaged vein on the affected side, superficial vein of abdominal wall, and great saphenous vein, etc., in 14 affected limbs, and the great saphenous vein was grafted in 3 of them with impeded distal return for recanalization of distal limb veins. The wound in the donor area was repaired by direct suture or grafting with split-thickness scalp. After the wound was basically healed, the functional rehabilitation training was started gradually, and the functional reconstruction and scar rectification surgery were started 3 months after tissue flap transplantation. The survival of tissue flaps/skin grafts, wound healing, limb salvage, and follow-up status after surgery were recorded. At the last follow-up, the function of the successfully salvaged limb was evaluated and scored by the disabilities of the arm, shoulder and hand (DASH) scoring scale. Results: After surgery, the grafted tissue flap in the affected limb and the skin grafts transplanted on the wound at flap donor site survived, and wounds at the recipient and donor sites healed well. Two affected limbs had distal necrosis within 10 days after tissue flap transplantation, and the middle and upper forearms were amputated. The remaining 18 affected limbs were successfully salvaged (including shortened replantation and cross heterotopic replantation). During 6-48 months of follow-up, 5 affected limbs that were successfully salvaged developed aseptic dissolution of residual tendon and bone tissue 3 to 18 months after tissue flap transplantation, which gradually healed after surgical debridement combined with vacuum sealing drainage treatment. At the last follow-up, the stump of two affected limbs healed well after amputation; 18 affected limbs that were successfully salvaged all survived well, of which 8 affected limbs had good recovery of finger flexion and extension function and thumb opponensplasty and could complete daily activities independently, 9 affected limbs regained partial mobility and could complete daily activities such as dressing and eating with the assistance of the opposite upper limb or auxiliary devices, and one affected limb had no function. At the last follow-up, the functional scores of DASH scoring scale of the 18 affected limbs that were successfully salvaged ranged from 30.0 to 100. Conclusions: Timely surgical debridement, proper treatment of the injured bone tissue, effective vascular bridging for reconstruction of the distal artery of the affected limb, and the use of blood-rich tissue flap to repair the wound, combined with early rehabilitation and functional restoration treatment, are beneficial to salvage the upper limb with destructive electric burns and improve the function of the affected limb.

[A case with giant ulcer caused by skin diffuse large B-cell lymphoma in the axilla].

In May 16th, 2019, a male patient (aged 51 years) with a rare giant ulcer caused by skin diffuse large B-cell lymphoma in the axilla was admitted to Tongren Hospital of Wuhan University & Wuhan Third Hospital, and the ulcer wound was confirmed by biopsy and immunohistochemical analysis after extensive excision. Ultimately, a good prognosis was obtained by transplantation of flap and skin graft in combination with radiotherapy and chemotherapy.

[Recompensation of complications in patients with hepatitis B virus-related decompensated cirrhosis treated with entecavir antiviral therapy].

Objective: To analyze the occurrence of recompensation conditions in patients with chronic hepatitis B virus-related decompensated cirrhosis after entecavir antiviral therapy. Methods: Patients with hepatitis B virus-related decompensated cirrhosis with ascites as the initial manifestation were prospectively enrolled. Patients who received entecavir treatment for 120 weeks and were followed up every 24 weeks (including clinical endpoint events, hematological and imaging indicators, and others) were calculated for recompensation rates according to the Baveno VII criteria. Measurement data were compared using the Student t-test or Mann-Whitney U test between groups. Categorical data were compared by the χ (2) test or Fisher's exact probability method between groups. Results: 283 of the 320 enrolled cases completed the 120-week follow-up, and 92.2% (261/283) achieved a virological response (HBV DNA 20 IU/ml). Child-Pugh and MELD scores were significantly improved after treatment (8.33 ± 1.90 vs. 5.77 ± 1.37, t = 12.70, P < 0.001; 13.37 ± 4.44 vs. 10.45 ± 4.58, t = 5.963, P < 0.001). During the 120-week follow-up period, 14 cases died, two received liver transplants, 19 developed hepatocellular cancer, 11 developed gastroesophageal variceal bleeding, and four developed hepatic encephalopathy. 60.4% (171/283) (no decompensation events occurred for 12 months) and 56.2% (159/283) (no decompensation events occurred for 12 months and improved liver function) of the patients had achieved clinical recompensation within 120 weeks. Patients with baseline MELD scores > 15 after active antiviral therapy achieved higher recompensation than patients with baseline MELD scores ≤15 [50/74 (67.6%) vs. 109/209 (52.2%), χ (2) = 5.275, P = 0.029]. Conclusion: Antiviral therapy can significantly improve the prognosis of patients with hepatitis B virus-related decompensated cirrhosis. The majority of patients (56.2%) had achieved recompensation. Patients with severe disease did not have a lower probability of recompensation at baseline than other patients.

[Effects of macrophage glycolytic reprogramming on tuberculosis granuloma formation].

The formation of granulomatous lesions is a typical pathological feature of tuberculosis, and infection with Mycobacterium tuberculosis is the main cause. Although the mechanism underlying granuloma formation remains unclear, increasing evidence suggests that immune metabolism plays an important role. In this review, we summarized the latest advances in macrophage glycolytic reprogramming in tuberculosis granuloma formation to discover new methods for early diagnosis and provided new ideas for tuberculosis therapeutics based on the regulation of immune metabolism.

[Establishment of leukemia cell model with inducible AML1-ETO expression and its effect on fatty acid metabolism in leukemia cells].

Objective: To investigate the effect of the AML1-ETO (AE) fusion gene on the biological function of U937 leukemia cells by establishing a leukemia cell model that induces AE fusion gene expression. Methods: The doxycycline (Dox) -dependent expression of the AE fusion gene in the U937 cell line (U937-AE) were established using a lentivirus vector system. The Cell Counting Kit 8 methods, including the PI and sidanilide induction, were used to detect cell proliferation, cell cycle-induced differentiation assays, respectively. The effect of the AE fusion gene on the biological function of U937-AE cells was preliminarily explored using transcriptome sequencing and metabonomic sequencing. Results: ①The Dox-dependent Tet-on regulatory system was successfully constructed to regulate the stable AE fusion gene expression in U937-AE cells. ②Cell proliferation slowed down and the cell proliferation rate with AE expression (3.47±0.07) was lower than AE non-expression (3.86 ± 0.05) after inducing the AE fusion gene expression for 24 h (P<0.05). The proportion of cells in the G(0)/G(1) phase in the cell cycle increased, with AE expression [ (63.45±3.10) %) ] was higher than AE non-expression [ (41.36± 9.56) %] (P<0.05). The proportion of cells expressing CD13 and CD14 decreased with the expression of AE. The AE negative group is significantly higher than the AE positive group (P<0.05). ③The enrichment analysis of the transcriptome sequencing gene set revealed significantly enriched quiescence, nuclear factor kappa-light-chain-enhancer of activated B cells, interferon-α/γ, and other inflammatory response and immune regulation signals after AE expression. ④Disorder of fatty acid metabolism of U937-AE cells occurred under the influence of AE. The concentration of the medium and short-chain fatty acid acylcarnitine metabolites decreased in cells with AE expressing, propionyl L-carnitine, wherein those with AE expression (0.46±0.13) were lower than those with AE non-expression (1.00±0.27) (P<0.05). The metabolite concentration of some long-chain fatty acid acylcarnitine increased in cells with AE expressing tetradecanoyl carnitine, wherein those with AE expression (1.26±0.01) were higher than those with AE non-expression (1.00±0.05) (P<0.05) . Conclusion: This study successfully established a leukemia cell model that can induce AE expression. The AE expression blocked the cell cycle and inhibited cell differentiation. The gene sets related to the inflammatory reactions was significantly enriched in U937-AE cells that express AE, and fatty acid metabolism was disordered.

Influence of psychological intervention on patients undergoing spinal anesthesia: a randomized trial.

OBJECTIVE: The aim of this study is to evaluate the effects of positive intervention on the anxiety and the physiological and psychological aspects among preoperative and post-surgical patients with spinal anesthesia. PATIENTS AND METHODS: A randomized trial was conducted with an intervention group (n=58) and a control group (n=59). In the intervention group, the patients were well-informed of the details during spinal anesthesia. Multiple methods were performed to control anxiety before surgery, and nurses were not allowed to discuss the condition during surgery. Anesthesiologists were invited to visit patients to avoid excessive anxiety. RESULTS: The intervention group showed lower scores of State-Trait Anxiety Inventory (STAI) (p<0.05) than the control group 24 hours post-operation. Physiological indices such as systolic blood pressure, low frequency (LF) power, high frequency (HF) power and ration of LF/HF showed better surgery recovery (p<0.05) than the control group. The length of post-anesthesia care unit stay was also significantly shortened in the intervention group (p=0.001) compared with the control group. Positive intervention may alleviate the anxiety in surgical patients receiving spinal anesthesia and improve the physiological and psychological outcomes clinically. CONCLUSIONS: Our results provide evidence indicating that proper intervention can be promoted clinically to improve the satisfaction and quality of life of patients undergoing spinal anesthesia.

Bacterial antibiotic resistance among cancer inpatients in China: 2016-20.

BACKGROUND: The incidence of infections among cancer patients is as high as 23.2-33.2% in China. However, the lack of information and data on the number of antibiotics used by cancer patients is an obstacle to implementing antibiotic management plans. AIM: This study aimed to investigate bacterial infections and antibiotic resistance in Chinese cancer patients to provide a reference for the rational use of antibiotics. DESIGN: This was a 5-year retrospective study on the antibiotic resistance of cancer patients. METHODS: In this 5-year surveillance study, we collected bacterial and antibiotic resistance data from 20 provincial cancer diagnosis and treatment centers and three specialized cancer hospitals in China. We analyzed the resistance of common bacteria to antibiotics, compared to common clinical drug-resistant bacteria, evaluated the evolution of critical drug-resistant bacteria and conducted data analysis. FINDINGS: Between 2016 and 2020, 216 219 bacterial strains were clinically isolated. The resistance trend of Escherichia coli and Klebsiella pneumoniae to amikacin, ciprofloxacin, cefotaxime, piperacillin/tazobactam and imipenem was relatively stable and did not significantly increase over time. The resistance of Pseudomonas aeruginosa strains to all antibiotics tested, including imipenem and meropenem, decreased over time. In contrast, the resistance of Acinetobacter baumannii strains to carbapenems increased from 4.7% to 14.7%. Methicillin-resistant Staphylococcus aureus (MRSA) significantly decreased from 65.2% in 2016 to 48.9% in 2020. CONCLUSIONS: The bacterial prevalence and antibiotic resistance rates of E. coli, K. pneumoniae, P. aeruginosa, A. baumannii, S. aureus and MRSA were significantly lower than the national average.

Screening and validation for core genes in osteoarthritic cartilage based on weighted gene co-expression network analysis.

OBJECTIVE: Osteoarthritis (OA) has the highest disability rate among chronic diseases. The burden on patients and public health care resources is increasingly evident due to increasing obesity rates and aging populations. So, there is still a lack of early diagnosis and treatment for OA. MATERIALS AND METHODS: A total of three OA cartilage tissue datasets (GSE1919, GSE32317, and GSE5235) were obtained from the Gene Expression Omnibus (GEO) database. Screening of differentially expressed genes and WGCNA of overlapping genes were performed using the R language package. Functional and immune infiltration analyses of overlapping genes were also carried out while hub genes were screened through LASSO regression analysis method and ROC curve. Finally, experimental validation was carried out through PCR and Western Blot analysis of rat cartilage. RESULTS: A total of 149 differentially expressed genes were screened, and they were mainly enriched in the cytokine-cytokine receptor interaction, rheumatoid arthritis, and interleukin (IL-17) signaling pathways. Four co-expression modules were obtained, of which the blue module was the most substantial morbidity associated with OA. Thirteen overlapping genes were identified based on significant module network topology analysis and differential genes, upon which their validation through LASSO regression analysis method and ROC curve was performed. From these, five signature genes were determined, before three potential core genes were finally identified after confirmation using the validation set. CONCLUSIONS: ATF3, FOSL2, and GADD45B may be hub genes to the osteochondropathy, and they are expected to be new biomarkers and drug targets in OA research.

The Burden of Colorectal Cancer Attributable to Diet Low in Fiber from 1990 to 2019: A Global, Regional and National Analysis.

OBJECTIVES: The colorectal cancer (CRC) burden is increasingly high. The aim of this study was to investigate temporal and geographical trends in CRC deaths and disability-adjusted life-years (DALYs) attributable to diet low in fiber globally from 1990 to 2019. DESIGN: Cross-sectional study. SETTING: The study based on the Global Burden of Disease Study (GBD) 2019. PARTICIPANTS: The population comprised individuals from 204 countries and territories who were diagnosed with CRC attributable to diet low in fiber from 1990 to 2019. MEASUREMENTS: Deaths, DALYs, age-standardized mortality rates (ASMR), and age-standardized DALY rates (ASDR) for CRC attributable to diet low in fiber were described, and estimated annual percentage change (EAPC) was further calculated to assess the burden in different regions, countries, sexes, and age groups. Additionally, we explored the association between EAPC and ASMR/ASDR (in 1990) and Human Development Index (HDI, in 2019). RESULTS: From 1990 to 2019, global ASMR and ASDR for CRC attributable to diet low in fiber decreased slightly, but the corresponding deaths and DALYs increased by 63.37% and 51.36%, respectively. Those burden varied considerably between regions and countries. The burden was higher in high, high-middle and middle SDI regions, especially in Asia and Western Europe, but when HDI > 0.7, an increasingly rapid decline in ASMR and ASDR was revealed. Unexpectedly, many less well-developed countries within the traditionally low deaths and DALYs regions of Africa, Central Latin America, and Middle East showed gradual increases in ASMR and ASDR. CONCLUSION: The global burden of CRC attributable to diet low in fiber has decreased over the last 30 years, but remains at a high level. It is essential for decision-makers to take targeted measures for improving population awareness and intake of dietary fiber.

[Analysis of the development trend of burn discipline from the literature published in Chinese Journal of Burns in 22 years].

Objective: To analyze the literature published in Chinese Journal of Burns (now Chinese Journal of Burns and Wounds) in the last 22 years, and to explore the development trend of burn discipline. Methods: The relevant clinical and research literature published in Chinese Journal of Burns from January 1, 2000 to December 31, 2021 were retrieved through China National Knowledge Infrastructure database. Bibliometrics was used to classify and analyze the literature by research types, involved research fields, and reported causes of injury, and compare them every 3 years according to the year of publication (with literature published in 2021 being included in the last time period). Keywords of all the literature were retrieved, which were corrected and conversed later. CiteSpace 6.1.R2 software was used to visually cluster the included keywords, count high-frequency and high-centrality keywords, and divide the high-frequency keywords by time as before for segment comparison. Results: A total of 4 485 relevant papers were included, with an average of about 204 papers each year. The research types analysis of literature showed that clinical diagnosis and treatment literature had the highest proportion, reaching 65.3% (2 929/4 485), followed by cell experiment and animal experiment literature, accounting for 18.1% (812/4 485) and 13.2% (591/4 485), respectively. The proportion of various research types of the literature in each time period was basically stable. The analysis of the research fields involved in the literature showed that the literature in the field of systemic treatment of burns accounted for the highest proportion, reaching 60.2% (2 699/4 485), followed by the literature in the fields of acute wounds and plastic surgery, accounting for 20.2% (908/4 485) and 7.3% (326/4 485), respectively. The proportion of the literature in the field of systemic treatment of burns decreased from 84.0% (430/512) in 2000-2002 to 40.3% (373/926) in 2018-2021, with a decreasing proportion of 43.7%. While compared with that in 2000-2002, the proportions of literature in the fields of acute wounds, plastic surgery, chronic wounds, and burn rehabilitation were on the rise, with the proportions in 2018-2021 increased by 11.7%, 9.1%, 10.7%, and 5.5%, respectively. In the first 6 time periods, the number of literature in the field of discipline management was few and remained in single digits, but it increased to 49 in 2018-2021. Among the 1 099 literature in the field of systemic treatment of burns with a clear cause of injury, the literature on thermal burns was the most, accounting for 58.5% (643/1 099), followed by the literature on electrical burns and chemical burns, accounting for 19.8% (218/1 099) and 12.6% (138/1 099), respectively. The comparison by time period showed that the proportion of literature reporting thermal burns showed a significant downward trend, while the proportion of literature reporting other causes of injury did not change significantly. A total of 6 822 keywords from 2 236 literature were included for analysis. Visual cluster analysis showed that relevant studies focused on burns, surgical flaps, scars, and wound healing. The top 3 keywords in frequency were burns, wound healing, and surgical flaps, and the top 3 keywords in centrality were burns, scars, and skin transplantation. The comparison by time period showed that the only keyword with a stable frequency in the top 10 ranks was burns; with the passage of time, some keywords such as endotoxin/endotoxins and fibroblasts gradually dropped out of the top 10 ranks, while keywords such as wounds and injuries, surgical flaps, and negative-pressure wound therapy gradually entered the top 10 ranks. Conclusions: Among the literature published in Chinese Journal of Burns during the last 22 years, the literature on systemic treatment of burns and thermal burns has gradually decreased, while the literature on chronic wounds and burn rehabilitation has increased. Surgical flaps, wound healing, and scar prevention and treatment are the current research hot spots in burn discipline.

[MiR-744-5p inhibits the proliferation, invasion, and migration of clear-cell renal cell carcinoma cells by targeting CCND1].

OBJECTIVE: To explore the role of miR-744-5p/CCND1 axis in clear-cell renal cell carcinoma (ccRCC). METHODS: We examined the expression levels of miR-744-5p in 65 pairs of ccRCC and adjacent tissue specimens and in 5 ccRCC cell lines and human renal tubular epithelial (HK2) cells using qRT-PCR. The ccRCC cell lines 786-O and OSRC2 were transfected with miR-744-5p mimic, CCND1 mimic, or their negative control mimics, and the changes in cell proliferation, migration, and invasion were evaluated with CCK-8, wound healing, and Transwell assays. The downstream target molecules of miR-744-5p were predicted by bioinformatics analysis, and the expression level of CCND1 in ccRCC cells was verified by qRT-PCR and Western blotting. The relationship between miR-744-5p and CCND1 was further validated by dual luciferase reporter assay, and the role of the miR-744-5p/CCND1 axis in ccRCC was explored by rescue experiments. RESULTS: MiR-744-5p was significantly downregulated in ccRCC tissues and cell lines (all P < 0.05), and its overexpression inhibited the proliferation, migration, and invasion of ccRCC cells (all P < 0.05). Bioinformatics analysis and dual luciferase reporter assay showed that CCND1 was a downstream target of miR-744-5p. The results of rescue experiments showed that upregulation of CCND1 could partially reverse the inhibitory effect of miR-744-5p overexpression on ccRCC cell proliferation, migration, and invasion (all P < 0.05). CONCLUSION: MiR-744-5p inhibits the malignant phenotype of ccRCC cells by targeting CCND1, and the miR-744-5p/CCND1 axis may be a novel target for diagnosis and treatment of ccRCC.