Hepatic perivascular epithelioid cell tumors: The importance of preoperative diagnosis.

Accurate preoperative diagnosis is highly important for the treatment of perivascular epithelioid cell tumors (PEComas) because PEComas are mainly benign tumors and may not require surgical intervention. By analyzing the causes, properties and clinical manifestations of PEComas, we summarize the challenges and solutions in the diagnosis of PEComas.

Epidemiological and etiological characteristics of 1266 patients with severe acute respiratory infection in central China, 2018-2020: a retrospective survey.

BACKGROUND: Severe acute respiratory infection (SARI), a significant global health concern, imposes a substantial disease burden. In China, there is inadequate data concerning the monitoring of respiratory pathogens, particularly bacteria, among patients with SARI. Therefore, this study aims to delineate the demographic, epidemiological, and aetiological characteristics of hospitalised SARI patients in Central China between 2018 and 2020. METHODS: Eligible patients with SARI admitted to the First Affiliated Hospital of Zhengzhou University between 1 January 2018 and 31 December 2020 were included in this retrospective study. Within the first 24 h of admission, respiratory (including sputum, nasal/throat swabs, bronchoalveolar lavage fluid, thoracocentesis fluid, etc.), urine, and peripheral blood specimens were collected for viral and bacterial testing. A multiplex real-time polymerase chain reaction (PCR) diagnostic approach was used to identify human influenza virus, respiratory syncytial virus, parainfluenza virus, adenovirus, human bocavirus, human coronavirus, human metapneumovirus, and rhinovirus. Bacterial cultures of respiratory specimens were performed with a particular focus on pathogenic microorganisms, including S. pneumoniae, S. aureus, K. pneumoniae, P. aeruginosa, Strep A, H. influenzae, A. baumannii, and E. coli. In cases where bacterial culture results were negative, nucleic acid extraction was performed for PCR to assay for the above-mentioned eight bacteria, as well as L. pneumophila and M. pneumoniae. Additionally, urine specimens were exclusively used to detect Legionella antigens. Furthermore, epidemiological, demographic, and clinical data were obtained from electronic medical records. RESULTS: The study encompassed 1266 patients, with a mean age of 54 years, among whom 61.6% (780/1266) were males, 61.4% (778/1266) were farmers, and 88.8% (1124/1266) sought medical treatment in 2020. Moreover, 80.3% (1017/1266) were housed in general wards. The most common respiratory symptoms included fever (86.8%, 1122/1266) and cough (77.8%, 986/1266). Chest imaging anomalies were detected in 62.6% (792/1266) of cases, and 58.1% (736/1266) exhibited at least one respiratory pathogen, with 28.5% (361/1266) having multiple infections. Additionally, 95.7% (1212/1266) of the patients were from Henan Province, with the highest proportion (38.3%, 486/1266) falling in the 61-80 years age bracket, predominantly (79.8%, 1010/1266) seeking medical aid in summer and autumn. Bacterial detection rate (39.0%, 495/1266) was higher than viral detection rate (36.9%, 468/1266), with the primary pathogens being influenza virus (13.8%, 175/1266), K. pneumoniae (10.0%, 127/1266), S. pneumoniae (10.0%, 127/1266), adenovirus (8.2%, 105/1266), P. aeruginosa (8.2%, 105/1266), M. pneumoniae (7.8%, 100/1266), and respiratory syncytial virus (7.7%, 98/1266). During spring and winter, there was a significant prevalence of influenza virus and human coronavirus, contrasting with the dominance of parainfluenza viruses in summer and autumn. Respiratory syncytial virus and rhinovirus exhibited higher prevalence across spring, summer, and winter. P. aeruginosa, K. pneumoniae, and M. pneumoniae were identified at similar rates throughout all seasons without distinct spikes in prevalence. However, S. pneumoniae showed a distinctive pattern with a prevalence that doubled during summer and winter. Moreover, the positive detection rates of various other viruses and bacteria were lower, displaying a comparatively erratic prevalence trend. Among patients admitted to the intensive care unit, the predominant nosocomial bacteria were K. pneumoniae (17.2%, 43/249), A. baumannii (13.6%, 34/249), and P. aeruginosa (12.4%, 31/249). Conversely, in patients from general wards, predominant pathogens included influenza virus (14.8%, 151/1017), S. pneumoniae (10.4%, 106/1017), and adenovirus (9.3%, 95/1017). Additionally, paediatric patients exhibited significantly higher positive detection rates for influenza virus (23.9%, 11/46) and M. pneumoniae (32.6%, 15/46) compared to adults and the elderly. Furthermore, adenovirus (10.0%, 67/669) and rhinovirus (6.4%, 43/669) were the primary pathogens in adults, while K. pneumoniae (11.8%, 65/551) and A. baumannii (7.1%, 39/551) prevailed among the elderly, indicating significant differences among the three age groups. DISCUSSION: In Central China, among patients with SARI, the prevailing viruses included influenza virus, adenovirus, and respiratory syncytial virus. Among bacteria, K. pneumoniae, S. pneumoniae, P. aeruginosa, and M. pneumoniae were frequently identified, with multiple infections being very common. Additionally, there were substantial variations in the pathogen spectrum compositions concerning wards and age groups among patients. Consequently, this study holds promise in offering insights to the government for developing strategies aimed at preventing and managing respiratory infectious diseases effectively.

Clinical study of electroacupuncture on the recovery of gastrointestinal dysfunction after laparoscopic surgery for gastrointestinal cancer - study protocol for a randomized controlled trial.

BACKGROUND: Gastrointestinal dysfunction is one of the common complaints for patient post-surgery. Acupuncture has been employed to improve gastrointestinal function and sleeping quality and has confirmed clinical efficacy for emotional problems. This study aims to evaluate the clinical effect of electroacupuncture for postoperative rapid recovery. METHODS: This study design is a two-arm, parallel, double-blinded randomized controlled trial. 104 subjects, aged from 40 to 89 years old, diagnosed with gastrointestinal cancer undergoing laparoscopic surgery, will be divided into Interventional Group and Control Group. Patients of both groups receive perioperative care under the guidance of ERAS guidance. The Interventional Group receives electroacupuncture treatment starting from the first day post-surgery for a consecutive 5 days, whereas the Control Group receives placebo electroacupuncture treatment. The primary outcome will be the first flatus time whereas the secondary outcomes will be the first sign of borborygmus, recovery of defecation, laboratory tests and questionnaires including Self-rating anxiety scale, Ford Insomnia Response to Stress Test, TCM rating scale of Gastrointestinal symptoms and Gastrointestinal Symptoms Rating Scales. DISCUSSION: This study aims to provide timely intervention for post-laparoscopic patients with gastrointestinal tumour using the ERAS concept combined with electroacupuncture, observe the efficacy of this therapy in treating PGID, and contribute reliable scientific evidence for postoperative rapid recovery. TRIAL REGISTRATION: Chictr.org.cn Identifier: ChiCTR2300078710. Registered on 15th December 2023.

Effects of Dexmedetomidine on Cognitive Function, Oxidative Stress and Brain Protection in Patients Undergoing Craniocerebral Surgery.

BACKGROUND: The protective mechanism of dexmedetomidine on the brains of patients undergoing craniocerebral surgery remains unclear. The aim of this study was to examine the impact of dexmedetomidine on cognitive function, oxidative stress, and brain protection in such patients. METHODS: Fifty-four patients who underwent craniocerebral surgery at our hospital from January 2020 to June 2023 were retrospectively selected as study subjects. They were divided into two groups: the control group (n = 27) and the study group (n = 27), based on different auxiliary anesthesia protocols. Patients in the study group received dexmedetomidine before anesthesia induction, using a midline intravenous pump to assist anesthesia, while the control group received an equivalent amount of normal saline. The remaining anesthesia induction and maintenance protocols were consistent for both groups. Cognitive function was assessed using the Mini Mental State Examination (MMSE) before and 1 day after surgery for both groups. Oxidative stress indicators, including malondialdehyde (MDA), glutathione peroxidase (GSH-Px), and superoxide dismutase (SOD) levels in the serum of both groups, were measured using enzyme-linked immunosorbent assay (ELISA). Additionally, changes in postoperative brain injury indicators, namely neuron-specific enolase (NSE) and central nervous system-specific protein (S100ß), were detected and compared in the serum of both groups. Concurrently, postoperative adverse reactions were recorded for both groups. RESULTS: The MMSE scale scores of both groups of patients 24 hours after surgery were significantly lower than those before surgery. However, the MMSE scale scores of the study group patients were notably higher than those in the control group, with a statistically significant difference (p < 0.05). One hour after surgery, the serum levels of MDA, GSH-Px, and SOD in both groups of patients were significantly elevated compared to pre-surgery levels. Yet, the study group exhibited significantly lower levels of MDA, GSH-Px, and SOD in comparison to the control group, and these differences were statistically significant (p < 0.05). The serum levels of NSE and S100ß in both groups were markedly higher than preoperative levels 24 hours after surgery. However, the study group demonstrated significantly lower levels of serum NSE and S100ß compared to the control group, with a statistically significant difference (p < 0.05). The incidence of postoperative complications in the study group was 7.41% (2/27), indicating a decreasing trend compared to 18.52% (5/27) in the control group. However, this difference did not reach statistical significance (χ2 = 1.477, p = 0.224). CONCLUSION: Dexmedetomidine-assisted anesthesia in craniocerebral surgery can effectively enhance postoperative cognitive function, mitigate oxidative stress, and facilitate overall postoperative recovery for patients. The intervention exhibits a favorable safety profile with no reported serious adverse reactions, establishing it as a relatively safe and reliable approach.

[Tetramethylpyrazine regulates angiogenesis of endothelial cells in cerebral ischemic stroke injury via SIRT1/VEGFA signaling pathway].

This study aims to investigate whether tetramethylpyrazine(TMP) can stimulate angiogenesis in cerebral microvascular endothelial cells and alleviate cerebral ischemic stroke(CIS) and to explore the underlying mechanisms. In the animal study, adult Sprague-Dawley rats(n=15) were assigned into sham surgery(sham), middle cerebral artery occlusion/reperfusion(MCAO/R), and MCAO/R+TMP(intraperitoneal injection of 20 mg·kg~(-1)) groups. The neurological function was evaluated by the Z-Longa method. The cerebral infarction volume was detected by TTC staining. Enzyme-linked immunosorbent assay(ELISA) was employed to detect the expression of vascular endothelial growth factor(VEGF), angiopoietin(Ang), and platelet-derived growth factor(PDGF). Immunofluorescence staining was employed to detect Ki67 and the expression of vascular endothelial growth factor A(VEGFA) and slient information regulator 1(SIRT1). Western blot was employed to determine the expression levels of VEGFA, SIRT1, angiopoietin-2(Ang-2), and platelet-derived growth factor B(PDGFB). In the cell study, mouse brain-derived endothelial cells(Bend.3) were cultured, and the optimal concentration of TMP was determined. Then, VEGF, Ang, and PDGF were detected by ELISA after the addition of cabozantinib. Western blot was employed to measure the expression of VEGFA, Ang-2, and PDGFB. Immunofluorescence staining was used to detect CD31, CD34, and Ki67, and the proliferation, migration, and tube formation ability of Bend.3 cells were observed in vitro. Western blot and immunofluorescence staining were performed to measure the expression of SIRT1 and VEGFA after addition of the SIRT1-specific inhibitor selisistat(EX-527). The results showed that compared with the sham group, the MCAO/R group had severe neurological function damage, increased infarction volume, up-regulated expression of VEGF, VEGFA, Ang, Ang-2, PDGF, and PDGFB, and down-regulated expression of Ki67 and SIRT1(P<0.01). Compared with the MCAO/R group, the MCAO/R+TMP group presented alleviated neurological function damage, reduced infarction volume, and activated expression of VEGF, VEGFA, Ang, Ang-2, PDGF, PDGFB, Ki67, and SIRT1(P<0.01). The cell experiments showed that compared with the normal group, Bend.3 cells were activated by oxygen glucose deprivation/reoxygenation(OGD/R) treatment(P<0.05, P<0.01). Compared with the OGD/R group, the OGD/R+TMP group upregulated the expression levels of VEGF, VEGFA, Ang, Ang-2, PDGF, PDGFB, SIRT1, Ki67, CD31, and CD34, enhanced the angiogenic ability of Bend.3 cells without being inhibited by BMS or EX-527(P<0.05, P<0.01, P<0.001). The results suggest that TMP can activate the SIRT1/VEGFA signaling pathway to stimulate angiogenesis and alleviate CIS injury.

Tumor Microenvironment-Responsive Drug Delivery Based on Polymeric Micelles for Precision Cancer Therapy: Strategies and Prospects.

In clinical practice, drug therapy for cancer is still limited by its inefficiency and high toxicity. For precision therapy, various drug delivery systems, including polymeric micelles self-assembled from amphiphilic polymeric materials, have been developed to achieve tumor-targeting drug delivery. Considering the characteristics of the pathophysiological environment at the drug target site, the design, synthesis, or modification of environmentally responsive polymeric materials has become a crucial strategy for drug-targeted delivery. In comparison to the normal physiological environment, tumors possess a unique microenvironment, characterized by a low pH, high reactive oxygen species concentration, hypoxia, and distinct enzyme systems, providing various stimuli for the environmentally responsive design of polymeric micelles. Polymeric micelles with tumor microenvironment (TME)-responsive characteristics have shown significant improvement in precision therapy for cancer treatment. This review mainly outlines the most promising strategies available for exploiting the tumor microenvironment to construct internal stimulus-responsive drug delivery micelles that target tumors and achieve enhanced antitumor efficacy. In addition, the prospects of TME-responsive polymeric micelles for gene therapy and immunotherapy, the most popular current cancer treatments, are also discussed. TME-responsive drug delivery via polymeric micelles will be an efficient and robust approach for developing clinical cancer therapies in the future.

Pathogenic mycobacterium upregulates cholesterol 25-hydroxylase to promote granuloma development via foam cell formation.

Pathogenic mycobacteria orchestrate the complex cell populations known as granuloma that is the hallmark of tuberculosis. Foam cells, a lipid-rich cell-type, are considered critical for granuloma formation; however, the causative factor in foam cell formation remains unclear. Atherosclerosis is a chronic inflammatory disease characterized by the abundant accumulation of lipid-laden-macrophage-derived foam cells during which cholesterol 25-hydroxylase (CH25H) is crucial in foam cell formation. Here, we show that M. marinum (Mm), a relative of M. tuberculosis, induces foam cell formation, leading to granuloma development following CH25H upregulation. Moreover, the Mm-driven increase in CH25H expression is associated with the presence of phthiocerol dimycocerosate, a determinant for Mm virulence and integrity. CH25H-null mice showed decreased foam cell formation and attenuated pathology. Atorvastatin, a recommended first-line lipid-lowering drug, promoted the elimination of M. marinum and concomitantly reduced CH25H production. These results define a previously unknown role for CH25H in controlling macrophage-derived foam cell formation and Tuberculosis pathology.

Upregulation of vesicle-associated membrane protein 7 in breast cancer tissues.

BACKGROUND: Vesicle-associated membrane protein 7 (VAMP7) plays oncogenic roles in cancers. However, its clinical significance in breast cancer (BC) tissues remains unknown. OBJECTIVE: To elucidate the clinical implications of VAMP7, as well as its involvement in the tumor microenvironment and molecular pathways of breast cancer. METHODS: BC (n=100) and non-cancerous breast tissues (n= 100) were collected for an immunohistochemical experiment (1:200). The protein expression level of VAMP7 was determined by using a semi-quantitative scoring method. High-throughput RNA-sequencing data of BC tissues were analyzed to confirm the mRNA expression trend of VAMP7. Additionally, the largest BC prognosis cohort data were collected to mine the potential impact VAMP7 has on BC progression. The association between VAMP7 and the microenvironment of BC was evaluated by using a CIBERSORT algorithm. Moreover, we explored the co-expressed molecular mechanisms of VAMP7 in BC by calculating Pearson correlation coefficients and overexpressed genes. Finally, the biological mechanism underlying the relationship between VAMP7 and the key pathways was also explored using gene set enrichment analysis (GSEA). Potential therapeutic strategies were predicted targeting VAMP7. RESULTS: VAMP7 protein was significantly over-expressed in BC tissue than that in controls (p< 0.001). Compared with 459 normal breast tissues and 113 non-cancerous breast tissues, the expression level of VAMP7 mRNA was significantly increased in 1111 BC tissues. CD4+T cells, macrophages, and naïve B cells had a higher infiltration rate in BC tissues with high VAMP7 expression, while regulatory T cells and CD8+T cells had a lower infiltration rate. Over-expressed VAMP7 was associated with macrophages activation and transition from M1 to M2 polarization. Upregulated VAMP7 could predicted poorer OS, DMFS, PPS, and RFS outcomes. Upregulated VAMP7 co-expressed genes were significantly enriched in the cell cycle checkpoints. GSEA confirmed that over-expressed VAMP7 are markedly associated with functional enrichment in cell cycle related categories, including mitotic spindle, G2M checkpoint, and E2F targets. KU-55933 was predicted as a putative therapeutic drug for BC targeting VAMP7. CONCLUSIONS: VAMP7 was upregulated in BC tissue and correlated with poor prognosis of BC patients. VAMP7 may promote BC progression by targeting the cell cycle pathway.

Effect and Safety of Herbal Medicine Foot Baths in Patients with Diabetic Peripheral Neuropathy: A Multicenter Double-Blind Randomized Controlled Trial.

OBJECTIVE: To evaluate the effect and safety of foot baths with Tangbi Waixi Decoction (TW) in treating patients with diabetic peripheral neuropathy (DPN). METHODS: It is a multicenter double-blinded randomized controlled trial. Participants with DPN were recruited between November 18, 2016 and May 30, 2018 from 8 hospitals in China. All patients received basic treatments for glycemic management. Patients received foot baths with TW herbal granules either 66.9 g (intervention group) or 6.69 g (control group) for 30 min once a day for 2 weeks and followed by a 2-week rest, as a therapeutic course. If the Toronto Clinical Scoring System total score (TCSS-TS) ⩾6 points, the patients received a total of 3 therapeutic courses (for 12 weeks) and were followed up for 12 weeks. The primary outcome was change in TCSS-TS score at 12 and 24 weeks. Secondary outcomes included changes in bilateral motor nerve conduction velocity (MNCV) and sensory nerve conduction velocity (SNCV) of the median and common peroneal nerve. Safety was also assessed. RESULTS: Totally 632 patients were enrolled, and 317 and 315 were randomized to the intervention and control groups, respectively. After the 12-week intervention, patients in both groups showed significant declines in TCSSTS scores, and significant increases in MNCV and SNCV of the median and common peroneal nerves compared with pre-treatment (P<0.05). The reduction of TCSS-TS score at 12 weeks and the increase of SNCV of median nerve at 24 weeks in the control group were greater than those in the intervention group (P<0.05). The number of adverse events did not differ significantly between groups (P>0.05), and no serious adverse event was related with treatment. CONCLUSION: Treatment of TW foot baths was safe and significantly benefitted patients with DPN. A low dose of TW appeared to be more effective than a high dose. (Registry No. ChiCTR-IOR-16009331).

Efficacy of Warm Acupuncture Therapy Combined with Kegel Exercise on Postpartum Pelvic Floor Dysfunction in Women.

INTRODUCTION AND HYPOTHESIS: The objective was to observe the clinical efficacy of warm acupuncture combined with Kegel exercise in treating postpartum pelvic floor dysfunction in women. METHODS: A total of 70 primiparous women with postpartum pelvic floor muscle (PFM) injury were randomly divided into a combination group (n = 35, receiving warm acupuncture at Zhibian (BL54) acupoint and Kegel exercise) and a sham control group (n = 35, receiving sham warm acupuncture and Kegel exercise). Both groups were treated three times a week for 4 consecutive weeks. The recovery of PFM strength and changes in Urethral Rotation Angle (URA), Bladder Neck Descent (BND), and Retrovesical Angle (RVA) in pelvic floor ultrasound reports, the scores of pelvic floor dysfunction-related questionnaires, and the efficacy of urinary incontinence treatment of the two groups were compared before and after treatment. RESULTS: After treatment, the recovery rates of type I and II PFM strength, pelvic floor ultrasound parameters, pelvic floor dysfunction-related scale scores, and urinary incontinence treatment efficacy in the combination group were significantly better than those in the sham control group (p < 0.05). CONCLUSION: Warm acupuncture combined with Kegel exercise can significantly improve PFM strength and promote the recovery of postpartum pelvic floor function in women.

Comparison of robotic versus thoracoscopic repair for congenital esophageal atresia: a propensity score matching analysis.

BACKGROUND: Despite the rapid advancement of robotic surgery across various surgical domains, only cases of robotic repair (RR) for neonates with esophageal atresia (EA) have been reported. Comprehensive studies comparing RR and thoracoscopic repair (TR) are lacking. The authors aimed to compare the safety and efficacy of RR and TR for EA. METHODS: A retrospective multicenter study was conducted on 155 EA neonates undergoing RR (79 patients) or TR (76 patients) between August 2020 and February 2023 using propensity score matching. Asymmetric port distribution and step-trocar insertion techniques were applied during RR. Demographics and surgical outcomes were compared. RESULTS: After matching, 63 patients (out of 79) in RR group and 63 patients (out of 76) in TR group were included. There were no significant differences in short-term outcomes between two groups, except for longer total operative time (173.81 vs. 160.54 min; P <0.001) and shorter anastomotic time (29.52 vs. 40.21 min; P <0.001) in RR group. Compared with TR group, the RR group had older age at surgery (8.00 vs. 3.00 days; P <0.001), but a comparable pneumonia rate. More importantly, the incidence of anastomotic leakage (4.76 vs. 19.05%, P =0.013), anastomotic stricture (15.87 vs. 31.74%, P =0.036) within 1 year postoperatively, and unplanned readmission (32.26 vs. 60.00%, P =0.030) within 2 years postoperatively were lower in RR group than in TR group. CONCLUSIONS: RR is a technically safe and effective option for EA patients. This approach delays the age of surgery without increasing respiratory complication rates while reducing the incidence of postoperative anastomotic complications and unplanned readmission.

Tauroursodeoxycholic acid protects Schwann cells from high glucose-induced cytotoxicity by targeting NLRP3 to regulate cell migration and pyroptosis.

Diabetic peripheral neuropathy (DPN) is the most prevalent complication of type 2 diabetes mellitus (T2DM), and it seriously affects the quality of life of patients. Tauroursodeoxycholic acid (TUDCA) is a bile acid that plays a protective role against various diseases. However, the function of TUDCA in DPN progression needs to be elucidated. Hence, this study clarified the action of TUDCA on DPN development and explored its mechanism of action. Fecal samples were collected from 50 patients with T2DM or DPN. Schwann cells induced by high levels were constructed to simulate an uncontrolled diabetic state. Cell viability and migration were measured using the CCK-8 and wound-healing assays, respectively. Reactive oxygen species and pyroptosis were detected using flow cytometry. Parabacteroides goldsteinii and Parabacteroides distasonis levels were decreased in the feces of patients with DPN. TUDCA enhanced the viability and migration ability of high glucose-stimulated Schwann cells. In addition, Schwann cell pyroptosis stimulated by high glucose levels was inhibited by TUDCA. Furthermore, the protective roles of TUDCA in cell viability, migration ability, and pyroptosis of Schwann cells stimulated by high glucose were suppressed by the overexpression of NLRP3. TUDCA enhanced cell viability and migration and suppressed pyroptosis in Schwann cells stimulated by high glucose levels by modulating NLRP3 expression. Thus, TUDCA may be a promising drug for DPN therapy.

Development and validation of a sensitive UPLC-MS/MS analytical method for GFH009 in rat plasma and its application to toxicokinetics studies.

GFH009 is a potent, highly selective, small molecule that targets and inhibits the activity of the CDK9/cyclin T1 regulatory complex of P-TEFb. This study aimed to develop and validate a highly selective and sensitive ultrahigh-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method for precise quantification of GFH009 in rat plasma. This method was subsequently employed for conducting toxicokinetic studies of GFH009 in rats. Plasma was prepared using a simple protein precipitation method by acetonitrile. Chromatographic separation of the analytes was achieved on a BEH C18 analytical column with a rapid 3.0 min run time and a flow rate of 0.5 ml/min. The calibration curves for plasma samples exhibited excellent linearity over a wide concentration range of 1.0-1,000 ng/ml for GFH009. Intra- and inter-day accuracies were within 92.7-105.7%, and precisions were no more than 6.7%. Furthermore, the analyte demonstrated stability under four different storage conditions, with variations of <15.0%. This study pioneers a methodological innovation by introducing a highly reliable, specific and sensitive analytical method for GFH009 in rat plasma. The successful application of this method in toxicokinetic studies further underscores its significance, offering valuable insights for the methodology of clinical pharmacokinetic research.

Effects of Dexmedetomidine on Cognitive Function, Oxidative Stress and Brain Protection in Patients Undergoing Craniocerebral Surgery

Background: The protective mechanism of dexmedetomidine on the brains of patients undergoing craniocerebral surgery remains unclear. The aim of this study was to examine the impact of dexmedetomidine on cognitive function, oxidative stress, and brain protection in such patients. Methods: Fifty-four patients who underwent craniocerebral surgery at our hospital from January 2020 to June 2023 were retrospectively selected as study subjects. They were divided into two groups: the control group (n = 27) and the study group (n = 27), based on different auxiliary anesthesia protocols. Patients in the study group received dexmedetomidine before anesthesia induction, using a midline intravenous pump to assist anesthesia, while the control group received an equivalent amount of normal saline. The remaining anesthesia induction and maintenance protocols were consistent for both groups. Cognitive function was assessed using the Mini Mental State Examination (MMSE) before and 1 day after surgery for both groups. Oxidative stress indicators, including malondialdehyde (MDA), glutathione peroxidase (GSH-Px), and superoxide dismutase (SOD) levels in the serum of both groups, were measured using enzyme-linked immunosorbent assay (ELISA). Additionally, changes in postoperative brain injury indicators, namely neuron-specific enolase (NSE) and central nervous system-specific protein (S100β), were detected and compared in the serum of both groups. Concurrently, postoperative adverse reactions were recorded for both groups. Results: The MMSE scale scores of both groups of patients 24 hours after surgery were significantly lower than those before surgery. However, the MMSE scale scores of the study group patients were notably higher than those in the control group, with a statistically significant difference (p < 0.05). One hour after surgery, the serum levels of MDA, GSH-Px, and SOD in both groups of patients were significantly elevated compared to pre-surgery levels. ... (AU)

Clinical study of standard residual liver volume and transient elastography in predicting poor prognosis of patients after hemihepatectomy.

BACKGROUND: Liver cancer resection, especially in patients with hemihepatectomy or extended hemihepatectomy, often leads to poor prognosis, such as liver insufficiency and even liver failure and death, because the standard residual liver volume (SRLV) cannot be fully compensated after surgery. AIM: To explore the risk factors of poor prognosis after hemihepatectomy for hepatocellular carcinoma and evaluate the application value of related prognostic approaches. METHODS: The clinical data of 35 patients with primary liver cancer in Nantong Third People's Hospital from February 2016 to July 2020 were retrospectively analyzed. The receiver operating characteristic curve was created using medcac19.0.4 to compare the critical values of the SRLV in different stages of liver fibrosis after hemihepatectomy with those of liver dysfunction after hemihepatectomy. It was constructed by combining the Child-Pugh score to evaluate its application value in predicting liver function compensation. RESULTS: The liver stiffness measure (LSM) value and SRLV were associated with liver dysfunction after hemihepatectomy. Logistic regression analysis showed that an LSM value ≥ 25 kPa [odds ratio (OR) = 6.254, P < 0.05] and SRLV ≤ 0.290 L/m2 (OR = 5.686, P < 0.05) were independent risk factors for postoperative liver dysfunction. The accuracy of the new liver reserve evaluation model for predicting postoperative liver function was higher than that of the Child-Pugh score (P < 0.05). CONCLUSION: SRLV and LSM values can be used to evaluate the safety of hemihepatectomy. The new liver reserve evaluation model has good application potential in the evaluation of liver reserve function after hemihepatectomy.

Clinical study of NFNC in the treatment of acute exacerbation chronic obstructive pulmonary disease patients with respiratory failure.

BACKGROUND: Most patients with acute exacerbation chronic obstructive pulmonary disease (AECOPD) have respiratory failure that necessitates active correction and the improvement of oxygenation is particularly important during treatment. High flow nasal cannula (HFNC) oxygen therapy is a non-invasive respiratory aid that is widely used in the clinic that improves oxygenation state, reduces dead space ventilation and breathing effort, protects the loss of cilia in the airways, and improves patient comfort. AIM: To compare HFNC and non-invasive positive pressure ventilation in the treatment of patients with AECOPD. METHODS: Eighty AECOPD patients were included in the study. The patients were in the intensive care department of our hospital from October 2019 to October 2021. The patients were divided into the control and treatment groups according to the different treatment methods with 40 patients in each group. Differences in patient comfort, blood gas analysis and infection indices were analyzed between the two groups. RESULTS: After treatment, symptoms including nasal, throat and chest discomfort were significantly lower in the treatment group compared to the control group on the 3rd and 5th days (P < 0.05). Before treatment, the PaO2, PaO2/FiO2, PaCO2, and SaO2 in the two groups of patients were not significantly different (P > 0.05). After treatment, the same indicators were significantly improved in both patient groups but had improved more in the treatment group compared to the control group (P < 0.05). After treatment, the white blood cell count, and the levels of C-reactive protein and calcitonin in patients in the treatment group were significantly higher compared to patients in the control group (P < 0.05). CONCLUSION: HFNC treatment can improve the ventilation of AECOPD patients whilst also improving patient comfort, and reducing complications. HFNC is a clinically valuable technique for the treatment of AECOPD.

Establishing chromosomal design-build-test-learn through a synthetic chromosome and its combinatorial reconfiguration.

Chromosome-level design-build-test-learn cycles (chrDBTLs) allow systematic combinatorial reconfiguration of chromosomes with ease. Here, we established chrDBTL with a redesigned synthetic Saccharomyces cerevisiae chromosome XV, synXV. We designed and built synXV to harbor strategically inserted features, modified elements, and synonymously recoded genes throughout the chromosome. Based on the recoded chromosome, we developed a method to enable chrDBTL: CRISPR-Cas9-mediated mitotic recombination with endoreduplication (CRIMiRE). CRIMiRE allowed the creation of customized wild-type/synthetic combinations, accelerating genotype-phenotype mapping and synthetic chromosome redesign. We also leveraged synXV as a "build-to-learn" model organism for translation studies by ribosome profiling. We conducted a locus-to-locus comparison of ribosome occupancy between synXV and the wild-type chromosome, providing insight into the effects of codon changes and redesigned features on translation dynamics in vivo. Overall, we established synXV as a versatile reconfigurable system that advances chrDBTL for understanding biological mechanisms and engineering strains.

Short- and long-term results of open vs laparoscopic multisegmental resection and anastomosis for synchronous colorectal cancer located in separate segments.

BACKGROUND: It remains unclear whether laparoscopic multisegmental resection and anastomosis (LMRA) is safe and advantageous over traditional open multisegmental resection and anastomosis (OMRA) for treating synchronous colorectal cancer (SCRC) located in separate segments. AIM: To compare the short-term efficacy and long-term prognosis of OMRA as well as LMRA for SCRC located in separate segments. METHODS: Patients with SCRC who underwent surgery between January 2010 and December 2021 at the Cancer Hospital, Chinese Academy of Medical Sciences and the Peking University First Hospital were retrospectively recruited. In accordance with the inclusion and exclusion criteria, 109 patients who received right hemicolectomy together with anterior resection of the rectum or right hemicolectomy and sigmoid colectomy were finally included in the study. Patients were divided into the LMRA and OMRA groups (n = 68 and 41, respectively) according to the surgical method used. The groups were compared regarding the surgical procedure's short-term efficacy and its effect on long-term patient survival. RESULTS: LMRA patients showed markedly less intraoperative blood loss than OMRA patients (100 vs 200 mL, P = 0.006). Compared to OMRA patients, LMRA patients exhibited markedly shorter postoperative first exhaust time (2 vs 3 d, P = 0.001), postoperative first fluid intake time (3 vs 4 d, P = 0.012), and postoperative hospital stay (9 vs 12 d, P = 0.002). The incidence of total postoperative complications (Clavien-Dindo grade: ≥ II) was 2.9% and 17.1% (P = 0.025) in the LMRA and OMRA groups, respectively, while the incidence of anastomotic leakage was 2.9% and 7.3% (P = 0.558) in the LMRA and OMRA groups, respectively. Furthermore, the LMRA group had a higher mean number of lymph nodes dissected than the OMRA group (45.2 vs 37.3, P = 0.020). The 5-year overall survival (OS) and disease-free survival (DFS) rates in OMRA patients were 82.9% and 78.3%, respectively, while these rates in LMRA patients were 78.2% and 72.8%, respectively. Multivariate prognostic analysis revealed that N stage [OS: HR hazard ratio (HR) = 10.161, P = 0.026; DFS: HR = 13.017, P = 0.013], but not the surgical method (LMRA/OMRA) (OS: HR = 0.834, P = 0.749; DFS: HR = 0.812, P = 0.712), was the independent influencing factor in the OS and DFS of patients with SCRC. CONCLUSION: LMRA is safe and feasible for patients with SCRC located in separate segments. Compared to OMRA, the LMRA approach has more advantages related to short-term efficacy.

Hydroxyfasudil regulates immune balance and suppresses inflammatory responses in the treatment of experimental autoimmune encephalomyelitis.

Multiple sclerosis (MS) is a central nervous system (CNS) disease with complicated etiology. Multifocal demyelination and invasion of inflammatory cells are its primary pathological features. Fasudil has been confirmed to improve experimental autoimmune encephalomyelitis (EAE), an animal model of MS. However, Fasudil is accompanied by several shortcomings in the clinical practice. Hydroxyfasudil is a metabolite of Fasudil in the body with better pharmaceutical properties. Therefore, we attempted to study the influence of Hydroxyfasudil upon EAE mice. The results demonstrated that Hydroxyfasudil relieved the symptoms of EAE and the associated pathological damage, reduced the adhesion molecules and chemokines, decreased the invasion of peripheral immune cells. Simultaneously, Hydroxyfasudil modified the rebalance of peripheral T cells. Moreover, Hydroxyfasudil shifted the M1 phenotype to M2 polarization, inhibited inflammatory signaling cascades as well as inflammatory factors, and promoted anti-inflammatory factors in the CNS. In the end, mice in the Hydroxyfasudil group expressed more tight junction proteins, indirectly indicating that the blood-brain barrier (BBB) was protected. Our results indicate that Hydroxyfasudil may be a prospective treatment for MS.