ObjectiveTo screen the differential markers by analyzing volatile components in Dalbergia odorifera and its counterfeits， in order to provide reference for authentication of D. odorifera. MethodThe volatile components in D. odorifera and its counterfeits were detected by headspace gas chromatography-mass spectrometry（HS-GC-MS）， and the GC conditions were heated by procedure（the initial temperature of the column was 50 ℃， the retention time was 1 min， and then the temperature was raised to 300 ℃ at 10 ℃ for 10 min）， the carrier gas was helium， and the flow rate was 1.0 mL·min^-1， the split ratio was 10∶1， and the injection volume was 1 mL. The MS conditions used electron bombardment ionization（EI） with the scanning range of m/z 35-550. The compound species were identified by database matching， the relative content of each component was calculated by the peak area normalization method， and principal component analysis（PCA）， orthogonal partial least squares-discrimination analysis（OPLS-DA） and cluster analysis were performed on the detection results by SIMCA 14.1 software， and the differential components of D. odorifera and its counterfeits were screened out according to the variable importance in the projection（VIP） value>2 and P<0.05. ResultA total of 26， 17， 8， 22， 24 and 7 volatile components were identified from D. odorifera， D. bariensis， D. latifolia， D. benthamii， D. pinnata and D. cochinchinensis， respectively. Among them， there were 11 unique volatile components of D. odorifera， 6 unique volatile components of D. bariensis， 3 unique volatile components of D. latifolia， 6 unique volatile components of D. benthamii， 8 unique volatile components of D. pinnata， 4 unique volatile components of D. cochinchinensis. The PCA results showed that， except for D. latifolia and D. cochinchinensis， which could not be clearly distinguished， D. odorifera and other counterfeits could be distributed in a certain area， respectively. The OPLS-DA results showed that D. odorifera and its five counterfeits were clustered into one group each， indicating significant differences in volatile components between D. odorifera and its counterfeits. Finally， a total of 31 differential markers of volatile components between D. odoriferae and its counterfeits were screened. ConclusionHS-GC-MS combined with SIMCA 14.1 software can systematically elucidate the volatile differential components between D. odorifera and its counterfeits， which is suitable for rapid identification of them.

AIM: To investigate the preoperative ocular symptoms and the characteristics of asymptomatic ocular surface abnormalities in hospitalized patients with primary pterygium.METHODS: Cross-sectional study. Hospitalized patients diagnosed with primary pterygium and scheduled to receive pterygium excision surgery at the Xiamen Eye Center of Xiamen University from August 2022 to October 2022 were enrolled. Ocular surface disease index questionnaire(OSDI), six examinations including non-invasive tear film break-up time, Schirmer I test, tear meniscus height, lid margin abnormality, meibomian gland dropout and tear film lipid layer thickness, and anterior segment optical coherence tomography(AS-OCT)were performed and statistically analyzed.RESULTS: A total of 178 cases(178 eyes), with a mean age of 54.39±10.75 years old, were recruited, including 75 males(42.1%)and 103 females(57.9%). The average values of ocular surface parameters in these patients included OSDI: 11.47±9.69, tear film break-up time: 7.10±3.86 s; tear meniscus height: 0.16±0.07 mm, Schirmer I test values: 14.39±7.29 mm/5 min, and pterygium thickness: 504.74±175.87 μm. Totally 161 eyes(90.4%)presented with abnormal lid margin, 44 eyes(24.7%)presented with meibomian gland dropout score ≥4, 52 eyes(29.2%)presented with low lipid layer thickness. In the 6 objective examinations, abnormalities in at least 4 of these tests were found in 85.4% of eyes. Pterygium morphology was classified into four grades: 10 eyes(5.6%)of grade Ⅰ, 93 eyes(52.2%)of grade Ⅱ, 60 eyes(33.7%)of grade Ⅲ, and 15 eyes(8.4%)of grade Ⅳ. In patients with a higher grade of pterygium, the tear film break-up time was lower, and the proportion of abnormal lid margin was also significantly higher(P<0.05). The patients were further divided into two subgroups, including 121 eyes(68.0%)with normal OSDI <13 in the normal group and 57 eyes(32.0%)with OSDI ≥13 in the abnormal group. No significant difference was found in the proportion of meibomian gland dysfunction between the two groups of patients(71.9% vs. 71.9%, P=0.872). In addition, there were differences in the number of abnormal objective examinations(4.11±0.85 vs. 4.91±0.99, P<0.001).CONCLUSIONS: Asymptomatic ocular surface abnormalities were present preoperatively in patients hospitalized for primary pterygium. A comparable high incidence of structural or functional meibomian gland dysfunction existed in pterygium patients with or without apparent ocular discomfort. More attention should be paid to the ocular surface abnormalities in those asymptomatic patients before primary pterygium surgery.

Objective This study was to develop a HPLC-MS/MS method for determination of etomidate and etomidate acid in blood samples.Methods The blood samples were deproteinized with acetonitrile and supernatant was achieved by shake,sonication,centrifuge and filtration using 0.22 μm membrane.Then,supernatant was performed on an analytical column Poroshell 120 EC-C18(150 mm×3.0 mm,2.7 μm)and flowed with 0.1%formic acid(mobile phase A)and acetonitrile(mobile phase B).The gradient elution at a flow rate of 0.8 mL/min was determined using an electrospray ionization source in positive ion mode and multiple reaction monitoring mode.Results The linearities of etomidate and etomidate acid in blood samples were good within the corresponding range and the correlation coefficients(r)were over 0.9988.The limit of detection(LOD)of etomidate and etomidate acid were 19.94 and 40.25 ng/mL,and the limit of quantitation(LOQ)of them were 50 and 100 ng/mL,respectively.Moreover,matrix effects were ranged from 1.47%to 10.34%and recoveries ranged from 82.81%to 90.07%.The detection of a positive case using our method was successfully determined to be 1 138.89 and 3 126.41 ng/mL for the contents of etomidate and etomidate acid,respectively.Conclusion Our study has further confirmed that this method with simple pretreatment,little sample usage and wide linear range,can be successfully applied to the detection of forensic sciences on etomidate and etomidate acid.

Objective:Cardiac arrest (CA) represents a significant public health challenge, posing a substantial threat to individual health and survival. To enhance the survival rates of patients experiencing out-of-hospital cardiac arrest (OHCA), Baoan District in Shenzhen City has undertaken exploratory initiatives and practical interventions, yielding promising preliminary outcomes.Methods:1.Innovate emergency medical services by developing a "four-circle integration" system that connects to the hospital. This system encompasses the social emergency medical system, the out-of-hospital emergency medical system, the in-hospital emergency medical service system, and the intensive care treatment system. 2.Develop a comprehensive model for the construction of a social emergency medical training system, characterized by party leadership, government oversight, departmental coordination, professional guidance, technological support, and community involvement, termed the "Baonan Model." Additionally, establish evaluation criteria to assess the effectiveness of the social emergency medical training system in Baonan District; 3. Develop a cardiac arrest registration system and a social emergency medical training management system for Baonan District; 4. Enhance the proficiency in treatment techniques and the quality of cardiopulmonary resuscitation among emergency medical professionals; 5. Strengthen and advance the development of a "five-minute social rescue network" to address the critical "emergency window period." .Result:In Baonan District, 9.18% of the public is trained in emergency medical skills. The bystander CPR rate for OHCA is 26.11%, AED use is at 4.78%, the 30-day survival rate is 6.31%, and the discharge survival rate is 4.44%.Conclusion:The implementation of the aforementioned measures can substantially enhance the survival rate of patients experiencing OHCA at the time of discharge.

Objective To investigate the effect of Yiqi Jiedu Recipe(YQ)on the proliferation,migration,and invasion of nasopharyngeal carcinoma cells,and to explore its mechanisms of action on proliferation,migration,and invasion through the TGF-β1/SMAD3 signaling pathway.Methods(1)The 5-8F cells were divided into four groups:solvent control group,YQ 0.5 mg·mL-1 group,YQ 1.0 mg·mL-1 group,and 5-fluorouracil 2 μg·mL-1 group.Cell proliferation was monitored using real-time cell analysis(RTCA).Wound healing experiment was conducted to assess cell migration.After 24 hours of drug intervention,transwell assay was employed to measure cell invasion.The protein expression levels of β-catenin,E-cadherin,N-cadherin,TGF-β1,and SMAD3 in the cells were evaluated using the Western Blot method.(2)The 5-8F cells were divided into five groups:solvent control group,TGF-β1 10 ng·mL-1 group,TGF-β1 10 ng·mL-1+YQ 1.0 mg·mL-1 group,YQ 1.0 mg·mL-1 group,and LY3200882 10 μmol·L-1 group.Cell proliferation was monitored using RTCA.Wound healing experiment was conducted to assess cell migration.After 24 hours of drug intervention,transwell assay was employed to measure cell invasion.The protein expression levels of β-catenin,E-cadherin,N-cadherin,TGF-β1,and SMAD3 in the cells were evaluated using Western Blot.(3)The nude mice were randomly assigned into the model group,YQ group,and 5-fluorouracil group.Subcutaneous injection of 5-8F cell suspension was performed to establish the xenograft nude mouse model of nasopharyngeal carcinoma.After the tumors reached a certain size,the 5-fluorouracil group received intraperitoneal injection of 5-Fu once every 2 days,while the other groups were orally administered corresponding drugs once a day for three consecutive weeks.Tumor volume was measured every 3 days.Western Blot was conducted to assess the protein expression levels of β-catenin,E-cadherin,and N-cadherin in the tissues of each group.Results Compared with the solvent control group,the proliferation curves of 5-8F cells in the YQ(0.5 mg·mL-1,1.0 mg·mL-1)groups showed a decrease.The migration and invasion abilities of the cells were both reduced(P＜0.05,P＜0.01).Additionally,the expression of E-cadherin protein significantly increased(P＜0.01),while the protein expression of β-catenin,N-cadherin,TGF-β1,and SMAD3 all decreased(P＜0.05,P＜0.01).Compared with the model group,the transplanted tumor volume of nasopharyngeal carcinoma in the YQ group significantly decreased(P＜0.05).Furthermore,the protein expression of β-catenin and N-cadherin in the transplanted tissues of the YQ group was significantly downregulated(P＜0.05,P＜0.01),while the expression of E-cadherin protein was significantly upregulated(P＜0.01).After the addition of the activator and inhibitor of TGF-β1 signaling pathway,compared with the YQ 1.0 mg·mL-1 group,the TGF-β1 10 ng·mL-1+YQ 1.0 mg·mL-1 group showed a significant increase in the expression of TGF-β1,SMAD3,β-catenin,and N-cadherin proteins(P＜0.05,P＜0.01)and obvious enhancement of the abilities of cell proliferation,migration,and invasion(P＜0.01).Conclusion Yiqi Jiedu Recipe can inhibit the proliferation,migration,and invasion by regulating the TGF-β1/SMAD3 signaling pathway.

ObjectiveTo establish the identification method of Dalbergiae Odoriferae Lignum（DOL） and its counterfeits by nuclear magnetic resonance hydrogen spectrum（¹H-NMR） combined with multivariate statistical analysis. Method¹H-NMR spectra of DOL and its counterfeits were obtained by NMR， and the full composition information was established and transformed into a data matrix， and the detection conditions were as follows：taking dimethyl sulfoxide-d₆（DMSO-d₆） containing 0.03% tetramethylsilane（TMS） as the solvent， the constant temperature at 298 K（1 K=-272.15 ℃）， pulse interval of 1.00 s， spectrum width of 12 019.23 Hz， the scanning number of 16 times， and the sampling time of 1.08 s. Similarity examination and hierarchical cluster analysis（HCA） were performed on the data matrix of DOL and its counterfeits， and orthogonal partial least squares-discriminant analysis（OPLS-DA） was used to analyze the data matrix and identify the differential components between them. In the established OPLS-DA category variable value model， the category variable value of DOL was set as 1， and the category variable value of the counterfeits was set as 0， and the threshold was set as ±0.3， in order to identify the commercially available DOL. The OPLS-DA score plot was used to determine the types of counterfeits in commercially available DOL， and it was verified by thin layer chromatography（TLC）. ResultThe results of similarity analysis and HCA showed that there was a significant difference between DOL and its counterfeits. OPLS-DA found that the differential component between DOL and its counterfeits was trans-nerolidol. The established category variable value model could successfully identify the authenticity of the commercially available DOL. The results of the OPLS-DA score plot showed that there were heartwood of Dalbergia pinnata and D. cochinchinensis in the commercially available DOL， and were consistent with the TLC verification results. ConclusionThere is a phenomenon that heartwood of D. pinnata and D. cochinchinensis are sold as DOL in the market. ¹H-NMR combined with multivariate statistical analysis can effectively distinguish DOL and its counterfeits， which can provide a reference for the identification of them.

Tacrolimus (FK506) is a 23-membered macrolide with immunosuppressant activity that is widely used clinically for treating the rejection after organ transplantation. The research on tacrolimus production was mainly focused on biosynthesis methods, within which there are still some bottlenecks. This review summarizes the progress made in tacrolimus biosynthesis via modification of metabolic pathways and control of fermentation process, with the hope to address the technical bottlenecks for tacrolimus biosynthesis and improve tacrolimus production by fermentation engineering and metabolic engineering.
Tacrolimus ; Immunosuppressive Agents ; Fermentation ; Macrolides ; Anti-Bacterial Agents

OBJECTIVE: To investigate the prevalence, risk factors, duration and outcome of delirium in intensive care unit (ICU) patients. METHODS: A prospective observational study was conducted for critically ill patients admitted to the department of critical care medicine, the Affiliated Hospital of Guizhou Medical University from September to November 2021. Delirium assessments were performed twice daily using the Richmond agitation-sedation scale (RASS) and confusion assessment method of ICU (CAM-ICU) for patients who met the inclusions and exclusion criteria. Patient's age, gender, body mass index (BMI), underlying disease, acute physiologic assessment and chronic health evaluation (APACHE) at ICU admission, sequential organ failure assessment (SOFA) at ICU admission, oxygenation index (PaO₂/FiO₂), diagnosis, type of delirium, duration of delirium, outcome, etc. were recorded. Patients were divided into delirium and non-delirium groups according to whether delirium occurred during the study period. The clinical characteristics of the patients in the two groups were compared, and risk factors for the development of delirium were screened using univariate analysis and multivariate Logistic regression analysis. RESULTS: A total of 347 ICU patients were included, and delirium occurred in 57.6% (200/347) patients. The most common type was hypoactive delirium (73.0% of the total). Univariate analysis showed statistically significant differences in age, APACHE score and SOFA score at ICU admission, history of smoking, hypertension, history of cerebral infarction, immunosuppression, neurological disease, sepsis, shock, glucose (Glu), PaO₂/FiO₂ at ICU admission, length of ICU stay, and duration of mechanical ventilation between the two groups. Multivariate Logistic regression analysis showed that age [odds ratio (OR) = 1.045, 95% confidence interval (95%CI) was 1.027-1.063, P < 0.001], APACHE score at ICU admission (OR = 1.049, 95%CI was 1.008-1.091, P = 0.018), neurological disease (OR = 5.275, 95%CI was 1.825-15.248, P = 0.002), sepsis (OR = 1.941, 95%CI was 1.117-3.374, P = 0.019), and duration of mechanical ventilation (OR = 1.005, 95%CI was 1.001-1.009, P = 0.012) were all independent risk factors for the development of delirium in ICU patients. The median duration of delirium in ICU patients was 2 (1, 3) days. Delirium was still present in 52% patients when they discharged from the ICU. CONCLUSIONS The prevalence of delirium in ICU patients is over 50%, with hypoactive delirium being the most common. Age, APACHE score at ICU admission, neurological disease, sepsis and duration of mechanical ventilation were all independent risk factors for the development of delirium in ICU patients. More than half of patients with delirium were still delirious when they discharged from the ICU.
Humans ; Prevalence ; Critical Care ; Risk Factors ; Sepsis ; Intensive Care Units

Objective:To evaluate the efficacy and safety of apatinib in combination with chemoradiotherapy for head and neck squamous cell carcinoma (HNSCC).Methods:37 patients orally received apatinib at 250 mg/d during concurrent chemoradiotherapy until completion of radiotherapy, complete remission assessed by imaging examination, the onset of unacceptable toxicity or death. Baseline characteristics, objective response rates (ORR) and adverse events were assessed in all enrolled patients with complete baseline and safety data. Progression-free survival (PFS) and overall survival (OS) were calculated by Kaplan-Meier method. Prognostic factors were statistically identified using Cox regression models.Results:The ORR was 85%(95% CI: 72%-98%). The median PFS was 17.9 months and the 2-year OS rate was 62%(95% CI: 48%-80%). Ineffective short-term efficacy ( HR=0.035, 995% CI: 0.02-0.652, P=0.025) was an independent risk factor for poor OS. In addition, ineffective short-term efficacy ( HR=0.104, 95% CI: 0.017-0.633, P=0.014) and lymphocytopenia ( HR=17.539, 95% CI: 2.040-150.779, P=0.009) were independent risk factors for poor PFS. Common adverse events (>60%) included lymphocytopenia (76%), leukopenia (68%) and irradiation-induced mucosal injury (65%). The most common treatment-associated grade 3 adverse event was lymphopenia (49%). Conclusions:Apatinib combined with chemoradiotherapy yield significant anti-tumor activity for HNSCC with controllable toxicity. For patients with advanced HNSCC, short-term efficacy and lymphocytopenia may be potential predictors for clinical efficacy of apatinib combined with chemoradiotherapy.

ObjectiveBy comparing the difference of volatile components of the decoction pieces before and after being processed by braising method of Jianchangbang and steaming method included in the 2020 edition of Chinese Pharmacopoeia， the influence of processing methods on the flavor formation of Polygoni Multiflori Radix （PMR） was compared. MethodHeadspace-gas chromatography-mass spectrometry （HS-GC-MS） was used to detect the volatile components of 30 batches of PMR samples from 3 origins with 3 processing methods. The GC was performed under programmed temperature （starting temperature of 40 ℃， rising to 150 ℃ at 5 ℃·min^-1， and then rising to 195 ℃ at 10 ℃·min^-1） with high purity helium as carrier gas and the split ratio of 10∶1. Mass spectrometry conditions were electron impact ion source （EI） and the detection range of m/z 50-650， the peak area normalization method was used to calculate the relative mass fraction of each component. The chromaticity values of different processed products were measured by a precision colorimeter， the relationship between chromaticity values and relative contents of volatile components was investigated by OriginPro 2021， principal component analysis （PCA） and orthogonal partial least squares-discriminant analysis （OPLS-DA） were performed on the sample data by SIMCA14.1. The differential components of different processed products of PMR were screened according to the principle of variable importance in the projection （VIP） value>1.5， and the material basis of different odor formation of PMR and its processed products was explored. ResultA total of 59 volatile components were identified， among which 34 were raw products， 33 were braised products， and 27 were steamed products. PCA and OPLS-DA results showed that there were significant differences between the three， but there was no significant difference between samples from different origins of the same processing method. Color parameters of a^*， b^*， E^*ab had no significant correlation with contents of volatile components， while L^* was negatively correlated with contents of 2-methyl-2-butenal， 2-methyltetrahydrofuran-3-one and 2，3-dihydro-3，5-dihydroxy-6-methyl-4（H）-pyran-4-one （P<0.05）. The contents of pungent odor components such as caproic acid， nonanoic acid and synthetic camphor decreased after processing， while the contents of sweet flavor components such as 2-methyl-2-butenal， furfural and 5-hydroxymethylfurfural increased after processing， and the contents of furfural， 5-methyl-2-furanmethanol， 5-hydroxymethylfurfural and other aroma components in the braised products were significantly higher than that in the steamed products. ConclusionHS-GC-MS can quickly identify the volatile substance basis that causes the different odors of PMR and its processed products. The effect of processing methods on the odor is greater than that of origin. There is a significant correlation between the color parameter of L^* and contents of volatile components， the "raw" taste of PMR may be related to volatile components such as caproic acid， pelargonic acid and synthetic camphor， the "flavor" after processing may be related to the increase of the contents of 2-methyl-2-butenal， furfural， 5-hydroxymethylfurfural， methyl maltol and furfuryl alcohol.