Detection of 14 sulfonate esters impurities of active pharmaceutical ingredients based on GC-MS/MS and LC-MS/MS / 药学学报

Two methods including gas chromatography tandem mass spectrometry (GC-MS/MS) and high-performance liquid chromatography tandem mass spectrometry (LC-MS/MS) were established to detect common alkyl sulfonates and aryl sulfonates genotoxic impurities. Four alkyl sulfonates and methyl benzenesulfonate were determined by GC-MS/MS using butyl methanesulfonate as the internal standard, the chromatographic column was HP-5MS UI (30 mm × 0.25 mm, 0.25 µm), the carrier gas was helium, the flow rate was 1.0 mL·min-1 in a constant flow mode, the sample inlet temperature was set to 250 ℃, the split ratio was 10∶1, and the initial temperature of the heating program was 80 ℃, maintained for 1 minute, and then increased to 240 ℃ at a heating rate of 30 ℃·min-1 for 2 minutes. The mass spectrometry detector was an electron bombardment ion source (EI source), the data collection condition was multi reaction monitoring mode (MRM), and method validation using the raw material of clinical drug citalopram hydrobromide as a sample. The results showed that the linear range of four alkyl sulfonates and methyl benzenesulfonate were good at 3-50 ng·mL-1 and 9-150 ng·mL-1, with a correlation coefficient of r > 0.999, The spiked recovery was 80%-120%. The detection limits were 1 and 3 ng·mL-1; Ten aryl sulfonates determined by LC-MS/MS, the chromatographic column was CSH Fluoro phenyl (100 mm × 2.1 mm, 1.7 µm), the mobile phase was methanol (B)-5 mmol·L-1 ammonium formate (D), with a flow rate of 0.2 mL·min-1, and gradient elution was performed. The gradient program (T/% B) was set as 0/20, 25/90, 35/90, 42/20. The mass spectrometer detector was electro spray ionization with positive ionization mode (ESI+), the data collection was in dynamic multi reaction monitoring mode (dMRM), and the method was validated using the raw material of the clinical drug citalopram hydrobromide as a sample. The results showed that the linear range of aryl sulfonates were good at 9-2 000 ng·mL-1, 3-100 ng·mL-1 and 0.9-30 ng·mL-1, respectively. The correlation coefficient r > 0.999, the spiked recovery was 80%-120%. The detection limits were 30, 1 and 0.3 ng·mL-1. Two detection methods did not detect potential sulfonate genotoxicity impurities in the above APIs. The established analytical methods are reliable and effective, which can provide reference for drug quality control and detection.

Culture of rabbit corneal stromal cells on thermo-sensitive materials by the radiation polymerization / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To explore the synthesis of thermo-sensitive poly N-isopropylacry-lamide(PNIPAAm)and the petri dish grafted with PNIPAAm hydrogels by the electron accelerator, as well as the growth conditions and the biological characteristics of rabbit corneal stromal cells on thermo-sensitive PNIPAAm hydrogels, and the cell sheets obtained from the PNIPAAm hydrogels.METHODS: NIPAAm monomer was dissolved in 2-propanol at concentrations of 55% with 0.5% N,N'-Methylenebisacry-lamide(MBA). Solution(70 μL)was added and spread uniformly over 35 mm petri dish. These dishes were immediately subjected to irradiation. After follow-up treatment, rabbit corneal stromal cells were cultured on thermo-sensitive petri dish in vitro.RESULTS: According to the monomer formula and radiation synthesis scheme in this experiment, PNIPAAm can be synthesized on the surface of the petri dish. Rabbit corneal stromal cells grew well in the thermo- sensitive surface and can be separated into sheets.CONCLUSION: The single and multilayer carrier-free cell sheets can be obtained from the use of thermo-sensitive petri dish.

Viral pathogen spectrum analysis of acute intestinal infection in Hanzhong in 2019-2022 / 公共卫生与预防医学

Objective To explore the viral pathogen spectrum characteristics of acute intestinal infection in Hanzhong from 2019 to 2022. Methods Fecal samples from patients with acute intestinal infection in the outpatient clinic of 3201 Hospital from January 2019 to December 2022 were collected. Common enteroviruses such as enterovirus 71 (EV-A71), coxsackievirus 16 (CV-A16), CV-A10, CV-A6, CV-A2, CV-A4, and CV-B3 were detected and analyzed by real-time fluorescence quantitative PCR. Results A total of 5 194 fecal samples were collected, and the positive rate of nucleic acid detection was 23.95%. In terms of the enteroviruses, the highest detection rate was 9.82% for EV-A71, followed by 4.58% for CV-A16 and 3.37% for CV-A6. The positive detection rate of common enteroviruses showed statistical difference among different age groups (P0.05). EV-A71 infection showed no seasonal characteristics, whereas the detection of CV-A16 and CV-A6 infections was concentrated in summer and autumn. There were 106 cases of mixed infection, and the prevalence rate was 2.04%, with EV-A71 and CV-A6 mixed infections accounting for the majority of cases. Conclusion The main pathogens of acute intestinal infections in the Hanzhong area from 2019 to 2022 are EV-A71, CV-A16, and CV-A6. It is necessary to strengthen the monitoring of acute intestinal infections in children aged 4 years and below.

Dynamic changes in cytoskeletal elements following acute cerebral ischemia and reperfusion in rats / 中国药理学通报

Aim To investigate the dynamic time-course changes in neuronal cytoskeleton after acute ischemia and reperfusion in rats. Methods Reperfusion was performedin rats by blocking the middle cerebralarteryfor 90 min, then therats wereobserved and collected at different time points. The brain damage wasobserved by Nissl staining,and neurobehavioural function was evaluated with neurological deficit score and forelimb placement test. The cellular changes in the alternations of cytoskeletal elements including microtubule associated protein 2 (MAP2) and neurofilament heavy chain (NF-H) were observed by immunohistochemistry staining and Western blot. Impaired axons, dendrites and cytoskeletal alternations were detected by electron microscope. Results Brain damage and neurobehavioural function were gradually aggravated with the prolongation of reperfusion. Brain damage appeared earlier and more severe in striatum than in cortex. Moreover, decreased MAP2-related and increased NF-H-related immunoreactive intensities were found in the ischemic areas. Impaired cytoskeletal arrangement and reduced dense were indicated. Damaged cytoskeletal components such as microtubules and neurofilament arrangement, decreased axonal filament density, and swelled dendrites were observed after cerebral ischemia reperfusion by ultrastructural observations. Conclusions Different brain regions have diverse tolerance to ischemia-reperfusion injury. Major elements of neuronal cytoskeleton show dynamic responses to ischemia and reperfusion, which may further contribute to brain damage and neurological impairment following MCAO and reperfusion.

Efficacy of high-intensity focused ultrasound cycloplasty in glaucoma and its influencing factor / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To evaluate the efficacy of high-intensity focused ultrasound cyclo plasty(UCP)in the treatment of glaucoma and to investigate related influencing factors.METHODS: The study involved a total of 110 patients(134 eyes)who received UCP treatment between January 2019 and January 2022 at three medical centers: Tianjin Eye Aier Eye Hospital, Chongqing Aier Eye Hospital, and Chongqing Nanping Aier Eye Hospital. Patients were classified into three categories: primary angle-closure glaucoma, primary open-angle glaucoma, and secondary glaucoma. Best corrected visual acuity, intraocular pressure, and the usage of anti-glaucoma medications, etc., were recorded at 6 and 12 mo postoperatively.RESULTS: After 6 months of the UCP procedure, statistically significant differences in intraocular pressure were observed across all groups(all P<0.05). At 12 mo postoperatively, intraocular pressure of the primary angle-closure and primary open-angle glaucoma groups showed differences(all P<0.05). Notably, there were no significant changes in visual acuity at either the 6 or 12 mo compared to preoperative values across all patient groups(all P>0.05). Furthermore, the study identified a statistically significant correlation between the changes in intraocular pressure at 6 mo and factors such as age, history of previous glaucoma surgery, baseline white-to-white(corneal diameter), and the extent of UCP treatment(all P<0.05).CONCLUSION: The UCP procedure has been demonstrated to effectively lower intraocular pressure in patients with glaucoma. The efficacy appears to be influenced by variables including patient age, previous glaucoma surgery history, baseline white-to-white(corneal diameter), and the scope of UCP treatment. Importantly, UCP treatment did not adversely affect visual acuity, underscoring its favorable safety profile.

Therapeutic Effect of Gandou Decoction on Wilson's Disease with Dampness Heat Accumulation Accompanied by Rapid Eye Movement Sleep Behavior Disorder / 中国实验方剂学杂志

ObjectiveTo explore the clinical efficacy of Gandou decoction in treating Wilson's disease （WD） with dampness heat accumulation accompanied by rapid eye movement （REM） sleep behavior disorder （RBD）. MethodFrom April 2019 to August 2023，62 patients with dampness heat accumulation type WD accompanied by RBD who met the inclusion criteria were selected from the Department of Encephalopathy at the First Affiliated Hospital of Anhui University of Chinese Medicine. They were randomly divided into a control group and an observation group with 31 cases each using a computer distributor. The control group received routine copper removal treatment，while the observation group received additional treatment with Gandou decoction on the basis of the control group. Eight days was one course of treatment，totaling three courses. The scores of traditional Chinese medicine syndromes，RBD screening questionnaire （RBDSQ） scores，RBD questionnaire-Hong Kong （RBDQ-HK） scores，polysomnography （PSG） parameters，24-hour urine copper （24 h U-Cu） levels，and non-ceruloplasmin-bound copper （NCC） levels between the two groups before and after treatment were compared，and adverse reactions were observed. ResultSixty trial cases were ultimately completed，with 30 cases in each group. Before treatment，there was no statistically significant difference in various indicators between the two groups， and thus they were comparable. Compared with those before treatment，the traditional Chinese medicine syndrome scores，RBDSQ scores and RBDQ-HK scores of the two groups were significantly reduced，the 24 h U-Cu levels were significantly increased，and the NCC levels were significantly reduced （P<0.05，P<0.01）. Compared with the control group， the observation group showed better improvement in traditional Chinese medicine syndrome scores， RBDSQ scores， RBDQ-HK scores， and NCC levels （P<0.05，P<0.01）. Compared with those before treatment，the total sleep time （TST），sleep efficiency （SE），sleep/REM latency，the proportion of N1/N2/REM stages，arousal index （ARI），and proportion of phasic electromyographic activity （P-EMG-A） were significantly improved in both groups （P<0.05）. Compared with the control group after treatment，the observation group showed more significant improvements in the proportion of TST，SE，REM stages，ARI，and P-EMG-A proportion （P<0.05）. ConclusionGandou decoction can not only improve the traditional Chinese medicine syndrome of WD patients with dampness heat accumulation accompanied by RBD but also alleviate their RBD symptoms.

The protective effect and mechanism of cornuside on diabetic nephropathy model mice / 中国药房

OBJECTIVE To investigate the protective effect and potential mechanism of cornuside on diabetic nephropathy （DN） model mice. METHODS Male KK-Ay mice were fed with high-fat and high-sugar diet for two weeks to reproduce the DN model. The successfully modeled mice were randomly grouped into model group， aminoguanidine group （positive control，100 mg/kg） and cornuside group （100 mg/kg）， and male C57BL/6J mice were included as normal group， with 6 mice in each group. Administration groups were given relevant medicine intragastrically， and normal group and model group were given a constant volume of normal saline intragastrically， once a day， for 8 consecutive weeks. The levels of fasting blood glucose （FBG）， 24 h urinary protein， serum interleukin-12 （IL-12）， IL-10， blood urea nitrogen （BUN） and serum creatinine （Scr） were detected； the pathological injury， fibrotic change and glomerular microstructure of renal tissue were observed； the expressions of the receptor of advanced glycation end products （RAGE）， collagen type Ⅳ （COL-Ⅳ） and inducible nitric oxide synthase （iNOS） in renal cortex were detected in each group. RESULTS Compared with normal group， the renal cortex of mice in model group showed obvious inflammatory cell infiltration and fibrotic changes； the mesangial hyperplasia of glomerulus was serious and the basement membrane had a large number of irregular dark dense deposits； the levels of FBG and 24 h urinary protein， the serum levels of IL- 12， BUN and Scr， and the expression levels of RAGE， COL-Ⅳ and iNOS in the renal cortex were significantly increased， while the serum level of IL-10 was significantly decreased （P＜0.01）. Compared with the model group， the renal pathological injuries， fibrotic changes and glomerular microstructure of mice in administration groups were improved significantly， and the above quantitative indexes were generally improved （P＜0.05 or P＜0.01）. CONCLUSIONS Cornuside has a certain protective effect on DN model mice. It can inhibit the inflammatory response， reduce urinary protein excretion， and alleviate renal fibrosis， which may be related to the inhibition of the advanced glycation end products/RAGE signaling pathway.

Oral anti-coagulants use in Chinese hospitalized patients with atrial fibrillation / 中华医学杂志(英文版)

BACKGROUND@#Oral anti-coagulants (OAC) are the intervention for the prevention of stroke, which consistently improve clinical outcomes and survival among patients with atrial fibrillation (AF). The main purpose of this study is to identify problems in OAC utilization among hospitalized patients with AF in China.@*METHODS@#Using data from the Improving Care for Cardiovascular Disease in China-Atrial Fibrillation (CCC-AF) registry, guideline-recommended OAC use in eligible patients was assessed.@*RESULTS@#A total of 52,530 patients with non-valvular AF were enrolled from February 2015 to December 2019, of whom 38,203 were at a high risk of stroke, 9717 were at a moderate risk, and 4610 were at a low risk. On admission, only 20.0% (6075/30,420) of patients with a diagnosed AF and a high risk of stroke were taking OAC. The use of pre-hospital OAC on admission was associated with a lower risk of new-onset ischemic stroke/transient ischemic attack among the diagnosed AF population (adjusted odds ratio: 0.54, 95% confidence interval: 0.43-0.68; P  <0.001). At discharge, the prescription rate of OAC was 45.2% (16,757/37,087) in eligible patients with high stroke risk and 60.7% (2778/4578) in eligible patients with low stroke risk. OAC utilization in patients with high stroke risk on admission or at discharge both increased largely over time (all P  <0.001). Multivariate analysis showed that OAC utilization at discharge was positively associated with in-hospital rhythm control strategies, including catheter ablation (adjusted odds ratio [OR] 11.63, 95% confidence interval [CI] 10.04-13.47; P <0.001), electronic cardioversion (adjusted OR 2.41, 95% CI 1.65-3.51; P <0.001), and anti-arrhythmic drug use (adjusted OR 1.45, 95% CI 1.38-1.53; P <0.001).@*CONCLUSIONS@#In hospitals participated in the CCC-AF project, >70% of AF patients were at a high risk of stroke. Although poor performance on guideline-recommended OAC use was found in this study, over time the CCC-AF project has made progress in stroke prevention in the Chinese AF population.Registration:ClinicalTrials.gov, NCT02309398.

Optimization of ethanol extraction process for Yihuang powder by orthogonal experiment combined with AHP and GA-BP neural network / 中国药房

OBJECTIVE To optimize ethanol extraction process of Yihuang powder. METHODS An orthogonal experiment was designed by reflux extraction with ethanol volume fraction， liquid-to-material ratio， and extraction time as investigation factors. The parameters used were the contents of hesperidin， nobiletin， tangeretin， gallic acid， chebulagic acid， chebulinic acid， liquiritin， glycyrrhizin， eugenol， and the paste-forming rate. The analytic hierarchy process （AHP） was used to calculate the comprehensive score. The optimal ethanol extraction process parameters of Yihuang powder were determined by verifying the results predicted by orthogonal experiment and genetic algorithm （GA）-back propagation neural network （BP neural network）. RESULTS The optimal ethanol extraction process parameters， as optimized by orthogonal experiment， were as follows: ethanol volume fraction of 60%， liquid-solid ratio of 14∶1 （mL/g)， extraction time of 90 min， and extraction for 2 times. The comprehensive score obtained by verification was 79.19. Meanwhile， the optimal ethanol extraction process parameters， optimized by GA-BP neural network， were ethanol volume fraction of 65%， liquid-solid ratio of 14∶1 （mL/g )， extraction time of 60 min， and extraction for 2 times. The comprehensive score obtained by verification was 85.30， higher than the results obtained from orthogonal experiment. CONCLUSIONS The optimization method of orthogonal experiment combined with GA-BP neural network is superior to the traditional orthogonal experiment optimization method. The optimized ethanol extraction process of Yihuang powder is stable and reliable.

Invasiveness assessment by CT quantitative and qualitative features of lung cancers manifesting ground-glass nodules in 555 patients: A retrospective cohort study / 中国胸心血管外科临床杂志

@#Objective     To explore the correlation between the quantitative and qualitative features of CT images and the invasiveness of pulmonary ground-glass nodules, providing reference value for preoperative planning of patients with ground-glass nodules. Methods    The patients with ground-glass nodules who underwent surgical treatment and were diagnosed with pulmonary adenocarcinoma from September 2020 to July 2022 at the Third Affiliated Hospital of Kunming Medical University were collected. Based on the pathological diagnosis results, they were divided into two groups: a non-invasive adenocarcinoma group with in situ and minimally invasive adenocarcinoma, and an invasive adenocarcinoma group. Imaging features were collected, and a univariate logistic regression analysis was conducted on the clinical and imaging data of the patients. Variables with statistical difference were selected for multivariate logistic regression analysis to establish a predictive model of invasive adenocarcinoma based on independent risk factors. Finally, the sensitivity and specificity were calculated based on the Youden index. Results     A total of 555 patients were collected. The were 310 patients in the non-invasive adenocarcinoma group, including 235 females and 75 males, with a meadian age of 49 (43, 58) years, and 245 patients in the invasive adenocarcinoma group, including 163 females and 82 males, with a meadian age of 53 (46, 61) years. The binary logistic regression analysis showed that the maximum diameter (OR=4.707, 95%CI 2.060 to 10.758), consolidation/tumor ratio (CTR, OR=1.027, 95%CI 1.011 to 1.043), maximum CT value (OR=1.025, 95%CI 1.004 to 1.047), mean CT value (OR=1.035, 95%CI 1.008 to 1.063), spiculation sign (OR=2.055, 95%CI 1.148 to 3.679), and vascular convergence sign (OR=2.508, 95%CI 1.345 to 4.676) were independent risk factors for the occurrence of invasive adenocarcinoma (P<0.05). Based on the independent predictive factors, a predictive model of invasive adenocarcinoma was constructed. The formula for the model prediction was: Logit(P)=–1.293+1.549×maximum diameter of lesion+0.026×CTR+0.025×maximum CT value+0.034×mean CT value+0.72×spiculation sign+0.919×vascular convergence sign. The area under the receiver operating characteristic curve of the model was 0.910 (95%CI 0.885 to 0.934), indicating that the model had good discrimination ability. The calibration curve showed that the predictive model had good calibration, and the decision analysis curve showed that the model had good clinical utility. Conclusion     The predictive model combining quantitative and qualitative features of CT has a good predictive ability for the invasiveness of ground-glass nodules. Its predictive performance is higher than any single indicator.

Source analysis and health risk assessment of polycyclic aromatic hydrocarbons in atmospheric PM2.5 in a district of Taizhou City from 2019 to 2021 / 环境与职业医学

Background Polycyclic aromatic hydrocarbons (PAHs), one of the main components of fine particulate matter (PM2.5), have a certain impact on ambient air quality, and long-term exposure to PAHs may pose potential health risks to human beings. Objective To identify the distribution characteristics and sources of PAHs in atmospheric PM2.5 in a district of Taizhou City from 2019 to 2021, and to evaluate the health risks of PAHs to the population in the area through the inhalation pathway. Methods From 2019 to 2021, air PM2.5 sampling was carried out at a state-controlled surveillance point in a district of Taizhou City for 7 consecutive days on the 10th-16th of each month, the sampling time was 24 h·d−1, and the sampling flow rate was 100 L·min−1. PM2.5 mass concentration was calculated by gravimetric method. A total of 16 PAHs were determined by ultrasonic extraction-liquid chromatography. Kruskal-Wallis H test was used to compare the distribution charac teristics of PAHs concentrations by years and seasons, characteristic ratio and principal component analysis (PCA) was used to analyze their sources, and a lifetime carcinogenic risk (ILCR) model was used to assess the health risk of PAHs. Results From 2019 to 2021, the annual average concentrations [M (P25, P75)] of ∑PAHs in atmospheric PM2.5 in the selected district of Taizhou City were 6.52 (2.46, 10.59), 8.52 (4.56, 12.29), and 3.72 (1.51, 7.11) ng·m−3, respectively, and the annual benzo[a]pyrene (BaP) excess rates (national limit: 1 ng·m−3) were 27.38% (23/84), 47.62% (40/84), and 19.04% (16/84), respectively, both presenting 2020> 2019 > 2021 (P<0.001, P<0.05). The ∑PAHs concentration distribution showed a seasonal variation, with the highest value in winter and the lowest value in summer (P<0.05). Among the atmospheric PM2.5 samples, the proportion of 5-ring PAHs was the highest, the proportion of 2-3-ring PAHs was the lowest; the proportion of 2-4-ring PAHs showed a yearly upward trend, and the proportion of 5-6-ring PAHs showed yearly downward trend (P<0.05). The characteristic ratio and PCA results suggested that the sources of sampled PAHs were mainly mixed sources such as dust, fossil fuel (natural gas), coal combustion, industrial emissions, and motor vehicle exhaust emissions. The ILCR (RILCR) of PAHs by inhalation for men, women, and children were 1.83×10−6, 2.35×10−6, and 2.04×10−6, respectively, and the annual average RILCR was 2.07×10−6, all greater than 1×10−6. Conclusion For the sampled time period, the main sources of PAHs pollution in atmospheric PM2.5 in the target district of Taizhou City are dust, fossil fuel (natural gas), coal combustion, industrial emissions, motor vehicle emissions, etc., and PAHs may have a potential carcinogenic risk to local residents.

Optimal diagnosis and treatment for renal allograft fibrosis / 器官移植

Renal allograft fibrosis is one of the common and severe complications after kidney transplantation, which seriously affects the function and survival rate of renal allograft, and may even lead to organ failure and patient death. At present, the researches on renal allograft fibrosis are highly complicated, including immunity, ischemia-reperfusion injury, infection and drug toxicity, etc. The diagnosis and treatment of renal allograft fibrosis remain extremely challenging. In this article, the latest research progress was reviewed and the causes, novel diagnosis and treatment strategies for renal allograft fibrosis were investigated. By improving diagnostic accuracy and optimizing treatment regimen, it is expected to enhance clinical prognosis of kidney transplant recipients, aiming to provide reference for clinicians to deliver proper management for kidney transplant recipients.

Chemical Constituents， Pharmacological Effect， and Product Development of Eucommia ulmoides with Both Medicinal and Edible Values： A Review / 中国实验方剂学杂志

Eucommia ulmoides， a plant belonging to Eucommiaceae， has a history of medical use for over two thousand years in China. The dried bark and leaves of this plant are usually used as medicinal materials. Due to the high safety in clinical application， E. ulmoides leaves were officially recognized for both medicinal and edible use by the food safety evaluation in 2019， providing a valuable resource for the development of food and health products. According to the traditional Chinese medicine theory， E. ulmoides has the effects of nourishing the liver and kidneys， strengthening sinews and bones， and calming fetus. Modern research has shown that different parts such as the bark， leaves， flowers， and seeds of E. ulmoides contain similar chemical components， including phenylpropanoids， terpenoids， flavonoids， phenolic acids， steroids， and polysaccharides. E. ulmoides exhibits diverse pharmacological activities such as lowering blood pressure and blood lipid and glucose levels， preventing osteoporosis and possesses anti-tumor， anti-bacterial， antiviral， anti-inflammatory， antioxidant， and hepatoprotective effects. Therefore， it holds great potential for the development of products with both medicinal and edible values. This review systematically summarizes the chemical constituents， pharmacological activities， and representative medicinal and edible products of different parts of E. ulmoides. It is expected to provide theoretical references for the clinical application of E. ulmoides and its active components and the development and utilization of the products with both medicinal and edible values. This review contributes to a deeper understanding of the medicinal properties of E. ulmoides and provides guidance for further exploration of its applications in the healthcare field. As a plant with both medicinal and edible values， E. ulmoides is expected to attract more attention in future research and contribute to human health.

Advances of metal nanoadjuvant for cancer immunotherapy / 药学学报

Immunotherapy has become another effective tumor treatment after surgical resection, chemotherapy, radiotherapy and targeted therapy. However, due to the low immunogenicity of tumor cells and immunosuppressive tumor microenvironment, antigen-presenting cells inefficiently process and present tumor antigens, thus leading to insufficient activation of cytotoxic T lymphocytes and tumor infiltration, which significantly affects the effectiveness of tumor immunotherapy. In recent years, it has been demonstrated that multiple metal ions exhibit distinguished modulatory effects in activating innate immune stimulation and conquering acquired immune tolerance. Based on this, scientists have designed a series of nano-adjuvant delivery systems with metal ions or metal nanoparticles to enhance the targeted accumulation of metal ions in tumor tissues or lymphoid organs for efficiently inducing immunogenic cell death or directly activating antigen-presenting cells to initiate anti-tumor specific immune response. This review briefly outlines the role of various metal ions in anti-tumor immunomodulation, summarizes the research progress in using metal nanoadjuvant delivery systems to achieve efficient anti-tumor immunotherapy, and provides foresight on the main challenges and potential directions in this field.

Inhibitory effects of a TRPM4 inhibitor 9-phenanthrol on electrical activity of INS-1 pancreatic β-cells / 药学学报

The Ca2+-activated monovalent cation selective transient receptor potential melastatin 4 (TRPM4) channel expressed in pancreatic β-cells is implicated in the β-cell function and insulin secretion, but how pharmacological function of TRPM4 channel affects membrane excitability of β-cells remains largely unknown. Here, we report that pharmacological inhibition of TRPM4 by specific inhibitor 9-phenanthrol attenuates electrical activities of pancreatic β-cells. In whole-cell current clamp recordings, 9-phenanthrol results in inhibition of action potential frequency induced by tolbutamide of the INS-1 pancreatic β-cells in a dose-dependent manner with an IC50 value of 14.99 ± 7.93 μmol·L-1. Similarly, 9-phenanthrol also inhibited action potential firing in INS-1 cells stimulated by current injection. Further recordings of β-cells demonstrate the significant inhibitory effects on action potential peak and action potential amplitude by 9-phenanthrol. Taken together, our results show the involvement of TRPM4 channel function in pancreatic β-cells depolarization and action potential, it provides pharmacological experimental methods and theoretical support for the study of TRPM4 channel in pancreatic β-cells.

Advances in peptidyl Asx-specific ligases for the application of cyclic peptides / 药学学报

Asparaginyl endopeptidases (AEPs) in plants belong to the family of cysteine protease that undergo self-activation in the form of zymogen in acidic vacuole and play important physiological roles in maturation of seed storage proteins, protein degradation, programmed cell death and host defense. Bioprocessing enzymes (peptidyl Asx-specific ligases, PALs) that promote the maturation of cyclotides have recently been isolated and identified from several cyclotide-rich plants. PALs derived from AEPs can site-specifically catalyze the formation of asparagine or aspartate peptide bonds. Due to the advantages of relatively traceless peptide bonds and broad substrate spectrum and high catalytic efficiency, they have been playing important roles in the cyclization and modification of peptides and proteins, and are powerful tools for improving the stability of peptide drugs. This review describes the physiological functions of AEPs in plants and summarizes the discoveries, structural characteristics, catalytic mechanism and protein engineering of PALs, as well as the limitation of their applications and future trends. In addition, the applications of PALs in cyclotides biosynthesis and the development of macrocyclic peptides are highlighted, with the aim of providing a new idea for the biocatalytic synthesis of cyclic peptides.

Different concentrations of fluorometholone eye drops on the treatment of children with severe mixed vernal keratoconjunctivitis / 国际眼科杂志(Guoji Yanke Zazhi)

AIM:To observe the clinical effect of different concentration of fluorometholone eye drops on severe mixed vernal keratoconjunctivitis in children.METHODS: A total of 50 cases(100 eyes)of children with severe mixed vernal keratoconjunctivitis treated in the outpatient department of our hospital from March to September, 2022 were selected and randomly divided into two groups. Group A consisted of 25 cases(50 eyes)who were treated with 0.1% fluorometholone eye drops combined with 0.05% cyclosporine eye drops(Ⅱ), while 25 patients(50 eyes)in group B were treated with 0.02% fluorometholone eye drops combined with 0.05% cyclosporine eye drops(Ⅱ). After 1mo of treatment, SPEED questionnaire score, corneal fluorescein staining(FL)score, tear break-up time(TBUT), Schirmer I test(SⅠt), R-scan, non-invasive tear meniscus height(NIKTMH), corneal optical density and other ocular parameters of the two groups were observed, and the occurrence of adverse reactions were recorded.RESULTS: After 1mo of treatment, there were significant differences in SPEED score, FL score and R-scan results between the two groups(all P&#x003C;0.05), and no differences in TBUT, SⅠt and NIKTMH results(all P&#x003E;0.05). However, there were statistical significance in corneal optical density in different corneal depth and diameter ranges(all P&#x003C;0.05). After 1mo of treatment, there was no significant difference in intraocular pressure between the two groups(16.21±2.90mmHg vs. 16.05±2.75mmHg, P&#x003E;0.05), and no obvious adverse reactions occurred during treatment.CONCLUSION: The 0.1% fluorometholone eye drops can effectively treat severe mixed vernal keratoconjunctivitis in children, and its effect is better than 0.02% fluorometholone eye drops.

Transabdominal pericardial anastomosis of suprahepatic vena cava and right atrium in liver transplantation for Budd-Chiari syndrome complicated with liver cancer: a case report with surgical video / 器官移植

Objective To summarize clinical experience of transabdominal pericardial anastomosis of suprahepatic vena cava of the donor and right atrium of the recipient in liver transplantation for Budd-Chiari syndrome (BCS) complicated with liver cancer. Methods Clinical data of a BCS patient complicated with liver cancer undergoing transabdominal pericardial anastomosis of suprahepatic vena cava and right atrium in liver transplantation were retrospectively analyzed. Results The hepatic vein and suprahepatic vena cava were partially occluded in the patient. Liver transplantation was completed by transabdominal pericardial anastomosis of suprahepatic vena cava and right atrium with beating-heart. In addition, due to pathological changes of the recipient's hepatic artery, splenic artery of the recipient was cut off, distal ligation was performed, and the proximal end was reversed and anastomosed with the common hepatic artery of the donor liver, and the reconstruction of hepatic artery was completed. The surgery was successfully performed. At approximately postoperative 1 week, the function of the liver allograft was gradually restored to normal, and no major complications occurred. The patient was discharged at postoperative 25 d. No signs of BCS recurrence was reported after 8-month follow-up. Conclusions It is safe and feasible to treat BCS by liver transplantation with transabdominal pericardial anastomosis of suprahepatic vena cava and right atrium. BCS patients complicated with liver cancer obtain favorable prognosis.

Exploring occupational hazards and protective strategies in power generation enterprises / 中国职业医学

Currently, power generation in China is dominated by thermal power, wind power, nuclear power, and hydropower enterprises. The power source mainly comes from thermal power generation. The occupational hazards in thermal power station are noise, high temperature, power frequency electric fields, dust, and chemical toxins and so on, with noise and dust (silica and coal dust) being the primary factors. The occupational hazards in wind power station are noise, power frequency electric fields, high temperature, low temperature, and chemical toxins (sulfur hexafluoride, toluene, styrene, etc.), with noise and power frequency electric fields being the major concerns. The occupational radiation hazards in nuclear power station are gamma rays, beta rays, X-rays, neutrons, alpha rays, and radioactive aerosols. There is special attention in radiation protection but not enough protection in non-radioactive hazards such as noise, high temperature, and ammonia. The occupational hazards in hydropower station are noise, power frequency electric fields, vibration, radon and its de-composites, and chemical toxins, with noise and power frequency electric fields being the primary hazards. Different categories of power generation enterprises should identify key hazards and work site for occupational disease prevention and control based on the features of occupational hazards. Improving occupational health management and protection levels are essential measures.

Guidelines for TCM Intervention After Conventional Western Medicine Treatment for Stage Ⅰ-Ⅲ Colorectal Cancer / 中国实验方剂学杂志

Colorectal cancer is one of the common malignant tumors with high morbidity， and changes in lifestyle， dietary structure and environment in China in recent decades have been associated with an increase in the incidence of colorectal cancer. A large number of studies have shown that traditional Chinese medicine（TCM） can be used as a complementary and alternative treatment for colorectal cancer after conventional western medicine treatment. TCM physicians have accumulated a lot of clinical experience in the treatment of patients with stage Ⅰ-Ⅲ colorectal cancer， and have proved that TCM has unique efficacy， but there is still a lack of relevant clinical practice guidelines to standardize and guide the diagnosis and treatment of TCM. Based on this， according to the guideline development process of the World Health Organization Handbook for Guideline Development and the Clinical Evidence Grading Criteria on TCM Based on Evidence Body， under the framework of relevant laws， regulations and technical guidance documents， combined with the evidence of relevant domestic and foreign clinical research in recent years for evidence grading and opinion recommendation， and then the Guidelines for TCM Intervention After Conventional Western Medicine Treatment for Stage Ⅰ-Ⅲ Colorectal Cancer were developed by expert consensus. This guideline introduces the etiology， pathogenesis， syndrome differentiation and treatment of TCM intervention for colorectal cancer， which can provide guiding opinions for TCM clinicians and clinicians of integrated traditional Chinese and western medicine engaged in the prevention and treatment of colorectal cancer.