GSDMD/Drp1 signaling pathway mediates hippocampal synaptic damage and neural oscillation abnormalities in a mouse model of sepsis-associated encephalopathy.

BACKGROUND: Gasdermin D (GSDMD)-mediated pyroptotic cell death is implicated in the pathogenesis of cognitive deficits in sepsis-associated encephalopathy (SAE), yet the underlying mechanisms remain largely unclear. Dynamin-related protein 1 (Drp1) facilitates mitochondrial fission and ensures quality control to maintain cellular homeostasis during infection. This study aimed to investigate the potential role of the GSDMD/Drp1 signaling pathway in cognitive impairments in a mouse model of SAE. METHODS: C57BL/6 male mice were subjected to cecal ligation and puncture (CLP) to establish an animal model of SAE. In the interventional study, mice were treated with the GSDMD inhibitor necrosulfonamide (NSA) or the Drp1 inhibitor mitochondrial division inhibitor-1 (Mdivi-1). Surviving mice underwent behavioral tests, and hippocampal tissues were harvested for histological analysis and biochemical assays at corresponding time points. Haematoxylin-eosin staining and TUNEL assays were used to evaluate neuronal damage. Golgi staining was used to detect synaptic dendritic spine density. Additionally, transmission electron microscopy was performed to assess mitochondrial and synaptic morphology in the hippocampus. Local field potential recordings were conducted to detect network oscillations in the hippocampus. RESULTS: CLP induced the activation of GSDMD, an upregulation of Drp1, leading to associated mitochondrial impairment, neuroinflammation, as well as neuronal and synaptic damage. Consequently, these effects resulted in a reduction in neural oscillations in the hippocampus and significant learning and memory deficits in the mice. Notably, treatment with NSA or Mdivi-1 effectively prevented these GSDMD-mediated abnormalities. CONCLUSIONS: Our data indicate that the GSDMD/Drp1 signaling pathway is involved in cognitive deficits in a mouse model of SAE. Inhibiting GSDMD or Drp1 emerges as a potential therapeutic strategy to alleviate the observed synaptic damages and network oscillations abnormalities in the hippocampus of SAE mice.

Long-term repetitive transcranial direct current stimulation in patients with disorders of consciousness: a preliminary study.

OBJECTIVES: To investigate the effects of long-term repetitive transcranial direct current stimulation on patients with DOC in the subacute phase. METHODS: In a randomized, double-blind, controlled study, 33 patients were randomly assigned to the active or sham group, and 28 patients completed the study. Patients in the active group received anodal stimulation over the DLPFC, while patients in the sham group received placebo stimulation (20 min/day, 5 days/week, for 4 weeks). The level of consciousness among patients was assessed with the Coma Recovery Scale-Revised (CRS-R) at baseline and at the end of every week from the first to the fourth week. RESULTS: The CRS-R scores of both the active and sham groups showed a consistent increasing trend over time; however, the treatment effect of the active group was better than that of the sham group. In addition, there was a statistically significant difference in the total CRS-R score between the two groups at weeks 1, 2, 3 and 4. Moreover, 10 patients (71.4%) in the active group and 3 patients (21.4%) in the sham group were regarded as responders. CONCLUSION: Long-term tDCS could improve the level of consciousness of patients with DOC in the subacute stage.

Efficiency and Safety of Baofei Granules in Chronic Obstructive Pulmonary Disease (Lung and Spleen Qi Deficiency Syndrome): A Multicenter, Randomized, Double-Blind, Placebo-Controlled Phase II Clinical Trial.

Background: Baofei Granules (BFGs) have been extensively applied in the clinical treatment of chronic obstructive pulmonary disease (COPD) and significantly have affected COPD patients with lung and spleen qi deficiency syndrome. However, the data from previous small-sample clinical trials are limited. This trial aimed to estimate the efficiency and safety of BFGs in COPD with lung and spleen qi deficiency syndrome. Methods: It is a multicenter, randomized, double-blind, placebo-controlled phase II clinical trial. The 216 stable COPD patients will be divided randomly in a ratio of 1:1. The whole trial period consists of a 4-week introductory period, a 52-week treatment period and a 48-week follow-up. Study visits occur every 4 weeks during the treatment period and every 12 weeks during the follow-up. All the subjects will receive 10g BFGs or placebo three times per day for 56 weeks and be followed up for 48 weeks. The primary efficiency evaluation outcome will be the frequency and duration of AECOPD, and the secondary efficiency evaluation outcome will be pulmonary function tests (PFTs), modified Medical Research Council (mMRC) dyspnoea scale, six-minute walking test (6MWT), COPD assessment test (CAT) score, traditional Chinese medicine (TCM) syndrome score, the frequency of emergency medication, BODE index, and the time to first Clinically important deterioration (CID). The safety evaluation outcomes will be adverse events (AEs), vital signs, physical examination, twelve-lead electrocardiogram (ECG), and laboratory examinations. All the data will be analyzed by SAS9.4. Discussion: This is the first and largest clinical trial that evaluates the efficiency and safety of BFGs for COPD with lung and spleen qi deficiency syndrome. It will provide valuable clinical evidence for recommendations on COPD management by the integrated TCM and western medicine. Trial Registration: CTR20211280. Date: June 09, 2021. http://www.chinadrugtrials.org.cn/clinicaltrials.searchlistdetail.dhtml?id=383a370ecd9f43d7af6f1c8585779e1a.

[Xingnao Kaiqiao acupuncture on promoting wake-up of vegetative state after brain injury].

OBJECTIVE: To observe the clinical effect of Xingnao Kaiqiao acupuncture on promoting wake-up of vegetative state after brain injury on the basis of comprehensive rehabilitation training. METHODS: A total of 100 patients with vegetative state after brain injury were randomly divided into an observation group (50 cases, 2 cases dropped off) and a control group (50 cases). Both groups were treated with routine clinical treatment. The patients in the control group were treated with rehabilitation and hyperbaric oxygen; on the basis of the control group treatment, the patients in the observation group were treated with Xingnao Kaiqiao acupuncture at Neiguan (PC 6), Shuigou (GV 26), Sanyinjiao (SP 6), Chize (LU 5), Weizhong (BL 40), Hegu (LI 4) and Taichong (LR 3). The acupuncture was given once a day, 5 days per week, for continuous 30 days. The Glasgow coma scale (GCS) and coma recovery scale-revised (CRS-R) scores were observed before treatment and 10, 20 and 30 days into treatment. The wake-up rate of the two groups was compared after treatment. RESULTS: On 10, 20 and 30 days into treatment, the GCS and CRS-R scores in the two groups were higher than those before treatment (P<0.01), and the scores in the observation group were higher than those in the control group (P<0.01). After treatment, the wake-up rate was 16.7% (8/48) in the observation group, which was higher than 12.0% (6/50) in the control group (P<0.01). CONCLUSION: On the basis of comprehensive rehabilitation and wake-up promotion therapy, the Xingnao Kaiqiao acupuncture could promote the recovery of consciousness level in patients with vegetative state after brain injury.

Experimental observation of the elastic range scaling in turbulent flow with polymer additives.

A minute amount of long-chain flexible polymer dissolved in a turbulent flow can drastically change flow properties, such as reducing the drag and enhancing mixing. One fundamental riddle is how these polymer additives interact with the eddies of different spatial scales existing in the turbulent flow and, in turn, alter the turbulence energy transfer. Here, we show how turbulent kinetic energy is transferred through different scales in the presence of the polymer additives. In particular, we observed experimentally the emerging of a previously unidentified scaling range, referred to as the elastic range, where increasing amount of energy is transferred by the elasticity of the polymers. In addition, the existence of the elastic range prescribes the scaling of high-order velocity statistics. Our findings have important implications to many turbulence systems, such as turbulence in plasmas or superfluids where interaction between turbulent eddies and other nonlinear physical mechanisms are often involved.

Early therapeutic interventions of traditional Chinese medicine in COVID-19 patients: A retrospective cohort study.

OBJECTIVE: To observe the early interventions of traditional Chinese Medicine (TCM) on the conversion time of nucleic acid in patients with coronavirus disease 2019 (COVID-19), and find possible underlying mechanisms of action. METHODS: A retrospective cohort study was conducted on 300 confirmed COVID-19 patients who were treated with TCM, at a designated hospital in China. The patients were categorized into three groups: TCM1, TCM2 and TCM3, who respectively received TCM interventions within 7, 8-14, and greater than 15 days of hospitalization. Different indicators such as the conversion time of pharyngeal swab nucleic acid, the conversion time of fecal nucleic acid, length of hospital stay, and inflammatory markers (leukocyte count, and lymphocyte count and percentage) were analyzed to observe the impact of early TCM interventions on these groups. RESULTS: The median conversion times of pharyngeal swab nucleic acid in the three groups were 5.5, 7 and 16 d (P < 0.001), with TCM1 and TCM2 being statistically different from TCM3 (P < 0.01). TCM1 (P < 0.05) and TCM3 (P < 0.01) were statistically different from TCM2. The median conversion times of fecal nucleic acid in the three groups were 7, 9 and 17 d (P < 0.001). Conversion times of fecal nucleic acid in TCM1 were statistically different from TCM3 and TCM2 (P < 0.01). The median lengths of hospital stay in the three groups were 13, 16 and 21 d (P < 0.001). TCM1 and TCM2 were statistically different from TCM3 (P < 0.01); TCM1 and TCM3 were statistically different from TCM2 (P < 0.01). Both leucocyte and lymphocyte counts increased gradually with an increase in the length of hospital stay in TCM1 group patients, with a statistically significant difference observed at each time point in the group (P < 0.001). Statistically significant differences in lymphocyte count and percentage in TCM2 (P < 0.001), and in leucocyte count (P = 0.043) and lymphocyte count (P = 0.038) in TCM3 were observed. The comparison among the three groups showed a statistically significant difference in lymphocyte percentage on the third day of admission (P = 0.044). CONCLUSION: In this study, it was observed that in COVID-19 patients treated with a combination of Chinese and Western medicines, TCM intervention earlier in the hospital stay correlated with faster conversion time of pharyngeal swab and fecal nucleic acid, as well as shorter length of hospital stay, thus helping promote faster recovery of the patient. The underlying mechanism of action may be related to improving inflammation in patients with COVID-19.

Effects of Tanreqing Capsule on the negative conversion time of nucleic acid in patients with COVID-19: A retrospective cohort study.

OBJECTIVE: Traditional Chinese medicine plays a significant role in the treatment of the pandemic of coronavirus disease 2019 (COVID-19). Tanreqing Capsule (TRQC) was used in the treatment of COVID-19 patients in the Shanghai Public Health Clinical Center. This study aimed to investigate the clinical efficacy of TRQC in the treatment of COVID-19. METHODS: A retrospective cohort study was conducted on 82 patients who had laboratory-confirmed mild and moderate COVID-19; patients were treated with TRQC in one designated hospital. The treatment and control groups consisted of 25 and 57 cases, respectively. The treatment group was given TRQC orally three times a day, three pills each time, in addition to conventional Western medicine treatments which were also administered to the control group. The clinical efficacy indicators, such as the negative conversion time of pharyngeal swab nucleic acid, the negative conversion time of fecal nucleic acid, the duration of negative conversion of pharyngeal-fecal nucleic acid, and the improvement in the level of immune indicators such as T-cell subsets (CD3, CD4 and CD45) were monitored. RESULTS: COVID-19 patients in the treatment group, compared to the control group, had a shorter negative conversion time of fecal nucleic acid (4 vs. 9 days, P = 0.047) and a shorter interval of negative conversion of pharyngeal-fecal nucleic acid (0 vs. 2 days, P = 0.042). The level of CD3+ T cells increased in the treatment group compared to the control group ([317.09 ± 274.39] vs. [175.02 ± 239.95] counts/µL, P = 0.030). No statistically significant differences were detected in the median improvement in levels of CD4+ T cells (173 vs. 107 counts/µL, P = 0.208) and CD45+ T cells (366 vs. 141 counts/µL, P = 0.117) between the treatment and control groups. CONCLUSION: Significant reductions in the negative conversion time of fecal nucleic acid and the duration of negative conversion of pharyngeal-fecal nucleic acid were identified in the treatment group as compared to the control group, illustrating the potential therapeutic benefits of using TRQC as a complement to conventional medicine in patients with mild and moderate COVID-19. The underlying mechanism may be related to the improved levels of the immune indicator CD3+ T cells.

[Midnight-noon ebb-flow acupuncture combined with rehabilitation therapy for severe craniocerebral trauma patients with vegetative state: a randomized controlled trial].

OBJECTIVE: To compare the clinical therapeutic effect of midnight-noon ebb-flow acupuncture combined with rehabilitation therapy and simple rehabilitation therapy in severe craniocerebral trauma patients with vegetative state. METHODS: A total of 100 patients were randomized into an observation group and a control group, 50 cases in each one. Basic treatment of medication, hyperbaric oxygen therapy and specialized nursing were given in both groups. In the control group, rehabilitation therapy was adopted for 30 min each time, once a day. On the basis of the control group, midnight-noon ebb-flow acupuncture was applied in the observation group, the needles were sustained for 30 min, once a day, 5 times a week. The treatment was for 30 days in both groups. Before treatment and after 10, 20, 30 days of treatment, scores of Glasgow coma scale (GCS) and coma recovery scale-revised (CRS-R) were observed, and the conscious rate after treatment was calculated in both groups. RESULTS: Compared before treatment, the GCS and CRS-R scores after 10, 20, 30 days of treatment were increased in both groups (P<0.01), and the scores in the observation group were superior to those in the control group (P<0.01). After treatment, the conscious rate was 20.0% (10/50) in the observation group, which was superior to 12.0% (6/50) in the control group (P<0.01). CONCLUSION: Midnight-noon ebb-flow acupuncture combined with rehabilitation therapy can effectively treat the severe craniocerebral trauma patients with vegetative state, improve the consciousness level, and have superior therapeutic effect compared with simple rehabilitation therapy.

Clinical efficacy and safety of limited internal fixation combined with external fixation for Pilon fracture: A systematic review and meta-analysis.

PURPOSE: To compare the clinical efficacy and complications of limited internal fixation combined with external fixation (LIFEF) and open reduction and internal fixation (ORIF) in the treatment of Pilon fracture. METHODS: We searched databases including Pubmed, Embase, Web of science, Cochrane Library and China Biology Medicine disc for the studies comparing clinical efficacy and complications of LIFEF and ORIF in the treatment of Pilon fracture. The clinical efficacy was evaluated by the rate of nonunion, malunion/delayed union and the excellent/good rate assessed by Mazur ankle score. The complications including infections and arthritis symptoms after surgery were also investigated. RESULTS: Nine trials including 498 pilon fractures of 494 patients were identified. The meta-analysis found no significant differences in nonunion rate (RR = 1.60, 95% CI: 0.66 to 3.86, p = 0.30), and the excellent/good rate (RR = 0.95, 95% CI: 0.86 to 1.04, p = 0.28) between LIFEF group and ORIF group. For assessment of infections, there were significant differences in the rate of deep infection (RR = 2.18, 95% CI: 1.34 to 3.55, p = 0.002), and the rate of arthritis (RR = 1.26, 95% CI: 1.03 to 1.53, p = 0.02) between LIFEF group and ORIF group. CONCLUSION: LIFEF has similar effect as ORIF in the treatment of pilon fractures, however, LIFEF group has significantly higher risk of complications than ORIF group does. So LIFEF is not recommended in the treatment of pilon fracture.

Application of stereotactic body radiation therapy to cancer liver metastasis.

As an accurate external beam irradiation method, stereotactic body radiotherapy (SBRT) has been increasingly used to deliver high dose in less fractions. The liver is one of the most common organs for cancer metastasis. Recently, there have been several trials applying SBRT to cancer liver metastasis and have proved to be effective and safe with local control (LC) rates ranging from 70% to 100% within one or two years and 2-year overall survival (OS) rates ranging from 30% to 38%. Many published studies indicate that SBRT for cancer liver metastasis results in good outcomes without severe toxicities. However, the validated contribution of SBRT to an improved progression-free survival is still missing and more randomized trials should be conducted.