Integration of plasma metabolomics and spectrum-effect correlation for profiling the mechanism and pharmacodynamic substances on attenuating hepatic fibrosis of Bupleuri Radix and Paeoniae Radix Alba before and after vinegar-processing and compatibility / 药学学报

Plasma metabolomics based on UHPLC-Q-TOF-MS/MS technique was developed for profiling the mechanism on attenuating hepatic fibrosis of Bupleuri Radix (BR) and Paeoniae Radix Alba (PRA) before and after vinegar-processing and compatibility, and to screen potential pharmacodynamic substances by spectrum-effect correlation method in this study. Firstly, SD rats with CCl4-induced hepatic fibrosis were used as an in vivo model. The blood and tissue samples were collected for the analyses of pharmacodynamic indexes and plasma metabolomics after six weeks’ administration of BR, vinegar-processed BR (VPBR), PRA, vinegar-processed PRA (VPPRA), BR-PRA herb-pair, and VPBR-VPPRA herb-pair. The experiment was approved by the experimental animal ethics committee from Nanjing University of Chinese Medicine (No.202103A002). The results of pharmacodynamics indicated that the levels of alanine aminotransferase (ALT, P < 0.01), aspartate aminotransferase (AST, P < 0.01), and hydroxyproline (HYP, P < 0.01) were decreased significantly, while the level of glutathione peroxidase (GSH-Px, P < 0.05) was increased obviously after administration of all treatment groups. Next, UHPLC-Q-TOF-MS/MS was performed to characterize the endogenous metabolites. A total of 20 differential endogenous metabolites related to the pathogenesis of hepatic fibrosis were identified in positive and negative ion modes, mainly involving five metabolic pathways of retinol metabolism, glycerol phospholipid metabolism, glyceride metabolism, fatty acid biosynthesis, and arachidonic acid metabolism. Meanwhile, a concept named correction rate was introduced to evaluate the back-regulation effects of all treatment groups on differential metabolites, and 10 differential metabolites were corrected by all treatment groups. The correction effects of the vinegar-processed herb groups were better than those of the crude ones, and the correction effects of the herb-pair groups were better than those of the single ones. Interestingly, the best correction effect was found in the VPBR-VPPRA herb-pair group, which further verified the efficacy improvement through vinegar-processing and compatibility. Partial least square method and VIP analysis combined with spectrum-effect correlation were applied for screening pharmacodynamic markers, and 38 ingredients with higher correlation with four classical pharmacodynamic indexes (ALT, AST, HYP, and GSH-Px) were identified as pharmacodynamic markers of the anti-hepatic fibrosis effects of BR and PRA before and after vinegar-processing and compatibility. The results of the investigation could not only lay a foundation for clarifying the pharmacodynamic materials and mechanism of vinegar-processing and compatibility of BR and PRA in the treatment of hepatic fibrosis as well as provide a theoretical basis for demonstrating the scientific connotation of processing and compatibility, but also provide a reference for further drug design and development of BR and PRA in clinic.

Tiaoqi Jieyu acupuncture for treatment-resistant depression: a randomized controlled trial / 中国针灸

OBJECTIVE@#To observe the effect of Tiaoqi Jieyu (regulating qi and relieving depression) acupuncture on the clinical symptoms of treatment-resistant depression (TRD), and to explore the relationship between the acupuncture pain sensitivity and symptom's improvement.@*METHODS@#A total of 78 patients with TRD were randomly divided into an observation group (39 cases, 3 cases dropped off) and a control group (39 cases, 4 cases dropped off). The patients in the control group were treated with medications according to the treatment plan of psychiatrists (at least one medication was 5-hydroxytryptamine reuptake inhibitor). On the basis of the control group, the patients in the observation group were treated with Tiaoqi Jieyu acupuncture, and Baihui (GV 20), Yintang (GV 24+), Yanglingquan (GB 34), Taichong (LR 3), Hegu (LI 4), Neiguan (PC 6), Yinlingquan (SP 9) and Zusanli (ST 36), etc. were selected. The acupuncture was given three times a week. Both groups were treated for 8 weeks. After 8-week treatment, the response rate of Hamilton depression scale-24 (HAMD-24) score after was evaluated in the two groups. The scores of HAMD-24 and Hamilton anxiety scale (HAMA) were compared between the two groups before treatment, after 4, 8-week treatment and 12 weeks after treatment (follow-up). After the first treatment and 8-week treatment, the visual analogue scale (VAS) score in the observation group was evaluated, and the correlation between VAS score after the first treatment and HAMD-24 score before treatment, between VAS score after the first treatment and the course of disease in the observation group was analyzed, and the correlation between difference of VAS after 8-week treatment and after the first treatment and difference of HAMD-24 score before treatment and after 8-week treatment was analyzed.@*RESULTS@#After 8-week treatment, the response rate of HAMD-24 score in the observation group was 52.8% (19/36), higher than 17.1% (6/35) in the control group (P<0.001). Compared before treatment, the scores of HAMD-24 and HAMA in the two groups were decreased after 4-week treatment, 8-week treatment and in follow-up (P<0.05), and those in the observation group were superior to the control group (P<0.05). After 8-week treatment, the acupuncture pain VAS score in the observation group was (5.28±2.13) points, which was higher than (3.33±1.62) points after the first treatment (P<0.001). There was a negative correlation between VAS score after the first treatment and HAMD-24 score before treatment in the observation group (r =-0.486, P=0.003); there was no correlation between acupuncture pain VAS score after the first treatment and the course of disease in the observation group (P>0.05). After 8-week treatment, there was a positive correlation between the difference of VAS score and the difference of HAMD-24 score in the observation group (r =0.514, P=0.001).@*CONCLUSION@#Tiaoqi Jieyu acupuncture could improve the depression and anxiety in patients with TRD, and the symptom's improvement is related to the recovery of acupuncture pain sensitivity.

Associated factors on smoking behavior among adolescents in Chongqing based on a multi level model / 中国学校卫生

Objective@#To investigate the current status of smoking behavior among adolescents in Chongqing and associated factors at both individual and school levels, so as to provide scientific evidence for the development of smoking control strategies for adolescents.@*Methods@#From September to October 2021, adolescents tobacco epidemic monitoring was carried out in Chongqing. A total of 9 588 students from 10 monitoring districts and counties in Chongqing were selected to complete the Chinese adolescent tobacco epidemic survey questionnaire by multi stage stratified cluster probability sampling method. Multi level Logistic regression model was used to analyze smoking behavior among adolescents and associated factors.@*Results@#The attempted smoking rate among young people was 17.1%, and the current smoking rate was 3.9% in Chongqing. There was a clustering of smoking behavior among participants the school level. Multi level Logistic regression models showed that general high school, vocational high school, male students, smoking at home, seeing someone smoking in indoor public places, seeing someone smoking at school, smoking among good friends (some smoking, most smoking, all smoking), feeling more comfortable of smoking in social occasions, using electronic cigarette, which were positively correlated with smoking attempts ( OR=1.45, 1.40, 1.91, 1.50, 1.42, 1.43, 2.05, 5.38, 6.53, 1.36 , 5.04, P <0.05). Smoking making people look less attractive and feeling more uncomfortable of smoking in social occasions were negatively correlated with smoking attempts ( OR=0.76, 0.48, P <0.05). Vocational high school, male students, smoking at home, seeing someone smoking in indoor public places, smoking among good friends and using electronic cigarette, which were positively correlated with smoking now ( OR=1.62, 1.67, 1.69, 1.83, 5.84, 23.02, 35.84, 6.28, P <0.05). Feeling more uncomfortable of smoking in social occasions was negatively correlated with current smoking ( OR=0.29, P <0.01).@*Conclusions@#There is a cluster of attempted smoking and current smoking behaviors at the school level among adolescents in Chongqing, and the influencing factors include school type, gender, family environment, social factors, etc. It should strengthen the implementation and broaden the scope of smoking control regulations in public places, and promote the healthy growth of young people through social school family cooperation.

Clinical study of macular retinal thickness in children with hyperopic amblyopia before and after treatment / 国际眼科杂志(Guoji Yanke Zazhi)

@#AIM: To discuss the measurement of retinal thickness in each macular region, fixation property, best corrected visual acuity(BCVA), eye axis and equivalent spherical power and treatment time for the children with hyperopia anisometropic amblyopia before and after treatment.<p>METHODS: This study was a prospective longitudinal controlled trial. The subjects were 40 hyperopia anisometropia children aged 4-8 years with monocular amblyopia who had not been treated with amblyopia before diagnosis in our hospital(20 cases of central fixation and 20 cases of paracentral fixation)from August 2018 to August 2019. Atropine mydriatic optometry, fundus macular fixation quality, ocular axis and optical coherence tomography(OCT)retinal thickness were used in the initial diagnosis and 6mo and 1a follow-up. Statistical analysis was used to analyze whether the macular retinal thickness of hyperopia amblyopia had changed in the treatment and the related factors, and whether had differences between different fixation properties.<p>RESULTS: There were significant differences in foveal retinal thickness and nasal retinal thickness of inner ring between central fixation group and paracentral fixation group at different measurement times(before treatment, 6 and 12mo after treatment)(<i>P</i><0.01). There were no significant changes in the other retinas in macular area(<i>P</i> >0.05). With the extension of treatment time, the foveal retinal thickness and the nasal retinal thickness of the inner ring in the central fixation group and the paracentral fixation group became thinner(all <i>P</i><0.05). At the same measurement time, the thickness of fovea and inner ring nasal retina in the central fixation group was thinner than that in the paracentral fixation group(all <i>P</i><0.05), and there were no significant differences in the thickness of other retinas in the macular region(all <i>P</i>>0.05). There were significant differences in ocular axis, BCVA and equivalent spherical power of amblyopia before and after treatment(all <i>P</i><0.05); With the extension of treatment time, the length of ocular axis and BCVA had increased and the degree of equivalent spherical mirror had decreased. The macular retinal thickness of hyperopia amblyopia was thicker than that of contralateral normal eyes, and the length of ocular axis was shorter than that of contralateral normal eyes(all <i>P</i><0.01). The axial length of amblyopia and normal eyes had changed significantly before and after treatment(all <i>P</i><0.01). The axial length of amblyopia was shorter than that of normal eyes. With the extension of treatment time, the axial length of amblyopia and normal eyes had become longer.<p>CONCLUSION:The thickness of macular retina in moderate and high amblyopic eyes was greater than that in contralateral normal eyes, and the ocular axis was shorter than that in contralateral normal eyes. After treatment, with the improvement of best corrected visual acuity, the retinal thickness of fovea and nasal side of inner ring in central fixation group and paracentral fixation group had decreased.

The repellent effect of tea tree oil emulsion on leeches / 药学学报

Leech bites usually lead to more bleeding, and dermal tissue is damaged to form lifelong scars. If leeches enter the body cavity, it will be more dangerous. Therefore, there is an urgent need to develop effective repellents. In this study, oil in water (O/W) emulsion of tea tree oil was prepared with tea tree oil as the main ingredient, and konjac glucomannan (KGM), ethyl cellulose (EC) as the main excipients. The filter-paper ring method and repellent test in water were used to evaluate the repellent effects on leeches. The animal experiments were approved by the Ethics Committee of Academy of Military Medical Sciences and were conducted in accordance with relevant guidelines and regulations. The activities of acetylcholinesterase (AchE), glutathione S-transferase (GST) and carboxylesterase (CarE) in vivo were measured to clarify the repellent mechanisms. The results showed that a uniform and stable tea tree oil emulsion was successfully prepared, which has excellent hydrophilicity and can effectively repel leeches. The tea tree oil emulsion has a good repellent effect on leeches, which can avoid the volatilization of tea tree oil and prolong the effective repelling time. The novel formulation of tea tree oil provides a new idea for repelling effects with long time and high efficiency based on similar essential oil.

Effects of polyol excipient stability during storage and use on the quality of biopharmaceutical formulations / 药物分析学报

Biopharmaceuticals are formulated using a variety of excipients to maintain their storage stability.However,some excipients are prone to degradation during repeated use and/or improper storage,and the impurities generated by their degradation are easily overlooked by end users and are usually not strictly monitored,affecting the stability of biopharmaceuticals.In this study,we evaluated the degra-dation profile of polyol excipient glycerol during repeated use and improper storage and identified an unprecedented cyclic ketal impurity using gas chromatography with mass spectrometry(GC-MS).The other polyol excipient,mannitol,was much more stable than glycerol.The effects of degraded glycerol and mannitol on the stability of the model biopharmaceutical pentapeptide,thymopentin,were also evaluated.The thymopentin content was only 66.4％in the thymopentin formulations with degraded glycerol,compared to 95.8％in other formulations after the stress test.Most glycerol impurities(i.e.,aldehydes and ketones)reacted with thymopentin,affecting the stability of thymopentin formulations.In conclusion,this work suggests that more attention should be paid to the quality changes of excipients during repeated use and storage.Additional testing of excipient stability under real or accelerated conditions by manufacturers would help avoid unexpected and painful results.

Diagnostic value of MDM2 RNA in situ hybridization in atypical lipomatous tumor/well-differentiated liposarcoma and dedifferentiated liposarcoma / 中华病理学杂志

Objective: To investigate the value of MDM2 RNA in situ hybridization (RNA-ISH) in diagnosing atypical lipomatous tumor/well-differentiated liposarcoma (ALT/WDL) and dedifferentiated liposarcoma (DDL). Methods: A total of 26 ALT/WDL/DDLs diagnosed from March 2017 to May 2019 in West China Hospital, Sichuan University, Chengdu, China and 18 control cases were included. MDM2 RNA-ISH was performed on all samples and compared with the fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) regarding their performance in detecting MDM2. Results: All samples were detected successfully using the three methods. Among 26 ALT/WDL/DDLs, all cases showed MDM2 amplification and positivity for MDM2 RNA-ISH (26/26, 100%). Twenty-four (24/26, 92.3%) of the 26 tested cases were positive for MDM2 IHC while two of them were negative. Eighteen control cases were all negative for MDM2 FISH and RNA-ISH, and 15 (15/18) cases were negative for MDM2 IHC. The sensitivity and specificity of RNA-ISH were both 100%, and those of MDM2 IHC were 92.3% and 83.3%, respectively. Diffuse staining was identified in all MDM2 RNA-ISH positive ALT/WDL/DDLs, but identified in only 8/24 (33.3%) of the MDM2 IHC positive cases. Among the 11 ALT/WDL/DDL samples evaluated on tissue microarray, the positive rate of MDM2 RNA-ISH was 100% with diffuse staining in all cases. The positive rate of MDM2 IHC was 9/11 while only 1 of the 9 cases showed diffuse staining. The result of MDM2 RNA-ISH was identical to that of MDM2 FISH and was overall consistent with that of MDM2 IHC (Kappa=0.763, P<0.001). Conclusions: In ALT/WDL/DDLs, results of MDM2 RNA-ISH are highly consistent with those of FISH. MDM2 RNA-ISH is more sensitive and more specific and has more diffuse positive signals than the IHC. The findings indicate that MDM2 RNA-ISH is highly valuable for the diagnosis and differential diagnosis of ALT/WDL/DDLs.

Advances in nutritional support therapy for stroke prevention and treatment / 中华预防医学杂志

As a serious disease of death and disability, stroke constitutes a serious threat to human health. Because of stroke patients often have high-risk factors of malnutrition such as dysphagia and autonomic eating disorder, the hospitalization time, mortality and disability rate of stroke patients increases. Nutritional therapy can effectively improve the malnutrition of patients, which are of great significance for the treatment and rehabilitation of stroke and the prevention of its complications. Nutrients are important components of nutrition therapy, and different ways of nutrition therapy directly affect the effect of treatment. This article summarizes effects of nutrients and different nutritional treatments on stroke prevention, morbidity and treatment, and provides a theoretical basis and new thinking for further reducing the incidence rate of stroke, improving the quality of life in patients and reducing the financial burden of society and family.

Analysis of clinical features and risk factors of necrotizing pneumonia in children / 北京大学学报(医学版)

OBJECTIVE@#To investigate the clinical characteristics and risk factor analysis of necrotizing pneumonia in children.@*METHODS@#A retrospective study was used to analyze the case data of 218 children with severe pneumonia hospitalized in the Department of Respiratory Medicine, Children's Hospital of Capital Institute of Pediatrics from January 2016 to January 2020, and they were divided into 96 cases in the necrotizing pneumonia group (NP group) and 122 cases in the non-necrotizing pneumonia group (NNP group) according to whether necrosis of the lung occurred. The differences in clinical characteristics (malnutrition, fever duration, hospitalization time, imaging performance, treatment and regression follow-up), laboratory tests [leukocytes, neutrophil ratio, platelet (PLT), C-reactive protein (CRP), procalcitonin (PCT), D-dimer, and lactate dehydrogenase (LDH)] and bronchoscopic performance between the two groups were compared, and Logistic regression analysis of clinical risk factors associated with necrotizing pneumonia was performed to further determine the maximum diagnostic value of each index by subject operating characteristic curve (ROC). The critical value of each index was further determined by the ROC.@*RESULTS@#The differences in age, gender, pathogenic classification, and bronchoscopic presentation between the two groups of children were not statistically significant (P>0.05); whereas the imaging uptake time of the children in the NP group was higher than that in the NNP group (P < 0.05). The differences in malnutrition, fever duration, length of stay, white blood cell count, neutrophil ratio, CRP, PCT, and D-dimer were statistically significant between the two groups (P < 0.05). The imaging uptake time was lower in children under 6 years of age than in those over 6 years of age, and the imaging uptake time for bronchoalveolar lavage within 10 d of disease duration was lower than that for those over 10 d; the imaging uptake time was significantly longer in the mixed infection group than that in the single pathogen infection group. Logistic regression analysis of the two groups revealed that the duration of fever, hospital stay, CRP, PCT, and D-dimer were risk factors for secondary pulmonary necrosis (P < 0.001, P < 0.001, P < 0.001, P=0.013, P=0.001, respectively). The ROC curves for fever duration, CRP, PCT, and D-dimer were plotted and found to have diagnostic value for predicting the occurrence of pulmonary necrosis when fever duration >11.5 d, CRP >48.35 mg/L, and D-dimer > 4.25 mg/L [area under ROC curve (AUC)=0.909, 0.836, and 0.747, all P < 0.001].@*CONCLUSION@#Children with necrotizing pneumonia have a longer heat course and hospital stay, and the imaging uptake time of mixed pathogenic infections is significantly longer than that of single pathogenic infections. Children with necrotizing pneumonia under 6 years of age have more advantageous efficacy of electronic bronchoscopic alveolar lavage within 10 d of disease duration compared with children in the group over 6 years of age and children in the group with disease duration >10 d. Inflammatory indexes CRP, PCT, and D-dimer are significantly higher. The heat course, CRP, PCT, and D-dimer are risk factors for secondary lung necrosis in severe pneumonia. Heat course >11.5 d, CRP >48.35 mg/L, and D-dimer >4.25 mg/L have high predictive value for the diagnosis of necrotizing pneumonia.

The impact of preoperative glycated hemoglobin (HbA1c) on postoperative complications after elective major abdominal surgery: a meta-analysis / 대한마취과학회지

Background@# Diabetes is a risk factor for postoperative complications. Previous meta-analyses have shown that elevated glycated hemoglobin (HbA1c) levels are associated with postoperative complications in various surgical populations. However, this is the first meta-analysis to investigate the association between preoperative HbA1c levels and postoperative complications in patients undergoing elective major abdominal surgery. @*Methods@# PRISMA guidelines were adhered to for this study. Six databases were searched up to April 1, 2020. Primary studies investigating the effect of HbA1c levels on postoperative complications after elective major abdominal surgery were included. Risk of bias and quality of evidence assessments were performed. Data were pooled using a random effects model. Meta-regression was performed to evaluate different HbA1c cut-off values. @*Results@# Twelve observational studies (25,036 patients) were included. Most studies received a ‘good’ and ‘moderate quality’ score using the NOS and GRADE, respectively. Patients with a high HbA1c had a greater risk of anastomotic leaks (odds ratio [OR]: 2.80, 95% CI [1.63, 4.83], P 7% may be putting pre-optimized patients at risk. Future randomized controlled trials are needed to explore causation before policy changes are made.

Influence of electroacupuncture on ghrelin and the phosphoinositide 3-kinase/protein kinase B/endothelial nitric oxide synthase signaling pathway in spontaneously hypertensive rats / 中西医结合学报

OBJECTIVE@#To investigate the influence of electroacupuncture (EA) on ghrelin and the phosphoinositide 3-kinase/protein kinase B/endothelial nitric oxide synthase (PI3K/Akt/eNOS) signaling pathway in spontaneously hypertensive rats (SHRs).@*METHODS@#Eight Wistar-Kyoto rats were used as the healthy blood pressure (BP) control (normal group), and 32 SHRs were randomized into model group, EA group, EA plus ghrelin group (EA + G group), and EA plus PF04628935 group (a potent ghrelin receptor blocker; EA + P group) using a random number table. Rats in the normal group and model group did not receive treatment, but were immobilized for 20 min per day, 5 times a week, for 4 continuous weeks. SHRs in the EA group, EA + G group and EA + P group were immobilized and given EA treatment in 20 min sessions, 5 times per week, for 4 weeks. Additionally, 1 h before EA, SHRs in the EA + G group and EA + P group were intraperitoneally injected with ghrelin or PF04628935, respectively, for 4 weeks. The tail-cuff method was used to measure BP. After the 4-week intervention, the rats were sacrificed by cervical dislocation, and pathological morphology of the abdominal aorta was observed using hematoxylin-eosin (HE) staining. Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of ghrelin, nitric oxide (NO), endothelin-1 (ET-1) and thromboxane A2 (TXA2) in the serum. Isolated thoracic aortic ring experiment was performed to evaluate vasorelaxation. Western blot was used to measure the expression of PI3K, Akt, phosphorylated Akt (p-Akt) and eNOS proteins in the abdominal aorta. Further, quantitative real-time polymerase chain reaction (qRT-PCR) was conducted to measure the relative levels of mRNA expression for PI3K, Akt and eNOS in the abdominal aorta.@*RESULTS@#EA significantly reduced the systolic BP (SBP) and diastolic BP (DBP) (P < 0.05). HE staining showed that EA improved the morphology of the vascular endothelium to some extent. Results of ELISA indicated that higher concentrations of ghrelin and NO, and lower concentrations of ET-1 and TXA2 were presented in the EA group (P < 0.05). The isolated thoracic aortic ring experiment demonstrated that the vasodilation capacity of the thoracic aorta increased in the EA group. Results of Western blot and qRT-PCR showed that EA increased the abundance of PI3K, p-Akt/Akt and eNOS proteins, as well as expression levels of PI3K, Akt and eNOS mRNAs (P < 0.05). In the EA + G group, SBP and DBP decreased (P < 0.05), ghrelin concentrations increased (P < 0.05), and the concentrations of ET-1 and TXA2 decreased (P < 0.05), relative to the EA group. In addition, the levels of PI3K and eNOS proteins, the p-Akt/Akt ratio, and the expression of PI3K, Akt and eNOS mRNAs increased significantly in the EA + G group (P < 0.05), while PF04628935 reversed these effects.@*CONCLUSION@#EA effectively reduced BP and protected the vascular endothelium, and these effects may be linked to promoting the release of ghrelin and activation of the PI3K/Akt/eNOS signaling pathway.

A retrospective clinical study of patients with pregnancy-associated breast cancer among multiple centers in China (CSBrS-008) / 中华医学杂志(英文版)

BACKGROUND@#Pregnancy-associated breast cancer (PABC) is a special type of breast cancer that occurs during pregnancy and within 1 year after childbirth. With the rapid social development and the adjustment of reproductive policies in China, the average age of females at first childbirth is increasing, which is expected to lead to an increase in the incidence of PABC. This study aimed to accumulate clinical experience and to investigate and summarize the prevalence, diagnosis, and treatment of PABC based on large multicenter samples in China.@*METHODS@#According to the Chinese Society of Breast Surgery, a total of 164 patients with PABC in 27 hospitals from January 2016 to December 2018 were identified. The pregnancy status, clinicopathological features, comprehensive treatment methods, and outcomes were retrospectively analyzed. Survival curves were plotted using the Kaplan-Meier method.@*RESULTS@#A total of 164 patients of PABC accounted for 0.30% of the total number of cases in the same period; of which, 83 patients were diagnosed during pregnancy and 81 patients during lactation. The median age of PABC was 33 years (24-47 years). Stage I patients accounted for 9.1% (15/164), stage II 54.9% (90/164), stage III 24.4% (40/164), and stage IV 2.4% (4/164). About 9.1% (15/164) of patients were luminal A. Luminal B patients accounted the most (43.3% [71/164]). About 15.2% (25/164) of patients were human epidermal growth factor receptor 2 (Her-2) overexpression and 18.9% (31/164) of patients were triple-negative breast cancer. For pregnancy breast cancer, 36.1% (30/83) of patients received direct surgery and 20.5% (17/83) received chemotherapy during pregnancy. About 31.3% (26/83) chose abortion or induction of labor. The median follow-up time was 36 months (3-59 months); 11.0% (18/164) patients had local recurrence or distant metastasis and 3.0% (5/164) died.@*CONCLUSIONS@#It is safe and feasible to standardize surgery and chemotherapy for PABC.

Anti-tumor nanoscale drug delivery systems based on photodynamic therapy / 药学学报

Photodynamic therapy (PDT) is a therapeutic strategy by which photosensitizers are excited by specific light irradiation to produce singlet oxygen for killing the surrounding cells. The advantages of PDT include weak invasion, slight side effect, and low resistance. The advantages of nanoscale drug delivery systems (DDS) include tumor-targeting, sustained release, and environmental-sensitivity. The combination of PDT and nanoscale DDS would likely lead to tumor targeting of photosensitizers and enhance their antitumor effectiveness. This review discusses the mechanism of PDT, photosensitizer-loaded nanoscale formulations, the combination of PDT and other antitumor therapies, and summarizes the applications and prospects of anti-tumor nanoscale DDS based on PDT. This review is a useful reference for its clinical application.

Mechanism of Resveratrol in Treatment of Lung Adenocarcinoma： An Exploration Based on Database Mining and Molecular Biology / 中国实验方剂学杂志

Objective:To explore the mechanism of resveratrol （RSV） in the treatment of lung adenocarcinoma （LUAD） based on bioinformatics and molecular biology. Method:The targets of RSV were retrieved from DrugBank and then imported into STRING for constructing a protein-protein interaction （PPI） network.TCGA database was utilized to analyze the expression of target genes in tumor and normal tissues， followed by the prediction of their impacts on tumor occurrence and development and the screening of target genes using random forest and univariate Cox regression models.With the results of bioinformatics taken into consideration， the mechanism of RSV in inhibiting LUAD was further explored by molecular biology. Result:Ten Hub genes were screened out from the PPI network of RSV targets.Among them， solute carrier family 2 member 1 （SLC2A1）， arachidonate 5-lipoxygenase （ALOX5）， peroxisome proliferative activated receptor gamma （PPARG）， and arachidonate 15-lipoxygenase （ALOX15） differed significantly in their expression in tumor and normal tissues.As revealed by random forest and univariate COX regression analysis， SLC2A1 was of great significance to the survival and prognosis of patients with LUAD.The survival analysis through Kaplan-Meier （KM） plotter indicated that the SLC2A1 expression was closely related to the overall survival （OS）， first progression （FP）， and post-progression survival （PPS） of LUAD patients.The molecular biological experiments further proved that RSV inhibited the proliferation and migration of LUAD cells by reducing the expression of SLC2A1.As verified by immunohistochemical scoring， SLC2A1 protein expression in tumor tissue was significantly different from that in normal tissue. Conclusion:RSV inhibits the proliferation and migration of LUAD cells by reducing the expression of SLC2A1， which has far-reaching significance in the clinical treatment of LUAD.

Effect of Modified Rehabilitation Program for Postoperative Management after Arthroscopic Latarjet Procedure / 中国康复理论与实践

Objective:To assess the clinical outcomes of our modified postoperative rehabilitation program after total arthroscopic Latarjet procedure. Methods:From July, 2017 to March, 2019, 32 patients suffered from habitual anterior shoulder dislocation were treated with arthroscopic Latarjet procedure in our medical center. They were randomly assigned to control group (n = 15) and experimental group (n = 17). The control group received conventional rehabilitation program after shoulder arthroscopic Bankart repair, while the experimental group received modified rehabilitation program after arthroscopic Latarjet procedure. After surgery, they followed our postoperative management and rehabilitation program, and finished every phase of follow-up. Before and three weeks and six weeks after surgery, they were accessed with Visual Analogue Score (VAS) for pain, active range of motion (AROM) and functional assessment. Twelve months after surgery, their satisfaction were compared. Results:None of them was lost at one-year follow-up postoperatively. No recurrent dislocation occurred. Three months after surgery, the VAS, AROM and the scores of shoulder functional assessments were better in the experimental group than in the control group (|t| > 2.149, P < 0.05). Six months after surgery, no significant difference was found in VAS and AROM between two groups (|t| < 1.481, P > 0.05), and the scores of shoulder functional assessments were better in the experimental group than in the control group (|t| > 2.300, P < 0.05). Twelve months after surgery, the percentage of restored throwing ability and patients' satisfaction (t = -4.564, P < 0.001) were higher in the experimental group than in the control group. Conclusion:Compared with the conventional rehabilitation program after shoulder arthroscopic Bankart repair, modified postoperative rehabilitation program for arthroscopic Latarjet procedure is safer and more effective, which could bring better functional outcomes and higher patients' satisfaction.

Alterations in thymocyte populations under conditions of endotoxin tolerance / 中华医学杂志(英文版)

BACKGROUND@#Endotoxin tolerance (ET) is a protective phenomenon in which pre-treatment with a tolerance dose of lipopolysaccharide (LPS) leads to dramatically elevated survival. Accumulating evidence has shown that peripheral T cells contribute to the induction of ET. However, what happens to T cell development in the thymus under ET conditions remains unclear. The purpose of this study was to analyze the alterations in thymocyte populations (double-positive [DP] and single-positive [SP] cells) under ET conditions.@*METHODS@#Mice were intraperitoneally injected with LPS at a concentration of 5 mg/kg to establish an LPS tolerance model and were divided into two groups: a group examined 72 h after LPS injection (72-h group) and a group examined 8 days after LPS injection (8-day group). Injection of phosphate-buffered saline was used as a control (control group). Changes in thymus weight, cell counts, and morphology were detected in the three groups. Moreover, surface molecules such as CD4, CD8, CD44, CD69, and CD62L were analyzed using flow cytometry. Furthermore, proliferation, apoptosis, cytokine production, and extracellular signal-regulated kinase (ERK) pathway signaling were analyzed in thymocyte populations. The polymorphism and length of the T-cell receptor (TCR) β chain complementarity-determining region 3 (CDR3) were analyzed using capillary electrophoresis DNA laser scanning analysis (ABI 3730).@*RESULTS@#Thymus weight and cell counts were decreased in the early stage but recovered by the late stage in a murine model of LPS-induced ET. Moreover, the proportions of DP cells (control: 72.130 ± 4.074, 72-h: 10.600 ± 3.517, 8-day: 84.770 ± 2.228), CD4+ SP cells (control: 15.770 ± 4.419, 72-h: 44.670 ± 3.089, 8-day: 6.367 ± 0.513), and CD8+ SP cells (control: 7.000 ± 1.916, 72-h: 34.030 ± 3.850, 8-day: 5.133 ± 0.647) were obviously different at different stages of ET. The polymorphism and length of TCR β chain CDR3 also changed obviously, indicating the occurrence of TCR rearrangement and thymocyte diversification. Further analysis showed that the expression of surface molecules, including CD44, CD69, and CD62L, on thymocyte populations (DP and SP cells) were changed to different degrees. Finally, the proliferation, apoptosis, cytokine production, and ERK pathway signaling of thymocyte populations were changed significantly.@*CONCLUSION@#These data reveal that alterations in thymocyte populations might contribute to the establishment of ET.

Mechanism of Huangqi Guizhi Wuwu Decoction in treatment of rheumatoid arthritis based on UPLC-LTQ-Orbitrap-MS, network pharmacology, and cell experiment / 中国中药杂志

In this study, ultra-high performance liquid chromatography-linear ion trap/electrostatic field orbit trap combined-type mass spectrometry(UPLC-LTQ-Orbitrap-MS) was used to analyze the main active components of Huangqi Guizhi Wuwu Decoction(HQGZ). A total of 50 active components were identified from HQGZ and 108 potential targets of the components related to the treatment of rheumatoid arthritis were retrieved based on network pharmacology, including 87 key targets, followed by Gene Ontology(GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment of the targets. The result indicated that HQGZ may exert therapeutic effects mainly through the sphingolipid signaling pathway, tumor necrosis factor(TNF) signaling pathway, as well as the positive regulation of ribonucleic acid(RNA) polymerase Ⅱ promoter transcription, inflammatory response and other biological processes. At the same time, cell experiment was performed to verify the key proteins in the TNF signaling pathway. The results demonstrated that HQGZ significantly reduced the expression of caspase-3(CASP3), TNF, relaxed(RELA) protein, and IkappaB kinase beta(IKBKB) in fibroblast-like synoviocytes induced by TNF-α. The results of UPLC-LTQ-Orbitrap-MS, network pharmacology and cell experiment showed that the active components in HQGZ may inhibit inflammatory response and regulate immune function and cell apoptosis by modulating key proteins in TNF signaling pathway to treat rheumatoid arthritis.

Effect of maternal vitamin A deficiency during pregnancy on neurodevelopment of offspring / 上海交通大学学报（医学版）

Vitamin A (VA) is a fat-soluble vitamin with all-trans-retinoic biological activities. In addition to maintaining the normal functions of the eye, skin, immune, and reproductive systems, VA is also widely distributed in brain tissues, and important to the generation and differentiation of neural progenitor cells in the developing nervous system. Pregnant women are susceptible to vitamin A deficiency (VAD). Retinoic acid, the active form of VA, is very important to the brain development of offspring. This article reviews the literatures of maternal VAD during pregnancy, summarizing the risk factors of maternal VAD during pregnancy, and the research findings of the effects of maternal VAD during pregnancy on offspring neurodevelopment based on both human studies and animal experiments, and the possible underlying mechanisms by which maternal VAD affects the development of embryonic layers, brain structures, hippocampal synaptic transmission, and the biological clock in offspring.

Impact of an interstitial lung disease service in the diagnosis and management of interstitial lung disease in Singapore

INTRODUCTION@#The current gold standard for diagnosing interstitial lung disease (ILD) involves an ILD clinic evaluation, followed by discussion in a multidisciplinary meeting (MDM). However, there is a paucity of data on the impact of ILD MDMs on the diagnosis and management of ILDs in Southeast Asia. We studied the clinical impact of the ILD service on the diagnosis and management of ILDs at a university-affiliated tertiary hospital in Singapore.@*METHODS@#A single-centre retrospective review was done on 97 consecutive patients referred for evaluation to the ILD service from March 2016 to August 2017.@*RESULTS@#Mean age of the patients was 67 ± 11 years. Gender distribution was almost equal (52% male), with a majority of never-smokers (63%). Mean forced vital capacity (FVC) was 1.81 ± 0.66 L (66% ± 20% predicted). The three commonest referral diagnoses were ILD of uncertain classification (n = 38, 39%), connective tissue disease-associated ILD (CTD-ILD) (n = 24, 25%) and idiopathic pulmonary fibrosis (IPF) (n = 16, 17%). Following evaluation by the ILD service, there was a change of diagnosis in 60 (62%) patients and a change of management in 71 (73%) patients. The majority of consensus MDM diagnoses were IPF (n = 35, 36%), CTD-ILD (n = 30, 30%) and others (n = 15, 15%). There was a significant prognostic separation between the IPF and non-IPF diagnoses made following evaluation by the ILD service.@*CONCLUSION@#The ILD service allowed for more precise subtyping of various ILDs. This is particularly useful for IPF patients, who can benefit from antifibrotic therapies.

Interactive effects of fine particulate matter and temperature on residents mortality in Pudong, Shanghai / 上海预防医学

Objective To evaluate the interactive effects of fine particulate matter and temperature on non-accidental mortality of residents in Pudong, Shanghai. Methods Daily mortality, air pollutants and meteorological data from Jan 1st.2016 to Dec 31st.2017 were collected.Generalized additive Poisson regression models was used to estimate the effects of PM2.5 pollution on daily mortality, bivariate response surface models and temperature stratified models were applied to examine the interaction of temperature with PM2.5 on mortality. Results A total of 43 345 non-accidental deaths were included, daily mean PM2.5 concentration was 39.1 μg/m3, daily mean temperature was 17.7 ℃.A 10 μg/m3 increase in the daily PM2.5 at lag 1 day was associated with a 0.56%(95%CI:0.11%-1.01%), 0.49%(95%CI:-0.19%-1.18%) and 0.22%(95%CI:-1.14%-1.60%) increase in non-accidental, cardiovascular and respiratory mortality, respectively.Higher risks were identified for males and the older (≥65 years).The effect estimates per 10 μg/m3 increase in PM2.5 in medium temperature level were 0.59%(95%CI:0.04%-1.14%)for non-accidental, 0.51%(95%CI:-0.32%-1.35%)for cardiovascular and 0.51%(95%CI:-0.32%-1.35%) for respiratory mortalities.The PM2.5 effects were approximately 2-4 times higher in higher temperature level for non-accidental and cardiovascular mortalities compared with other temperature levels; for respiratory mortality, the PM2.5 effects was approximately 2-fold higher in lower temperature levels than the medium, although the interactions between temperature and PM2.5 were statistically insignificant. Conclusions Temperature may modify the effects of PM2.5 on mortality in Pudong, Shanghai and the interactive pattern may be different across disease-specific mortalities.