Traditional Chinese Medicine Syndromes in Depressive Episodes of Bipolar Disorder Based on Cluster Analysis and Bayesian Network：A Cross-sectional Study / 中医杂志

ObjectiveTo explore the elements， distribution and characteristics of traditional Chinese medicine （TCM） syndromes in depressive episodes of bipolar disorder （BD）. MethodsBasic information， along with the four examination information， the Hamilton Depression Scale and Young Mania Rating Scale scores， were collected from 293 outpatients with BD at Beijing Anding Hospital， Capital Medical University. The four examination information with an occurrence rate greater than 12% were retained. The R language “dist” function was used to calculate the distances between samples using the Euclidean distance method. The hierarchical clustering of the four examination information was performed using the “hclust” function and the squared Euclidean distance method. A team of five researchers was formed to determine the nature and location of the essential elements of TCM syndrome in BD based on the clustering results. The PC algorithm was used to construct a Bayesian network model of the essential elements. The working group combined the essential elements of TCM syndromes in the Bayesian network according to the reference model results， and then extracted common TCM syndromes. The score of each patient based on the essential elements was matched with the common TCM syndromes to determine the syndrome type of each patient. The working group then performs conformity and revision based on this， obtaining the final distribution of TCM syndromes for the patients. ResultsThere were 77 common TCM symptoms in BD with a frequency greater than 12%. The top 15 symptoms with higher frequencies were slippery pulse， mental fatigue and lack of strength， wiry pulse， excessive rumination， preference for solitude， vexation， agitation and irritability， dry mouth， palpitations， profuse dreaming， unwarranted worries， chest oppression， thin white coating， amnesia， frequent sighing， and poor appetite. TCM syndrome elements of BD can be grouped into 11 categories. The nature of disease-related essential elements included fire， qi deficiency， blood deficiency， qi counterflow， yin deficiency， dampness， heat， fire from constraint， and phlegm. The location of disease-related essential elements included heart， liver， spleen， stomach， kidney， bladder channel， and gallbladder. By constructing a Bayesian network model and considering the opinions from the experts， six common syndromes of BD were identified， among which the highest proportion was heart-stomach heat accumulation， accounting for 27.99% （82 cases）， followed by heart-spleen deficiency （55 cases， 18.77%）， non-interaction between the heart and the kidney （49 cases， 16.72%）， liver constraint and blood deficiency （42 cases， 14.33%）， heart qi deficiency （37 cases， 12.63%）， and damp-heat in the liver and gallbladder （28 cases， 9.56%）. ConclusionsThe nature of disease-related elements of BD are predominantly fire and heat， while the location of disease-related essential elements are primarily associated with the heart， liver， and spleen. The most common TCM syndromes are heart-stomach heat accumulation and heart-spleen deficiency.

CD47 blockade improves the therapeutic effect of osimertinib in non-small cell lung cancer / 医学前沿

The third-generation epidermal growth factor receptor (EGFR) inhibitor osimertinib (OSI) has been approved as the first-line treatment for EGFR-mutant non-small cell lung cancer (NSCLC). This study aims to explore a rational combination strategy for enhancing the OSI efficacy. In this study, OSI induced higher CD47 expression, an important anti-phagocytic immune checkpoint, via the NF-κB pathway in EGFR-mutant NSCLC HCC827 and NCI-H1975 cells. The combination treatment of OSI and the anti-CD47 antibody exhibited dramatically increasing phagocytosis in HCC827 and NCI-H1975 cells, which highly relied on the antibody-dependent cellular phagocytosis effect. Consistently, the enhanced phagocytosis index from combination treatment was reversed in CD47 knockout HCC827 cells. Meanwhile, combining the anti-CD47 antibody significantly augmented the anticancer effect of OSI in HCC827 xenograft mice model. Notably, OSI induced the surface exposure of "eat me" signal calreticulin and reduced the expression of immune-inhibitory receptor PD-L1 in cancer cells, which might contribute to the increased phagocytosis on cancer cells pretreated with OSI. In summary, these findings suggest the multidimensional regulation by OSI and encourage the further exploration of combining anti-CD47 antibody with OSI as a new strategy to enhance the anticancer efficacy in EGFR-mutant NSCLC with CD47 activation induced by OSI.

Clinical Significance of Thrombospondin Type 1 Domain-Containing 7A and Neural Epidermal Growth Factor-Like 1 Protein in M-Type Phospholipase A2 Receptor-Negative Membranous Nephropathy / 中国医学科学院学报

Objective To investigate the clinical significance of thrombospondin type 1 domain-containing 7A (THSD7A) and neural epidermal growth factor-like 1 protein (NELL1) in phospholipase A2 receptor (PLA2R)-negative membranous nephropathy (MN). Methods A total of 116 PLA2R-negative MN patients treated in Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University from 2014 to 2021 were enrolled in this study.Immunohistochemistry was employed to detect THSD7A and NELL1 in the renal tissue.The pathological characteristics,treatment,and prognosis were compared between positive and negative groups. Results The 116 PLA2R-negative MN patients included 23 THSD7A-positive patients and 9 NELL1-positive patients.One patient was tested positive for both proteins.The THSD7A-positive group showed higher positive rate of IgG4 (P=0.010),more obvious glomerular basement membrane (GBM) thickening (P=0.034),and higher proportion of stage Ⅱ MN and lower proportion of stage I MN (P=0.002) than the THSD7A-negative group.The NELL1-positive group had lower positive rates of C1q and IgG2 (P=0.029,P=0.001),less obvious GBM thickening (P<0.001),more extensive inflammatory cell infiltration (P=0.033),lower proportion of deposits on multi-locations (P=0.001),and lower proportion of atypical MN (P=0.010) than the NELL1-negative group.One patient with THSD7A-positive MN was diagnosed with colon cancer,while none of the NELL1-positive patients had malignancy.Survival analysis suggested that THSD7A-positive MN had worse composite remission (either complete remission or partial remission) of nephrotic syndrome than the negative group (P=0.016),whereas NELL1-positive MN exhibited better composite remission of nephrotic syndrome than the negative group (P=0.015).The MN patients only positive for NELL1 showed better composite remission of nephrotic syndrome than the MN patients only positive for THSD7A (P<0.001). Conclusions THSD7A- and NELL1-positive MN is more likely to be primary MN,and there is no significant malignancy indication.However,it might have a predictive value for the prognosis of MN.

The combination of high-frequency ultrasound and thyroid-stimulating hormone/thyroglobulin ratio in the diagnostic value of benign and malignant lesions of thyroid nodules / 中国医师进修杂志

Objective:To analyze the diagnostic value of high-frequency ultrasound combined with serum thyroid-stimulating hormone (TSH) / thyroglobulin (Tg) ratio for the benign and malignant lesions of thyroid nodules (TN).Methods:A retrospective analysis was made on the clinical data of 772 patients with TN admitted to Changxing County People′s Hospital from June 2020 to June 2021. All patients received high-frequency ultrasound examination and serum TSH detection, 320 patients (41.45%) received Tg detection to calculate the TSH/Tg ratio. According to the benign and malignant thyroid nodules, they were divided into benign group and malignant group based on the pathological results as the "gold standard". The ultrasonographic characteristics, serum TSH and Tg levels and TSH/Tg ratio of the two groups were compared, and the accuracy of high-frequency ultrasound, TSH/Tg ratio and the combination in the diagnosis of benign and malignant thyroid nodules were evaluated.Results:A total of 83 patients with thyroid nodules were diagnosed as malignant by pathological results. In the malignant group, the nodules were mostly irregular in shape, extremely low in internal echo, accompanied by calcification, aspect ratio ≥1 and enlarged cervical lymph nodes. The levels of TSH and Tg as well as the ratio of TSH/Tg in the malignant group were higher than those in the benign group (16.52 ± 4.49) mU/L vs. (6.75 ± 1.18) mU/L, (11.37 ± 3.16) kU/L vs. (8.14 ± 1.40) kU/L, 1.45 ± 0.76 vs. 0.83 ± 0.06, there were statistical differences( P<0.05). The sensitivity and accuracy of high-frequency ultrasound combined with TSH/Tg ratio in the diagnosis of benign and malignant thyroid nodules were 92.77%, 95.47%, and higher than those in the single diagnosis. Conclusions:The morphological high-frequency ultrasonography features of malignant thyroid nodules are mostly irregular, with extremely low internal echo, accompanied by calcification, aspect ratio ≥1 and cervical lymph node enlargement. TSH/Tg ratio is higher than that of benign thyroid nodules. The combination of high-frequency ultrasonography and TSH/Tg ratio can improve the diagnosis rate of thyroid cancer.

Effect of Gandouling Decoction Combined with Cognitive Behavioral Therapy on Impulse Control Disorders in Wilson's Disease with Syndrome of Combined Phlegm and Stasis / 中国实验方剂学杂志

ObjectiveTo observe the clinical efficacy of Gandouling decoction combined with cognitive behavioral therapy （CBT） in the treatment of impulse control disorders in patients with Wilson's disease （WD， syndrome of combined phlegm and stasis）. MethodA prospective study was conducted on 90 WD patients with the syndrome of combined phlegm and stasis and impulse control disorders （ICD） treated in the Department of Encephalopathy of the First Affiliated Hospital of Anhui University of Chinese Medicine from August 2018 to February 2023. They were randomized into a control group， a CBT group， and a treatment group， with 30 patients in each group. The control group received routine Western medicine treatment （basic copper removal）. The CBT group received cognitive behavioral therapy in addition to the therapy in the control group， and the treatment group received Gandouling decoction in addition to the therapy in the CBT group. Each course of treatment was 8 days， and the patients were treated for 4 courses. Before and after treatment， the 24-hour urine copper （24 h U-Cu）， non-ceruloplasmin-bound copper （NCC）， traditional Chinese medicine （TCM） syndrome score， unified WD rating scale part Ⅲ （UWDRS Ⅲ） score， Barratt Impulse Scale Version 11 （BIS-11） score， Buss-Perry aggression questionnaire （BPAQ） score， modified overt aggression scale （MOAS） score， and treatment emergent symptom scale （TESS） score of three groups of patients were determined and statistically analyzed. ResultBefore treatment， there was no statistically significant difference in the level of 24 h U-Cu or NCC among the three groups. After treatment， all the three groups showed an increase in 24 h U-Cu （P<0.01） and a decrease in the NCC level （P<0.05， P<0.01）. There was no significant difference in the 24 h U-Cu level among the three groups after treatment. After treatment， the NCC level showed no significant difference between the control group and the CBT group， while the NCC level in the treatment group was lower than that in the control group and CBT group （P<0.05）. Before treatment， there was no statistically significant difference in the TCM syndrome score among the three groups. After treatment， the TCM syndrome scores of all the three groups decreased （P<0.01）. Moreover， the treatment group had lower TCM syndrome score than the control group and CBT group （P<0.05）. Before treatment， the UWDRS Ⅲ， BIS-11， BPAQ， and MOAS scores had no statistically significant differences among the three groups. After treatment， the UWDRS Ⅲ， BIS-11， BPAQ， and MOAS in all the three groups declined （P<0.05）. Moreover， the CBT group and treatment group had lower UWDRS Ⅲ， BIS-11， BPAQ， and MOAS scores than the control group （P<0.05）， and the treatment group had lower BIS-11 and BPAQ scores than the CBT group （P<0.05）. ConclusionThe combination of Gandouling decoction and CBT can ameliorate impulse control disorders in the WD patients with combined phlegm and stasis.

Occurrence and influencing factors of medication deviation in elderly patients with chronic diseases / 中华老年医学杂志

Objective:To observe the occurrence of medication deviation in elderly patients with chronic diseases, and analyze the related factors leading to its occurrence.Methods:Convenience sampling method was used to select 164 elderly patients with chronic diseases who were discharged from the hospital after treatment from April 2021 to March 2022 as the study subjects.The pharmacists reviewed the patient's discharge medication and counted the occurrence of medication deviation.The patients were divided into the occurrence group and the non-occurrence group, and the relevant data of the two groups and their attending physicians were analyzed and compared. Logistic regression analysis was used to test the influencing factors of medication deviation in elderly patients with chronic diseases. Results:Medication deviation were identified in 110 of the 164 patients, and the incidence of medication deviation was 67.1%.Compared with the non-occurrence group, the number of diseases, discharge prescriptions of patients were more, the differences were statistically significant( Z=2.552, t=3.063, both P<0.05). The age of attending physicians in the occurrence group were younger, and their working years were shorter, professional title was lower compared with those in the non-occurrence group( Z=3.754, 3.713, Z=2.016, P<0.05 for all); Logistic regression analysis showed that the number of diseases and discharge prescriptions were the risk factors for medication deviation in elderly patients with chronic diseases( OR=1.260, 1.227, both P<0.05); older age and longer working years of attending physicians were the protective factors for medication deviation( OR=0.925, 0.930, both P<0.05). Conclusions:The incidence of medication deviation in elderly patients with chronic diseases in our hospital is high.Number of chronic diseases, discharge prescriptions, younger age and relatively shorter working years of attending physicians may lead to medication deviation.

Factors associated with hyperopia reserve among preschoolers in Suzhou High tech Zone / 中国学校卫生

Objective@#To investigate the influencing factors of preschoolers hyperopia reserve, and to provide a scientific basis for preschoolers to prevent myopia.@*Methods@#Visual screening and a questionnaire survey were conducted on 5 087 4-year old children in Suzhou High-tech Zone from September to December in 2020. The influencing factors of children s hyperopia reserve were analyzed by univariate analysis and Logistic regression model.@*Results@#A total of 997(19.6%) children had hyperopia reserve deficiency. Logistic regression showed that the negative factors associated with hyperopia reserve included being girl( OR=0.81, 95%CI =0.70-0.93), no food allergy( OR=0.78, 95%CI =0.63-0.96); and the positive factors included father myopia( OR=1.20, 95%CI =1.03-1.39), mother myopia( OR=1.17, 95%CI =1.01-1.36), exposure of night lights(for less than 1 hour: OR=1.53, 95%CI =1.21-1.92; for 1 to 3 hours: OR=1.48, 95%CI =1.09-2.00), insufficient vegetable intake( OR=1.26, 95%CI =1.07- 1.46 )( P <0.05).@*Conclusion@#Parental myopia, nighttime sleep environment and dietary factors have potential associations with hyperopia reserve deficiency among children. Corresponding measures should be actively taken to improve the preschoolers hyperopia reserve.

Comparison of the positional stability of two different methods of marking surface landmarks in radiotherapy patients with abdominal and pelvic fixation / 国际生物医学工程杂志

Objective:To compare the effects of two methods of marking surface landmarks on the patient’s positional stability when using a multifunctional body board in combination with thermoplastics to fix the abdominal and pelvic areas for radiotherapy patients.Methods:50 subjects who underwent positional fixation using a multifunctional body board in combination with thermoplastics from August 2022 to January 2023. The subjects were divided into two groups, A and B, with 25 cases each, according to the different methods of body surface marking. In group A, landmarks were marked on the body surface on the top edge of the thermoplastics. In group B, three sets of surface landmarks were marked on the patient’s body according to the laser line on the projection of the patient’s body surface when the thermoplastics were completed. Manual registration is performed using L3 to L5 as the main registration targets. The pre-treatment CBCT image is used to analyze the first-time positioning pass rate, setup errors in the x-, y-, and z-axis directions, and the distribution of positive and negative setup errors in both groups of patients. Results:The pass rates of the first-time positioning of patients in Groups A and B were 76.9% and 86.1%, respectively, which met the clinical requirements. Group B had a better first-time positioning pass rate than group A, and the difference between the two groups was statistically significant ( P < 0.05). The pendulum errors of group B were smaller than those of group A in both the x-axis and y-axis (all P < 0.05), and the difference between the two groups in terms of the pendulum errors in the z-axis direction was not statistically significant (all P > 0.05). The difference in the frequency distribution of the pendulum error in the positive and negative directions of the x- and z-axis between the two groups was not statistically significant (all P > 0.05). The difference in the frequency of distribution of the pendulum error in the positive and negative directions of the y-axis between the two groups was statistically significant ( P < 0.05). Conclusions:The proposed two methods of surface landmark marking are generally in line with the positioning requirements for conventional fractionation radiotherapy for abdominal and pelvic patients. Using a laser line on the projection of the patient’s body surface for three sets of surface landmark markings produces smaller setup errors and is better than using the top edge of the thermoplastics for surface landmark markings, improving the positional stability of abdominal and pelvic patients.

41 cases of chronic obstructive pulmonary disease caused by occupational irritating chemicals / 中华劳动卫生职业病杂志

Objective: To analyze the case characteristics of Chronic obstructive pulmonary disease caused by occupational irritant chemicals (OI-COPD). To provide basis for revising its diagnostic criteria. Methods: From June to December 2021, we investigated the information of OI-COPD patients confirmed by Shandong Institute of Occupational Health and Prevention of Occupational Diseases, Guangxi Zhuang Autonomous Region Institute of Occupational Disease Prevention and Control, Qingdao Central Hospital affiliated to Qingdao University and other diagnostic institutions in the past five years, a total of 41 cases. The basic information of OI-COPD cases, occupational risk factors exposure information, medical history, smoking history and clinical symptoms were analyzed retrospectively. The measurement data were tested for normal distribution, which was described by x±s, and compared between groups by t test; Those who do not conform to the normal distribution are described by the median [M (Q(1), Q(3)) ] and analyzed by nonparametric test; The counting data were expressed in frequency and rate (% ), and the comparison between groups was tested. Results: Of the 41 cases, 33 were male and 8 were female. The age of the patient diagnosed with OI-COPD was (49.5±10.3) years old, and the minimum age was 30 years old; Among them, 8 patients had a definite long-term smoking history (more than 5 years) ; The exposure duration of occupational risk factors was (18.6±10.3) years, of which 3 patients had exposure duration of less than 5 years; The occupational risk factors leading to OI-COPD include acids and acid-forming compounds, bases, aldehydes, nitrogen oxides, chlorine and its compounds, etc. The exposure level of occupational risk factors is related to the degree of COPD airflow restriction (χ(2)=6.17, P <0.05). 18 patients with diagnosis age <50 years old were diagnosed as early-onset COPD. The incidence of respiratory symptoms in the early diagnosis COPD group was lower than that in the non-early diagnosis COPD group, and the FEV1% pred was significantly higher than that in the non-early diagnosis COPD group. The difference was statistically significant (P<0.01 ) . Conclusion: The exposure level of occupational risk factors may be the risk factor affecting the degree of COPD airflow restriction. With the increase of the exposure level of COPD patients, the proportion of respiratory symptoms will also increase accordingly.

Expert consensus on late stage of critical care management / 中华内科杂志

We wished to establish an expert consensus on late stage of critical care (CC) management. The panel comprised 13 experts in CC medicine. Each statement was assessed based on the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) principle. Then, the Delphi method was adopted by 17 experts to reassess the following 28 statements. (1) ESCAPE has evolved from a strategy of delirium management to a strategy of late stage of CC management. (2) The new version of ESCAPE is a strategy for optimizing treatment and comprehensive care of critically ill patients (CIPs) after the rescue period, including early mobilization, early rehabilitation, nutritional support, sleep management, mental assessment, cognitive-function training, emotional support, and optimizing sedation and analgesia. (3) Disease assessment to determine the starting point of early mobilization, early rehabilitation, and early enteral nutrition. (4) Early mobilization has synergistic effects upon the recovery of organ function. (5) Early functional exercise and rehabilitation are important means to promote CIP recovery, and gives them a sense of future prospects. (6) Timely start of enteral nutrition is conducive to early mobilization and early rehabilitation. (7) The spontaneous breathing test should be started as soon as possible, and a weaning plan should be selected step-by-step. (8) The waking process of CIPs should be realized in a planned and purposeful way. (9) Establishment of a sleep-wake rhythm is the key to sleep management in post-CC management. (10) The spontaneous awakening trial, spontaneous breathing trial, and sleep management should be carried out together. (11) The depth of sedation should be adjusted dynamically in the late stage of CC period. (12) Standardized sedation assessment is the premise of rational sedation. (13) Appropriate sedative drugs should be selected according to the objectives of sedation and drug characteristics. (14) A goal-directed minimization strategy for sedation should be implemented. (15) The principle of analgesia must be mastered first. (16) Subjective assessment is preferred for analgesia assessment. (17) Opioid-based analgesic strategies should be selected step-by-step according to the characteristics of different drugs. (18) There must be rational use of non-opioid analgesics and non-drug-based analgesic measures. (19) Pay attention to evaluation of the psychological status of CIPs. (20) Cognitive function in CIPs cannot be ignored. (21) Delirium management should be based on non-drug-based measures and rational use of drugs. (22) Reset treatment can be considered for severe delirium. (23) Psychological assessment should be conducted as early as possible to screen-out high-risk groups with post-traumatic stress disorder. (24) Emotional support, flexible visiting, and environment management are important components of humanistic management in the intensive care unit (ICU). (25) Emotional support from medical teams and families should be promoted through"ICU diaries"and other forms. (26) Environmental management should be carried out by enriching environmental content, limiting environmental interference, and optimizing the environmental atmosphere. (27) Reasonable promotion of flexible visitation should be done on the basis of prevention of nosocomial infection. (28) ESCAPE is an excellent project for late stage of CC management.

Safety of delayed vaccination with the national immunization program vaccines in children aged 0-6 years from 2019 to 2021 in Xuhui District, Shanghai City in China / 中华预防医学杂志

Objective: To understand the incidence of delayed vaccination with the national immunization program vaccines among children aged 0-6 years in Xuhui District, Shanghai, and to evaluate the safety of delayed vaccination. Methods: A stratified random sampling was used to obtain six vaccination clinics in Xuhui District, Shanghai. The vaccination records of children 0-6 years from these six vaccination clinics were collected from the Shanghai Immunization Program Information Management System. Adverse events following immunization (AEFI) data were collected from the China Information System for Disease Control and Prevention. Descriptive epidemiology was used to analyze the data. Children were divided into the timely vaccination group and delayed vaccination group according whether they were delayed in vaccination (received one month or more after the recommended age among children aged ≤1 year; received three months or more after the recommended age among children aged >1 year). The safety of four vaccination methods-individual vaccination, simultaneous vaccination, routine vaccination and combined vaccination-were further compared. Differences between groups were compared using chi-square test. Results: From 2019 to 2021, six vaccination clinics in Xuhui District administered 124 031 doses of the national immunization program vaccines among children aged 0-6 years, and delayed vaccinations accounted for 25.99% (32 234/124 031) of these doses. In 2020, the delayed vaccination rate during the first-level COVID-19 public health emergency response period in Shanghai was significantly higher than that in the same period in 2019 (34.70% vs. 24.19%, χ2=136.23, P<0.05). The delayed vaccination rate during the COVID-19 vaccination campaign in 2021 was significantly higher than that in the same period in 2019 (25.27% vs. 22.55%, χ2=82.80, P<0.05). From 2019 to 2021, a total of 475 cases of AEFI were reported in six vaccination clinics, with a reported incidence of 382.97 per 100 000 doses, including 421 cases of common adverse reaction (88.63%, 339.43 per 100 000 doses), 51 cases of rare adverse reaction (10.74%, 41.12 per 100 000 doses) and 3 cases of coincidences (0.63%, 2.42 per 100 000 doses). The reported incidence of AEFI among delayed vaccinations was significantly lower than that among timely vaccinations (291.62 per 100 000 doses vs. 415.05 per 100 000 doses). The incidence of AEFI for the four delayed vaccination methods (individual vaccination, simultaneous vaccination, routine vaccination and combined vaccination) was lower than that for timely vaccination. There were significant differences between the groups except for the routine vaccination group (χ2=9.82, P<0.05; χ2=5.46, P<0.05; χ2=2.97, P>0.05; χ2=11.89, P<0.05). Conclusions: In Xuhui District of Shanghai, 25.99% of doses of the national immunization program vaccines administered to children 0-6 years were delayed. Delayed vaccination does not increase the risk of AEFI compared with timely vaccination.

Mechanism of blue light-induced ferroptosis in retinal pigment epithelium cells / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the occurrence and possible mechanism of blue light-induced ferroptosis in retinal pigment epithelial cells.METHODS: ARPE-19 cells cultured in vitro were irradiated by 405 nm blue light at 50 mW/cm2 irradiance with different duration and were divided into control, 16.3J/cm2, 32.6J/cm2, and 65.2J/cm2 groups; the 65.2J/cm2 group was defined as the high-level blue light irradiation group and cells were further divided into control, high-level blue light irradiation group and high-level blue light irradiation + ferroptosis inhibitor group. CCK-8 assay was used to detect cell viability, commercial kits were used to detect intracellular glutathione(GSH), ferrous iron and malondialdehyde(MDA)concentration, and Western blot was used to detect the relative expression of glutathione peroxidase 4(GPX4)and xCT proteins in cells.RESULTS: The decrease of ARPE-19 cell viability caused by blue light irradiation was dose-dependent, and the reduction of intracellular GSH concentration, the increase of ferrous iron concentration and MDA concentration were all caused by high-level blue light irradiation(all P&#x0026;#x003C;0.05); the ferroptosis inhibitor partially restored cell viability and recovered intracellular GSH, reduced concentrations of MDA and ferrous iron in the blue light irradiation group(all P&#x0026;#x003C;0.05). The relative expressions of GPX4 and xCT proteins were significantly decreased in the blue light irradiation group, and such change was alleviated by the ferroptosis inhibitor(P&#x0026;#x003C;0.05).CONCLUSION: Blue light irradiation may induce ferroptosis in RPE cells by targeting the xCT and GPX4-associated antioxidant pathways.

Mechanism of Pachymic Acid in Inhibiting Invasion and Metastasis of Renal Carcinoma Cells via Regulating MMP/TIMP Balance by Smads / 中国实验方剂学杂志

ObjectiveTo investigate the effect and mechanism of pachymic acid （PA） in Poria on the invasion and metastasis of renal carcinoma cells. MethodThe effect of PA （0， 20， 40， 80， 160 μmol·L-1） on cell viability was detected by cell counting kit-8（CCK-8）， and the dose of PA was selected for subsequent experiments. The effect of PA （0， 20， 40， 80 μmol·L-1） on cell proliferation was evaluated by colony formation assay. The effect of PA （0， 20， 40， 80 μmol·L-1） on cell adhesion ability was observed by cell adhesion assay. The effect of PA （0， 20， 40， and 80 μmol·L-1） on cell invasion and metastasis was investigated by Wound healing assay and Transwell invasion assay. The inhibitory effect of PA （0， 20， 40， 80 μmol·L-1） on cell motility was further observed and verified by high-content imaging technology. The effects of PA （0， 20， 40， 80 μmol·L-1） on the expression of matrix metalloproteinase （MMP）/tissue inhibitor of metalloproteinasas （TIMP） related to invasion and metastasis and Smads were detected by Western blot. ResultCCK-8 results showed that compared with the blank group， the PA groups showed decreased cell viability（P<0.01）， with the half-maximal inhibitory concentration （IC50） of ACHN cells of 70.42 μmol·L-1 at 24 h. Colony formation assay showed that the number of cell clonal groups in the PA groups was reduced compared with that in the blank group（P<0.01）. Cell adhesion assay showed that compared with the blank group， the PA groups displayed reduced cell adhesion（P<0.01）. Wound healing assay showed that the wound healing rate of cells in the PA groups was lower than that in the blank group （P<0.05，P<0.01）. Transwell invasion assay showed that compared with the blank group， the number of transmembrane cells in PA groups was reduced（P<0.01）. High-content imaging showed that the cumulative migration distance of cells in the PA groups was shorter than that in the blank group（P<0.01）. The results of Western blot showed that the protein expression of MMP-2 and MMP-9 in the PA groups decreased （P<0.01）， and TIMP-1 protein expression increased （P<0.01） compared with those in the blank group. In addition， compared with the blank group， the PA groups showed decreased protein expression of Smad2 and Smad3 （P<0.01）. ConclusionPA can inhibit the invasion and metastasis of renal carcinoma cells presumably through regulating the homeostasis of MMP/TIMP by Smad2/3.

Methodology and application of process analytical technology (PAT) for traditional Chinese medicine manufacturing:a review / 中国中药杂志

Owing to the advancement in pharmaceutical technology, traditional Chinese medicine industry has seen rapid development. Preferring conventional manufacturing mode, pharmaceutical enterprises of traditional Chinese medicine have no effective process detection tools and process control methods. As a result, the quality of the final products mainly depends on testing and the quality is inconsistent in the same batch. Process analytical technology(PAT) for traditional Chinese medicine manufacturing, as one of the key advanced manufacturing techniques, can break through the bottleneck in quality control of medicine manufacturing, thus improving the production efficiency and product quality and reducing the material and energy consumption. It is applicable to the process control and real-time release of advanced manufacturing modes such as intelligent manufacturing and continuous manufacturing. This paper summarized the general idea of PAT for traditional Chinese medicine manufacturing. Through the analysis of the characteristics and status quo of the technology, we summed up the methodology for the continuous application and improvement of PAT during the whole life-cycle of traditional Chinese medicine. The five key procedures(process understanding, process detection, process modeling, process control, and continuous improvement) were summarized, and the application was reviewed. Finally, we proposed suggestions for the technical and regulatory challenges in implementing PAT in traditional Chinese medicine industry. This paper aims to provide a reference for development and application of PAT in advanced manufacturing, intelligent manufacturing, and continuous manufacturing of traditional Chinese medicine industry.

Effect of ACC oxidase gene AhACOs on salt tolerance of peanut / 生物工程学报

ACC oxidase (ACO) is one of the key enzymes that catalyze the synthesis of ethylene. Ethylene is involved in salt stress response in plants, and salt stress seriously affects the yield of peanut. In this study, AhACO genes were cloned and their functions were investigated with the aim to explore the biological function of AhACOs in salt stress response, and to provide genetic resources for the breeding of salt-tolerant varieties of peanut. AhACO1 and AhACO2 were amplified from the cDNA of salt-tolerant peanut mutant M29, respectively, and cloned into the plant expression vector pCAMBIA super1300. The recombinant plasmid was transformed into Huayu22 by pollen tube injection mediated by Agrobacterium tumefaciens. After harvest, the small slice cotyledon was separated from the kernel, and the positive seeds were screened by PCR. The expression of AhACO genes was analyzed by qRT-PCR, and the ethylene release was detected by capillary column gas chromatography. Transgenic seeds were sowed and then irrigated with NaCl solution, and the phenotypic changes of 21-day-seedings were recorded. The results showed that the growth of transgenic plants were better than that of the control group Huayu 22 upon salt stress, and the relative content of chlorophyll SPAD value and net photosynthetic rate (Pn) of transgenic peanuts were higher than those of the control group. In addition, the ethylene production of AhACO1 and AhACO2 transgenic plants were 2.79 and 1.87 times higher than that of control peanut, respectively. These results showed that AhACO1 and AhACO2 could significantly improve the salt stress tolerance of transgenic peanut.

An optimal medicinal and edible Chinese herbal formula attenuates particulate matter-induced lung injury through its anti-oxidative, anti-inflammatory and anti-apoptosis activities / 中草药·英文版

OBJECTIVE@#Identifying novel strategies to prevent particulate matter (PM)-induced lung injury is crucial for the reduction of the morbidity of chronic respiratory diseases. The combined intervention represented by herbal formulae for simultaneously targeting multiple pathological processes can provide a more beneficial effect than the single intervention. The aim of this paper is therefore to design a safe and effective medicinal and edible Chinese herbs (MECHs) formula against PM-induced lung injury.@*METHODS@#PM-induced oxidative stress, inflammatory response and apoptosis A549 cell model were used to screen anti-oxidant, anti-inflammatory and anti-apoptotic MECHs, respectively. A network pharmacology method was utilized to rationally design a novel herbal formula. Ultra performance liquid chromatography-mass spectrometer was utilized to assess the quality control of MECHs formula. The excretion of magnetic iron oxide nanospheres of the MECHs formula was estimated in zebrafish. The MECH formula against PM-induced lung injury was investigated with mice experiments.@*RESULTS@#Five selected herbs were rationally designed to form a new MECH formula, including Citri Exocarpium Rubrum (Juhong), Lablab Semen Album (Baibiandou), Atractylodis Macrocephalae Rhizoma (Baizhu), Mori Folium (Sangye) and Polygonati Odorati Rhizoma (Yuzhu). The formula effectively promoted the magnetic iron oxide nanospheres excretion in zebrafish. The mid/high dose formula significantly prevented PM-induced lung damage in mice by enhancing the activity of SOD and GSH-Px, reducing the MDA and ROS level and attenuating the upregulation of pro-inflammatory cytokine (IL-6, IL-8, IL-1β and TNF-α), down regulating the protein expression of NF-κB, STAT3 and Caspase-3.@*CONCLUSION@#Our findings suggest that the effective MECHs formula will become a novel strategy for preventing PM-induced lung injury and provide a paradigm for the development of functional foods using MECHs.

Common diseases and drug use of Pseudostellaria heterophylla / 中国中药杂志

Pseudostellaria heterophylla in large-scale cultivation needs to apply pesticides to control diseases, and non-standard use of pesticide may cause excessive pesticide residues in medicinal materials, increasing the risk of clinical medication. To accurately monitor the residual pesticides, this paper investigated the drug use during the process of P. heterophylla disease prevention in 25 P. he-terophylla planting enterprises or individual households in Guizhou province. It was found that there were 8 common diseases in P. he-terophylla planting, including leaf spot, downy mildew, virus disease, root rot, dropping disease, purple feather disease, white silk disease, and damping-off disease. Twenty-three kinds of pesticides were used in disease control, mainly chemical synthetic pesticides, accounting for 78.3%, followed by biological pesticides and mineral pesticides, accounting for 13.0% and 8.7%, respectively. The disease prevention and control drugs were all low-toxic pesticides, and there were no varieties banned in the Chinese Pharmacopoeia(2020 edition). However, the pesticides used have not been registered on P. heterophylla, and the excessive use of drugs was serious. The present monitoring of pesticide residues in P. heterophylla is mainly based on traditional pesticides such as organochlorine, organophosphorus, and carbamate, which does not effectively cover the production of drugs and had certain safety risks. It is suggested to speed up the research and registration of drug use in the production of P. heterophylla, increase the use of biological pesticides, and further improve the monitoring indicators of pesticide residues in combination with the actual production of drugs, so as to promote the high-quality development of P. heterophylla industry.

Recent advances in mechanisms of KRASG12C inhibitors anti-tumor resistance and relevant overcoming strategies / 药学学报

KRAS is one of the most frequently mutated human oncogenes. In spite of mounting efforts on the development of direct or indirect inhibition targeting KRAS, little has been achieved because of insurmountable difficulties, titling KRAS "undruggable". Recently, subtype-specific inhibitors have shown great hope. Some KRASG12C inhibitors have entered clinical trials, including adagrasib and sotorasib, and have shown preliminary clinical effectiveness. Experiences from the inhibitors targeting the downstream factors of RAS pathways show that the anticancer activity of these drugs will be limited due to the development of drug resistance. Preclinical studies of KRASG12C inhibitors have revealed that the application of these agents might be hampered by the drug resistance issue. The current review aims to describe the current status of KRASG12C inhibitors, and discuss the mechanisms underlying KRASG12C inhibitor resistance, so as to provide the clues for the combat of drug resistance.

Research on antitumor effects of small molecule inhibitors of deubiquitinases: new progress and new ideas / 药学学报

The abnormality of ubiquitin proteasome pathway is an important factor leading to the imbalance of protein homeostasis. In this process, the deubiquitinase responsible for removing the ubiquitin chain of protein substrate is very important. Its abnormal activity or expression can cause the functional changes of key oncogenic/tumor suppressor proteins, which directly or indirectly lead to the occurrence, development and malignant evolution of tumors. Based on this, the discovery and research of small molecule inhibitors targeting deubiquitinases have become a hot field of anti-tumor candidate drugs. This review will focus on the regulatory effect and mechanism of ubiquitin proteasome pathway, especially deubiquitinase on tumor, introduce the application of deubiquitinase small molecule inhibitors in tumor treatment, and discuss the research status and latest progress of small molecule inhibitors, so as to provide ideas for the research of new anti-tumor strategies based on deubiquitinase.

Imaging features of OCTA in the macular hemorrhage of pathologic myopia / 国际眼科杂志(Guoji Yanke Zazhi)

@#AIM:To observe the imaging features of optical coherence tomography angiography(OCTA)in the macular hemorrhage of pathologic myopia.METHODS:Designing a retrospective analysis collected clinical data of 100 patients(108 eyes)diagnosed as macular hemorrhage of pathological myopic in Nanjing Medical University Affiliated Eye Hospital from June 2016 to December 2020. All patients underwent refraction, eye axis,fundus photography, spectral-domain optical coherence tomography(SD-OCT), fundus fluorescein angiography(FFA), indocyanine green angiography(ICGA)and OCTA examination. All patients were divided into macular hemorrhage only with lacquer cracks and macular hemorrhage with choroidal neovascularization(CNV). All patients followed-up for more than 3mo by OCTA. RESULTS:There were 40 patients(42 eyes)diagnosed as macular hemorrhage only with lacquer cracks, OCTA showed bleed obscured by choroidal capillaries. After hemorrhage was being absorbed, lacquer cracks showed linear or stellate reflection completely in the choroidal capillary layer. B-scan image showed discontinuous retinal pigment epithelium(RPE), thinner choroid and an increased light. Penetrance into deeper tissues. After all macular hemorrhage only with lacquer cracks were absorbed, follow-up mode of OCTA found that 2 eyes(4.8%)without lacquer cracks, 28 eyes(66.7%)were linear and 12 eyes(28.6%)were stellate under the original hemorrhage. Follow-up mode also showed that 8 eyes of 8 patients(19.0%)relapsed macular hemorrhage only with lacquer cracks, and 4 eyes of 4 patients(9.5%)suffered secondary macular hemorrhage with CNV. There were 60 patients(66 eyes)diagnosed as macular hemorrhage with CNV,OCTA showed bleed obscured choroidal capillaries, the outer retinal and choroidal capillary layer also showed the shape of CNV around hemorrhage. B-scan showed CNV breaked through the RPE layer and blood flow signal in it. The area of CNV decreased after anti-vascular endothelial growth factor(VEGF)intravitreal injection treatment. Around all macular hemorrhage with CNV, OCTA found that 48 eyes(72.7%)had lacquer cracks, 28 eyes(42.4%)were linear and 20 eyes(30.3%)were stellate.CONCLUSION:OCTA has a great significance in the diagnosis of macular hemorrhage of pathological myopia, fast and non-invasive is the biggest advantage. Choroidal capillary layer can clearly observe the shape and location of hemorrhage,lacquer cracks and CNV. The follow-up mode can intuitively comprehend the changes of disease. To some extent, it can replace fundus angiography to directly judge the classification, and time to treat in the clinic.