Novel antibacterial drug target against Gram-negative bacteria: lipopolysaccharide transport protein LptDE and its inhibitors / 药学学报

The outer membrane composed predominantly of lipopolysaccharide (LPS) is an essential biological barrier for most Gram-negative (G-) bacteria. Lipopolysaccharide transport protein (Lpt) complex LptDE is responsible for the critical final stage of LPS transport and outer membrane assembly. The structure and function of LptDE are highly conserved in most G- bacteria but absent in mammalian cells, and thus LptDE complex is regarded as an attractive antibacterial target. In recent 10 years, the deciphering of the three-dimensional structure of LptDE protein facilities the drug discovery based on such "non-enzyme" proteins. Murepavadin, a peptidomimetic compound, was reported to be the first compound able to target LptD, enlightening a new class of antibacterial molecules with novel mechanisms of action. This article is devoted to summarize the molecular characteristics, structure-function of LptDE protein complex and review the development of murepavadin and related peptidomimetic compounds, in order to provide references for relevant researches.

Association between exposure to multiple metals and lung function in welders by multi-pollutant statistical models / 环境与职业医学

Background Welders' exposure to welding fumes with multiple metals leads to decreased pulmonary function. Previous studies have focused on single metal exposure, while giving little attention to the impact of metal mixtures. Objective To assess the association between metal levels in urine and blood of welders and pulmonary function indicators, and to identify key metals for occupational health risk assessment. Methods Questionnaire surveys, lung function tests, urine and blood sampling were conducted among welders and control workers in a shipyard in Shanghai. Inductively coupled plasma mass spectrometry (ICP-MS) was used to detect the concentrations of 12 metals such as vanadium, chromium, and manganese in urine and blood. Spearman correlation was applied to analyze the correlations between the metals in urine and blood. Multiple linear regression, weighted quantile sum (WQS) and Bayesian kernel machine regression (BKMR) were used to analyze the relationships between mixed metal exposure and pulmonary function parameters, such as forced vital capacity (FVC), forced vital capacity as a percentage of predicted value (FVC%), forced expiratory volume in the first second (FEV1), forced expiratory volume in the first second as a percentage of predicted value (FEV1%), and forced expiratory volume in the first second/forced vital capacity (FEV1/FVC). Results This study enrolled 445 subjects, including 322 welders (72.36%) and 123 controls (27.64%). The mean age of the 445 participants was (37.64±8.80) years, and 87.19% participants were male. The welders had significantly higher levels of urinary cadmium (0.88 vs 0.58 μg·L−1), blood chromium (5.86 vs 5.06 μg·L−1), and blood manganese (24.24 vs 21.38 μg·L−1) than the controls (P<0.05). The Spearman correlation coefficients between the metals in urine and blood ranged from −0.46 to 0.68. After adjustment for confounders, the multiple linear regression indicted that the urine molybdenum of the welders was negatively correlated with FVC and FEV1. There were also negative correlations between the molybdenum in blood and FVC, FVC%, FEV1, and FEV1%, and between the copper in blood and FEV1/FVC. The WQS model showed that FEV1 and FVC decreased by 0.112 L and 0.353 L with each quartile increase of metal mixture concentrations in urine and blood among the welders respectively, and the leading contributors were copper, zinc, vanadium, and antimony. The BKMR model showed a negative overall effect of metal mixtures in urine and blood among the welders on FVC, FVC%, FEV1, and FEV1%, and the univariate exposure response-relationship between the molybdenum concentration in urine or blood and FVC, FVC%, FEV1, or FEV1% had an approximately linear decreasing trend. Meanwhile, there may be an interaction of cadmium with manganese, nickel, or vanadium, and an interaction of vanadium with iron, molybdenum, zinc, or copper, when different metals in urine among the welders interacted with FEV1%. Conclusion Exposure to multiple metals in welders leads to a decline in lung function, with molybdenum, antimony, copper, and zinc as the leading contributors.

Quality evaluation of Chinese and global guidelines/consensus for TDM of anti-TNF-α agents in patients with inflammatory bowel disease / 中国药房

OBJECTIVE To evaluate the quality of guidelines/consensus on therapeutic drug monitoring （TDM） of anti-tumor necrosis factor-α （TNF-α） in patients with inflammatory bowel disease （IBD） in China and globally. METHODS PubMed， Embase， CNKI， Wanfang data， VIP， and release websites of guidelines/consensus in China and globally were searched to collect guidelines/expert consensus on TDM with anti-TNF-α for IBD patients. The search period was from database establishment to June 2023. After two investigators independently screened the literature and extracted the data， the methodological quality of the included guidelines/consensuses was evaluated using the Appraisal of Guidelines for Research and Evaluation Ⅱ. The main recommendations of the included guidelines/consensuses were summarized. RESULTS A total of 9 articles were included， 3 were guidelines and 6 were expert consensus. The standardized percentages of the 9 guidelines/consensus in the 6 dimensions （scope and aims， participants， rigor of formulation， clarity of expression， application， and editorial independence） were 90.43%， 41.98%， 52.55%， 85.49%， 19.00%， and 76.85%， respectively. Eight guidelines/consensus had a recommendation of grade B and one consensus of grade C. The main recommendations involve TDM application scenarios， threshold ranges， strategy adjustments， detection methods， and interpretation of results. Most guidelines/consensus recommend passive TDM for non-responders. It is recommended to set the TDM concentration range according to the expected treatment results and make strategy adjustments in combination with the disease condition and TDM results. Additionally， the same test method is recommended for the same patient. Some guidelines/consensus hold that no differences were noted in the interpretation of results between biosimilar and original drug. CONCLUSIONS The overall quality of the included guidelines/consensus was fair， with relatively consistent recommendation. Clinicians need to understand the characteristics and limitations of TDM with this class of drugs， and interpret and apply results of TDM in combination with specific clinical treatment goals.

Interventional effect and mechanism of 1，8-cineole on pancreatic β cell ferroptosis induced by type 2 diabetes / 中国药房

OBJECTIVE To study the interventional effect and mechanism of 1，8-cineole on pancreatic β cell ferroptosis induced by type 2 diabetes. METHODS In vitro ferroptosis model was established in pancreatic β cells of mice by using high glucose. The effects of low-dose and high-dose 1，8-cineole （0.25， 0.5 μmol/L） on the level of Fe2+ in pancreatic β cells were investigated. The effects of 1，8-cineole （0.5 μmol/L） combined with ferroptosis inducer Erastin （20 μmol/L） and ferroptosis inhibitor Ferrostatin-1 （20 μmol/L） on the protein expressions of glutathione peroxidase-4 （GPX4） and cyclooxygenase-2 （COX2） were also detected. The type 2 diabetes model mice were established by feeding high-sugar and high-fat diet combined with intraperitoneal injection of streptozotocin. The effects of low-dose and high-dose 1，8-cineole （50， 200 mg/kg） on the pathological morphology of pancreatic tissue， the content of iron as well as the protein expressions of GPX4 and COX2 were investigated. RESULTS The results of the cell experiment showed that compared with the model group， pretreatment with 1，8-cineole significantly reduced intracellular Fe2+ levels and upregulated GPX4 protein expression， while downregulated COX2 protein expression in pancreatic β cells （P＜0.05）. After combining with Ferrostatin-1， the expression trends of the above two proteins were the same， while there was no statistically significant difference after combining with Erastin. The results of animal experiments showed that compared with the model group， after intervention with 1，8-cineole， the structure of the pancreatic islets in mice recovered intact and their morphology improved； the iron content of pancreatic tissue and protein expression of COX2 were decreased significantly （P＜0.05）， while protein expression of GPX4 was increased significantly （P＜0.05）. CONCLUSIONS 1，8-cineole could ameliorate pancreatic β cell injury induced by diabetes， the mechanism of which may be related to reducing intracellular iron deposition and regulating ferroptosis-related proteins.

Effects and clinical significance of NLRP3 inflammasome activated by IL-17A in CRSwNP / 中华耳鼻咽喉头颈外科杂志

Objective: To investigate the effects and clinical significance of NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome activated by interleukin (IL)-17A in chronic rhinosinusitis with nasal polyps (CRSwNP). Methods: Patients underwent nasal endoscopic surgery in the Third Affiliated Hospital of Sun Yat-sen University from January 2020 to December 2021 were collected, including 28 CRSwNP (including 19 males and 9 females, aged 19 to 67 years), 22 chronic rhinosinusitis without nasal polyps (CRSsNP) and 22 controls. qRT-PCR was used to detect the expressions of IL-17A, NLRP3, IL-1β and IL-18 in the three groups, and their correlations were analyzed. The positions of IL-17A, NLRP3 and IL-18 in nasal polys were analyzed by immunofluorescence. Western Blotting and ELISA were employed to detect the expression of NLRP3, IL-1β and IL-18 in the human nasal epithelial cells after using IL-17A stimulation or IL-17A receptor inhibitor. Immunofluorescence was used to observe the NLRP3, IL-1β, and IL-18 protein expression after IL-17A stimulating human nasal epithelial cells, and after the use of IL-17A receptor inhibitor and NLRP3 inhibitor MCC950. The correlations between NLRP3, IL-1β, IL-18 and CT scores, nasal endoscopic scores, visual analogue scale (VAS) scores, and sino-nasal outcome test (SNOT) 22 scores of CRSwNP patients were analyzed. SPSS 20.0 software was used for statistical analysis. Results: The expressions of IL-17A, NLRP3, IL-1β and IL-18 in the tissues of CRSwNP patients were significantly higher than those in CRSsNP group(P=0.018,P<0.001,P=0.005, P=0.016) and the control group(all P<0.001). IL-17A was positively correlated with the expression of NLRP3, IL-1β, and IL-18(r ralue was 0.643,0.650,0.629,respectively, all P<0.05). IL-17A, NLRP3, and IL-18 were co-localized in the epithelial propria of polyp tissue. IL-17A stimulated the expressions of NLRP3, IL-1β, and IL-18 in human nasal epithelial cells. After the use of IL-17A receptor inhibitor, the expressions of NLRP3, IL-1β, and IL-18 were significantly down-regulated. After the use of NLRP3 inhibitor MCC950, IL-17A was significantly down-regulated to promote the expression of NLRP3, IL-1β, and IL-18. The expressions of NLRP3, IL-1β and IL-18 were positively correlated with CT, nasal endoscopy, VAS, and SNOT22 scores in patients with CRSwNP. Conclusions: IL-17A promotes the release of IL-1β and IL-18 by activating the NLRP3 inflammasome and aggravates the severity of the disease in CRSwNP.

Mechanism of obesity affecting periodontal tissue regeneration and therapeutic strategies / 中华口腔医学杂志

Obesity is an important health problem in our society today, which can lead to the chronic low-grade inflammation state, to be an inducement for many chronic diseases such as hypertension, type 2 diabetes and non-alcoholic fatty liver disease. As a common oral chronic infectious disease, periodontitis is mainly characterized by gingival inflammation, periodontal pocket formation, alveolar bone resorption and tooth mobility. The ultimate goal of periodontitis treatment is to achieve periodontal tissue regeneration in the defect area. As a major risk factor for periodontitis, obesity can alter the periodontal inflammatory microenvironment in multiple ways, affecting the effects of periodontal tissue regeneration ultimately. Therefore, this paper will review the relationship between obesity and periodontal tissue regeneration, mechanism of obesity affecting periodontal tissue regeneration and the therapeutic strategies of periodontal tissue regeneration, providing new ideas for periodontal tissue regeneration treatment in obesity.

Analysis of the burden of disease attributable to high temperature exposure in China and globally from 1990 to 2019 / 中华劳动卫生职业病杂志

Objective: To analyze the burden of disease attributable to high temperature exposure in China and globally from 1990 to 2019, and to study the current burden of disease in relevant populations. Methods: In October 2021, based on data from the global burden of disease 2019 (GBD 2019) study, population attributable fraction (PAF), number of deaths, mortality, disability-adjusted life year (DALY) and DALY rate of Chinese and global populations with different ages and genders in 1990 and 2019 were extracted and analyzed. The rate of change was calculated, the mortality rate was normalized by the age structure of the world standard population, and the causes of disease burden caused by high temperature exposure of Chinese residents were analyzed. Results: In 2019, compared with 1990, the PAF of Chinese and global population decreased by 43.98% and 12.41% respectively, the number of deaths increased by 29.55% and 49.40% respectively, the crude mortality rate increased by 7.81% and 3.30% respectively, the DALY decreased by 48.12% and 14.41% respectively, and the DALY rate decreased by 56.82% and 40.82% respectively. The mortality rate of the ≥70 age group was higher than that of other groups. The disease burden indicators such as PAF, standardized mortality and DALY attributable to high temperature exposure in men were higher than those in women. In 2019, the main cause of DALY affected by high temperature exposure in Chinese population was ischemic heart disease (84400 person-years), and the main cause of death was ischemic heart disease (4900 cases). Conclusion: The burden of diseases attributable to high temperature exposure is still serious in China and the world at large. Targeted interventions should be formulated for men, the elderly and people with occupational exposure, and a sound surveillance system should be established to reduce the burden of diseases caused by high temperature exposure.

Clinical and pathological characteristics of immune-mediated liver injury caused by immune checkpoint inhibitors / 中华内科杂志

Objective: Cancer immunotherapy can lead to various side effects, termed immune-related adverse events (irAE). This study summarized and analyzed the clinical and pathological characteristics of immune-mediated liver injury caused by immune checkpoint inhibitors (ILICI). Methods: This is a retrospective case series study involving 11 patients diagnosed with ILICI at the Peking Union Medical College Hospital from November 2019 to November 2021. Patient demographic information and clinical data, including gender, age, ILICI onset, clinical and radiological manifestations, pathological features, treatment, and resumption of ICI were retrospectively collected and analyzed. Results: The patients were primarily males (9/11) with a median age of 65 (range: 32-73) years. ICI mainly resulted in either partial remission (4/11) or stable disease (3/11). ILICI occurred after a median of two cycles of anti-programmed cell death-1 (PD-1) therapy, with a median time from the initial and last anti-PD-1 therapy to ILICI onset of 57 days and 17 days, respectively. ILICI was mostly severe (3/11) or very severe (6/11). While the clinical and radiological manifestations were non-specific, the pathological features were active lobular hepatitis and portal inflammation, with prominent CD8+T lymphocyte infiltration. The basic treatment was hepatoprotective drugs (10/11). Glucocorticoids were used as the primary therapy (9/11) but were ineffective in 4 of 9 cases. Of these, 3 of 9 cases received combined treatment with mycophenolate mofetil (MMF), only one of whom achieved remission. By the end of the study, 2 of 11 cases had resumed ICI and neither had experienced an ILICI relapse. Conclusion: The ILICI patients in this study had a corresponding history of ICI treatment and pathological features. The main treatment included hepatoprotective drugs and glucocorticoids. Immunosuppressive drugs were added for some cases but had poor efficacy.

A cohort study of infant development and health in Tianjin / 中国学校卫生

Objective@#To investigate the current situation of obesity and related metabolic abnormalities among preschool children, so as to provide theoretical support for future intervention.@*Methods@#A cohort of 3 952 children, born in Tianjin and enrolled in the kindergarten from September 2017 to October 2018, were selected to conduct a baseline survey and a three-year follow-up (questionnaire survey, physical examination and laboratory testing). At the same time, a two-way cohort study was conducted to retrospectively collect maternal prenatal examination, delivery and regular physical examination information of children from birth to preschool age from Tianjin Maternal and Child Health Information System.@*Results@#A total of 3 935, 3 654 and 2 739 children completed the follow up in the primary, middle and senior classes of kindergarten respectively. The height and weight of pre-school children increased with age, while the percentage of body fat decreased with age ( β-trend =-0.74, P <0.01). During three-year follow up, height, weight and body mass index of boys were higher than girls (P<0.05), while the percentage of body fat was lower than girls (primary class: 17.5%,18.5%; middle class: 16.4%,17.2%; senior class: 16.1%,17.1%, P <0.05). The detection rate of overweight (including obesity) and obesity increased with age( χ 2 trend were 15.51,38.72, P <0.05). The total detection rate of obesity increased from 5.4% at the baseline level to 9.6%. Laboratory test results showed that the detection rates of fasting blood glucose of boys were higher than that of girls in primary class, but blood lipid abnormalities were in the opposite (glucose: 7.7%, 4.8 %; lipid: 23.8% , 27.7%)( χ 2=12.01, 6.63, P <0.05).@*Conclusion@#The study has established a large growth cohort starting from the early embryonic stage, which will help to establish the strategies to promote children s health and prevent obesity and chronic diseases from multidimensional perspectives.

Research Progress on the Mechanism of Macrophages Regulating Hematopoiesis in Bone Marrow Microenvironment--Review / 中国实验血液学杂志

Bone marrow macrophage is an important component of bone marrow microenvironment, which is closely related to hematopoietic regulation and hematopoietic stem cell transplantation(HSCT). Recent studies have shown that bone marrow macrophage is an important part of hematopoietic stem cell niche, which can help regulate the mobilization and function of hematopoietic stem/progenitor cells. After HSCT, the microenvironment of bone marrow is damaged and a large number of macrophages infiltrate into the bone marrow. Regulating the macrophage-related signal pathways can promote the recovery of hematopoiesis and the reconstruction of hematopoietic function. Co-culture of macrophages and hematopoietic stem cells (HSC) in vitro significantly increased the number of HSCs and their ability of clone formation, which suggests that macrophages play an important role in the regulation of hematopoiesis in the hematopoietic microenvironment of bone marrow. This paper reviews the recent research progress on the role of macrophages in bone marrow hematopoietic microenvironment.

Hepatocyte steatosis activates macrophage inflammatory response accelerating atherosclerosis development / 浙江大学学报·医学版

OBJECTIVES@#To investigate the mechanism of comorbidity between non-alcoholic fatty liver disease (NAFLD) and atherosclerosis (AS) based on metabolomics and network pharmacology.@*METHODS@#Six ApoE－/－ mice were fed with a high-fat diet for 16 weeks as a comorbid model of NAFLD and AS (model group). Normal diet was given to 6 wildtype C57BL/6J mice (control group). Serum samples were taken from both groups for a non-targeted metabolomics assay to identify differential metabolites. Network pharmacology was applied to explore the possible mechanistic effects of differential metabolites on AS and NAFLD. An in vitro comorbid cell model was constructed using NCTC1469 cells and RAW264.7 macrophage. Cellular lipid accumulation, cell viability, morphology and function of mitochondria were detected with oil red O staining, CCK-8 assay, transmission electron microscopy and JC-1 staining, respectively.@*RESULTS@#A total of 85 differential metabolites associated with comorbidity of NAFLD and AS were identified. The top 20 differential metabolites were subjected to network pharmacology analysis, which showed that the core targets of differential metabolites related to AS and NAFLD were STAT3, EGFR, MAPK14, PPARG, NFKB1, PTGS2, ESR1, PPARA, PTPN1 and SCD. The Kyoto Encyclopedia of Genes and Genomes showed the top 10 signaling pathways were PPAR signaling pathway, AGE-RAGE signaling pathway in diabetic complications, alcoholic liver disease, prolactin signaling pathway, insulin resistance, TNF signaling pathway, hepatitis B, the relax in signaling pathway, IL-17 signaling pathway and NAFLD. Experimental validation showed that lipid metabolism-related genes PPARG, PPARA, PTPN1, and SCD were significantly changed in hepatocyte models, and steatotic hepatocytes affected the expression of macrophage inflammation-related genes STAT3, NFKB1 and PTGS2; steatotic hepatocytes promoted the formation of foam cells and exacerbated the accumulation of lipids in foam cells; the disrupted morphology, impaired function, and increased reactive oxygen species production were observed in steatotic hepatocyte mitochondria, while the formation of foam cells aggravated mitochondrial damage.@*CONCLUSIONS@#Abnormal lipid metabolism and inflammatory response are distinctive features of comorbid AS and NAFLD. Hepatocyte steatosis causes mitochondrial damage, which leads to mitochondrial dysfunction, increased reactive oxygen species and activation of macrophage inflammatory response, resulting in the acceleration of AS development.

Pathological Changes and Cause of Death Associated with the Global Novel Coronavirus Disease (COVID-19) / 法医学杂志

The coronavirus disease 2019 (COVID-19) has been a global epidemic for more than three years, causing more than 6.9 million deaths. COVID-19 has the clinical characteristics of strong infectivity and long incubation period, and can cause multi-system damage, mainly lung damage, clinical symptoms of acute respiratory distress syndrome (ARDS) and systemic multiple organ damage. The SARS-CoV-2 virus is still constantly mutating. At present, there is no global consensus on the pathological changes of COVID-19 associated deaths and even no consensus on the criteria for determining the cause of death. The investigation of the basic pathological changes and progression of the disease is helpful to guide the clinical treatment and the development of therapeutic drugs. This paper reviews the autopsy reports and related literature published worldwide from February 2020 to June 2023, with a clear number of autopsy cases and corresponding pathological changes of vital organs as the inclusion criteria. A total of 1 111 autopsy cases from 65 papers in 18 countries are included. Pathological manifestations and causes of death are classified and statistically analyzed, common pathological changes of COVID-19 are summarized, and analytical conclusions are drawn, suggesting that COVID-19 infection can cause life-threatening pathological changes in vital organs. On the basis of different health levels of infected groups, the direct cause of death is mainly severe lung damage and secondary systemic multiple organ failure.

Analysis of clinical features and ATRX gene variants in a Chinese pedigree affected with X-linked alpha thalassemia mental retardation (ATR-X) syndrome / 中华医学遗传学杂志

OBJECTIVE@#To explore the clinical characteristics and genetic basis of two brothers featuring X-linked alpha thalassemia mental retardation (ATR-X) syndrome.@*METHODS@#An infant who had presented at the Qilu Children's Hospital in 2020 for unstable upright head and inability to roll over and his family were selected as the study subjects. The clinical features of the child and one of his brothers were summarized, and their genomic DNA was subjected to targeted capture and next generation sequencing (NGS).@*RESULTS@#The brothers had presented with mental retardation and facial dysmorphisms. NGS revealed that they had both harbored a hemizygous c.5275C>A variant of the ATRX gene located on the X chromosome, which was inherited from their mother.@*CONCLUSION@#The siblings were diagnosed with ATR-X syndrome. The discovery of the c.5275C>A variant has enriched the mutational spectrum of the ATRX gene.

Application and prospect of natural active ingredients of traditional Chinese medicine in immunological adjuvant for influenza vaccine / 中国中药杂志

Vaccination is an effective method for preventing influenza, and adjuvants can enhance the immune response intensity and persistence of influenza vaccines. However, there are currently shortcomings in clinical adjuvant approvals, ineffectiveness against weak antigens, and a tendency to cause headaches. Therefore, the development of safe and effective novel adjuvants for influenza vaccines is particularly important to enhance vaccine immunogenicity and safety. Given the wide range of sources, high safety, and biodegradability of traditional Chinese medicine(TCM), some studies have described it as a vaccine adjuvant. This article reviewed the current status and challenges of influenza vaccine adjuvants, summarized the types of TCM adjuvants, the safety and immunomodulatory effects of natural active ingredients from TCM combined with influenza vaccines, the role of TCM adjuvants in antigen storage, antigen presentation capability, immune cells and cytokines, and immune responses, and analyzed the advantages and disadvantages of TCM adjuvants compared with small molecule adjuvants, with the aim of promoting the clinical development and commercialization of TCM adjuvants for influenza vaccines.

Clinical symptoms and distribution characteristics traditional Chinese medicine syndromes of pulmonary nodules / 中国中药杂志

A cross-sectional study method combined with two types of traditional Chinese medicine(TCM) syndrome differentiation methods was adopted to investigate the clinical symptoms and distribution characteristics of TCM syndromes in patients with pulmonary nodules from the perspectives of number, size, nature, and stability of pulmonary nodules by using the χ~2 test, systematic clustering and Apriori algorithm correlation analysis. The common clinical symptoms of pulmonary nodules were fatigue(77.35%) and irritability(75.40%), and 40 symptoms were clustered into 3 groups(digestive system symptoms, respiratory system symptoms, and emotional and systemic symptoms) and 8 major symptom categories. The proportion of cold and heat in complexity syndrome(63.43%) was higher based on cold-heat syndrome differentiation. The top two syndromes were Qi deficiency syndrome(88.03%) and Qi depression syndrome(83.17%) based on disease syndrome differentiation. Yang deficiency syndrome(60.52%) was more than Yin deficiency syndrome(50.16%). There were higher proportions of phlegm syndrome(78.67%) and Yang deficiency syndrome(69.33%) of so-litary pulmonary nodules in terms of the number of pulmonary nodules. In terms of size, the proportion of phlegm syndrome decreased as the mean diameter of pulmonary nodules increased, while the proportions of Yang deficiency syndrome and blood stasis syndrome increased. The distribution of Qi depression syndrome was more in those with mean diameter<10 mm(85.02%, P=0.044) and cold syndrome was more in those with mean diameter ≥10 mm(16.67%, P=0.024). In terms of the nature of pulmonary nodules, the proportions of Qi depression syndrome and heat syndrome decreased with the increase in solid components of pulmonary nodules, while the proportions of Yin deficiency syndrome and cold and heat in complexity syndrome increased. The blood stasis syndrome accounted for a higher proportion of pulmonary nodules with solid components. In terms of the stability of pulmonary nodules, dampness syndrome(72.97%), blood stasis syndrome(37.84%), and cold and heat in complexity syndrome(70.27%) accounted for higher proportions. In addition, patients with new nodules presented higher proportions in Qi inversion syndrome(52.00%, P=0.007) and cold and heat in complexity syndrome(66.00%, P=0.008). Meanwhile, 11 syndromes were associated and 4 common compound syndromes were obtained(Qi deficiency and depression syndrome, Qi depression and phlegm coagulation syndrome, Qi deficiency and phlegm coagulation syndrome, and Qi deficiency and dampness obstruction syndrome). Qi deficiency syndrome and Qi depression syndrome could be associated with other syndromes. The results show that the main clinical symptoms of pulmonary nodules are fatigue and irritability. The main TCM syndromes of pulmonary nodules are Qi deficiency syndrome, Qi depression syndrome, Yang deficiency syndrome, and cold and heat in complexity syndrome. The distribution of TCM syndromes is significantly correlated with the size of pulmonary nodules and the presence or absence of new nodules. The common compound syndromes are Qi deficiency and depression syndrome, Qi depression and phlegm coagulation syndrome, Qi deficiency and phlegm coagulation syndrome, and Qi deficiency and dampness obstruction syndrome.

Effects of long-term oral administration of antipsychotic clozapine on the ocular surface / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To study the effects of long-term use of clozapine on tear film stability and ocular surface tissue structure.METHODS: Case-control study was conducted on 45 patients(group 1)who were diagnosed with schizophrenia and treated with clozapine for 3.45±0.72a between March 2021 and December 2021. Another 45 healthy subjects(group 2)served as controls, whose demographic characteristics were similar to those of group 1. Patients' dry eye symptoms were investigated using OSDI questionnaire, tear secretion was detected by the Schirmer I test, ocular surface damage was assessed by the ocular surface staining score, and comprehensive ophthalmic examination was performed on all patients through LipiView ocular surface interferometer, ocular surface integrated analyzer, corneal confocal microscope and slit lamp photographic system.RESULTS: Slit-lamp photography showed diffuse grayish-white spot-like opacification in the corneal stroma of group 1, accompanied by brown star-like opacification in the center of the anterior capsule of the lens. OSDI scores were 38.00(31.50, 48.50)and 15.00(9.00, 19.50)in the two groups respectively. Schirmer test showed that the group 1 was 5.27±2.18mm/5min, while group 2 was 15.62±3.05mm/5min. Corneal fluorescein staining score: 4.00(2.50, 5.00)for group 1 and 1.00(0.00, 1.50)for group 2. The lissamine green staining score for the conjunctiva was 9.00(6.50, 10.00)and 3.00(2.00, 3.50)for the two groups, respectively. LipiView detected lipid layer thickness(LLT), suggesting that the results of group 1 and group 2 were similar, respectively 75.91±15.51 and 77.24±12.11nm; and the results were similar for the lid gland deficiency score, with 1.37±0.26 and 1.29±0.31 points, respectively. The mean tear meniscus height in group 1 was 0.13±0.06mm, which was lower than 0.23±0.04mm of group 2. Non-invasive breakup time(NIBUT)was 6.04±2.62 and 11.4±2.74s in group 1 and group 2 respectively. OSDI score, Schirmer Ⅰ test, ocular surface staining score, tear meniscus height and NIBUT were significantly different between the two groups(P&#x003C;0.05). Confocal corneal microscopy suggested decreased corneal nerve fiber density with stromal layer inflammatory cell infiltration and pigmentation in group 1.CONCLUSION: The antipsychotic drug clozapine can induce dry eye with a range of ocular surface injuries such as corneal pigmentation, and patients who taking such drugs should be routinely examined by an ophthalmologist.

Bioorthogonal click-to-release reaction for regulating iodo-BODIPY PDT probe / 药学学报

In this study, we synthesized six tetrazine-dipyrromethene boron difluoride (BODIPY) probes and achieved a remarkable up to 14-fold increase in singlet oxygen yield via tetrazine bioorthogonal click-to-release reactions. We systematically investigated the photodynamic activity of these probes, revealing crucial structure-activity relationships. Additionally, we evaluated the stability and release kinetics of these probes and identified P5 and P6 as ideal candidates for photodynamic therapy in live cells. This innovative strategy opens new avenues for fine-tuning the photodynamic properties of BODIPY dyes, thereby expanding their utility in cancer therapy.

Status quo and disease burden of occupational pneumoconiosis in Qinghai Province from 2015 to 2019 / 环境与职业医学

Background Occupational pneumoconiosis is the most common occupational disease in Qinghai Province and China. From the perspective of public health, it is important to assess the disease burden using disability-adjusted life years (DALY) and economic losses. Objective To evaluate the disease burden of occupational pneumoconiosis in Qinghai Province, and to provide a basis for the formulation and implementation of relevant prevention and control strategies. Methods Based on the registered data, a database of occupational pneumoconiosis cases confirmed and reported in Qinghai Province was established. The survival status and death dateof occupational pneumoconiosis patients from 2015 to 2019 were confirmed by on-site visit, telephone survey, matching search of Death Information Registration and Management System, and consulting other departments. The life loss due to occupational pneumoconiosis from 2015 to 2019 was assessed using DALY as an indicator and data from the Global Burden of Disease 2019 (GBD 2019) study. Inpatients with officially diagnosed occupational pneumoconiosis from a hospital in Qinghai Province in 2019 were selected as study subjects, the direct economic loss was evaluated with hospitalization expenses, and the indirect economic loss due to occupational pneumoconiosis in Qinghai Province in 2019 was calculated by human capital approach. Results From 2015 to 2019, 505 new cases of occupational pneumoconiosis were reported in Qinghai Province, and there were 348 death cases. Prevalent cases and years lost due to disability (YLD) due to occupational pneumoconiosis were increased, while DALY and years of life lost (YLL) due to occupational pneumoconiosis decreased firstly and then increased. In each year, there were 87% or more of the DALY, YLL, or YLD attributed to silicosis and coal workers' pneumoconiosis. In 2019, the occupational pneumoconiosis-associated DALY was 2173.55 person years. The total hospitalization expense incurred by 42 inpatients with occupational pneumoconiosis was 1256345.19 yuan. The total hospitalization expense and average daily cost of the inpatients with stageⅡand Ⅲ pneumoconiosis were higher than that of the inpatients with stageⅠ (P<0.05), and the hospitalization expense was higher in the ≥60 years age group than in the <60 years age group (P<0.05). In 2019, the indirect economic burden incurred by occupational pneumoconiosis in Qinghai Province was 44108581.65 yuan, and accounted for 0.15‰ of the gross domestic product (GDP) of the province. Conclusion The disease burden associated with occupational pneumoconiosis in Qinghai Province are outstanding. Silicosis and coal workers' pneumoconiosis are the key contributors. Targeted intervention measures including dust hazard control, enterprise management, follow-up and rehabilitation management of pneumoconiosis should be taken to prevent and control the occurrence and progression of pneumoconiosis and alleviate disease burden of pneumoconiosis.

Didangtang： A Review / 中国实验方剂学杂志

As one of the classic prescriptions of traditional Chinese medicine， Didangtang is an effective prescription for breaking and expelling blood stasis. It was considered that Didangtang damage the healthy qi and contained toxic Chinese medicinal materials such as leeches and gadflies， and thus it was rarely used. However， as the attention to classic prescriptions increases， Didangtang has been widely used in clinical practice and demonstrated definite efficacy in treating diabetes mellitus and its complications， malignant tumors， Alzheimer's disease， stroke， renal diseases， cardiovascular diseases， peripheral vascular diseases， gynecological disease， and male diseases according to the disease location， pathogenesis， symptoms， and pharmacological effects. Didangtang has the effects of mitigating insulin resistance， improving microvascular and peripheral vascular circulation， delaying diabetic macrovascular lesions， preventing vascular fibrosis， improving immunity， inhibiting tumor growth， protecting the brain tissue， nerve cells， vascular endothelial function， and kidney， reducing inflammation， and delaying aging. This paper summarizes the clinical application of Didangtang and initially explores the underlying mechanism.

Retrospective Clinical Study on Integrated Chinese and Western Medicine in Treatment of Limited-Stage Small Cell Lung Cancer / 中国结合医学杂志

OBJECTIVE@#To investigate the efficacy of integrated Chinese and Western medicine extending the progression-free survival (PFS) and overall survival (OS) of limited-stage small cell lung cancer (LS-SCLC) patients after the first-line chemoradiotherapy.@*METHODS@#The data of 67 LS-SCLC patients who received combined treatment of CM and Western medicine (WM) between January 2013 and May 2020 at the outpatient clinic of Guang'anmen Hospital were retrospectively analyzed. Thirty-six LS-SCLC patients who received only WM treatment was used as the WM control group. The medical data of the two groups were statistically analyzed. Survival analysis was performed using the product-limit method (Kaplan-Meier analysis). The median OS and PFS were calculated, and survival curves were compared by the Log rank test. The cumulative survival rates at 1, 2, and 5 years were estimated by the life table analysis. Stratified survival analysis was performed between patients with different CM administration time.@*RESULTS@#The median PFS in the CM and WM combination treatment group and the WM group were 19 months (95% CI: 12.357-25.643) vs. 9 months (95% CI: 5.957-12.043), HR=0.43 (95% CI: 0.27-0.69, P<0.001), respectively. The median OS in the CM and WM combination group and the WM group were 34 months (95% CI could not be calculated) vs. 18.63 months (95% CI: 16.425-20.835), HR=0.40 (95% CI: 0.24-0.66, P<0.001), respectively. Similar results were obtained in the further stratified analysis of whether the duration of CM administration exceeded 18 and 24 months (P<0.001).@*CONCLUSION@#The combination treatment of CM and WM with continuing oral administration of CM treatment after the first-line chemoradiotherapy for LS-SCLC patients produced better prognosis, lower risks of progression, and longer survival than the WM treatment alone. (Registration No. ChiCTR2200056616).