Natural products (NPs) are an important source of new drugs for the treatment of stroke. Identifying cellular targets for bioactive molecules is a major challenge and critical issue in the development of new drugs for stroke. Small-molecule probes play a unique role in target discovery. However, drawbacks to these probes include non-specificity, unstable activity, and difficulty in synthesis. Small-molecule probes based on NPs at least partially compensate for these shortcomings. NPs feature rich chemical and structural diversity, biocompatibility, and unique biological activities. These features could be exploited to provide new ideas and tools for target discovery. Small-molecule probes based on NPs provide a precise and direct search for interacting protein targets of NPs-active small molecules. This review explores the properties of small-molecule probes based on NPs and their applications in mechanistic studies of stroke and other diseases. We hope that this review will bring new perspectives to the mechanistic study of NPs-active small molecules and accelerate the translation of these ingredients into drug candidates for the treatment of stroke.

ObjectiveTo observe the effect of bilateral sequential repetitive transcranial magnetic stimulation on the motor function of upper limbs in stroke patients. MethodsFrom December, 2020 to December, 2022, 62 stroke inpatients in the Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine were included. They were randomly divided into control group (n = 31) and observation group (n = 31). Both groups accepted conventional medicine and rehabilitation, as well as electroacupuncture antagonistic muscle therapy. Before electroacupuncture, the observation group acceped low-frequency repetitive transcranial magnetic stimulation at primary motor cortex (M1) on the healthy side, followed by intermittent theta burst stimulation at M1 on the affected side, for four weeks. They were assessed with Fugl-Meyer Assessment-Upper Extremities (FMA-UE), modified Barthel Index (MBI) and modified Ashworth Scale (MAS), and motor evoked potential (MEP) latency was compared before and after treatment. ResultsOne patient dropped down in the observation group, and no adverse event happened. After treatment, the scores of FMA-UE and MBI significantly increased (|t| > 9.953, P < 0.001), and the score of MAS and the latency of MEP significantly decreased (|t| > 5.043, P < 0.001) in both groups; while all of them were better in the observation group than in the control group (|t| > 2.237, P < 0.05). ConclusionBilateral sequential repetitive transcranial magnetic stimulation can effectively promote the recovery of upper limb motor function in stroke patients.

ObjectiveTo explore the current status, hot spots and development of researches on post-stroke dysphagia in recent five years with visualization analysis. MethodsResearches on post-stroke dysphagia were retrieved from Web of Science Core Collection, from January 1st, 2017 to December 31st, 2021, and reviewed with CiteSpace 5.7.R5 software. ResultsA total of 857 articles were included. The annual number of articles increased with time, published from 61 countries/regions, by 211 institutions and 247 authors. The United States, Japan and China were the most prolific countries, and the University of Manchester was the leading institution. The top three authors were Dziewas R, Wakabayashi H and Hamdy S. The keywords bursting in recent three years included prediction, severity, percutaneous endoscopic gastrostomy, accuracy and early management; co-word clustering showed that researches might be mainly about neuromuscular electrical stimulation, swallowing screening, stroke-associated pneumonia, evidence-based practice, etc. ConclusionThe researches in the field of post-stroke dysphagia have been increasing.

Objective:To compare the therapeutic effect of fluid resuscitation strategy guided by pulse-indicated continuous cardiac output (PiCCO) monitoring and early goal-directed therapy (EGDT) on renal function of acute kidney injury (AKI) patients caused by septic shock.Methods:Septic shock patients with AKI admitted to the intensive care unit (ICU) of Tianjin Fifth Central Hospital and Teda International Cardiovascular Hospital from March 2017 to February 2020 were enrolled. All patients were given fluid resuscitation. Patients were divided into PiCCO-guided fluid resuscitation group [PiCCO group, intrathoracic blood volume index (ITBVI) was maintained between 850-1 000 mL/m 2] and EGDT-guided fluid resuscitation group [EGDT group, central venous pressure (CVP) was maintained between 8-12 mmHg (1 mmHg = 0.133 kPa) or CVP ≤ 15 mmHg when patients received mechanical ventilation (MV)] according to both the patient's condition and the informed consent of the patient's family. The changes of heart rate (HR), mean arterial pressure (MAP), CVP, blood lactic acid (Lac), fluid balance, urine volume and serum creatinine (SCr) at 6, 24, and 48 hours after fluid resuscitation in the two groups were observed, and the renal replacement therapy (RRT), duration of MV, length of ICU stay and 28-day mortality between the two group were compared. Results:① A total of 94 patients were enrolled, including 51 in the EGDT group and 43 in the PiCCO group. There was no significant difference in gender, age, acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) score, sequential organ failure assessment (SOFA) score, procalcitonin (PCT), HR, MAP, CVP, Lac or SCr at ICU admission between the two groups. ② The parameters of hemodynamics, fluid balance, urine volume and SCr were improved with the time of resuscitation in the two groups, and there was no significant difference in HR, MAP or Lac between the two groups. Compared with the EGDT group, the CVP decreased significantly at 24 hours and 48 hours after fluid resuscitation in the PiCCO group (mmHg: 9.1±0.9 vs. 12.0±1.3 at 24 hours, 8.0±1.0 vs. 10.2±1.3 at 48 hours), the fluid balance significantly decreased (mL: 2 929.8±936.3 vs. 3 898.4±923.5 at 24 hours, 3 143.5±1 325.4 vs. 4 843.8±1 326.7 at 48 hours), and the condition of urine volume and SCr were better in the PiCCO group [urine volume (mL·kg -1·h -1): 1.02±0.21 vs. 0.79±0.14 at 24 hours, 1.28±0.18 vs. 0.94±0.22 at 48 hours; SCr (μmol/L): 145.7±37.6 vs. 164.3±46.4 at 24 hours, 128.4±33.6 vs. 143.5±37.7 at 48 hours), with significant differences (all P < 0.05). ③ Compared with the EGDT group, the rate of RRT in the PiCCO group was lower [11.6% (5/43) vs. 17.6% (9/51)], the duration of MV and the length of ICU stay were shorter [duration of MV (days): 4.64±1.31 vs. 6.50±2.19, length of ICU stay (days): 10.35±3.50 vs. 14.50±5.78), with significant differences (all P < 0.05). There was no significant difference in the 28-day mortality between the PiCCO group and EGDT group [14.0% (6/43) vs. 15.7% (8/51), P > 0.05]. Conclusion:Fluid resuscitation strategy guided by PiCCO in septic shock patients with AKI can reduce the amount of fluid load, improve renal function, shorten the MV duration and length of ICU stay, and shows clinical significance.