ObjectiveTo observe ovarian microvascular damage in rats with cold coagulation and blood stasis syndrome and to explore the mechanism by which Liangfang Wenjing decoction improves this condition in rats. MethodsFifty SPF female SD rats were randomly divided into a blank group， a model group， low-dose （8.1 g·kg^-1） and high-dose groups （16.2 g·kg^-1） of Liangfang Wenjing decoction， and a 4-phenylbutyric acid （0.1 g·kg^-1） group， with 10 rats in each group. The ice-water bath method was employed to establish the rat model of cold coagulation and blood stasis syndrome. Concurrent with modeling， Liangfang Wenjing decoction was administered continuously for 21 days， once daily. The rats' syndrome manifestations and estrous cycles were recorded. The enzyme-linked immunosorbent assay （ELISA） was used to detect serum reproductive hormone levels and levels of endothelin-1 （ET-1）， nitric oxide （NO）， thrombomodulin （TM）， and von Willebrand factor （vWF） in ovarian tissue. Prothrombin time （PT）， activated partial thromboplastin time （APTT）， thrombin time （TT）， and fibrinogen （FIB） were measured. The ovarian microcirculatory blood perfusion was detected by laser speckle contrast imaging. Hematoxylin-eosin （HE） staining was performed to observe the ovarian histopathology， flow cytometry to detect ovarian apoptosis rate， and transmission electron microscopy to observe the ultrastructure of ovarian microvascular endothelial cells. Western blot was employed to detect the protein expression of endothelial nitric oxide synthase （eNOS）， phosphorylated eNOS （p-eNOS）， Caspase-3， B-cell lymphoma-2 （Bcl-2）， Bcl-2-associated X protein （Bax）， glucose-regulated protein 78 （GRP78）， C/EBP homologous protein （CHOP）， inositol-requiring enzyme1α （IRE1α）， p-IRE1α， apoptosis signal-regulating kinase 1 （ASK1）， p-ASK1， c-Jun N-terminal kinase （JNK）， and p-JNK. Immunofluorescence was used to detect ovarian Bax and Bcl-2 expression in microvascular endothelial cells. ResultsCompared with the blank group， the model group showed signs of cold coagulation and blood stasis syndrome， prolonged estrus cycles， and reproductive hormone disorders. Histopathological results revealed a decrease in follicle counts at all stages and disorganized granulosa cell arrangement. Ovarian microcirculatory perfusion was significantly decreased （P<0.01）. PT， APTT， and TT were reduced （P<0.05， P<0.01）， while FIB levels were increased （P<0.05）. In ovarian tissue， NO content was decreased， while ET-1， vWF， and TM levels were increased significantly （P<0.01）. The apoptosis rate of ovarian cells was markedly increased （P<0.01）. Furthermore， p-eNOS/eNOS and Bcl-2 were decreased （P<0.05）， whereas Bax， cleaved-Caspase-3/Caspase-3， GRP78， CHOP， p-IRE1α/IRE1α， p-ASK1/ASK1， and p-JNK/JNK expression showed significant increases （P<0.05， P<0.01）. Compared with the model group， Liangfang Wenjing decoction intervention alleviated the symptoms of cold coagulation and blood stasis， gradually restored the estrus cycle， and improved ovarian histopathology and endothelial cell ultrastructure. Microcirculatory blood perfusion was significantly elevated （P<0.05）. NO content in ovarian tissue was elevated， while ET-1， vWF， and TM levels were significantly decreased （P<0.05， P<0.01）. The p-eNOS/eNOS ratio and Bcl-2 expression were significantly elevated （P<0.05）， while the expression of Bax， cleaved-Caspase-3/Caspase-3， GRP78， CHOP， p-IRE1α/IRE1α， p-ASK1/ASK1， and p-JNK/JNK was significantly decreased （P<0.05， P<0.01）. ConclusionLiangfang Wenjing decoction may regulate the IRE1α/ASK1/JNK signaling pathway to inhibit endoplasmic reticulum stress， attenuate apoptosis， and improve microvascular endothelial injury in ovaries of rats with cold coagulation and blood stasis syndrome.

Objective:To prepare hydroxyapatite(HA)coating on polyether ether ketone(PEEK)surface by magnetron sputtering technique and to study its biosafety.Methods:Sulfonated PEEK was used to increase the binding area and HA coating was constructed on it using magnetron sputtering technology.SEM and energy dispersive spectroscopy(EDAX)were used to detect the construction effect.Cell adhesion assay,cytoskeletal fluorescence staining and SEM validation were used to assess cytologrcal safety.In vivo safety tests were conducted in SD rats and golden hamsters.Results:HA coating with gradient morphology was successfully constructed on the PEEK surface using above technique.The coating promoted cell adhesion,extension and proliferation.No systemic toxicity and no sig-nificant influence in HE staining of the main infernal organs samples were observed.The coating alleviated the oral mucosal irritation caused by simple sulfonation to a certain extent.Conclusion:HA coating can be prepared stably with magnetron sputtering technology and can meet the biosafety needs for clinical applications.

Objective:To investigate the clinical features and therapeutic efficacy of patients with hereditary leiomyomatosis and renal cell carcinoma(RCC) syndrome-associated RCC (HLRCC-RCC) in China.Methods:The clinical data of 119 HLRCC-RCC patients with fumarate hydratase (FH) germline mutation confirmed by genetic diagnosis from 15 medical centers nationwide from January 2008 to December 2021 were retrospectively analyzed. Among them, 73 were male and 46 were female. The median age was 38(13, 74) years. The median tumor diameter was 6.5 (1.0, 20.5) cm. There were 38 cases (31.9%) in stage Ⅰ-Ⅱand 81 cases (68.1%) in stage Ⅲ-Ⅳ. In this group, only 11 of 119 HLRCC-RCC patients presented with skin smooth muscle tumors, and 44 of 46 female HLRCC-RCC patients had a history of uterine fibroids. The pathological characteristics, treatment methods, prognosis and survival of the patients were summarized.Results:A total of 86 patients underwent surgical treatment, including 70 cases of radical nephrectomy, 5 cases of partial nephrectomy, and 11 cases of reductive nephrectomy. The other 33 patients with newly diagnosed metastasis underwent renal puncture biopsy. The results of genetic testing showed that 94 patients had FH gene point mutation, 18 had FH gene insertion/deletion mutation, 4 had FH gene splicing mutation, 2 had FH gene large fragment deletion and 1 had FH gene copy number mutation. Immunohistochemical staining showed strong 2-succinocysteine (2-SC) positive and FH negative in 113 patients. A total of 102 patients received systematic treatment, including 44 newly diagnosed patients with metastasis and 58 patients with postoperative metastasis. Among them, 33 patients were treated with tyrosine kinase inhibitor (TKI) combined with immune checkpoint inhibitor (ICI), 8 patients were treated with bevacizumab combined with erlotinib, and 61 patients were treated with TKI monotherapy. Survival analysis showed that the median progression-free survival (PFS) of TKI combined with ICI was 18 (5, 38) months, and the median overall survival (OS) was not reached. The median PFS and OS were 12 (5, 14) months and 30 (10, 32) months in the bevacizumab combined with erlotinib treatment group, respectively. The median PFS and OS were 10 (3, 64) months and 44 (10, 74) months in the TKI monotherapy group, respectively. PFS ( P=0.009) and OS ( P=0.006) in TKI combined with ICI group were better than those in bevacizumab combined with erlotinib group. The median PFS ( P=0.003) and median OS ( P=0.028) in TKI combined with ICI group were better than those in TKI monotherapy group. Conclusions:HLRCC-RCC is rare but has a high degree of malignancy, poor prognosis and familial genetic characteristics. Immunohistochemical staining with strong positive 2-SC and negative FH can provide an important basis for clinical diagnosis. Genetic detection of FH gene germ line mutation can confirm the diagnosis. The preliminary study results confirmed that TKI combined with ICI had a good clinical effect, but it needs to be confirmed by the results of a large sample multi-center randomized controlled clinical study.

Objective:To analyze the changes of thyroid volume before and after supplementation with lipiodol pills in children with goiter, and to evaluate the recovery effect of lipiodol pills supplementation on children with goiter in the short term.Methods:In October 2018, 4 townships and towns in Linxia Hui Autonomous Prefecture with relatively serious historical conditions and high goiter rate of children aged 8 to 10 were selected for thyroid examination in 19 primary schools within the jurisdiction. Sixty children with goiter were selected as research subjects; at the same time, 138 children of the same age with normal thyroid B-ultrasound examination results were selected as control in the same period. Under the condition of normal diet, children with goiter were intervened by taking 200 mg lipiodol pills at one time. After 6 months, the thyroid volume of children with goiter and control children was measured by B-ultrasound.Results:Fifty-three children with goiter were finally included, with a sex ratio of 1.00 ∶ 1.04 (26 ∶ 27). There were 138 control children in the same period, with a sex ratio of 1.00 ∶ 1.30 (60 ∶ 78). Six months after taking lipiodol pills, the median thyroid volume of children with goiter was 3.7 ml, which was significantly different from that before supplementing with lipidol pills (5.8 ml, Z = - 7.95, P < 0.001), and not significantly different from that of control children (4.1 ml) in the same period ( Z = - 0.91, P = 0.365). Among them, 90.6% (48/53) of children with goiter recovered to the normal range, and 100.0% (15/15), 81.8% (18/22) and 93.8% (15/16) children's thyroid recovered returned to the normal range in the 8-, 9-, and 10-year-old age groups, respectively, and the highest proportion was in the 8-year-old age group. Stratified by age and gender, the thyroid volume of children with goiter in all age groups and gender after supplementation with lipiodol pills was lower than that before supplementation with lipiodol pills ( P < 0.001), but there was no difference compared with the control children in the same period ( P > 0.05). After supplementing with lipiodol pills, the diameters of thyroid in children with goiter were significantly lower than those before supplementing with lipiodol pills ( P < 0.001). Compared with the control children in the same period, there were significant differences in the right width, left length and right long diameter of the thyroid ( P < 0.05). Conclusion:Supplementing lipiodol pills can restore the thyroid volume of 8 - 10 year old children with goiter to normal range in a short term, and can effectively treat simple goiter.

ABSTRACT OBJECTIVE：To make a textual research on ethnic medicine Paederiae Herba，and to provide reference for further research and comprehensive development and utilization of Paederiae Herba. METHODS：Five materia medica works such as Compendium of Materia Medica Collection and Examination of Plant Names and Actual Maps，55 modern materia medica works such as Chinese materia medica and Flora of China published from 1960 to 2016，and a number of literatures were synthesized and sorted out. The name，original species，origins，harvesting and processing，flavor and meridian tropism and so on of P. scandens were studied. Its mainstream varieties were mainly clarified and use of them in various nationalities were sorted out. RESULTS & CONCLUSIONS：The name of“Paederiae Herba”was first recorded in the Qing Dynasty’s Examination of Plant Names and Actual Maps. The main variety of Paederiae Herba was Paederia scandens （Lour.） Merr.，also known as “Jishiteng”. The medicinal part was the aboveground part. It distributed in bushes of hillsides，forests，forest margins，valleys and shrubs at an altitude of 200 to 2 000 meters or wound around shrubs. It was mainly produced in the Yangtze River Valley of China and its southern regions. The processing methods are mostly shade-drying or removing impurities，washing，cutting and drying. Its sweet， astringent，flat，and it can be used for digestion，pain relief，detoxification and clearing damp，and can be used for food retention， chest，abdomen and abdomen pain，eczema，sores，swelling and pain. It was used in the folk of Miao，Tujia and Zhuang nationalities in China. There are still some problems such as mixed varieties and different processing methods in the market circulation. All these have brought many challenges to the research of quality standard of Paederiae Herba.

Objective To evaluate the therapeutic effect of thymosin alpha -1 with glucocorticoid in treat-ment of HBV -related hepatic failure.Methods 130 cases were randomly divided into two groups,they were all giv-en antiviral therapy,protect liver,anti -inflammatory,yellow suit the back support,etc.comprehensive treatment;and patients in treatment group were given thymosin alpha -1 with methyl -prednisone intravenously at the early stage of treating process,and then observed the clinic situation and cure rate of those sufferers,The biochemiccal indicator, PTA and blood serum HBV DNA capacity ending with the period of 4 weeks were tested.Results In both groups,the TBil,TC in serum had apparently improved compared with the baseline after the medication,the difference was signifi-cant (t =3.12,P <0.05 and t =3.05,P <0.05).The time of gastrointestinal symptoms improvement and bilirubin subsided time in treatment group were significantly shorter than those of the control group(t =3.34,P <0.01 and t =4.52,P <0.01 ).During the treatment,there was no significant adverse reaction,and there were no differences between two groups in Alt,PTA,HBV DNA,infection,gastrointestinal bleeding,hepatic encephalopathy and hepatore-nal syndrome.The effective rate of treatment group was 75.2%,which was higher than 50.3% of the control group (χ2 =11.02,P <0.01).Conclusion Patients with HBV -related hepatic failure of short -term application of thy-mosin alpha -1 with glucocorticoid treatment,can quickly improve symptoms,greatly improve the efficiency of survival rate,shortem hospitalization period,reduce side effects and enhance security.

This study is to evaluate the therapeutic effect of fibroblast growth factor 21 (FGF21) on NAFLD in MSG-IR mice and to provide mechanism insights into its therapeutic effect. The MSG-IR mice with insulin resistance were treated with high dose (0.1 micromol.kg-1d-1) and low dose (0.025 micromol.kg-1d-1) of FGF21 once a day for 5 weeks. Body weight was measured weekly. At the end of the experiment, serum lipids, insulin and aminotransferases were measured. Hepatic steatosis was observed. The expression of key genes regulating energy metabolism were detected by real-time PCR. The results showed that after 5 weeks treatment, both doses of FGF21 reduced body weight (P<0.01), corrected dyslipidemia (P<0.01), reversed steatosis and restored the liver morphology in the MSG model mice and significantly ameliorated insulin resistance. Additionally, real-time PCR showed that FGF21 significantly reduced transcription levels of fat synthetic genes, decreased fat synthesis and promoted lipolysis and energy metabolism by up-regulating key genes of lipolysis, thereby liver fat accumulation was reduced and liver function was restored to normal levels. In conclusion, FGF21 significantly reduces body weight of the MSG-IR mice, ameliorates insulin resistance, reverses hepatic steatosis. These findings provide a theoretical support for clinical application of FGF21 as a novel therapeutics for treatment of NAFLD.

Objective To explore the relationship between trace elements proportion in food and health. Methods 45 mice aged 12 month were randomly divided into 3 groups: control group(n=16) and two experimental groups(n=15).The mice in the experimental groups were given Zn, Li, Fe, Se, Mn, Cu, Co in different proportion by food for 60 days, then all mice were sacrificed, thymus weight, spleen weight, thymus coefficient, spleen coefficient, bone indexes were determined. Results Supplementation of the trace elements in food increased the content of Ca2+ in the bone of the aged mice and proportion variety of trace elements might induce the changes of thymus weight, spleen weight, spleen coefficient and bone indexes. Conclusion The reasonable proportion of trace elements in food could increase the content of bone Ca2+ in aged mice.

Objective Artificial mineral water pills were made by loading many kinds of trace elements into the ceramic carrier.Pure water could be mineralized after dipping the pills into the water.To assess the possible hazardous effects on the human health induced by the pills,a series of hygienic and toxicological experiments on the pills were carried out.Methods Acute oral toxicity test,micronucleus test of mice bone marrow cells,sperm abnormality test in mice and Ames test were con-ducted.Contents of trace elements,heavy metals and radioactivity in the mineralized water were determined according to the examination methods in Standard Examination Methods for Drinking Water and Examination Methods for Drinking Natural Min-eral Water.Results The contents of trace elements,heavy metals and radioactivity in mineralized water met the requirements of GB5749-1985Sanitary Standard for Drinking Water and GB8537-1995Sanitary Standard for Drinking Natural Mineral Wa-ter.Mineral pills were classified as actually non-toxic and the results of micronucleus test of mice bone marrow cells,sperm ab-normality test in mice and Ames test were negative.Conclusion Mineralized drinking water treated by artificial mineral pills were safe.