Study on the Teaching Path of Medical Ethics in Medical Colleges and Universities in Ethnic Areas by Integrating the Consciousness of the Chinese National Community / 中国医学伦理学

From an ethical point of view, the ethical characteristics of the consciousness of the Chinese national community contain an ethical starting point based on "love"; ethical path with "people first" as the core; ethical vision for the purpose of "prosperity". The consciousness of the Chinese national community greatly conforms to the teaching objectives and teaching content of medical ethics. Therefore, medical ethics teaching from the perspective of the Chinese national community should implement the fundamental task of helping students develop good morals and enhance the moral quality of "love"; take the "community of doctor-patient destiny" as the starting point of education and build the concept of "people first"; strengthen the country’s sense of responsibility of "prosperity and strength" and establish the mission of "rooting and maintaining health at the grassroots level", build a strong consciousness of the Chinese national community.

Expert Consensus on Clinical Diseases Responding Specifically to Traditional Chinese Medicine： Threatened Abortion / 中国实验方剂学杂志

Threatened abortion is a common disease of obstetrics and gynecology and one of the diseases responding specifically to traditional Chinese medicine （TCM）. The China Association of Chinese Medicine organized experts in TCM obstetrics and gynecology， Western medicine obstetrics and gynecology， and pharmacology to deeply discuss the advantages of TCM and integrated Chinese and Western medicine treatment as well as the medication plans for threatened abortion. After discussion， the experts concluded that chromosome， endocrine， and immune abnormalities were the key factors for the occurrence of threatened abortion， and the Qi and blood disorders in thoroughfare and conception vessels were the core pathogenesis. In the treatment of threatened abortion， TCM has advantages in preventing miscarriages， alleviating clinical symptoms and TCM syndromes， relieving anxiety， regulating reproductive endocrine and immune abnormalities， personalized and diversified treatment， enhancing efficiency and reducing toxicity， and preventing the disease before occurrence. The difficulty in diagnosis and treatment of threatened abortion with traditional Chinese and Western medicine lies in identifying the predictors of abortion caused by maternal factors and the treatment of thrombophilia. Recurrent abortion is the breakthrough point of treatment with integrated traditional Chinese and Western medicine. It is urgent to carry out high-quality evidence-based medicine research in the future to improve the modern diagnosis and treatment of threatened abortion with TCM.

Expert Consensus on Clinical Diseases Responding Specifically to Traditional Chinese Medicine：Fibromyalgia Syndrome / 中国实验方剂学杂志

Fibromyalgia syndrome （FMS） is a refractory， chronic non-articular rheumatic disease characterized by widespread pain throughout the body， for which there are no satisfactory therapeutic drugs or options. There are rich Chinese medical therapies， and some non-drug therapies， such as acupuncture， Tai Chi， and Ba-Duan-Jin， have shown satisfactory efficacy and safety and definite advantages of simultaneously adjusting mind and body. FMS is taken as a disease responding specifically to traditional Chinese medicine （TCM） by the National Administration of Traditional Chinese Medicine in 2018. In order to clarify the research progress in FMS and the clinical advantages of TCM/integrated Chinese and Western medicine， the China Academy of Chinese Medicine organized a seminar for nearly 20 experts in Chinese and Western medicine， including rheumatology， psychology， acupuncture and moxibustion， and encephalopathy， with the topic of difficulties in clinical diagnosis and treatment of FMS and advantages of TCM and Western medicine. The recommendations were reached on the difficulties in early diagnosis and solutions of FMS， mitigation of common non-specific symptoms， preferential analgesic therapy， TCM pathogenesis and treatment advantages， and direction of treatment with integrated Chinese and Western medicine. FMS is currently facing the triple dilemma of low early correct diagnosis， poor patient participation， and unsatisfactory benefit from pure Western medicine treatment. To solve the above problems， this paper suggests that rheumatologists should serve as the main diagnostic force of this disease， and they should improve patient participation in treatment decision-making， implement exercise therapy， and fully utilize the holistic and multidimensional features of TCM， which is effective in alleviating pain， improving mood， and decreasing adverse events. In addition， it is suggested that FMS treatment should rely on both TCM and Western medicine and adopt multidisciplinary joint treatment， which is expected to improve the standard of diagnosis and treatment of FMS in China.

Specific DNA barcodes screening, germplasm resource identification, and genetic diversity analysis of Platycodon grandiflorum / 药学学报

Platycodonis Radix is the dry root of Platycodon grandiflorum of Campanulaceae, which has a variety of pharmacological effects and is a commonly used bulk Chinese medicine. In this study, the chloroplast genome sequences of six P. grandiflorum from different producing areas has been sequenced with Illumina HiSeq X Ten platform. The specific DNA barcodes were screened, and the germplasm resources and genetic diversity were analyzed according to the specific barcodes. The total length of the chloroplast genome of 6 P. grandiflorum samples was 172 260-172 275 bp, and all chloroplast genomes showed a typical circular tetrad structure and encoded 141 genes. The comparative genomics analysis and results of amplification efficiency demonstrated that trnG-UCC and ndhG_ndhF were the potential specific DNA barcodes for identification the germplasm resources of P. grandiflorum. A total of 305 P. grandiflorum samples were collected from 15 production areas in 9 provinces, for which the fragments of trnG-UCC and ndhG_ndhF were amplificated and the sequences were analyzed. The results showed that trnG-UCC and ndhG_ndhF have 5 and 11 mutation sites, respectively, and 5 and 7 haplotypes were identified, respectively. The combined analysis of the two sequences formed 13 haplotypes (named Hap1-Hap13), and Hap4 is the main genotype, followed by Hap1. The unique haplotypes possessed by the three producing areas can be used as DNA molecular tags in this area to distinguish from the germplasm resources of P. grandiflorum from other areas. The haplotype diversity, nucleotide diversity and genetic distance were 0.94, 4.79×10-3 and 0.000 0-0.020 3, respectively, suggesting that the genetic diversity was abundant and intraspecific kinship was relatively close. This study laid a foundation for the identification of P. grandiflorum, the protection and utilization of germplasm resources, and molecular breeding.

Effect of fosinopril on angiotensin converting enzyme 2 and vascular endothelial growth factor in diabetic retinopathy mice / 解剖学报

Objective To explore the protective effect of fosinopril (Fos) on streptozotocin ( STZ) induced diabetic retinopatfry( DR) mice and on the expression of angiotensin converting enzyme 2(ACE2) and vascular endothelial growth factor (VEGF) in DR mice. Methods Totally forty-eight healthy male Kunming mice, thirty-six were randomly selected, and a diabetic mouse model induced by STZ was constructed after 6 weeks of high-fat diet. After the successful establishment of the model, the thirty-six mice were randomly divided into three groups: model group, Fos low concentration ( 5 mg/kg) group, and Fos high concentration ( 10 mg/kg) group. The remaining twelve mice were served as the control group. After 8 weeks administration, the bod)' weight and blood glucose level of mice in each group were determined. The change in the retinal structure was verified by HE staining. The serum level of VEGF was measured by ELISA. The expression of ACE2 in the retina tissue was verified by immunohistochemistry. The expression of ACE2 mRNA in diabetic retinopatlry was analyzed by Real-time PCR. The levels of ACE2 and VEGF protein in diabetic retinopatlry were detected by Western blotting. Results Fos ( 5 mg/kg, 10 mg/kg ) reduced significantly the proliferation of neovascularization in the inner boundaiy layer, down-regulated the expression of VEGF in the serum of diabetic mice and promoted the expression of ACE2 in the retina tissue of diabetic mice. In addition, the effect of the high concentration group of Fos had a stronger effect than the lower concentration group (P<0. 0 5 ) . Conclusion Fos has a protective effect on the retinopatlry of diabetic mice. This protective effect ma)' be mediated through the increased expression of ACE2 and the reduction of VEGF expression.

GPER inhibitor increases tamoxifen-induced apoptosis in T-47DTR-resistant cells / 中国药理学通报

Aim To study the effect of G protein-coupled estrogen receptor(GPER)inhibitor G15 on the sensitivity of breast cancer tamoxifen-resistant cells to T-47DTR. Methods Experiments were carried out with 4-hydroxytamoxifen(4-OHT),the active form of tamoxifen in vivo. The sensitivity of tamoxifen-resistant breast cancer cell line T-47DTR and its parental cell line T-47D to tamoxifen was detected by MTT assay; the expression of GPER protein was analyzed by plasma separation of inhibitor G15; the effect of 4-OHT combined with G15 on the apoptosis of T-47DTR cells was analyzed by flow cytometry AnnexinV-FITC/PI double staining; the expression levels of apoptosis-related proteins Bax,Bcl-2,caspase-3,cleaved caspase-3,caspase-9,cleaved caspase-9 were analysed by Western blot. Results(1)Compared with the parental cell T-47D,the resistance of T-47DTR-resistant cells to 4-OHT was significantly enhanced.(2)When 4-OHT(2 μmol·L-1)was administered,the membrane distribution of GPER increased,indicating that GPER was activated in T-47DTR-resistant cells compared with the control group; Compared with OHT,the use of G15(5 μmol·L-1)and OHT significantly reduced the expression of GPER.(3)GPER inhibitor G15 could increase the apoptotic rate of T-47DTR-resistant cells while down-regulating the anti-apoptotic protein Bcl-2 and up-regulating the expression of pro-apoptotic proteins Bax,cleaved caspase-3,cleaved caspase-9. Conclusions The GPER inhibitor G15 increases the apoptosis of T-47DTR cells and restores the sensitivity of drug-resistant cells to tamoxifen.

Updated growth standards for Chinese children under 7 years of age / 中华儿科杂志

Objective: To construct growth standards for Chinese children under 7 years of age. Methods: Cross-sectional study design based on national representative data on children's growth and development in 2015 was used. Stratified cluster sampling method was used. A total of 83 628 healthy children aged 0-<7 years from 9 cities, including Beijing, Harbin, Xi'an, Shanghai, Nanjing, Wuhan, Guangzhou, Fuzhou, and Kunming, were investigated from June to November 2015, excluding those with adverse conditions that may impact the establishment of the growth standards. Weight, length (height) and head circumference were measured using unified measurement tools and measurement methods. The Lambda-Mu-Sigma method was employed to establish percentile and standard deviation score reference values of weight-for-age, length (height)-for-age, head circumference-for-age, weight-for-length (height) and body mass index (BMI)-for-age of the study population. The standard deviation score curves of the new-established growth standards were compared with the 2009 reference standards. Results: Reference values of percentile (P3, P10, P25, P50, P75, P90, P97) and standard deviation score (-3, -2, -1, 0,+1,+2,+3) of weight-for-age, length (height)-for-age, head circumference-for-age, weight-for-length (height) and BMI-for-age were obtained. Compared with the 2009 growth standards, the difference of weight at P50 was -0.1-0.4 kg, the difference of length (height) at P50 was 0.1-1.3 cm, the difference of head circumference at P50 was -0.2-0.2 cm, the difference of weight for length (height) at P50 was -0.2-0.5 kg, and the difference of BMI at P50 was -0.2-0.2 kg/m2. The main differences were as follows: weight for girls aged 5.0-<7.0 years was 0.4-0.6 kg higher at +2 s, height for boys and girls aged 2.0-<7.0 years was 0.4-1.4 cm higher at -2 s, and BMI for boys and girls aged 5.0-<7.0 years was 0.1-0.3 kg/m2 higher at +2 s than the 2009 reference standards. Conclusion: The newly established growth standards for Chinese children under 7 years of age that have achieved a minor revision to the 2009 reference standards, are recommended for nationwide use in growth monitoring and nutritional assessment.

Effect of Enolase inhibitor on autophagy and motor function after spinal cord injury in rats / 中华创伤杂志

Objective:To investigate the effect of Enolase inhibition (ENOblock) on autophagy- related protein expression and motor function promotion after spinal cord injury in rats.Methods:A total of 160 female SD rats were divided into sham-operation group, 3-methyladenine (3-MA) autophagy inhibitor treatment group (3-MA group), spinal cord injury group and ENOblock treatment group (ENOblock group) according to the random number table, with 40 rats per group. Back laminectomy without injury to the spinal cord was performed in sham-operation group. Spinal cord injury at T 8 was induced by using a modified Allen weight-drop apparatus to establish a spinal cord injury model in the rest three groups. 3-MA and ENOblock groups were injected 3-MA (2.5 mg/kg) and ENOblock (100 μg/kg) into the caudal vein immediately after injury, respectively. Sham-operation and spinal cord injury groups were injected same dose of isotonic sodium chloride solution into the caudal vein. At 1, 3, 7, 14 and 21 days after injury, BBB score was used to evaluate lower limb motor function. At day 3 after injury, the ratio of microtubule-associated protein 1 light chain 3 (LC3)-II to LC3-I and protein expressions of autophagy effector protein (Beclin-1) and polyubiq-uitinbinding protein (p62) were detected by Western blotting. At day 7 after injury, LC3-Ⅱ and Beclin-1 positive cells in the injured area of the spinal cord were determined by immunofluorescence staining. At day 3 after injury, the mRNA expressions of Beclin-1 and Enolase in the injured area of the spinal cord were detected by RT-PCR. Results:At 1, 3, 7, 14 and 21 days after injury, BBB score was lowered in 3-MA group [(1.4±1.1)points, (2.4±0.9)points, (3.8±1.8)points, (7.6±1.1)points, (9.0±2.1)points], spinal cord injury group [(0.8±0.5)points, (1.8±0.9)points, (3.6±0.9)points, (6.2±1.3)points, (8.0±0.7)points] and ENOblock group [(2.0±0.9)points, (2.2±0.8)points, (4.8±1.1)points, (10.6±1.5)points, (13.2±0.8)points] compared to sham-operation group [(21.0±0.0)points at all time points] (all P<0.05). Moreover, the score in ENOblock group was significantly higher than that in spinal cord injury group at 14, 21 days after injury, and the score in 3-MA group was significantly higher than that in spinal cord injury group at day 21 after injury (all P<0.05). At day 3 after injury, Western blotting showed that the ratio of LC3-II to LC3-I and protein expressions of Beclin-1 and p62 were 0.46±0.10, 0.41±0.03, 0.81±0.03 in sham-operation group, 0.66±0.06, 0.69±0.02, 0.59±0.05 in 3-MA group, 0.85±0.06, 1.07±0.03, 0.41±0.02 in spinal cord injury group and 0.68±0.06, 0.66±0.08, 0.55±0.02 in ENOblock group. By comparison, spinal cord injury group showed significantly higher ratio of LC3-II to LC3-I and protein expression of Beclin-1 and significantly lower protein expression of p62 than sham-operation group (all P<0.05); 3-MA and ENOblock groups showed significantly lower ratio of LC3-II to LC3-I and protein expression of Beclin-1 and significantly higher protein expression of p62 than spinal cord injury group (all P<0.05); there was no significant difference in the ratio of LC3-II to LC3-I and protein expressions of Beclin-1 and p62 between 3-MA and ENOblock groups (all P>0.05). At day 7 after injury, immunofluorescence staining showed that LC3-II and Beclin-1 positive cells in 3-MA and ENOblock groups were less than those in spinal cord injury group. At day 3 after injury, RT-PCR showed that mRNA expressions of Beclin-1 and Enolase in spinal cord injury group (1.08±0.16, 0.98±0.17) were higher than those in sham-operation group (0.25±0.06, 0.29±0.03). Moreover, mRNA expressions of Beclin-1 and Enolase in 3-MA group (0.77±0.11, 0.72±0.04) and ENOblock group (0.81±0.10, 0.64±0.09) were lower than those in spinal cord injury group (all P<0.05). There was no significant difference in mRNA expressions of Beclin-1 and Enolase between 3-MA and ENOblock groups (all P>0.05). Conclusions:Autophagy activity is significantly up-regulated after spinal cord injury in rats. ENOblock can inhibit autophagy and promote motor function recovery in rats by regulating the expression of autophagy-related proteins.

Clinical characteristics and prognosis of bacterial liver abscess in patients with diabetes mellitus / 中华传染病杂志

Objective:To compare the clinical characteristics and prognosis of bacterial liver abscess in patients with or without diabetes mellitus (DM), to provide a reference for clinical diagnosis and treatment.Methods:Patients with bacterial liver abscesses hospitalized in Tongren Hospital, Shanghai Jiao Tong University School of Medicine from January 2016 to August 2021 were enrolled, and their clinical data were collected. The patients were divided into diabetic and non-diabetic groups for comparison according to whether they had comorbid DM. Statistical analysis was performed by chi-square test or Fisher′s exact test, and multivariate logistic regression analysis.Results:A total of 131 patients with bacterial liver abscesses were included, including 47 cases in the diabetic group and 84 cases in the non-diabetic group. The percentages of platelet count <100×10 9/L, C-reactive protein>10 mg/L, and total bilirubin>17.5 μmol/L were lower in the diabetic group than that in the non-diabetic group, and the differences were all statistically significant ( χ2=3.90, 6.44 and 5.56, respectively, all P<0.05). The percentage of multiple abscesses in the diabetic group was 10.6%(5/47), which was lower than 29.8%(25/84) in the non-diabetic group, and the difference was statistically significant ( χ2=6.24, P=0.012). The positive rate of pus culture for Klebsiella pneumoniae was 64.9%(24/37) in the diabetic group, which was higher than 41.5%(27/65) in the non-diabetic group, with a statistically significant difference ( χ2=5.13, P=0.023). The incidences of pleural effusion and abscesses at other sites in the diabetic group were 29.8%(14/47) and 10.6%(5/47), respectively, which were both higher than 14.3%(12/84) and 1.2%(1/84) in the non-diabetic group, respectively, and the differences were statistically significant ( χ2=4.55, Fisher′s exact test, both P<0.05). The proportion of hospital stays>21 d was 34.0%(16/47) in the diabetic group, which was higher than 16.7%(14/84) in the non-diabetic group, with a statistically significant difference ( χ2=5.15, P=0.023). DM (odds ratio ( OR)=2.654, 95% confidence interval ( CI) 1.020 to 6.907, P=0.046) and abscess maximum diameter>10 cm ( OR=11.045, 95% CI 4.493 to 27.154, P<0.001) were significant risk factors for hospital stay>21 d. Conclusions:Bacterial liver abscesses combined with DM are more common with single abscess, a higher rate of Klebsiella pneumoniae infection, and more likely to develop pleural effusions and abscesses at other sites. Liver abscesses>10 cm in maximum diameter and comorbid DM would prolong hospital stay.

Study on the application effects of the mode of "Multidisciplinary integration, Doctors & patients co-teaching, Simulated practice" in the teaching of spinal surgery / 中华医学教育探索杂志

Objective:To explore the application effects of the mode of "Multidisciplinary integration, Doctors & patients co-teaching, Simulated practice" in the teaching of spinal surgery.Methods:A total of 64 eight-year program clinical medical students who practiced in Peking Union Medical College Hospital in 2021 were taken as research objects and randomly divided into experimental group ( n=33) and control group ( n=31). The experimental group received the new teaching mode of "Multidisciplinary integration, Doctors & patients co-teaching, Simulated practice", and the control group received regular teaching mode. At the end of teaching, the teaching effects were evaluated from several aspects, including the scores of theoretical examinations, anatomical marks identification tests, and anonymous questionnaires. SPSS 22.0 software was used for paired t-test and two independent-samples t-test. Results:The theoretical test scores [(51.25±6.99) points] and anatomical structure identification scores [(37.56±1.83) points] of the experimental group were higher than those of the control group [(42.46±6.13) points and (30.37±3.46) points], and the differences were statistically significant ( P<0.001). The effective recovery rate of the questionnaire was 100%. The results of the questionnaire showed that the experimental group was significantly higher than the control group in terms of teaching attractiveness, attention, learning interest, learning efficiency, anatomical identification ability, problem-finding and problem-solving ability and overall teaching method satisfaction ( P<0.05). Conclusion:The teaching mode of "Multidisciplinary integration, Doctors & patients co-teaching, Simulated practice" can effectively improve students' theoretical knowledge, learning interest, learning efficiency, operation proficiency and problem-finding and problem-solving ability, which is worth promoting.

Neonatal Glanzmann thrombasthenia: a case report and literature review / 中国新生儿科杂志

Objective:To study the clinical features and genotypes of neonatal Glanzmann thrombasthenia(NGT).Methods:A male neonate with NGT admitted to the Department of Neonatology of our hospital was retrospectively reviewed. CNKI, Wangfang database, VIP, the Chinese Medical Journal Full Text database, PubMed and Embase database were searched using key words '(neonate OR newborn) AND (Glanzmann thrombasthenia)' both in English and Chinese. The clinical features and genotypes of NGT were summarized and analyzed.Results:A male full-term neonate was admitted to our hospital for mass on the forehead and ecchymosis and petechiae on the body within half an hour after birth. He gradually developed subgaleal hemorrhage and severe anemia. Platelet count, mean platelet volume and coagulation functions were normal. The platelet aggregation test indicated decreased platelet aggregation rate induced by arachidonic acid and adenosine diphosphate. Genetic testing revealed two heterozygous mutations in the patient's ITGA2B gene: NM_000419.4: c.886G>A(p.Gly296Arg) and NM_000419.4: c.2855dup(p.Phe953Valfs*83). A total of 42 literature involving 44 patients (our case included) with NGT were retrieved. 33 cases (75.0%) of NGT showed ecchymosis or petechiae on the first day after birth. For 13 cases with detailed information, 5 cases with severe anemia were given erythrocyte and plasma transfusion and platelet transfusion was given in 1 case. 4 cases had homozygous variants and 4 cases showed compound heterozygous variants. 10 cases had follow-up records, including 2 cases without any bleeding and 8 cases with varying degrees of bleeding during follow-up. No deaths were reported.Conclusions:Neonates with ecchymosis and petechiae in the early postnatal period should be suspected of NGT. Blood transfusion is preferred when the indication for transfusion is met.

CircFhit Modulates GABAergic Synaptic Transmission via Regulating the Parental Gene Fhit Expression in the Spinal Dorsal Horn in a Rat Model of Neuropathic Pain / 神经科学通报·英文版

Effective treatments for neuropathic pain are lacking due to our limited understanding of the mechanisms. The circRNAs are mainly enriched in the central nervous system. However, their function in various physiological and pathological conditions have yet to be determined. Here, we identified circFhit, an exon-intron circRNA expressed in GABAergic neurons, which reduced the inhibitory synaptic transmission in the spinal dorsal horn to mediate spared nerve injury-induced neuropathic pain. Moreover, we found that circFhit decreased the expression of GAD65 and induced hyperexcitation in NK1R+ neurons by promoting the expression of its parental gene Fhit in cis. Mechanistically, circFhit was directly bound to the intronic region of Fhit, and formed a circFhit/HNRNPK complex to promote Pol II phosphorylation and H2B monoubiquitination by recruiting CDK9 and RNF40 to the Fhit intron. In summary, we revealed that the exon-intron circFhit contributes to GABAergic neuron-mediated NK1R+ neuronal hyperexcitation and neuropathic pain via regulating Fhit in cis.

Transcutaneous Electrical Acupoint Stimulation Combined with Warm Acupuncture for Breast Cancer Related Upper Limb Lymphedema: A Retrospective Cohort Study / 中国结合医学杂志

OBJECTIVE@#To observe the clinical efficacy of transcutaneous electrical acupoint stimulation (TEAS) combined with warm acupuncture in treating breast cancer associated with upper limb lymphedema (BCRL).@*METHODS@#This was a retrospective cohort study using a paired control design. Fifty-two BCRL patients were assigned to the control group (27 cases) and the treatment group (25 cases). The patients in the control group were treated with lymphedema comprehensive detumescence treatment (CDT) for 4 weeks, including systematic therapy composed of manual lymphatic drainage, compression bandage, skincare, and functional exercise. The patients in the treatment group were treated with TEAS combined with warm acupuncture based on the control group methods. Each treatment lasted for 30 min and was applied twice a week for 4 weeks. The arm circumference (AC) of different positions of the affected limb and the degree of swelling of the affected limb were evaluated before the first treatment and after the last treatment. The clinical efficacy was evaluated according to the degree of edema before and after treatment. All adverse events during treatment were recorded.@*RESULTS@#The patients' AC and the swelling feeling of the affected limb in the treatment group and the control group were both reduced compared with those before treatment. Compared with the control group, AC of the wrist joint transverse stria, the midpoint between the wrist joint transverse stria and the elbow joint transverse stria in the treatment group were significantly reduced (P<0.05). The decrease in AC diameter at the midpoint between the elbow joint transverse stria and the axillary transverse stria was the most significant (P<0.01). The swelling degree of the affected limbs in the treatment group was significantly lower than before treatment, and was significantly lower compared with the control group after treatment (P<0.01). The total effective rate was 72% in the treatment group, significantly higher than that in the control group (55.56%, P<0.05). No serious adverse events occured in either group.@*CONCLUSIONS@#TEAS combined with warm acupuncture can effectively reduce AC and swelling feeling of the affected limb in patients with BCRL. The effect is better than that of CDT therapy alone. (Registration No. ChiCTR2200062075).

Ginsenoside Rg_3 based liposomes target delivery of dihydroartemisinin and paclitaxel for treatment of triple-negative breast cancer / 中国中药杂志

Ginsenoside Rg_3, an active component of traditional Chinese medicine(TCM), was used as the substitute for cholesterol as the membrane material to prepare the ginsenoside Rg_3-based liposomes loaded with dihydroartemisinin and paclitaxel. The effect of the prepared drug-loading liposomes on triple-negative breast cancer in vitro was evaluated. Liposomes were prepared with the thin film hydration method, and the preparation process was optimized by single factor experiments. The physicochemical properties(e.g., particle size, Zeta potential, and stability) of the liposomes were characterized. The release behaviors of drugs in different media(pH 5.0 and pH 7.4) were evaluated. The antitumor activities of the liposomes were determined by CCK-8 on MDA-MB-231 and 4T1 cells. The cell scratch test was carried out to evaluate the effect of the liposomes on the migration of MDA-MB-231 and 4T1 cells. Further, the targeting ability of liposomes and the mechanism of lysosome escape were investigated. Finally, H9c2 cells were used to evaluate the potential cardiotoxicity of the preparation. The liposomes prepared were spheroid, with uniform particle size distribution, the ave-rage particle size of(107.81±0.01) nm, and the Zeta potential of(2.78±0.66) mV. The encapsulation efficiency of dihydroartemisinin and paclitaxel was 57.76%±1.38% and 99.66%±0.07%, respectively, and the total drug loading was 4.46%±0.71%. The accumulated release of dihydroartemisinin and paclitaxel from the liposomes at pH 5.0 was better than that at pH 7.4, and the liposomes could be stored at low temperature for seven days with good stability. Twenty-four hours after administration, the inhibition rates of the ginsenoside Rg_3-based liposomes loaded with dihydroartemisinin(70 μmol·L~(-1)) and paclitaxel on MDA-MB-231 and 4T1 cells were higher than those of the positive control(adriamycin) and free drugs(P<0.01). Compared with free drugs, liposomes inhibited the migration of MDA-MB-231 and 4T1 cells(P<0.05). Liposomes demonstrated active targeting and lysosome escape. In particular, liposomes showed lower toxicity to H9c2 cells than free drugs(P<0.05), which indicated that the preparation had the potential to reduce cardiotoxicity. The findings prove that ginsenoside Rg_3 characterized by the combination of drug and excipient is an ideal substitute for lipids in liposomes and promoted the development of innovative TCM drugs for treating cancer.

Reference values and growth curves of length for weight and head circumference for weight among Chinese newborns / 中华儿科杂志

Objective: To establish the reference values and growth curves of length for weight and head circumference for weight among Chinese newborns in order to provide a reference for the assessment of body proportionality at birth. Methods: A cross-sectional design was applied. A total of 24 375 singleton live birth newborns with gestational ages at birth of 24+0 to 42+6 weeks were recruited from June 2015 to November 2018 from 13 cities including Beijing, Harbin, Xi'an, Shanghai, Nanjing, Wuhan, Guangzhou, Fuzhou, Kunming, Tianjin, Shenyang, Changsha, and Shenzhen, excluding those with maternal or newborn conditions that may impact the establishment of the reference values. The generalized additive model for location, scale, and shape was employed to establish reference values in terms of percentile and growth curves of length for weight and head circumference for weight for male and female newborns. The random forest machine learning method was employed to analyze the importance of variables between the established reference values in this study and the previous published weight/length, body mass index (BMI), ponderal index (PI), weight/head circumference, length/head circumference in the assessment of symmetrical and asymmetrical small for gestational age (SGA) newborns. Results: A total of 24 375 newborns with 13 197 male infants (preterm birth 7 042 infants and term birth 6 155 infants) and 11 178 female infants (preterm birth 5 222 infants and term birth 5 956 infants) were included in this study. The reference values in terms of percentile (P3, P10, P25, P50, P75, P90, P97) and growth curves of length for weight and head circumference for weight were obtained for male and female newborns with gestational ages of 24+0 to 42+6 weeks. The median birth lengths corresponding to the birth weights of 1 500, 2 500, 3 000, and 4 000 g were 40.4, 47.0, 49.3 and 52.1 cm for males and 40.4, 47.0, 49.2, and 51.8 cm for females, respectively; the median birth head circumferences were 28.4, 32.0, 33.2 and 35.2 cm for males and 28.4, 32.0, 33.1, and 35.1 cm for females, respectively. The differences of length for weight between males and females were minimum, with the difference range of -0.3 to 0.3 cm at P50; the differences of head circumference for weight between males and females were minimum, with the difference range of 0 to 0.2 cm at P50. Based on the match between birth length and birth weight for classifying symmetrical and asymmetrical SGA, length for weight and PI contributed the most, accounting for 0.32 and 0.25, respectively; based on the match between birth head circumference and birth weight, head circumference for weight and weight/head circumference contributed the most, accounting for 0.55 and 0.12, respectively; based on the match between birth length or head circumference with birth weight, head circumference for weight and length for weight contributed the most, accounting for 0.26 and 0.21, respectively. Conclusion: The establishment of the new standardized growth reference values and growth curves of length for weight and head circumference for weight among Chinese newborns are useful for clinical practice and scientific research.

Clinical characteristics of severe pre-eclampsia in a single tertiary referral center of Xiamen City / 中华妇产科杂志

Objective: To explore the key points for preventing and reducing severe pre-eclampsia (SPE) and its severe complications in the tertiary medical referral system of a second-tier city by analyzing the clinical characteristics of SPE. Methods: The clinical data of 341 patients with SPE who terminated pregnancy in Women and Children's Hospital, School of Medicine, Xiamen University, from January 1, 2020 to December 31, 2022 were retrospectively analyzed, and the pre-eclampsia (PE) risk factors, clinical characteristics and severe complications of SPE between the patients referred from primary hospitals (referral group) and the patients received regular prenatal care in the tertiary referral center (central group) were compared, as well as the influence of the referral timing on the maternal and perinatal outcomes. Results: Among the 341 cases of SPE, 92 cases were in the referral group and 249 cases were in the central group. (1) Analysis of PE risk factors: there was no statistical difference in the proportion of risk factors of PE between these two groups [75.0% (69/92) vs 71.9% (179/249); χ2=0.328, P=0.567]. (2) Analysis of clinical features: the gestational ages at the PE early warning factors onset, at the PE first symptom onset and at SPE diagnosed, pregnancy terminated and onset of SPE severe complications in the referral group were significantly earlier than those in the central group (all P<0.05), the proportions of terminating pregnancy before 32 weeks of gestation, between 32 and 34 weeks of gestation, intensive care unit (ICU), neonatal ICU hospitalization and fetal growth restriction in single pregnancies were higher than those in the central group, while the live birth rate was lower than that in the central group (all P<0.05). (3) Analysis of SPE severe complications: the rates of SPE severe complications in the referral group was higher than that in the central group [28.3% (26/92) vs 13.7% (34/249); χ2=9.885, P=0.002]. Among them, the rates of placental abruption [7.6% (7/92) vs 2.8% (7/249); χ2=3.927, P=0.048] and still birth [6.5% (6/92) vs 0.4% (1/249); χ2=9.656, P=0.002] in the referral group were significantly higher than those in the central group. (4) Analysis of referral timings: the timings included referral after onset of SPE severe complications (9.8%, 9/92), referral after SPE diagnosed (63.0%, 58/92), referral after detection of SPE early warning signs (20.7%, 19/92) and referral after detection of PE risk factors (6.5%, 6/92). The gestational ages at SPE diagnosed and pregnancy terminated in group of referral after onset of SPE severe complications and group of referral after SPE diagnosed were significantly earlier than those in group of referral after detection of PE early warning signs and group of referral after detection of PE risk factors (P<0.05). The earlier the referral, the higher the live birth rates (P<0.05). Conclusions: The tertiary referral center of the second-tier city plays an important role in reducing the maternal and perinatal damage of PE. The timing of referral in primary medical institutions is the key point of reducing the occurrence of SPE severe complications and maternal, perinatal damage of PE. It is necessary for medical institutions of all levels in all regions to improve the ability of early identification and early intervention for PE, to enhance the awareness of SPE and its severe complications prevention and control. Primary medical institutions should especially pay attention to raise the consciousness of PE risk factors and early warning signs, and to improve the ability of PE risk factors and early warning signs screening.

Causal links between long-term exposure to NO2 and the risk of cardiovascular hospitalization / 中华流行病学杂志

Objective: To determine the causal association between long-term Nitrogen dioxide (NO2) exposure and the risk of cardiovascular hospitalization. Methods: Based on a sub-cohort of a community-based prospective cohort study, a total of 36 271 participants were recruited from 35 communities randomly selected in Guangzhou in 2015. The annual average exposure of NO2, demographic characteristics, lifestyle factors, and information on the causes of hospitalization was collected. We applied marginal structural Cox models to investigate the effect of NO2 on cardiovascular hospitalization. Demographic and behavioral factors also stratified results. Results: The mean age of participants in the present study was (50.9±17.8) years, and the cardiovascular admission rate was 8.7%, with 203 822 person-years of follow-up. The annual mean NO2 concentration was 48.7 μg/m3 during 2015-2020. For each 10 μg/m3 increase in NO2 concentrations, the HRs (95%CIs) of total cardiovascular hospitalization, cardiovascular hospitalization, and cerebrovascular hospitalization were 1.33 (1.16-1.52), 1.36 (1.16-1.60) and 1.25 (1.00-1.55), respectively. Participants who were never married/married, with secondary education, high exercise frequency, or non-smokers/current smokers may be more susceptible than their counterparts. Conclusion: Long-term exposure to NO2 significantly increased hospitalization risk for cardiovascular disease.

Evidence mapping analysis of traditional Chinese medicine intervention in pulmonary fibrosis / 中国中药杂志

This study utilized evidence mapping methodology to systematically identify, describe, and evaluate the evidence from relevant research on traditional Chinese medicine(TCM) interventions in patients with pulmonary fibrosis. CNKI, Wanfang, VIP, SinoMed, PubMed, Web of Science, EMbase, and Cochrane Library were searched from database inception to March 2023 for systematic reviews/Meta-analysis/network Meta-analysis on TCM interventions in pulmonary fibrosis. The quality of included studies was assessed using the AMSTAR 2 scale, and the evidence mapping approach was employed to present comprehensive information on populations, intervention methods, the sample size in systematic reviews/Meta-analysis, and conclusion classifications. Ultimately, 44 systematic reviews/Meta-analysis/network Meta-analysis were included. Apart from syndrome differentiation and treatment, TCM injections accounted for a significant proportion of the observed interventions. The treatment methods were mainly focused on nourishing Qi and Yin, promoting blood circulation, resolving stasis, and dredging collaterals. The results from the included studies demonstrated that TCM treatment for pulmonary fibrosis could improve efficacy, increase lung function, improve PaO_(2 )levels, increase the 6-minute walk distance(6MWD), alleviate clinical symptoms, and enhance patients' quality of life. Based on the assessment using the AMSTAR 2 scale, methodological issues were identified, including the lack of protocol registration, failure to provide a list of excluded literature, and incomplete explanations regarding the impact of heterogeneity and bias on the results. The evidence mapping revealed that 42 conclusions were beneficial, while two conclusions were potentially beneficial. Overall, the quality of evidence was relatively low, primarily due to methodological imprecision and publication bias. Although TCM showed certain efficacy in the treatment of pulmonary fibrosis, the quality of reported literature, methodological quality, and overall evidence quality need improvement. It is recommended to conduct high-quality and standardized studies in the future to provide better evidence-based guidance.

Aqueous extract of Epimedium sagittatum mitigates pulmonary fibrosis in mice / 中国中药杂志

This study aims to investigate the intervention effect of the aqueous extract of Epimedium sagittatum Maxim on the mouse model of bleomycin(BLM)-induced pulmonary fibrosis, so as to provide data support for the clinical treatment of pulmonary fibrosis. Ninety male C57BL/6N mice were randomized into normal(n=10), model(BLM, n=20), pirfenidone(PFD, 270 mg·kg~(-1), n=15), and low-, medium-, and high-dose E. sagittatum extract(1.67 g·kg~(-1), n=15; 3.33 g·kg~(-1), n=15; 6.67 g·kg~(-1), n=15) groups. The model of pulmonary fibrosis was established by intratracheal instillation of BLM(5 mg·kg~(-1)) in the other five groups except the normal group, which was treated with an equal amount of normal saline. On the day following the modeling, each group was treated with the corresponding drug by gavage for 21 days. During this period, the survival rate of the mice was counted. After gavage, the lung index was calculated, and the morphology and collagen deposition of the lung tissue were observed by hematoxylin-eosin(HE) and Masson staining, respectively. The levels of reactive oxygen species(ROS) in lung cell suspensions were measured by flow cytometry. The levels of glutathione peroxidase(GSH-Px), total superoxide dismutase(T-SOD), and malondialdehyde(MDA) the in lung tissue were measured. Terminal-deoxynucleoitidyl transferase-mediated nick-end labeling(TUNEL) was employed to examine the apoptosis of lung tissue cells. The content of interleukin-6(IL-6), chemokine C-C motif ligand 2(CCL-2), matrix metalloproteinase-8(MMP-8), transforming growth factor-beta 1(TGF-β1), alpha-smooth muscle actin(α-SMA), E-cadherin, collagen Ⅰ, and fibronectin in the lung tissue was measured by enzyme-linked immunosorbent assay(ELISA). The expression levels of F4/80, Ly-6G, TGF-β1, and collagen Ⅰ in the lung tissue were determined by immunohistochemistry. The mRNA levels of CCL-2, IL-6, and MMP-7 in the lung tissue were determined by qRT-PCR. The content of hydroxyproline(HYP) in the lung tissue was determined by alkaline hydrolysation. The expression of α-SMA and E-cadherin was detected by immunofluorescence, and the protein levels of α-SMA, vimentin, E-cadherin in the lung tissue were determined by Western blot. The results showed the aqueous extract of E. sagittatum increased the survival rate, decreased the lung index, alleviated the pathological injury, collagen deposition, and oxidative stress in the lung tissue, and reduced the apoptotic cells. Furthermore, the aqueous extract of E. sagittatum down-regulated the protein levels of F4/80 and Ly-6G and the mRNA levels of CCL-2, IL-6, and MMP-7 in the lung tissue, reduced the content of IL-6, CCL-2, and MMP-8 in the alveolar lavage fluid. In addition, it lowered the levels of HYP, TGF-β1, α-SMA, collagen Ⅰ, fibronectin, and vimentin, and elevated the levels of E-cadherin in the lung tissue. The aqueous extract of E. sagittatum can inhibit collagen deposition, alleviate oxidative stress, and reduce inflammatory response by regulating the expression of the molecules associated with epithelial-mesenchymal transition, thus alleviating the symptoms of bleomycin-induced pulmonary fibrosis in mice.

Preparation and quality evaluation of total flavonoids microemulsion of "Pueraria lobata-Hovenia dulcis" / 中国中药杂志

The effective components of flavonoids in the "Pueraria lobata-Hovenia dulcis" drug pair have low bioavailability in vivo due to their unstable characteristics. This study used microemulsions with amphoteric carrier properties to solve this problem. The study drew pseudo-ternary phase diagrams through titration compatibility experiments of the oil phase with emulsifiers and co-emulsifiers and screened the prescription composition of blank microemulsions. The study used average particle size and PDI as evaluation indicators, and the central composite design-response surface method(CCD-RSM) was used to optimize the prescription; high-dosage drug-loaded microemulsions were obtained, and their physicochemical properties, appearance, and stability were evaluated. The results showed that when ethyl butyrate was used as the oil phase, polysorbate 80(tween 80) as the surfactant, and anhydrous ethanol as the cosurfactant, the maximum microemulsion area was obtained. When the difference in results was small, K_(m )of 1∶4 was chosen to ensure the safety of the prescription. The prescription composition optimized by the CCD-RSM was ethyl butyrate(16.28%), tween 80(9.59%), and anhydrous ethanol(38.34%). When the dosage reached 3% of the system mass, the total flavonoid microemulsion prepared had a clear and transparent appearance, with average particle size, PDI, and potential of(74.25±1.58)nm, 0.277±0.043, and(-0.08±0.07) mV, respectively. The microemulsion was spherical and evenly distributed under transmission electron microscopy. The centrifugal stability and temperature stability were good, and there was no layering or demulsification phenomenon, which significantly improved the in vitro dissolution of total flavonoids.