To evaluate the anesthetic effects of remimazolam in total intravenous anesthesia (TIVA) patients undergoing radical thyroidectomy.

Patients aged 18~65 with ASA physical status Ⅰ~Ⅱ were scheduled for radical thyroidectomy under TIVA. The current study consisted of two parts. Part Ⅰ: The anesthetic induction dose of remimazolam was determined using modified Dixon's up-and-down method. Part Ⅱ: The effect of remimazolam in anesthetic maintenance of TIVA was evaluated. The patients were randomly divided into two groups, propofol as control P group and remimazolam as experimental R group. After endotracheal intubation, propofol or remimazolam was continuously infused under TIVA to complete surgery. The onset time, intubation time, drug consumption and hemodynamics at certain time points were analyzed. In addition, the awakening time and adverse effects were also compared. The cognitive functions were evaluated by scale of MMSE and MoCA.

The anesthetic induction doses of propofol and remimazolam were 1.76 mg·kg^-1 and 0.43 mg·kg^-1 respectively. The onset time of the two groups had no significant difference (P>0.05). However, the intubation time of remimazolam group (103.23±9.14) s was significantly increased than that of the control group (86.58±8.32) s (P<0.05). The mean pump speed of remimazolam was 1.12 mg·kg^-1·h^-1 in TIVA. The hemodynamics of remimazolam group [MAP: (88.2±8.4) mmHg; HR: (74.2±7.1) per minute] was more stable than that of the control group [MAP: (77.9±7.4) mmHg; HR: (68.8±6.5) per minute] (P<0.05). The awakening time of remimazolam group (19.31±4.26) min was enhanced compared with the control group (13.86±3.65) min (P<0.05). The adverse effects and cognitive functions of the two groups had no statistical differences (P>0.05).

Remimazolam is safe for clinical anesthetic induction and intraoperative maintenance undergoing radical thyroidectomy, and the hemodynamics is more stable in TIVA.

To analyse and predict the potential quality markers of Aurantii fructus immaturus which based on HPLC fingerprint, chemical pattern recognition, the "Five Principles" of quality markers and network pharmacology.

The fingerprint of Aurantii fructus immaturus was established by HPLC; OPLS-DA was used to screen the main difference components among the common peak groups; the "active ingredient-target-pathway" network of differential components was constructed by network pharmacology method to further support its rationality as potential quality makers (Q-Marker) of Aurantii fructus immaturus.

The fingerprints of 22 batches of Aurantii fructus immaturus were established, and 36 common peaks were identified. Two different components of naringin and neohesperidin were screened by OPLS-DA analysis. Network pharmacology confirmed that naringin and neohesperidin can be used as potential Q-Markers of Aurantii fructus immaturus.

The established HPLC fingerprint method is stable and feasible, and the two differential components of naringin and neohesperidin screened can be used as potential Q-Markers of Aurantii fructus immaturus, which provided reference for the quality control and pharmacological mechanism research of Aurantii fructus immaturus.

To probe the effects of high-altitude hypoxia environment on the pharmacokinetic parameters of metformin after multiple administration in type 2 diabetes mellitus (T2DM) rats.

Liquid chromatography-mass spectrometry (LC-MS/MS) was used, separation was conducted by a Gemini C₁₈ (75 mm×3 mm, 3 μm) column, the mobile phase was acetonitrile-water-formic acid (85∶15∶0.1, v/v/v), the flow rate was 0.4 mL·min^-1, the injection volume was 2 μL, and the internal standard was ranitidine. T2DM rats were randomly divided into plain group and plateau group, and were given continuous gavage once a day for 7 days, and on the 7th day blood samples were collected before administration and at 0.083, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 12, 24 h after administration for determination of drug concentration. The DAS 2.0 software was used to simulate and fit the plasma concentration-time data to calculate the pharmacokinetic parameters.

Compared with the rats in the plain group, the peak time (T_max), clearance rate (CL_Z/F) and average residence time (MRT) of metformin were prolonged by 29.03%, 33.25% and 44.98% (P<0.05) in the rats under high-altitude environment, respectively. The AUC increased by 46.22% (P<0.01).

The elimination of metformin is slowed down in T2DM rats after multiple administration under high-altitude hypoxia environment.

To illustrate the overall differential material basis of three kinds of Ge-Gen Decoction (GGD) granules including Ge-Gen Decoction compound granules (CG), formula granules (mixed, FGm; decocted, FGd) and Kampo granules (KG) using UHPLC-Q-TOF-MS combining with multivariate statistical methods.

AcclaimTM RSLC120 C₁₈ chromatographic column (100 mm×2.1 mm, 2.2 μm) was employed to separate chemical compositions and gradient elution was performed with 0.1% formic acid-acetonitrile as mobile phase. ESI ion source was used to collect data in positive and negative ion modes respectively. The data were imported into SIMCA-P software for principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA). Student's t-text was utilized to measure the significance values of each metabolite. The m/z of differential components were filtered according to P<0.05, VIP>3. Then, HMDB, PubChem, TCMSP, MassBank database, MS/MS ion fragments, and related references were utilized to analyze qualitatively the differential components. Finally, combining with semi-quantitative data, a comprehensive characterization for the differential components of the three GGD granules was described.

There were 40 differential components between CG and KG, and the contents of most chemical components were higher in CG at the same dose. A total of 49 differential components were identified between CG and FGm. Some of the main active components such as puerarin and ephedrine had higher contents in CG. There were 45 differential components between FGm and FGd and there was no new component detected. The contents of most components increased after decocting. However, some important components in Paeoniae Radix Alba formula granules decreased. Fifty-nine differential components were detected totally in three kinds of Ge-Gen Decoction, and they mainly varied in the relative content, not the types. Puerariae Radix had the largest number of differential components.

UHPLC-Q-TOF-MS method can rapidly identify different components of three Ge-Gen Decoction granules, providing data support for the preparation process of Ge-Gen Decoction granules and laying a foundation for the quality control and clinical application of formula granules.

To explore the clinical characteristics and treatment strategies of central nervous system adverse events induced by atezolizumab to provide reference for recognition and treatment of such events.

Non-review articles on central nervous system adverse events caused by atezolizumab were screened, and relevant cases were summarized and analyzed. Furthermore, a case of anti-SOX1 paraneoplastic neurological encephalitis induced by atezolizumab in our hospital were discussed in combination with literature.

Atezolizumab-induced central nervous system adverse reactions have been reported, but anti-SOX1 paraneoplastic neurological encephalitis was reported for the first time. Autoimmune antibody test had reference value for clinical diagnosis of this case. And simultaneous steroid pulse therapy and plasmapheresis were performed, leading to ideal clinical outcome.

The nervous system manifestation of patients using atezolizumab should be closely monitored pre and post treatment and clinicians should be alert to the occurrence of paraneoplastic encephalitis. The relevant autoantibodies should be systematically evaluated in times of need.

To study venous thromboembolism associated with risperidone in the treatment of schizophrenia, so as to provide references for future clinical rational drug use.

A case of risperidone-associated pulmonary thromboembolism was presented and the cases of risperidone-associated venous thromboembolism, deep vein thrombosis and pulmonary thromboembolism were collected from Chinese VIP journal database, Wanfang and PubMed database and analyzed.

A total of 13 cases were retrieved. Risperidone-induced venous thromboembolism has been reported in all age groups, and the dose ranged from 1 to 6 mg. Adverse reactions occurred within 2 months after the medication (10/13 cases), and the clinical manifestations were mainly respiratory symptoms or symptoms related to lower limb venous thromboembolism, such as lower limb edema and pain. Severe cases led to syncope, cardiopulmonary arrest or even death.

Clinicians and pharmacists should be familiarized with the characteristics of pulmonary thromboembolism associated with risperidone, weigh the advantages and disadvantages, and use it with caution. To reduce the occurrence of adverse reactions, coagulation function monitoring and venous ultrasound examination of lower limbs should be strengthened, and CT pulmonary angiography should be performed if necessary.

To analyze the absolute lag and relative lag time of new drug approvals in China from 2011 to 2021 and reasons causing the lag, and to preliminarily explore the potential factors that affect the new drug launch lag.

The information on new drugs approved for marketing in China, the United States, the European Union and Japan was collected from 2011 to 2021. The durations between the time when the new drugs approved for marketing in China were first approved for marketing in the world were calculated to analyze absolute lag and relative lag in China. Multiple regression analysis was used to determine the factors related to drug lag.

During the period from 2011 to 2021, a total of 280 new drugs were approved in China, among which 180, 82 and 154 drugs exist absolute lags with the United States, the European Union and Japan, respectively. The median duration of the overall relative lag was 1 359 days. The median length of the lag gradually increased from 2011 to 2014, and reached a peak (3 438 days) in 2014; the median length dropped significantly from 2015 to 2018; the median length in 2019 to 2021 decreased year by year. The overall lag in 2020 and 2021 were below the overall median lag, 1 134 days and 500 days respectively (B=-1 153.840, P<0.05). New drugs in theraprutic area of sensory organs were related to a shorter median approval lag, and new drugs of orphan drug designation (B=441.147, P<0.01) and classified as biological products (B=502.205, P<0.01) were related to a longer median approval lag.

In the past years of 2011—2021, the drug lag issue in China has been significantly improved, but the lag phenomenon still exists in new drugs in various therapeutic fields. Under the background of the new policy implement, key factors to reduce the delay in the launch of new drugs include further improving the quality and efficiency of new drug review and approval, strengthening the communication between government approval agencies and applying companies, connecting with international common rules, and encouraging companies to conduct international multi-center clinical trials.