Objective To establish and validate a method for simultaneous determination of 9 sedative-hypnotics in human plasma,and to explore the preliminary clinical application.Methods Plasma samples were precipitated with acetonitrile and determined by high performance liquid chromatography tandem mass spectrometry.The column was Agilent Poroshell 120 EC-C18(2.1 mm × 50.0 mm,2.7μm)and eluted with acetonitrile water containing 0.1％formic acid in an equal degree program at a flow rate of 0.3 mL·min-1.The column temperature was 20 ℃ and injection volume was 5 μL.The deprotonated ions of analytes were ionized by positive ion,electron spray ionization and multiple reaction monitoring mode.The specificity,standard curve and lower limit of quantification,precision and recovery,matrix effect,stability and dilution effect of the method were investigated.Results Excellent linear relationship with correlation coefficient of r2 ≥ 0.997 7 was obtained.The linear of esazolam,alprazolam,oxazepam,clonazepam,lorazepam,triazolam,midazolam,diazepam and zolpidem were 18-1 800,4.5-450,25-2 500,3.5-350,25-2 500,1.5-150,5.5-550,35-3 500,4-400 ng·mL-1,respectively.The lower limit of quantification were 18,4.5,25,3.5,25,1.5,5.5,35,4 ng·mL-1.The method was accurate and precise with acceptable intra-day and inter-day precisions(relative standard deviations were less than 20％for a lower limit of quantification and less than 15％for other quality control samples)and an accuracy of 86.21％-112.38％.The extraction recovery rate were 93.07％-110.50％.The matrix factors normalized by internal standard were 86.61％-108.41％,relative standard deviations were less than 15％.Plasma samples remained stable under various storage conditions.The precision and accuracy of plasma samples were acceptable after dilution.Conclusion The method is simple,rapid,sensitive and specific,and it can be used for simultaneous detection of the 9 sedative-hypnotics in human plasma.

Objective To measure and compare the lateral posterior tibial slope (LPTS) , medial posterior tibial slope ( MPTS) and tibial torsion angle ( TTA) between the patients of recuiTent patellar dislocation and the heathy people, and to analyze the correlation between LPTS, MPTS and TTA and the risk factors of recuiTent patellar dislocation. Methods A total of 33 patients (44 knees) with recuiTent patellar dislocation in our hospital from July 2019 to June 2021 were selected and listed as the stud)' group. Twenty-three subjects (46 knees) who were suspected iliac vascular and lower limb vascular diseases during the same period were selected and listed as the control group. All the enrolled researchers had fulllength CT scans date of the lower limbs. Three-dimensional models were reconstructed using Mimics 21. 0 software and then imported into 3-matic software. The LPTS, MPTS and TTA were measured and compared between the two groups. Results In the study group, the LPTS, MPTS and TTA were (7. 69} 1. 42) ° , ( 10. 06} 1. 71) ° , ( 36. 42}8. 13 ) ° , respectively while the control group, the LPTS, MPTS and TTA were ( 8. 42 } 1. 65 ) ° , ( 10. 44 } 0. 86 ) ° , ( 25. 77} 3. 90 ) ° , respectively. There were no signiiicant differences in the LPTS, MPTS and TTA between different genders and sides both in the stud)' group and the control group ( P > 0. 0 5 ) . Compared with the control group, the LPTS in the stud)' group was smaller, and the difference was statistically significant (P<0. 0 5 ) . There was no statistically significant difference between the stud)' group and the control group in the MPTS (P>0. 05). Compared with the control group, the TTA in the stud)' group was higher, and the difference was statistically significant (P< 0. 0 5 ) . Compared with the control group, the LPTS and MPTS in the study group were significant asymmetry, and the difference was statistically significant ( P < 0 . 0 5 ). Conclusion The lateral posterior tibial slope of patients with recurrent patellar dislocation is significantly smaller than that in the healthy people, while there is no significant difference in the medial posterior tibial slope; The tibial torsion angle of patients with recurrent patellar dislocation is significantly larger than in the healthy people; The lateral posterior tibial slope and tibial torsion angle have certain correlation with recurrent patellar dislocation, which can conduct the diagnosis of recurrent patellar dislocation.

Pulmonary blast injury has become the main type of trauma in modern warfare, characterized by externally mild injuries but internally severe injuries, rapid disease progression, and a high rate of early death. The injury is complicated in clinical practice, often with multiple and compound injuries. Currently, there is a lack of effective protective materials, accurate injury detection instrument and portable monitoring and transportation equipment, standardized clinical treatment guidelines in various medical centers, and evidence-based guidelines at home and abroad, resulting in a high mortality in clinlcal practice. Therefore, the Trauma Branch of Chinese Medical Association and the Editorial Committee of Chinese Journal of Trauma organized military and civilian experts in related fields such as thoracic surgery and traumatic surgery to jointly develop the Clinical treatment guideline for pulmonary blast injury ( version 2023) by combining evidence for effectiveness and clinical first-line treatment experience. This guideline provided 16 recommended opinions surrounding definition, characteristics, pre-hospital diagnosis and treatment, and in-hospital treatment of pulmonary blast injury, hoping to provide a basis for the clinical treatment in hospitals at different levels.

Recent studies have shown that the occurrence and development of common liver diseases, including non-alcoholic fatty liver disease, cirrhosis, and liver cancer, are related to liver aging(LA). Therefore, to explore the effect and mechanism of Dahuang Zhechong Pills(DHZCP), a traditional classic prescription in improving LA with multiple targets, the present study randomly divided 24 rats into a normal group, a model group, a DHZCP group, and a vitamin E(VE) group, with six rats in each group. The LA model was induced by continuous intraperitoneal injection of D-galactose(D-gal) in rats. For the LA model rats, the general situation was evaluated by aging phenotype and body weight(BW). LA was assessed by the pathological characteristics of hepatocyte senescence, hepatic function indexes, the staining characteristics of phosphorylated histone family 2A variant(γ-H2AX), and the expression levels of cell cycle arrest proteins(P21, P53, P16) and senescence-associated secretory phenotype(SASP) in the liver. The activation of the reactive oxygen species(ROS)-mediated phosphatidylinositol-3 kinase(PI3K)/protein kinase B(Akt)/forkhead box protein O4(FoxO4) signaling pathway was estimated by hepatic ROS expression feature and the protein expression levels of the key signaling molecules in the PI3K/Akt/FoxO4 signaling pathway. The results showed that after the treatment with DHZCP or VE for 12 weeks, for the DHZCP and VE groups, the characterized aging phenotype, BW, pathological characteristics of hepatocyte senescence, hepatic function indexes, relative expression of ROS in the liver, protein expression levels of key signaling molecules including p-PI3K, p-Akt, and FoxO4 in the liver, staining characteristics of γ-H2AX, and the protein expression levels of P16, P21, P53, interleukin-6(IL-6), and tumor necrosis factor-α(TNF-α) in the liver were improved, and the effects of DHZCP and VE were similar. Based on the D-gal-induced LA model in rats, this study demonstrates that DHZCP can ameliorate LA with multiple targets in vivo, and its effects and mechanism are related to regulating the activation of the ROS-mediated PI3K/Akt/FoxO4 signaling pathway in the liver. These findings are expected to provide new pharmacological evidence for the treatment of DHZCP in aging-related liver diseases.
Animals ; Rats ; Proto-Oncogene Proteins c-akt/genetics* ; Phosphatidylinositol 3-Kinases/genetics* ; Reactive Oxygen Species ; Tumor Suppressor Protein p53/genetics* ; Signal Transduction ; Liver ; Aging ; Cell Cycle Proteins ; Interleukin-6

Objective: To analyze and compare therapy responses, outcomes, and incidence of severe hematologic adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia (CML) . Methods: Data of patients with chronic phase CML diagnosed between January 2006 and November 2022 from 76 centers, aged ≥18 years, and received initial flumatinib or imatinib therapy within 6 months after diagnosis in China were retrospectively interrogated. Propensity score matching (PSM) analysis was performed to reduce the bias of the initial TKI selection, and the therapy responses and outcomes of patients receiving initial flumatinib or imatinib therapy were compared. Results: A total of 4 833 adult patients with CML receiving initial imatinib (n=4 380) or flumatinib (n=453) therapy were included in the study. In the imatinib cohort, the median follow-up time was 54 [interquartile range (IQR), 31-85] months, and the 7-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.2%, 88.4%, 78.3%, and 63.0%, respectively. The 7-year FFS, PFS, and OS rates were 71.8%, 93.0%, and 96.9%, respectively. With the median follow-up of 18 (IQR, 13-25) months in the flumatinib cohort, the 2-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.4%, 86.5%, 58.4%, and 46.6%, respectively. The 2-year FFS, PFS, and OS rates were 80.1%, 95.0%, and 99.5%, respectively. The PSM analysis indicated that patients receiving initial flumatinib therapy had significantly higher cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) and higher probabilities of FFS than those receiving the initial imatinib therapy (all P<0.001), whereas the PFS (P=0.230) and OS (P=0.268) were comparable between the two cohorts. The incidence of severe hematologic adverse events (grade≥Ⅲ) was comparable in the two cohorts. Conclusion: Patients receiving initial flumatinib therapy had higher cumulative incidences of therapy responses and higher probability of FFS than those receiving initial imatinib therapy, whereas the incidence of severe hematologic adverse events was comparable between the two cohorts.
Adult ; Humans ; Adolescent ; Imatinib Mesylate/adverse effects* ; Incidence ; Antineoplastic Agents/adverse effects* ; Retrospective Studies ; Pyrimidines/adverse effects* ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy* ; Treatment Outcome ; Benzamides/adverse effects* ; Leukemia, Myeloid, Chronic-Phase/drug therapy* ; Aminopyridines/therapeutic use* ; Protein Kinase Inhibitors/therapeutic use*

In view of the limitations of the existing moxibustion instruments, i.e. possible accidental injury when using moxibustion instruments, the negative effects of products from moxibustion instruments on treatment efficacy and health of medical staff and patients, a moxibustion instrument with multi-jointed manipulator is designed. This moxibustion instrument could accurately control the temperature, maintain a safe moxibustion distance, automatically process the burning ashes of moxa and selectively handle moxa smoke. The experimental results shows that this instrument could maintain the constant temperature of target acupoint, reduce the risk of empyrosis, and reasonably deal with the products of moxibustion. The purification rate of moxa smoke is 44.9%, which not only ensures the therapeutic effect of moxa smoke, but also reduces the negative effects of high-concentration moxa smoke on the health of medical staff and patients.
Acupuncture Points ; Humans ; Moxibustion ; Smoke/analysis* ; Temperature

Chalcone isomerases (CHIs) play an essential role in the biosynthesis of flavonoids important in plant self-defense. Based on the transcriptome data of Aquilaria sinensis Calli, a full-length cDNA sequence of CHI1 (termed as AsCHI1) was cloned by reverse transcription PCR. AsCHI1 contains a complete open frame (ORF) of 654 bp. The deduced protein is composed of 217 amino acids, with a predicted molecular weight of 23.11 kDa. The sequence alignment and phylogenetic analysis revealed that AsCHI1 has conserved most of the active site residues in type I CHIs, indicating a close relationship with the CHI from Gossypium hirsutum. The recombinant AsCHI1 protein was obtained by heterologous expression of AsCHI1 in E. coli BL21(DE3). The purified AsCHI1 protein exhibited CHI activity by catalyzing the production of naringenin from naringenin chalcone. Remarkably, AsCHI1 expression in A. sinensis Calli treated with various abiotic stresses including salt, mannitol, cold, and heavy metals could be markedly increased, and plant hormones such as abscisic acid (ABA), gibberellin (GA3), and salicylic acid (SA) could also increase the expression of AsCHI1, suggesting that AsCHI1 might play an important role in plant self-defense. The results expand our understanding of the biosynthesis of flavonoids in A. sinensis and give further insight into the defensive responses of A. sinensis to abiotic and biotic stresses.

Curcumin is exclusively isolated from Zingiberaceae plants with a broad spectrum of bioactivities. In the present study, we used the diketide-CoA synthase (DCS) and curcumin synthase (CURS) genes to construct a non-natural fusion gene encoding diketide-CoA synthase::curcumin synthase (DCS::CURS). This fusion protein, together with the acetyl coenzyme A carboxylase (ACC) and the 4-coumarate coenzyme A ligase (4CL), were introduced into Escherichia coli for the production of curcumin from ferulic acid. The process is divided into two stages, the growth stage using LB medium and the fermentation stage using the modified M9 medium. The yield of curcumin reached 386.8 mg/L by optimizing the induction of protein expression in the growth stage, and optimizing the inoculum volume, medium composition and fermentation time in the fermentation stage, as well as the addition of macroporous resin AB-8 into the second medium to attenuate the toxicity of the end product. The exploitation of the non-natural fusion protein DCS::CURS for the production of curcumin provides a new alternative to further promoting the production of curcumin and the related analogues.
Curcumin/pharmacology* ; Escherichia coli/genetics* ; Fermentation

OBJECTIVE: To conduct a pilot trial to explore the effectiveness and safety of moxibustion robots in treating primary dysmenorrhea (PD) and evaluate its feasibility in clinic. METHODS: A total of 70 participants with PD were allocated to either moxibustion robot (MR) group (35 cases) or manual moxibustion (MM) group (35 cases) using computer-generated randomization. One acupoint Guanyuan (CV 4) was selected to receive moxa heat stimulation. Two groups of participants were given 3 menstrual cycles of MM and MR treatment respectively (once a day, 5 days a session) and received another 3 menstrual cycles follow-up. The degree of pain was evaluated by short-form McGill pain questionnaire (SF-MPQ) and the symptoms of dysmenorrhea were evaluated by Cox Menstrual Symptom Scale (CMSS). The safety was measured by the occurrence rate of adverse events (AEs), including burns (blisters, red and swollen), itching, bowel changes, menstrual cycle disorder, menorrhagia and fatigue, etc. RESULTS: A total of 62 patients completed the trial, 32 in MR group and 30 in MM group. Compared with baseline, scores of SF-MPQ and CMSS significantly decreased in both groups (P<0.05), and no significant difference was observed between the two groups in the 3rd and 6th menstrual cycles (P>0.05). The total occurrence rate of AEs in MR group was 2.1%, which was significantly lower than MM group (7.2%, P<0.05). CONCLUSIONS MR has the same effect as MM at SF-MPQ and CMSS in patients with PD. However, MR is safer than MM (Trial registration No. ChiCTR1800018236).

OBJECTIVE: To explore the temperature field distribution and variation rules during treatment with mild moxibustion and sparrow-pecking moxibustion of TCM. METHODS: Six healthy subjects were selected. Mild moxibustion and sparrow-pecking moxibustion were exerted at Zusanli (ST 36) respectively, for 25 min. Using infrared thermal imaging instrument, the temperature field distribution was measured during moxibustion at Zusanli (ST 36). The simulated thermometer was adopted to measure the temperature field distribution during moxibustion at the imitated cortex. At 20 min of mild moxibustion and sparrow-pecking moxibustion, the temperature field distribution generated by moxibustion was observed at the imitated cortex and Zusanli (ST 36) separately. The temperature values were collected at the sites 0.7, 2.1 and 3.5 cm far from the center of the moxibustion-exerted places successively, and then the characteristics of temperature field distribution and variation rules were compared between different moxibustion methods at the imitated cortex and Zusanli (ST 36). RESULTS: At 20 min of mild moxibustion and sparrow-pecking moxibustion at Zusanli (ST 36), the temperature field distribution focused on the center of moxibustion-exerted site and the temperature was reduced to all directions and illustrated as a curved surface graph, whereas, the temperature field distribution at the imitated cortex was consistent with that at Zusanli (ST 36). With mild moxibustion, the temperature field was distributed uniformly along the longitudinal temperature gradient; whereas, with sparrow-pecking moxibustion, the longitudinal temperature of the temperature field was greatly different, in which, the maximum temperature and the average temperature were higher than those with mild moxibustion respectively and the first time up to the peak value of sparrow-pecking moxibustion was shorter than that with mild moxibustion. The thermal transfer was presented at the non-moxibustion exerted areas during the moxibustion experiment at Zusanli (ST 36). CONCLUSION A distance feature is presented in the temperature field measured by simulated thermometer and generated under suspension moxibustion at Zusanli (ST 36). The warm stimulation effect of sparrow-pecking moxibustion is much more obvious at the moxibustion-exerted center as compared with mild moxibustion and the area of warm stimulation generated by sparrow-pecking moxibustion is more concentrated as compared with mild moxibustion. The radiation energy produced by suspension moxibustion is scattered and attenuated in skin tissue, resulting in a certain temperature gradient in the temperature field. The warm stimulation generated at skin surface by moxibustion has a warming-dredging effect.
Acupuncture Points ; Animals ; Humans ; Moxibustion ; Sparrows ; Temperature ; Torso