Hsa_circ_0013561 promotes progression of nasopharyngeal carcinoma by activating JAK2/STAT3 signaling pathway

Abstract Objective Nasopharyngeal Carcinoma (NPC) is a malignancy of epithelium of epithelium of the nasopharynx, with the highest incidence of otolaryngeal malignancies. A growing number of studies confirm that Circular RNA (circRNA) plays an important role in tumor development, including Hsa_circ_0013561. This study aims to elucidate the process and mechanism of NPC regulation hsa_circ_0013561. Methods In this study, circRNA expression nodes and subcellular localization in NPC tissues were analyzed by fluorescence in situ hybridization. The expression of hsa_circ_0013561 in NPC cells was further clarified by RT-qPCR. At the same time, the lentivirus vector interfered by hsa_circ_0013561 was constructed and transfected. The cell proliferation was detected by CCK-8 method, EdU assay and plate cloning assay. The cell cycle and apoptosis were detected by flow cytometry, and the cell migration ability was detected by wound healing assay and Transwell assay. Western blotting examined the expression of apoptosis, Epithelial-Mesenchymal Transition (EMT)-associated proteins, and Janus Kinase/Signal Transductor and Activator of Transcription (JAK/STAT) signaling pathway-related proteins. Results The results showed that the expression of hsa_circ_0013561 in NPC samples was significantly upregulated and hsa_circ_0013561 localized in the cytoplasm. After down-regulating hsa_circ_0013561 expression, it significantly inhibited the proliferation and metastasis ability of NPC, inhibited EMT progression, and promoted apoptosis. Further studies showed that interference hsa_circ_0013561 significantly inhibited JAK2/STAT3 signaling pathway activation and induced the expression of apoptosis-related proteins. Conclusion In summary, we found that hsa_circ_0013561 is a pro-tumor circRNA in NPC, which can reduce the activation of JAK2/STAT3 pathway by knocking down hsa_circ_0013561, thereby slowing down the malignant progression of NPC. Oxford Centre for Evidence-Based Medicine 2011 Levels of Evidence Level 4.

Establishment of a rat model with aortic dissection induced by β-aminopropionitrile combined with angiotensin Ⅱ / 中国胸心血管外科临床杂志

@#Objective    To investigate the optimal administration combination of β-aminopropionitrile (BAPN) and Angiotensin Ⅱ (Ang-Ⅱ) in the establishment of SD rat aortic dissection (AD) model and the related complications. Methods    Forty-two three-week-old male SD rats were randomly divided into 7 groups: a group A (0.25% BAPN), a group B (0.40% BAPN), a group C (0.80% BAPN), a group D [1 g/(kg·d) BAPN], a group E [1 g/(kg·d) BAPN+ 1 μg/(kg·min) saline], a group F [1 g/(kg·d) BAPN+1 μg/(kg·min) Ang-Ⅱ] and a group G (control group). There were 6 rats in each group. The intervention period was 4 weeks (groups E and F were 4 weeks+5 days). Rats were dissected immediately if they died during the experiment. After the intervention, the surviving rats were sacrificed by pentobarbital sodium, and the whole aorta was separated and retained. Hematoxylin-eosin staining was used to observe the changes of aorta from the pathological morphology. Results    There was no statistical difference in the survival rate among the groups after 4 weeks of BAPN intervention (P>0.05). After 5 days of mini-osmotic pumps implantation, the survival rate of rats was higher in the group E than that in the group F (P=0.008), and the incidence of AD in the group E was lower than that in the group F (P=0.001). BAPN could affect the food and water intake of rats. After BAPN intervention for 4 weeks, the body weight of rats in the group G was higher than those in the intervention groups (P<0.05). BAPN combined with Ang-Ⅱ could make the aortic intima thick, elastic fiber breakage, arrangement disorder, and inflammatory cell infiltration in rats, which conformed to the pathological and morphological changes of AD. BAPN could also affect mental state and gastrointestinal tract. Conclusion    The combination of BAPN [1 g/(kg·d)] and Ang-Ⅱ [1 μg/(kg·min)] can stably establish AD model in rats, which will provide a stable carrier for further study of the pathogenesis and therapeutic targets of AD. However, the complications in this process are an unstable factor. How to balance the influence of BAPN on other tissues and organs in the process of AD model establishment remains to be further studied.

Mechanisms of brain damage caused by inorganic fluoride using proteomics-based techniques / 环境与职业医学

Background Chronic excessive exposure to fluoride can cause damage to the central nervous system and a certain degree of learning and memory impairment. However, the associated mechanism is not yet clear and further exploration is needed. Objective Using 4D unlabelled quantitative proteomics techniques to explore differentially expressed proteins and their potential mechanisms of action in chronic excessive fluoride exposure induced brain injury. Methods Twenty-four SPF-grade adult SD rats, half male and half male, were selected and divided into a control group and a fluoride group by random number table method, with 12 rats in each group. Among them, the control group drank tap water (fluorine content<1 mg·L−1), the fluoride group drank sodium fluoride solution (fluorine content 10 mg·L−1), and both groups were fed with ordinary mouse feed (fluoride content<0.6 mg·kg−1). After 180 d of feeding, the SD rats were weighed, and then part of the brain tissue was sampled for pathological examination by hematoxylin-eosin (HE) staining and Nissl staining. The rest of the brain tissue was frozen and stored at −80 ℃. Three brain tissue samples from each group were randomly selected for proteomics detection. Differentially expressed proteins were screened and subcellular localization analysis was performed, followed by Gene Ontology (GO) function analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, cluster analysis, and protein-protein interaction analysis. Finally, Western blotting was used to detect the expression levels of key proteins extracted from the brain tissue samples. Results After 180 d of feeding, the average weight of the rats in the fluoride group was significantly lower than that in the control group (P<0.05). The brain tissue stained with HE showed no significant morphological changes in the cerebral cortex of the fluoride treated rats, and neuron loss, irregular arrangement of neurons, eosinophilic changes, and cell body pyknosis were observed in the hippocampus. The Nissl staining results showed that the staining of neurons in the cerebral cortex and hippocampus of rats exposed to fluoride decreased (Nissl bodies decreased). The proteomics results showed that a total of 6927 proteins were identified. After screening, 206 differentially expressed proteins were obtained between the control group and the fluoride group, including 96 up-regulated proteins and 110 down-regulated proteins. The differential proteins were mainly located in cytoplasm (30.6%), nucleus (27.2%), mitochondria (13.6%), plasma membrane (13.6%), and extracellular domain (11.7%). The GO analysis results showed that differentially expressed proteins mainly participated in biological processes such as iron ion transport, regulation of dopamine neuron differentiation, and negative regulation of respiratory burst in inflammatory response, exercised molecular functions such as ferrous binding, iron oxidase activity, and cytokine activity, and were located in the smooth endoplasmic reticulum membrane, fixed components of the membrane, chloride channel complexes, and other cellular components. The KEGG significantly enriched pathways included biosynthesis of secondary metabolites, carbon metabolism, and microbial metabolism in diverse environments. The results of differential protein-protein interaction analysis showed that the highest connectivity was found in glucose-6-phosphate isomerase (Gpi). The expression level of Gpi in the brain tissue of the rats in the fluoride group was lower than that in the control group by Western blotting (P<0.05). Conclusion Multiple differentially expressed proteins are present in the brain tissue of rats with chronic fluorosis, and their functions are related to biosynthesis of secondary metabolites, carbon metabolism, and microbial metabolism in diverse environments; Gpi may be involved in cerebral neurological damage caused by chronic overdose fluoride exposure.

Construction and application of the “school-enterprise-community”linkage community pharmaceutical care mode based on the WeChat mini program / 中国药房

OBJECTIVE To construct the “school-enterprise-community” linkage community pharmaceutical care mode based on the WeChat mini program， upgrade the content and mode of community pharmaceutical care， and improve the quality of healthy life of the residents. METHODS Focusing on the pharmaceutical care needs of community residents， by integrating school， enterprise and community pharmaceutical resources， the WeChat mini program of “drug enjoying health” was created and the “online+offline” community pharmaceutical care mode was built. Using classified random sampling， mini program users were randomly selected as the observation group， and offline pair-assisted community residents as the control group. The intervention effects of the two groups were compared around the three aspects of medication health knowledge mastery， medication compliance and medication behavior. RESULTS The “drug enjoying health” mini program consisted of four modules：“ drug for health”，“ drug for warmth”，“ drug for safety”， and “personal information”. The “school-enterprise-community” linkage community pharmaceutical care mode based on the “drug enjoying health” mini program began to be applied in July 2022， with 6 185 users， 2 732 recovery records of expired drugs， 941 times of pharmaceutical care， and 3 354 consultation orders. After the intervention， the qualified rate of medication health knowledge mastery， complete compliance rate， and the correct rate of medication behavior in the observation group increased from 33.53% to 76.87%， 20.23% to 46.26%， and 49.71% to 89.80%， respectively； the proportion of the increase after the intervention was higher than that of the control group （P＜0.05）. CONCLUSIONS This mode has effectively improved the quality of community pharmaceutical care， improves the health awareness of community residents in drug use， and promotes the standardization， rationalization and safety of residents’ drug use.

The Effect of Modified Shugan Dingji Decoction （疏肝定悸汤） on the Occurrence of Endpoint Events in Patients with Paroxysmal Atrial Fibrillation of Liver Constraint and Qi Stagnation： A Retrospective Cohort Study / 中医杂志

ObjectiveTo retrospectively analyze the effect of modified Shugan Dingji Decoction （疏肝定悸汤） on the occurrence of endpoint events in patients with paroxysmal atrial fibrillation of liver constraint and qi stagnation. MethodsA retrospective cohort study was conducted using the electronic medical record database of Longhua Hospital affiliated to Shanghai University of Traditional Chinese Medicine to screen and include patients with paroxysmal atrial fibrillation of liver constraint and qi stagnation from January 1st， 2018， to December 31th， 2021. The included patients were divided into an exposure group and a non-exposure group， each consisting of 100 cases， based on whether they received modified Shugan Dingji Decoction. General information of the patients including age， gender， body mass index， duration of illness and comorbidities， medication history， cardiac structure and function indicators such as left atrial diameter， left ventricular end-diastolic diameter， stroke volume and ejection fraction， and the occurrence of endpoint events assessed through 24-hour dynamic electrocardiography or electrocardiogram to determine the recurrence of paroxysmal atrial fibrillation were collected. Kaplan-Meier （K-M） curves and Log-Rank tests were used to conduct survival analysis on the occurrence of endpoint events in the two groups of patients. Univariate and multivariate Cox regression analyses were used to analyze the impact of various factors on entry into endpoint events. Additionally， a safety assessment was performed by comparing liver and kidney function indicators before and after treatment. ResultsIn the non-exposure group， a total of 49 cases （49.0%） experienced endpoint events， while in the exposure group， there were 26 cases （26.0%）. The Log-rank test indicated significant difference between the two groups （χ2=11.211， P=0.001）. Univariate Cox regression analysis showed that age， duration of illness， hypertension， diabetes， chronic heart failure， left atrial diameter， stroke volume， and the use of modified Shugan Dingji Decoction may be the influencing factors for the occurrence of endpoint events in patients with paroxysmal atrial fibrillation of liver constraint and qi stagnation （P＜0.05 or P＜0.01）. Multivariate Cox regression analysis showed that the risk of endpoint events in the exposure group was significantly lower than that in the non-exposure group （P＜0.01）. Patients with a duration of illness ＞12 months had a significantly higher risk of endpoint events compared to those with a duration of illness ≤12 months （P＜0.01）. Patients without concomitant hypertension had a lower risk of endpoint events compared to those with hypertension （P＜0.05）. Patients with left atrial diameter ＞40 mm had significantly higher risk of endpoint events than those with left atrial diameter ≤40 mm （P＜0.01）. There was no statistically significant difference in liver and kidney function indicators between the two groups before and after treatment （P＞0.05）. ConclusionThe use of modified Shugan Dingji Decoction is a protective factor for patients with paroxysmal atrial fibrillation of liver constraint and qi stagnation， which can help to reduce the recurrence and progression of atrial fibrillation. Long duration of illness， concomitant hypertension， and enlarged left atrial diameter are risk factors for patients to experience endpoint events.

Potential of human induced pluripotent stem cells differentiating into corneal epithelial cells in simulated limbal stem cell microenvironment / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the potential of human induced pluripotent stem cells(hiPSCs)differentiating into corneal epithelial cells in the simulated limbal stem cells(LSCs)microenvironment.METHODS: The hiPSC cell lines were established in vitro, and hiPSCs were co-cultured with corneal stromal cells in transwell system, which simulated the LSC microenvironment. Bone morphogenetic protein 4(BMP4)and a specific transforming growth factor β inhibitor(SB431542)were added to improve the differentiation efficacy. The expression of corneal epithelial cell-specific markers CK3 and CK12, corneal epithelial cell precursor CK15, and the limbal stem cell markers ABCG5 were determined by immunofluorescence staining and flow cytometry.RESULTS: The hiPSCs were actively proliferated in vitro, and immunofluorescence staining showed positive stem cell-specific markers OCT4, SOX2, TRA-1-60 and NANOG. Furthermore, hiPSCs co-cultured with corneal stromal cells exhibited LSCs markers ABCG5 and corneal epithelial cell precursor markers CK15 were positive; however, corneal epithelial cell markers CK3 and CK12 were negative. With the addition of BMP4 and SB431542, hiPSCs showed positive expression of CK3, and the CK3 expression increased over the time.CONCLUSION: With the addition of SB431542 and BMP4, hiPSCs cultured in simulated LSCs microenvironment could differentiate into corneal epithelial cells.

Similarities and differences of myocardial metabolic characteristics between HFpEF and HFrEF mice based on LC-MS/MS metabolomics / 中华心血管病杂志

Objective: To reveal the similarities and differences in myocardial metabolic characteristics between heart failure with preserved ejection fraction (HFpEF) and heart failure with reduced ejection fraction (HFrEF) mice using metabolomics. Methods: The experimental mice were divided into 4 groups, including control, HFpEF, sham and HFrEF groups (10 mice in each group). High fat diet and Nω-nitroarginine methyl ester hydrochloride (L-NAME) were applied to construct a"two-hit"HFpEF mouse model. Transverse aortic constriction (TAC) surgery was used to construct the HFrEF mouse model. The differential expression of metabolites in the myocardium of HFpEF and HFrEF mice was detected by untargeted metabolomics (UHPLC-QE-MS). Variable importance in projection>1 and P<0.05 were used as criteria to screen and classify the differentially expressed metabolites between the mice models. KEGG functional enrichment and pathway impact analysis demonstrated significantly altered metabolic pathways in both HFpEF and HFrEF mice. Results: One hundred and nine differentially expressed metabolites were detected in HFpEF mice, and 270 differentially expressed metabolites were detected in HFrEF mice. Compared with the control group, the most significantly changed metabolite in HFpEF mice was glycerophospholipids, while HFrEF mice presented with the largest proportion of carboxylic acids and their derivatives. KEGG enrichment and pathway impact analysis showed that the differentially expressed metabolites in HFpEF mice were mainly enriched in pathways such as biosynthesis of unsaturated fatty acids, ether lipid metabolism, amino sugar and nucleotide sugar metabolism, glycerophospholipid metabolism, arachidonic acid metabolism and arginine and proline metabolism. The differentially expressed metabolites in HFrEF mice were mainly enriched in arginine and proline metabolism, glycine, serine and threonine metabolism, pantothenate and CoA biosynthesis, glycerophospholipid metabolism, nicotinate and nicotinamide metabolism and arachidonic acid metabolism, etc. Conclusions: HFpEF mice have a significantly different myocardial metabolite expression profile compared with HFrEF mice. In addition, biosynthesis of unsaturated fatty acids, arachidonic acid metabolism, glycerophospholipid metabolism and arginine and proline metabolism are significantly altered in both HFpEF and HFrEF mice, suggesting that these metabolic pathways may play an important role in disease progression in both types of heart failure.

Chinese Medicine Treatment of Chronic Obstructive Pulmonary Disease by Regulating Th1/Th2 Immune Balance： A Review / 中国实验方剂学杂志

Chronic obstructive pulmonary disease （COPD） is characterized by long treatment course and poor prognosis. The pathogenesis has not been fully elucidated but is mostly related to the non-specific inflammation of the airway and surrounding tissues. T helper 1 （Th1） and T helper 2 （Th2） are generated by CD4+ T cell differentiation， and are in a dynamic equilibrium when the body is in normal state. The balance between pro-inflammatory cytokines and anti-inflammatory cytokines regulated by Th1/Th2 is vital for maintaining the immune homeostasis in respiratory tract. Chronic inflammatory state changes the level of inflammatory cells in the body， and there is immune disorder in T lymphocytes in the onset stage of COPD. Th1 cells are predominantly expressed in the stable stage of COPD， while Th2 cells are predominantly expressed in the acute exacerbations of COPD （AECOPD）. Th1/Th2 immune imbalance aggravates the inflammatory reaction， and thus restoring the immune balance between them and inhibiting the inflammatory reaction are critical for the treatment of COPD. At present， there has been no satisfactory treatment plan for COPD. Chinese medicine has a long history of preventing and treating COPD， with remarkable curative effect and few adverse reactions. A large number of animal experiments and clinical studies on Chinese medicine intervention of Th1/Th2 immune balance in COPD have indicated that Th1/Th2 immune balance is an important potential target for treating COPD by Chinese medicine， which can correct chronic inflammatory state by regulating the immune disorder of the body. It has also been found that Th1/Th2 balance plays an important immunoregulatory role in inflammatory response， but little is known about its specific mechanism in the pathogenesis of COPD. On this basis， this paper summarized and analyzed the biological characteristics of Th1/Th2 and their mechanism in the pathogenesis of COPD， as well as the intervention effect of single Chinese medicine or its effective components and Chinese medicine compound on Th1/Th2 immune balance in COPD. It further explored the pathogenesis of COPD and the potential therapeutic targets of Chinese medicine in interfering with Th1/Th2 immune balance in COPD， providing reference for further study on prevention and treatment of COPD with Chinese medicine.

Research Progress on Genetic Susceptibility to Triple-Negative Breast Cancer / 肿瘤防治研究

Triple-negative breast cancer (TNBC) is a type of breast cancer that is difficult to treat, has a poor prognosis, and is prone to recurrence and metastasis in the early postoperative period. The age of patients is tending younger, and the racial difference is large. It is also related to family history, and genetic susceptibility is obvious. So, elucidating the genetic risk factors of TNBC and obtaining precise therapeutic targets are urgent tasks. Obtaining reliable characteristic genes and their polymorphisms between TNBC of different subtypes is difficult. This review summarizes the susceptibility genes and the polymorphisms of TNBC susceptibility genes of different molecular subtypes, in order to develop effective TNBC prevention strategies and find effective therapeutic targets. This review provides a theoretical basis for promoting the study of TNBC from the perspective of genetics.

Efficacy comparison of robot-assisted anterior column screw and anterior subcutaneous internal fixation for the treament of unstable pelvic fracture / 中华创伤杂志

Objective:To compare the clinical efficacy of minimally invasive anterior column screw placement assisted by orthopedic robot with anterior subcutaneous internal fixation (INFIX) in the treatment of unstable pelvic fracture.Methods:A retrospective cohort study was conducted to analyze 42 patients (25 males and 17 females; aged 16-68 years [(41.8±3.2)years] with unstable pelvic fracture admitted to Guizhou Provincial People′s Hospital from June 2018 to December 2021. Anterior column screw group ( n=22) received orthopedic robot-assisted anterior column screw fixation of anterior pelvic ring fracture, and INFIX group ( n=20) received subcutaneous INFIX of anterior pelvic ring fracture. Posterior pelvic ring injuries were treated with closed reduction and percutaneous sacroiliac screw internal fixation. The operation time of anterior pelvic ring fixation, intraoperative blood loss, intraoperative fluoroscopy times, off-bed activity time when the visual analogue scale (VAS) was<3 points during weight-bearing and fracture healing time were compared between the two groups. The quality of pelvic fracture reduction was assessed according to the Matta scoring criteria at 2 days after surgery. The Majeed functional score was used to assess the functional status at the last follow-up. Intraoperative and postoperative complications were observed in both groups. Results:All patients were followed up for 6-24 months [(11.3±0.5)months].The operation time of anterior pelvic ring fixation was (33.4±2.6)minutes in anterior column screw group and (30.2±2.9)minutes in INFIX group ( P>0.05). The intraoperative blood loss was (15.9±3.1)ml in anterior column screw group and (41.4±6.2)ml in INFIX group ( P<0.01). The intraoperative fluoroscopy times were 12.2±2.4 in anterior column screw group and 14.7±2.5 in INFIX group ( P>0.05). The off-bed activity time was (3.2±0.4) weeks in anterior column screw group and (6.6±1.2)weeks in INFIX group ( P<0.01). The fracture healing time was (12.7±1.4)weeks in anterior column screw group and (16.2±1.9) weeks in INFIX group ( P<0.01). According to Matta scoring criteria, the excellent and good rate of posterior pelvic ring reduction quality was 100% in both groups, while the excellent and good rate of the quality of anterior pelvic ring reduction was 100% (excellent in 16 patients and good in 6) in anterior column screw group compared with 90.0% (excellent in 11 patients, good in 7, and fair in 2) in INFIX group ( P<0.05). During the final follow-up, the excellent and good rate of Majeed functional score was 90.9% (excellent in 16 patients, good in 4 and fair in 2) in anterior column screw group, significantly different from 80.0% (excellent in 10 patients, good in 6 and fair in 4) in INFIX group ( P<0.05). During the operation, no important tissue injuries such as blood vessels, nerves or spermatic cord occurred in either group. In anterior column screw group, no postoperative complications such as infection, spermatic cord injury or implant breakage occurred; in INFIX group, there were 2 patients with incision fat liquefaction, 4 with lateral femoral cutaneous nerve symptoms and 1 with heterotopic ossification, without the occurrence of implant breakage. Conclusion:Compared with anterior subcutaneous INFIX, orthopedic robot-assisted anterior column screw internal fixation for the treatment of unstable pelvic fracture has advantages of less bleeding, earlier tambulation, faster fracture healing, better fracture reduction quality, more satisfied postoperative functional recovery, and fewer complications.

Research progress on biomarkers related to ACPA-negative rheumatoid arthritis / 中国基层医药

Rheumatoid arthritis (RA) is a group of heterogeneous autoimmune diseases with erosive arthritis as the main clinical feature. The pathogenesis of RA remains unclear. Autoantibodies can be detected in blood or synovial fluid in approximately 70% of patients with RA in the early stage of the disease. Anti-citrullinated protein antibody (ACPA) is the most commonly used autoantibody in the diagnosis of RA. However, ACPA is not a specific antibody for RA. The discovery and clinical application of serum ACPA-negative RA biomarkers is of positive significance for the early diagnosis and prognosis improvement of RA. This paper reviews the research progress of ACPA-negative RA biomarkers.

Neurotoxicity mechanism of aconitine in HT22 cells studied by microfluidic chip-mass spectrometry / 药物分析学报

Aconitine,a common and main toxic component of Aconitum,is toxic to the central nervous system.However,the mechanism of aconitine neurotoxicity is not yet clear.In this work,we had the hypothesis that excitatory amino acids can trigger excitotoxicity as a pointcut to explore the mechanism of neurotoxicity induced by aconitine.HT22 cells were simulated by aconitine and the changes of target cell metabolites were real-time online investigated based on a microfluidic chip-mass spectrometry system.Meanwhile,to confirm the metabolic mechanism of aconitine toxicity on HT22 cells,the levels of lactate dehydrogenase,intracellular Ca2+,reactive oxygen species,glutathione and superoxide dismutase,and ratio of Bax/Bcl-2 protein were detected by molecular biotechnology.Integration of the detected results revealed that neurotoxicity induced by aconitine was associated with the process of excitotoxicity caused by glutamic acid and aspartic acid,which was followed by the accumulation of lactic acid and reduction of glucose.The surge of extracellular glutamic acid could further lead to a series of cascade reactions including intracellular Ca2+overload and oxidative stress,and eventually result in cell apoptosis.In general,we illustrated a new mechanism of aconitine neurotoxicity and presented a novel analysis strategy that real-time online monitoring of cell metabolites can provide a new approach to mechanism analysis.

Application of preoperative localization coupled with CT three-dimensional reconstruction in pulmonary nodule-centered uniportal thoracoscopic combined subsegmental/segmental resection / 中国胸心血管外科临床杂志

@#Objective     To assess the clinical value of preoperative localization coupled with computed tomography (CT) three-dimensional reconstruction in pulmonary nodule-centered uniportal thoracoscopic combined subsegmental/segmental resection. Methods     The clinical data of 30 patients of combined subsegmental/segmental resection in our hospital from December 2019 to October 2021 were retrospectively collected. There were 19 males and 11 females with the mean age of 56.4 (32.0-71.0) years. The pulmonary nodules were located by CT-guided injection of glue before operation. The three-dimensional reconstruction image and operation planning were carried out by Mimics 21.0 software. Results    The operations were all successfully performed, and there was no conversion to open thoracotomy or lobectomy. The mean tumor diameter was 11.6±3.5 mm, the mean distance between the nodule and the visceral pleura was 13.6±5.6 mm, the mean width of the actual cutting edge was 25.0±6.5 mm, the mean operation time was 110.2±23.8 min, the mean number of lymph node dissection stations was 6.5±2.4, the mean amount of intraoperative bleeding was 50.8±20.3 mL, the mean retention time of thoracic catheter was 3.2±1.1 d, and the mean postoperative hospital stay was 4.5± 1.7 d. There was 1 patient of subcutaneous emphysema, 1 patient of atrial fibrillation and 1 patient of blood in sputum. Conclusion     Preoperative CT-guided injection of medical glue combined with CT three-dimensional reconstruction of pulmonary bronchus and blood vessels is safe and feasible in pulmonary nodule-centered uniportal thoracoscopic  combined subsegmental/segmental resection, which ensures the surgical margin and reserves lung tissues.

Traditional Chinese Medicine in Treatment of Ulcerative Colitis Based on NLRP3 Inflammasome： A Review / 中国实验方剂学杂志

Ulcerative colitis （UC） is a common inflammatory bowel disease （IBD） in clinical practice， characterized by symptoms such as abdominal pain， diarrhea， and bloody mucus in the stool. It is difficult to cure and has a high recurrence rate. The pathogenesis of UC is related to abnormal immune response， oxidative stress in intestinal tissues， and inflammatory reactions. As reported， the abnormal activation of the NOD-like receptor pyrin domain-containing protein 3 （NLRP3） inflammasome is involved in the pathological process of UC. This activation triggers pathological mechanisms such as oxidative stress， pyroptosis， and inflammation in intestinal epithelial cells. Therefore， blocking the abnormal activation of NLRP3 is beneficial for alleviating UC. Currently， western medicine treatment for UC mainly includes salicylic acid derivatives， corticosteroids， and biologics， but the overall efficacy is unsatisfactory. Traditional Chinese medicine （TCM） treatment of this disease has the advantages of significant efficacy and low recurrence rate. In recent years， great advances have been made in the basic research of using TCM methods to treat UC. Studies have found that TCM intervention targeting the NLRP3 inflammasome can significantly promote intestinal mucosal healing and treat UC， and the mechanism of action involves multiple targets， levels， and pathways. This article summarized the experimental research on the impact of TCM targeting the NLRP3 inflammasome on UC in recent years， and found that NLRP3 interacted with factors such as Caspase-1 and nuclear factor-κB （NF-κB）， thereby promoting the release of pro-inflammatory factors and cell pyroptosis in intestinal epithelial cells. This activation triggered oxidative stress， inflammatory reactions， and other pathological mechanisms. TCM acted on the NLRP3 inflammasome and its upstream and downstream factors to block the pathological process of UC， inhibit the pathological damage to the intestinal mucosa， and thereby alleviate colonic ulcers. The findings of this study provide a theoretical basis for the prevention and treatment of UC and further drug development.

Analysis of refractive parameters and theirs correlation with spherical equivalent in preschool children aged 3 to 6 years / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the distribution of refractive parameters and theirs correlation with spherical equivalent(SE)in preschool children aged 3 to 6 years, and evaluate the accuracy of each screening index in diagnosing refractive errors.METHODS: Cross-sectional study. A total of 791 preschool children, ranging from 3 to 6 years old, who consented to undergo mydriatic refraction were selected. Axial length(AL), corneal refractive power(K), and SE were measured after microcoria optometry and mydriatic optometry. Additionally, the corneal radius of curvature(CR)and the axial length/corneal radius of curvature(AL/CR)ratio were calculated.RESULTS: A total of 791 students participated in the study, out of which 400(50.6%)were male and 391(49.4%)were female. The mean values for AL, CR, AL/CR, and SE were 22.62±0.94mm, 7.81±0.29mm, 2.90±0.09, and +1.95±1.31D, respectively. AL, CR, and AL/CR increased with age. AL and CR were significantly higher in males than in females(all P&#x003C;0.001), while there was no statistically significant difference between AL/CR and SE in males and females(P=0.82, 0.19). The correlation coefficients of SE and AL/CR, AL and CR were -0.86, -0.50 and 0.16, respectively. The results of multiple linear regression analysis indicate that for each unit increase in AL/CR, there was a corresponding shift of 10.91 towards myopia in SE. The sensitivity of AL/CR in screening for myopia was 94.44%, with a specificity of 90.46% and a Youden index of 0.84. For screening myopia under microcoria optometry, the sensitivity was 100%, with a specificity of 66.09% and a Youden index of 0.66. The area under the curve was 0.967 and 0.809 when the ROC curves were plotted using AL/CR and AL as indicators for screening myopia, respectively.CONCLUSION: For large group screening activities where mydriatic optometry is not feasible, AL/CR is better for evaluating refractive status and identifying children with myopia and hyperopia reserve that are lower than normal for their age, compared to AL and microcoria optometry.

Retrospective multicenter nested case-control safety study of Ilaprazole sodium for injection / 中国药房

OBJECTIVE To understand the safety of Ilaprazole sodium for injection in clinical practice. METHODS From Jan. 1st 2019 to Feb. 29th 2020， the data of 3 926 valid hospitalized patients receiving Ilaprazole sodium for injection were collected prospectively from 5 third-level hospitals through CHPS， and the post-marketing safety analysis was performed by using retrospective multicenter single cohort study. At the same time， a nested case-control study （the ratio of trial group and control group was 1∶4） was used to confirm the baseline stability of this study cohort and the correlation between adverse reactions and Ilaprazole sodium for injection. RESULTS Among 3 926 patients， 3 patients experienced 5 adverse drug events after using Ilaprazole sodium for injection， with the incidence of 0.076%. There was no serious adverse event， and the occurrence time was 2 days after medication； adverse drug events mainly include elevated liver function indicators （alanine transaminase， aspartate transaminase， total bilirubin）， which were mild and untreated， and all adverse drug events were improved. The results of the nested case-control study showed that the trial group and the control group belonged to the same background baseline， and the occurrence of adverse drug events was more closely related to Ilaprazole sodium for injection. CONCLUSIONS The overall safety of Ilaprazole sodium for injection is relatively high， and the occurrence of adverse events is more related to it.

Sodium alginate coating simultaneously increases the biosafety and immunotherapeutic activity of the cationic mRNA nanovaccine

The extraordinary advantages associated with mRNA vaccines, including their high efficiency, relatively low severity of side effects, and ease of manufacture, have enabled them to be a promising immunotherapy approach against various infectious diseases and cancers. Nevertheless, most mRNA delivery carriers have many disadvantages, such as high toxicity, poor biocompatibility, and low efficiency in vivo, which have hindered the widespread use of mRNA vaccines. To further characterize and solve these problems and develop a new type of safe and efficient mRNA delivery carrier, a negatively charged SA@DOTAP-mRNA nanovaccine was prepared in this study by coating DOTAP-mRNA with the natural anionic polymer sodium alginate (SA). Intriguingly, the transfection efficiency of SA@DOTAP-mRNA was significantly higher than that of DOTAP-mRNA, which was not due to the increase in cellular uptake but was associated with changes in the endocytosis pathway and the strong lysosome escape ability of SA@DOTAP-mRNA. In addition, we found that SA significantly increased the expression of LUC-mRNA in mice and achieved certain spleen targeting. Finally, we confirmed that SA@DOTAP-mRNA had a stronger antigen-presenting ability in E. G7-OVA tumor-bearing mice, dramatically inducing the proliferation of OVA-specific CLTs and ameliorating the antitumor effect. Therefore, we firmly believe that the coating strategy applied to cationic liposome/mRNA complexes is of potential research value in the field of mRNA delivery and has promising clinical application prospects.

Chinese consensus guidelines for therapeutic drug monitoring of polymyxin B, endorsed by the Infection and Chemotherapy Committee of the Shanghai Medical Association and the Therapeutic Drug Monitoring Committee of the Chinese Pharmacological Society / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Polymyxin B, which is a last-line antibiotic for extensively drug-resistant Gram-negative bacterial infections, became available in China in Dec. 2017. As dose adjustments are based solely on clinical experience of risk toxicity, treatment failure, and emergence of resistance, there is an urgent clinical need to perform therapeutic drug monitoring (TDM) to optimize the use of polymyxin B. It is thus necessary to standardize operating procedures to ensure the accuracy of TDM and provide evidence for their rational use. We report a consensus on TDM guidelines for polymyxin B, as endorsed by the Infection and Chemotherapy Committee of the Shanghai Medical Association and the Therapeutic Drug Monitoring Committee of the Chinese Pharmacological Society. The consensus panel was composed of clinicians, pharmacists, and microbiologists from different provinces in China and Australia who made recommendations regarding target concentrations, sample collection, reporting, and explanation of TDM results. The guidelines provide the first-ever consensus on conducting TDM of polymyxin B, and are intended to guide optimal clinical use.

Clinical features and correlation analysis of the 24h intraocular pressure and water drinking test in patients with primary open angle glaucoma and ocular hypertension / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To summarize the clinical features of the 24h intraocular pressure data and the water drinking test(WDT)results in patients with primary open angle glaucoma(POAG)and ocular hypertension(OHT), and analyze the correlation.METHODS: To collect the data of 87 cases(174 eyes)with POAG and OHT, who had completed 24h intraocular pressure(IOP)(measured every 2h)and WDT(drink 1 000mL water off within 5min and then measure every 15min within 1h)in the ophthalmology department of Shenzhen University General Hospital from December 2019 to March 2022. They were divided into three groups, with 33 cases(66 eyes)in high tension glaucoma(HTG)group, 28 cases(56 eyes)in normal tension glaucoma(NTG)group and 26 cases(52 eyes)in OHT group. The clinical features of 24h IOP and WDT among the patients in three groups were summarized, and Spearman correlation was used to analyze the peak and fluctuation values of IOP.RESULTS: Clinical features among the patients in three groups:(1)the proportion of peak IOP of HTG, NTG and OHT group:(2:00-6:00 a.m.): 40.9%, 23.2% and 26.9%;(8:00-12:00 a.m.): 34.8%, 46.4% and 55.8%;(14:00-18:00 p.m.): 18.2%, 21.4% and 11.5%;(20:00-24:00 p.m.): 6.1%, 8.9% and 5.8%. Valley proportion among groups: early morning: 21.2%, 25.0% and 30.8%; morning: 22.7%, 10.7% and 13.5%; afternoon: 19.7%, 17.9% and 17.3%; evening: 36.4%, 46.4% and 38.5%. The proportion of 24h IOP fluctuation &#x0026;#x003C;6mmHg: 9.1%, 62.5% and 17.3%; 6-&#x0026;#x003C;8mmHg: 24.2%, 32.1% and 40.4%; ≥8mmHg: 66.7%, 5.4% and 42.3%.(2)WDT: The proportion of the three groups that could reach peak IOP within 30min was 81.8%, 76.8% and 80.8%, respectively. The proportion of IOP fluctuations in the three groups &#x0026;#x003C;6mmHg: 10.6%, 78.6% and 38.5%; 6-&#x0026;#x003C;8mmHg: 22.7%, 16.1% and 28.8%; ≥8mmHg: 66.7%, 5.4% and 32.7%.(3)the proportions of WDT peak higher than 24h peak IOP in the three groups were 80.3%, 80.4% and 80.8%. Correlation: the peak values of 24h IOP were positively correlated with the peak values of WDT(all P&#x0026;#x003C;0.01), the fluctuation of 24h IOP was positively correlated with the fluctuation of WDT in HTG and OHT group(P&#x0026;#x003C;0.01, P&#x0026;#x003C;0.05), while it showed no significant correlation in NTG group(P&#x0026;#x003E;0.05).CONCLUSION: Diurnal measurements of IOP during office hours(08:00 a.m.-18:00 p.m.)may fail to capture the peak values and underestimate IOP fluctuations. The 24h IOP fluctuation ≥HTG group of 8mmHg&#x0026;#x003E;OHT group&#x0026;#x003E;NTG group. The peak WDT in over 75% patients could be achieved within 30min, and it was higher than 24h peak IOP of over 80% patients. There was a positive correlation between the 24h IOP fluctuations and the WDT fluctuations in HTG and OHT patients. Therefore, WDT has clinical significance in assessing fluctuations in patients' IOP.

Exploration on "Efficacy-toxicity" Association Mechanisms of Tripterygium wilfordii Polyglycoside Tablets Against Rheumatoid Arthritis Based on Multi-omics Integrated Regulatory Network / 中国实验方剂学杂志

ObjectiveTo explore the "efficacy-toxicity" association mechanisms of Tripterygium wilfordii polyglycoside tablets （TWPT） by establishing and analyzing an interaction network associated with the clinical efficacy of TWPT in the treatment of rheumatoid arthritis （RA） and TWPT-induced liver injury. MethodOn the basis of the TWPT efficacy-related gene expression profile and TWPT-induced liver injury-related protein expression profile which were both obtained from our clinical cohorts， the "efficacy-toxicity" association network of TWPT was constructed， and the key network targets were identified by calculating the topological values of the nodes， including the degree， closeness and betweenness. After that， the biological functions and pathways of the key network targets were investigated by enrichment analysis. ResultA total of 119 differentially expressed genes （58 up-regulated and 61 down-regulated） between RA patients with TWPT well and weak response were identified as TWPT efficacy-related genes by clinical transcriptomics， and 49 differentially expressed proteins （36 up-regulated and 13 down-regulated） were demonstrated to be TWPT-induced liver injury-related proteins by clinical proteomics. In addition， the clinical symptom enrichment analysis indicated that the TWPT efficacy-related genes were significantly associated with various clinical symptoms of arthralgia in traditional Chinese medicine and clinical phenotypes of modern medicine， and most of the TWPT-induced liver injury-related proteins were involved in digestive system abnormalities. Therefore， the aforementioned multi-omics data represented the main clinical symptoms of TWPT treating RA and inducing liver injury. Mechanically， the "efficacy-toxicity" association network revealed that both TWPT efficacy-related genes and TWPT-induced liver injury-related core proteins were involved in the "immune-inflammatory" imbalance， especially playing an important role in neutrophil degranulation， complement cascade reaction， and immune-inflammatory response mediated by protein post-translational modification. Notably， the above genes and proteins were also enriched in various signaling pathways related to cell proliferation and cell cycle regulation， such as RAS and mitogen-activated protein kinase （MAPK） signaling pathway， and in several liver functional processes， such as glycogen metabolism and redox reaction. ConclusionThis study systematically explained the "efficacy-toxicity" association characteristics and molecular mechanisms of TWPT by applying a research strategy integrating clinical phenomics， transcriptomics and proteomics， laying a good data foundation for exploring the "efficacy enhancing and toxicity-reducing" mechanisms of TWPT.