An integrated approach of high-performance liquid chromatography-mass spectrometry-based chemical profiling, network pharmacology, and molecular docking to reveal the potential mechanisms of Qishen Gubiao granules for treating coronavirus disease 2019.

Qishen Gubiao granules, a traditional Chinese medicine preparation composed of nine herbs, have been widely used to prevent and treat coronavirus disease 2019 with good clinical efficacy. In the present study, an integrated strategy based on chemical profiling followed by network pharmacology and molecular docking was employed, to explore the active components and potential molecular mechanisms of Qishen Gubiao granules in the therapy of coronavirus disease 2019. Using the ultra-high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry technique, a total of 186 ingredients corresponding to eight structure types in Qishen Gubiao preparation were identified or structurally annotated with the elucidation of the fragmentation pathways in the typical compounds. The network pharmacology analysis screened 28 key compounds including quercetin, apigenin, scutellarein, luteolin and naringenin acting on 31 key targets, which possibly modulated signal pathways associated with immune and inflammatory responses in the treatment of coronavirus disease 2019. The molecular docking results observed that the top 5 core compounds had a high affinity for angiotensin-converting enzyme 2 and 3-chymotrypsin-like protease. This study proposed a reliable and feasible approach for elucidating the multi-components, multi-targets, and multi-pathways intervention mechanism of Qishen Gubiao granules against coronavirus disease 2019, providing a scientific basis for its further quality evaluation and clinical application.

Integrated analysis of comprehensive metabolomics and network pharmacology to reveal the mechanisms of abelmoschus manihot (L.) medik. in the treatment of cisplatin-induced chronic kidney disease.

Background: Abelmoschus manihot (L.) Medik ("Huangkui" in Chinese, HK) has been widely used for the treatment of kidney diseases. Nephrotoxicity is the side effect of cisplatin (CDDP), which greatly limits its clinical application. Therefore, CDDP could be used to establish the chronic kidney disease (CKD) model. However, the protective effects of HK on CDDP-induced CKD have not been investigated. Purpose: To explore the protective effect and underlying mechanisms of HK on multiple low-dose CDDP-induced CKD in rats by the integrated analysis of serum, kidney, and urine metabolomics and network pharmacology. Methods: The CKD model was induced by multiple low-dose CDDP. Body weight, organ index, serum biochemical, and kidney histology were examined to evaluate the effect of HK. Serum, kidney, and urine were collected and profiled by HILIC/RPLC-Q-TOF/MS-based metabolomics. Potential biomarkers (PBs) were screened according to the criteria of VIP >1, p < 0.01, and FC > 2, and then identified or assigned. The pathway analysis and PBs enrichment were conducted by MetaboAnalyst and ChemRICH. Furthermore, network pharmacology was adopted to dig out the active components and targets. Finally, the results from metabolomics and network pharmacology were integrated to confirm each other. Results: HK could recover the CDDP-induced abnormal pharmacological and metabolic profile changes. A total of 187 PBs were screened and identified from the serum, kidney, and urine metabolomics. Pathway analysis showed that multiple metabolic pathways, mainly related to amino acid and lipid metabolisms, were involved in the nephroprotective effect of HK, and especially, HK could significantly alleviate the disorder of tryptophan metabolism pathway in serum, kidney, and urine. Meanwhile, network pharmacology analysis revealed that 5 components in HK and 4 key genes could be responsible for the nephroprotection of HK, which also indicated that the metabolism of tryptophan played an important role in HK against CKD. Conclusion: HK has a nephroprotection on CDDP-induced CKD, mainly by restoring the dysregulation of tryptophan metabolism. Integrated analysis of serum, kidney, and urine metabolomics and network pharmacology was a powerful method for exploring pharmacological mechanisms and screening active components and targets of traditional Chinese medicine.

Prognostic data analysis of surgical treatments for intracerebral hemorrhage.

Spontaneous intracerebral hemorrhage (ICH) is a commonly occurring disease in neurosurgery, yet its surgical treatment is controversial. This paper pertains to the study of the effects of different treatment regimens on the outcome of ICH population. Based on a globally shared third-party MIMIC-III database, the researchers firstly described the dissimilarities in survival probability, mortality, and neurological recovery among mainstream treatments for ICH; secondly, patient classification was determined by important clinical features; and outcome variations among treatment groups were compared. The 28-day, 90-day, and in-hospital mortality in the craniotomy group were significantly lower than minimally invasive surgery (MIS) and non-surgical group patients; and, the medium/long-term mortality in MIS group was significantly lower than the non-surgical group. The craniotomy group positively correlated with short-term GCS recovery compared with the MIS group; no difference existed between the non-surgical and MIS groups. The craniotomy group 90-day survival probability and short-term GCS recovery were superior to the other two treatments in the subgroups of first GCS 3-12; this tendency also presented in the MIS group over non-surgical group. For milder patients (first GCS > 12), the three treatment regimens had a minimal effect on patient survival, but the non-surgical group showed an advantage in short-term GCS recovery. Craniotomy patients have a lower mortality and a better short-term neurological recovery in an ICH population, especially in short-to-medium term mortality and short-term neurological recovery over MIS patients. In addition, surgical treatment is recommendable for patients with a GCS ≤ 12.

Cerebrospinal fluid leak management in anterior basal skull fractures secondary to head trauma.

OBJECTIVE: To summarize the presentation, diagnosis, and management of cerebrospinal fluid (CSF) leaks in the setting of traumatic anterior skull base fracture. METHODS: Wide literature research has been performed as well as the authors' own clinical experience has been summarized. RESULTS: Articles from the most recent 30 years have been reviewed and a typical case of our own has been presented. Based on the most updated evidence, a treatment algorithm for CSF leaks has been proposed. CONCLUSION: Anterior skull base fracture accounts for about 4% of all head injuries and CSF leaks is a complication that commonly presents with clear fluid emanating from the nasal passage. A positive beta-2-transferrin study is highly specific for diagnosis, while thin-slice CT scanning and MRI cisternography are also useful tools. The majority of the CSF leaks tend to be resolved spontaneously, and conservative management is attempted first with or without the augmentation of a lumbar drain. Surgical management mainly includes open surgery and endoscopic surgery, which have their own pros and cons.

Unexpected BrdU inhibition on astrocyte-to-neuron conversion.

5-Bromo-2'-deoxyuridine (BrdU) is a halogenated pyrimidine that can be incorporated into newly synthesized DNA during the S phase of the cell cycle. BrdU is widely used in fate-mapping studies of embryonic and adult neurogenesis to identify newborn neurons, however side effects on neural stem cells and their progeny have been reported. In vivo astrocyte-to-neuron (AtN) conversion is a new approach for generating newborn neurons by directly converting endogenous astrocytes into neurons. The BrdU-labeling strategy has been used to trace astrocyte-converted neurons, but whether BrdU has any effect on the AtN conversion is unknown. Here, while conducting a NeuroD1-mediated AtN conversion study using BrdU to label dividing reactive astrocytes following ischemic injury, we accidentally discovered that BrdU inhibited AtN conversion. We initially found a gradual reduction in BrdU-labeled astrocytes during NeuroD1-mediated AtN conversion in the mouse cortex. Although most NeuroD1-infected astrocytes were converted into neurons, the number of BrdU-labeled neurons was surprisingly low. To exclude the possibility that this BrdU inhibition was caused by the ischemic injury, we conducted an in vitro AtN conversion study by overexpressing NeuroD1 in cultured cortical astrocytes in the presence or absence of BrdU. Surprisingly, we also found a significantly lower conversion rate and a smaller number of converted neurons in the BrdU-treated group compared with the untreated group. These results revealed an unexpected inhibitory effect of BrdU on AtN conversion, suggesting more caution is needed when using BrdU in AtN conversion studies and in data interpretation.

Open biopsy with posterior instrumentation followed by anterolateral approach for removal of an uncommon tumor in the cervical spine.

The conventional treatment for the resection of cervical spinal tumors comprises anterior, posterior, and combined surgical approaches. However, these approaches have certain limitations when tumors invade the vertebrae, vertebral artery, or spinal nerves. Herein, we report an interesting case where a 45-year-old patient was admitted for neck pain. An invasive cervical spinal tumor was discovered and approached in two stages: stage 1 was open biopsy with posterior instrumentation, which was followed by stage 2 with an anterolateral approach for definitive surgical resection. A series of preoperative tests including angiography as well as a balloon occlusion test of the vertebral artery facilitated stage 2 surgical planning for gross total resection of the tumor while minimizing surgical complications.

Early tracheostomy is associated with better prognosis in patients with brainstem hemorrhage.

Brainstem hemorrhage is presumed to be invariably associated with a poor prognosis in people with spontaneous hypertensive cerebral hemorrhage. The optimal timing of tracheostomy placement in brainstem hemorrhage patients, who generally require endotracheal intubation for airway protection, remains uncertain. Our research aim was to analyze the impact of early tracheostomy versus late tracheostomy on brainstem hemorrhage patients related outcomes and prognostic factors at 30 days. We identified early tracheostomy and how it could benefit the patients with brainstem hemorrhage and ameliorate the predictors of functional recovery at 30 days. Data on 136 patients with brainstem hemorrhage and Glasgow Coma Scale score ≤ 8, were retrospectively collected from 2012 to 2019. Patients were divided into the early tracheostomy group and the late tracheostomy group. Patients in the early tracheostomy group had a significantly lower neurosurgical intensive care unit stay (both overall and survival) compared with the late tracheostomy group (15.6 days vs. 19.0 days, P = 0.041, overall and 14.5 vs. 19.5 days, P = 0.023, survival). Also, the good outcomes (modified Rankin Score ≤ 3) were higher in the early tracheostomy group (P = 0.036). Multivariate analysis demonstrated that less hemorrhagic volume, high Glasgow Coma Scale score on admission, young age, and early tracheostomy were significantly associated with a better 30-day functional outcome. In conclusion, an early tracheostomy in patients with brainstem hemorrhage can reduce neurosurgical intensive care unit stay, and in addition to improvements in prognosis at 30 days.

Revision Surgery Technique in the Treatment of Refractory Subcutaneous Cerebrospinal Fluid Collection Combined with Intracranial Infection Following Posterior Fossa Surgery.

Objective Cerebrospinal fluid (CSF) leakage remains the most common and serious complication following posterior fossa surgery. Persistent subcutaneous CSF collections can cause wound dehiscence and predispose patients to intracranial infection. Management with conservative treatment fails in up to 40% of patients, and revision surgery remains the last resort. We hereby introduce a novel surgical technique using muscle graft or pedicled trapezius muscle flaps to repair dura and skull base defect for the treatment of subcutaneous CSF collections refractory to conservative management. Methods A retrospective chart review was conducted for six patients who presented to our institution from 2012 to 2020, with subcutaneous CSF collections following posterior fossa surgeries and had undergone revision surgeries after unsuccessful management with conservative treatments. Patient demographics, etiologies, culture results, revision procedures, follow-ups, and recurrences of fluid collections were collected. Results Of these six patients, two underwent repair of dura and skull base defect with pedicled trapezius muscle flaps, and four had arachnoid fistula repaired with autologous muscle graft. All six patients fully recovered. CSF leakage and subcutaneous fluid collections were resolved. No recurrences occurred upon the last follow-ups. Conclusion A revision surgery using muscle graft or pedicled trapezius muscle flaps to repair the dura and skull base defect is effective at treating persistent cerebrospinal fluid leakage and subcutaneous fluid collection refractory to conservative treatment.