Antiosteoporosis effect of bryodulcosigenin on ovariectomy-induced osteoporosis in experimental rats

Purpose: Osteoporosis is a bone disease which commonly occurred in postmenopausal women. Almost 10 percent of world population and approximately 30% of women (postmenopausal) suffer from this disease. Alternative medicine has great success in the treatment of osteoporosis disease. Bryodulcosigenin, a potent phytoconstituent, already displayed the anti-inflammatory and antioxidant effect. In this study, we made effort to analyze the antiosteoporosis effect of bryodulcosigenin against ovariectomy (OVX) induced osteoporosis in rats. Methods: Swiss albino Wistar rats were grouped into fIve groups and given an oral dose of bryodulcosigenin (10, 20 and 30 mg/kg) for eight weeks. Body weight, uterus, bone mineral density, cytokines, hormones parameters, transforming growth factor (TGF)-ß, insulin-like growth factor (IGF), osteoprotegerin (OPG), receptor activator of nuclear factor kappa-Β ligand (RANKL), and its ratio were estimated. Results: Bryodulcosigenin significantly (p < 0.001) suppressed the body weight and enhanced the uterine weight and significantly (p < 0.001) increased the bone mineral density in whole femur, caput femoris, distal femur and proximal femur. Bryodulcosigenin significantly (P < 0.001) altered the level of biochemical parameters at dose dependent manner, significantly (P < 0.001) improved the level of estrogen and suppressed the level of follicle stimulating hormone and luteinizing hormone. Bryodulcosigenin significantly (P < 0.001) improved the level of OPG and suppressed the level of RANKL. Conclusions: Bryodulcosigenin reduced the cytokines level and suppressed the TGF-ß and IGF. We concluded that bryodulcosigenin is an antiosteoporosis medication based on the findings.

Correlation between iodine nutrition and thyroid function of pregnant women in Xinjiang Uygur Autonomous Region / 中华地方病学杂志

Objective:Through the detection of iodine nutrition level and thyroid function of pregnant women in Xinjiang Uygur Autonomous Region (Xinjiang), to preliminary study the pregnant women's iodine nutrition level, thyroid function status and the relationship between the two and influencing factors.Methods:From March to June in 2020, stratified cluster random sampling method was adopted. Two counties (cities) in Southern and Northern Xinjiang were selected as survey sites, and about 100 pregnant women (a total of 412) were selected from each county (city) as survey subjects. Random urine samples and blood samples were collected to detect urinary iodine and serum thyroid function indicators [thyroid stimulating hormone (TSH), free triiodothyronine (FT 3), free thyroxine (FT 4), anti-thyroglobulin antibody (Tg-Ab) and anti-thyroid peroxidase antibody (TPO-Ab)]. Results:The median and interquartile range [ M ( Q1, Q3)] of pregnant women's urinary iodine was 228.4 (143.15, 327.95) μg/L. Serum FT 3, FT 4 and TSH levels [ M ( Q1, Q3)] were 4.22 (3.92, 4.61), 13.79 (12.63, 15.26) pmol/L and 1.82 (1.26, 2.52) mU/L, respectively. The overall positive rates of Tg-Ab and TPO-Ab were 5.61% (23/412) and 11.95% (49/412), respectively. The positive rates of Tg-Ab and TPO-Ab in Southern and Northern Xinjiang were 4.78% (10/209), 10.05% (21/209), 6.40% (13/203) and 13.79% (28/203), respectively. The positive rates of Tg-Ab and TPO-Ab in Northern Xinjiang were higher than those in Southern Xinjiang, but the difference was not statistically significant (χ 2 = 1.31, 2.17, P > 0.05). The positive rate of TPO-Ab in pregnant women was the influencing factor of abnormal thyroid function, and the odds ratio ( OR) [95% confidence interval ( CI)] was 3.22 (1.31 - 7.93). Conclusions:Pregnant women in Xinjiang are generally at an appropriate level of iodine, but the state of thyroid function still needs continuous attention. In addition, it is necessary to strengthen the thyroid function examination of pregnant women with positive thyroid autoantibodies to prevent and control the occurrence of abnormal thyroid function in pregnant women.

Development of radiolabeled tetramer that targeting fibroblast activation protein and theranostic research in tumor xenografts / 中华核医学与分子影像杂志

Objective:To develop a tetramer probe targeting fibroblast activation protein (FAP), named 1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid (DOTA)-4P(FAP inhibitor (FAPI)) 4, evaluate its biodistribution and PET image in FAP-positive-tumor bearing nude mice, and explore its feasibility as a novel radio-regent for treatment of FAP-positive tumor. Methods:FAP tetramer probe was constructed on the FAPI-46 motif with four mini-polyethylene glycol (PEG)(PEG 3) spacers between the four FAPI motifs, denoted as 4P(FAPI) 4. DOTA was used as the chelator for radiolabeling with 68Ga and 177Lu. The FAP binding characteristics were test by in vitro cell competitive binding experiment. Small-animal PET, in vivo biodistribution, and radionuclide targeting therapy were performed in HT-1080-FAP tumor bearing nude mice ( n=39). Independent-sample t test was performed to analyze tumor uptake data, and two-factor repeated measures analysis of variance was utilized to compare tumor volume data in radioactive isotope therapy. Results:Cell experiment showed that FAPI-tetramer and FAPI-monomer had similar half maximal inhibitory concentration values (3.29 and 2.15 nmol/L). 68Ga/ 177Lu radiolabeled FAPI-tetramer had better tumor uptake and retention than FAPI-monomer in small-animal PET and in vivo biodistribution experiment, with the tumor uptake for 177Lu-DOTA-4P(FAPI) 4 and 177Lu-FAPI-46 at 48 h of (18.72±1.32) vs (2.72±1.20) percentage activity of injection dose per gram of tissue (%ID/g) ( t=15.55, P<0.001). 177Lu-DOTA-4P(FAPI) 4 group showed best anti-tumor efficacy compared with 177Lu-FAPI-46 and control group in radionuclide targeting therapy. On the 2nd day after the start of treatment, the tumor volume in the tetramer treatment group was significantly smaller than that in the control group (mean difference 67.19 mm 3, P=0.049); on the 14th day after the start of treatment, the tumor volume in the tetramer treatment group was significantly smaller than that in the monomer treatment group (mean difference 414.33 mm 3, P=0.005). Conclusion:FAPI-tetramer can improve tumor uptake and retention ability compared with FAPI-46, and 177Lu-DOTA-4P(FAPI) 4 can be a promising radio-agent for FAP-positive tumor therapy.

Clinical observation of virtual reality technology combined with isokinetic strength training for patients after anterior cruciate ligament reconstruction / 中国骨伤

OBJECTIVE@#To explore application value and effectiveness of virtual reality technology combined with isokinetic muscle strength training in the rehabilitation of patients after anterior cruciate ligament (ACL) reconstruction surgery.@*METHODS@#Forty patients who underwent ACL reconstruction surgery from December 2021 to January 2023 were selected and divided into control group and observation group according to treatment methods, 20 patients in each group. Control group was received routine rehabilitation training combined with isokinetic muscle strength training, including 15 males and 5 females, aged from 17 to 44 years old, with an average of (29.10±8.60) years old. Observation group was performed virtual reality technology combined with isokinetic muscle strength training, including 16 males and 4 females, aged from 17 to 45 years old with an average of (30.95±9.11) years old. Lysholm knee joint score, knee extension peak torque, and knee flexion peak torque between two groups at 12 (before training) and 16 weeks (after training) after surgery were compared.@*RESULTS@#All patients were followed up for 1 to 6 months with an average of (3.30±1.42) months. There were no statistically significant difference in Lysholm knee joint score, peak knee extension peak torque, and peak knee flexion peak torque between two groups (P>0.05) before training. After training, Lysholm knee joint score, knee extension peak torque, and knee flexion peak torque of both groups were improved compared to before training (P<0.05);there were significant difference in Lysholm knee joint score, knee extension peak torque, and knee flexion peak torque between two groups(P<0.05).@*CONCLUSION@#The application of virtual reality technology combined with isokinetic muscle strength training could promote recovery of knee joint function and enhance muscle strength in patients after ACL reconstruction surgery in further.

Effects of chronic exposure to sodium arsenite on liver damage in rats / 预防医学

Objective@#To examine the effect of chronic exposure to sodium arsenite on liver damages in rats. @*Methods@#Fifty-six healthy adult SD rats (28 males and 28 females) were randomly divided into 4 groups. Rats in the low-, medium- and high-dose groups were given sodium arsenite solutions at doses of 2, 10 and 50 mg/L for successive 24 weeks, while animals in the control group were given deionized water. The rat body and liver weights were measured and the liver coefficient was estimated. The urine arsenic level was detected using atomic fluorescence spectrometry, and hepatic tissue sections were stained with uranium acetate and lead citrate for morphological observations under an electron microscope. @*Results@#The body weights of both male and female rats appeared a tendency towards a rise with the duration of exposure to sodium arsenite (male rat: Wald χ2=3 610.621, P<0.001; female rat: Wald χ2=2 186.217, P<0.001, and there were no significant differences in the rat body weight 24 weeks post-exposure to sodium arsenite in each group, while there was an interaction between time and group (male rat: Wald χ2=15.874, P=0.001; Wald χ2=9.460, P=0.024). There were significant differences in the rat liver weight and liver coefficient in each group (male rat: F=18.964 and 29.968, both P<0.001; female rat: F=11.919 and 15.070, both P<0.001), with the lowest liver weight (10.17±1.15) g and liver coefficient (1.99±0.21)% measured in male rats in the high-dose group, and the highest liver weight (12.91±1.29) g and liver coefficient (4.10±0.56)% in female rats in the high-dose group. The median urine arsenic levels (interquartile range) were 25.60 (30.27), 146.56 (101.06), 1 034.68 (600.06) and 3 796.98 (19 966.89) μg/L in rats in the control, low-dose, medium-dose and high-dose groups, respectively (χ2=50.211, P<0.001), and the urine arsenic level was significantly higher in the medium- and high-dose groups than in the control group (both P<0.001). Hepatic edema was seen in rats in the low- and medium-dose groups, and hepatic edema, focal hepatic cell necrosis, hyperplasia of bile capillaries and peri-bile capillary endolysis were observed in rats in the high-dose group.@*Conclusions@#Chronic exposure to arsenic may cause morphological alterations of rat hepatic tissues, and the rat hepatic damage aggravates with the dose of exposure to arsenic.

Effect of oral iodized oil pills on thyroid function of pregnant women / 中华地方病学杂志

Objective:To evaluate the effect of oral iodized oil pills on iodine nutrition and thyroid function of pregnant women in Xinjiang Uygur Autonomous Region (Xinjiang).Methods:From May to July 2017, one county was selected from Ili Prefecture without taking iodized oil pills, Aksu Prefecture taking iodized oil pills once a year, and Kashgar Prefecture taking iodized oil pills twice a year in Xinjiang as survey sites, respectively; 100 pregnant women (evenly distributed in early, middle and late pregnancy) were selected from each survey county, the general data, urine and blood samples were collected, and urinary iodine and thyroid function indicators [free triiodothyronine (FT 3), free thyroxine (FT 4), thyrotropin (TSH), anti thyroglobulin antibody (TgAb), and anti thyroid peroxidase antibody (TPOAb)] were tested. Results:A total of 308 pregnant women were investigated, and 289 were finally included in the analysis, with an average age of 25 years; the body mass index (BMI) was (22.69 ± 3.07) kg/m 2. The occupation distribution was mainly farmer, accounting for 93.77% (271/289); most of them had junior high school education or below, accounting for 71.97% (208/289). The median urinary iodine of early, middle and late pregnant women in Kashgar Prefecture was 712.87, 604.50 and 656.23 μg/L, respectively, which were in iodine excess state. The iodine nutrition level of early pregnant women in Ili Prefecture and Aksu Prefecture was in iodine super suitability state, and the iodine nutrition level of middle and late pregnant women was in the iodine suitability state. The difference of median urinary iodine in early, middle and late pregnancy women between different regions was statistically significant ( Z = 53.02, 49.60, 44.66, P < 0.001). In addition, the urinary iodine of women in Kashgar Prefecture during each pregnancy period was significantly higher than that in Ili Prefecture and Aksu Prefecture ( P < 0.05). There were statistically significant differences in the levels of FT 3 among women in early pregnancy, FT 4 and TSH among women in middle pregnancy between different regions ( F = 4.59, 10.92, Z = 8.61, P < 0.05 or < 0.001). Among them, the level of FT 3 in early pregnancy in Kashgar Prefecture was lower than that in Ili Prefecture ( P < 0.05); the level of FT 4 in Kashgar Prefecture during middle pregnancy was higher than that in Ili Prefecture, and the level of TSH was lower than that in Ili Prefecture ( P < 0.05). There was no significant difference in TgAb positive rate, TPOAb positive rate and double antibody positive rate of early, middle and late pregnant women between different regions ( P > 0.05). The detection rates of hypothyroxinemia in early pregnant women in Ili Prefecture, Aksu Prefecture and Kashgar Prefecture were 13.9% (5/36), 3.2% (1/31) and 0 (0/33), respectively, and there was a statistically significant difference between different regions ( P = 0.036). The detection rates of subclinical hyperthyroidism in middle pregnant women were 0 (0/35), 0 (0/40), 17.6% (6/34), respectively, and there was a statistically significant difference between different regions ( P = 0.001). Conclusions:The results of urinary iodine in the three regions are in line with the iodine nutrition distribution under their respective iodine supplement strategies. Pregnant women in Kashgar Prefecture present iodine excess status after taking iodized oil pills; at the same time, the serum FT 3, FT 4 and TSH levels of pregnant women in Kashgar Prefecture are affected by iodine nutrition levels. Although it is scientific and effective to implement the intensified iodine supplement measures for pregnant women, it is still necessary to further study the suitability of oral iodine oil pills to ensure that pregnant women are at an suitability iodine nutrition level.

Effects of different iodine levels on thyroid function in rats after pregnancy / 中华地方病学杂志

Objective:To investigate the effects of different levels of iodine intake on thyroid function in Wistar rats after pregnancy, and to provide experimental basis for scientific supplementation of iodine and thyroid function screening during pregnancy.Methods:One hundred and fifty female SPF Wistar rats weaned for 2 weeks were selected. Female Wistar rats were intervened with iodine nutrition by drinking deionized water containing potassium iodide (KI). According to the random number table, female Wistar rats were divided into 5 groups [severe iodine deficiency (SID) group, mild iodine deficiency (MID) group, control group (NI), mild iodine excess (MIE) group, and severe iodine excess (SIE) group, 30 rats per group]. The iodine doses of the five groups were 0.0, 1.5, 5.5, 70.0 and 350.0 μg/d, respectively. The animal model was established and intervened for 3 months to detect the 24 h urinary iodine content of rats, and compared with the NI group to determine the success of the model or not. After successful modeling, the tested female Wistar rats were mated with male Wistar rats (female : male=2-3 : 1). There were about 15 pregnant rats in each group, and continued to intervene the pregnant rats for 21 d with the same doses as the modeling conditions. The abdominal aortic blood of non-pregnant and pregnant rats was taken. After serum separation, 5 items [free thyroxine (FT 4), free triiodothyronine (FT 3), thyroid stimulating hormone (TSH), anti-thyroglobulin antibodies (TgAb), thyroid peroxidase antibody (TPOAb)] of serum thyroid function were detected in each group. Results:There was significant difference in urinary iodine content between the five groups (the medians urinary iodine were 3.540, 51.410, 286.801, 644.192 and 2 368.701, respectively, H = 94.791, P < 0.01). Rats with different iodine nutrition levels were successfully established. There were no significant differences in TSH level, TPOAb and double antibodies positive rates of non-pregnant rats among groups ( P > 0.05). There were statistically significant differences in the levels of FT 4, FT 3 and the positive rate of TgAb among groups ( P < 0.05). The level of FT 4 in SID group was lower than that in NI group ( P < 0.05). The level of FT 3 in SID group was higher than that in NI group ( P < 0.05). The positive rate of TgAb in SIE group was higher than that in NI group ( P < 0.05). There were no significant differences in TSH, FT 4 and FT 3 levels of pregnant rats among groups ( P > 0.05). There were significant differences in the positive rates of TgAb, TPOAb and double antibodies among the groups ( P < 0.05). The positive rates of TgAb, TPOAb and double antibodies in MIE and SIE groups were higher than those in NI group ( P < 0.05). The positive rate of TPOAb in MIE group was higher than that in NI group ( P < 0.05), and the positive rates of double antibodies in MID and MIE groups were higher than that in NI group ( P < 0.05). Conclusions:Iodine deficiency can lead to the change of thyroid hormone level in non pregnant rats, while iodine excess can increase the positive rate of related antibodies in non pregnant and pregnant rats.

Influencing factors of thyroid volume in school-age children aged 8 - 10 years in Xinjiang Uygur Autonomous Region in 2020 / 中华地方病学杂志

Objective:To investigate the influencing factors of thyroid volume in school-age children aged 8 - 10 years in Xinjiang Uygur Autonomous Region (Xinjiang for short).Methods:In 2020, counties (cities, districts) were taken as the units in the whole region of Xinjiang. Each county (city, district) was divided into 5 sampling areas according to the orientation of east, west, south, north, and middle, one township/street was selected from each area, and one primary school was selected from each township/street, 40 non-boarding children aged 8 - 10 years were selected from each primary school as the investigation subjects. Height and weight of children were measured, and body mass index (BMI) and body surface area were calculated; 24 h mixed urine samples of children and household edible salt samples were collected to detect the contents of urinary iodine and salt iodine; thyroid volume of children was measured by B-ultrasonography. Pearson correlation analysis was used to analyze the correlation between thyroid volume and age, height, weight, body surface area, BMI, urinary iodine content, and salt iodine content. Univariate and multiple linear regression analyses were used to evaluate the correlation variables affecting thyroid volume.Results:A total of 18 334 children aged 8 - 10 years were investigated. The median urinary iodine was 237.88 μg/L. There were 132 children with goiter, and the rate of goiter was 0.72%. Of these, 9 249 (50.45%) were girls and 9 085 (49.55%) were boys. Girls' thyroid volume was positively correlated with age, height, weight, body surface area, BMI, urinary iodine content, and salt iodine content ( r = 0.125, 0.135, 0.167, 0.167, 0.154, 0.031, 0.019, P < 0.05); boys' thyroid volume was positively correlated with age, height, weight, body surface area, and BMI ( r = 0.132, 0.326, 0.156, 0.149, 0.146, P < 0.05), and there was no correlation with urinary iodine content and salt iodine content ( r = 0.019, 0.017, P > 0.05). Univariate linear regression analysis showed that age, height, weight, BMI, body surface area and urinary iodine content were the influencing factors of thyroid volume ( t = 14.92, 12.54, 20.98, 17.98, 20.25, 4.28, P < 0.01). Further multiple linear regression analysis showed that age, BMI, body surface area and urinary iodine content had significant independent effects on thyroid volume ( t = 9.61, 8.57, 7.76, 4.89, P < 0.01), the coefficient of determination ( R2) of the model was 0.278 2. According to the regression coefficient (β), the body surface area (β = 0.522 6) had the greatest influence on thyroid volume. Conclusions:The iodine nutrition of children aged 8 - 10 years in Xinjiang is sufficient. Thyroid volume is affected by age, BMI, body surface area and urinary iodine content.

Clinical manifestation and treatment of temporal bone tympanic plate fracture / 中华耳鼻咽喉头颈外科杂志

Objective: To elucidate the clinical manifestations of temporal bone tympanic plate fracture and the correlation between treatment time after injury and its prognosis, and to discuss the importance of early treatment of tympanic fracture. Methods: Retrospective analysis was carried out on the clinical data of 15 patients(17 ears)with temporal bone tympanic plate fracture from March 2006 to July 2019. The course of disease was less than 1 month (initial stage) in 7 cases (7 ears), 1 month to 6 months (middle stage) in 2 cases (3 ears), and 6 months or more (late stage) in 6 cases (7 ears). The symptoms, signs, CT findings, pure tone audiometry results, surgical methods and clinical efficacy of each group were summarized. Results: Most patients with temporal bone tympanic plate fracture were referred to otology department by maxillofacial surgery. Fracture occured indirectly with the chin or zygomatic region as the direct stress point. Thirteen of the 15 patients had mental region wounds or scars, and 14 patients had external acoustic canal bleeding immediately after injury. In the initial-stage group, hearing was mostly unchanged, while in the middle and late-stage groups, hearing loss was mainly caused by conduction factors. In the initial stage group, 6 cases/7 cases were cured by external acoustic canal packing; External acoustic canal stenosis or atresia occurred in 2 cases in the middle-stage group and were cured by external acoustic canal plasty. All the 6 patients in the late-stage group had external acoustic canal stenosis or atresia, among whom 5 patients with external acoustic canal cholesteatoma were cured by external acoustic canal plasty, and the other one patient with middle ear cholesteatoma was cured by modified radical mastoidectomy and tympanoplasty after external acoustic canal plasty for three times. Conclusions: Temporal bone tympanic plate fracture is a special type of temporal bone fracture. In the early stage of temporal bone tympanic fracture, bleeding of the external acoustic canal is the main symptom, and hearing is normal mostly. Advanced conductive deafness may result from external acoustic canal stenosis and/or cholesteatoma formation later. Bleeding of the external acoustic canal and irregular bulge of the anterior wall of the external acoustic canal with mental region wound are important signs for early diagnosis of temporal bone fracture. Temporal bone tympanic fracture should be paid attention to, early detection and timely treatment can avoid external acoustic canal stenosis and atresia.

Clinical Characteristics, Prognostic Factors and Misdiagnosis of Bone Marrow Necrosis Patients / 中国实验血液学杂志

OBJECTIVE@#To analyze the clinical characteristics, diagnosis and prognostic factors of bone marrow necrosis (BMN) patients, aim to avoid misdiagnosis, missed diagnosis or delayed treatment.@*METHODS@#The clinical data of 51 BMN patients treated in the Affiliated Hospital of Xuzhou Medical University from January 2010 to December 2017 were retrospectively analyzed. The types of primary disease, etiology, clinical manifestations, laboratory tests, radiological findings, treatment outcomes and prognostic factors were summrized, and the reasons for misdiagnosis were analyzed.@*RESULTS@#Among 51 BMN patients, the hematologic tumor was detected out in 32 patients; solid tumors caused- BMN was detected out in 14 patients, benign lesions for 5 patients. The time of interval from the appearance of symptoms to the confirmation of BMN was 7 days to 6 months, with a median of 35 days. Misdiagnosis and missed diagnosis occurred in 25.5% of the BMN patients. Anemia was found in all of the 51 BMN patients, fever accounted for 58.8%, systemic bone pain for 52.9%, bleeding for 29.4%, lymphadenectasis for 37.3%, and hepatosplenomegaly for 19.6%. Leukoerythroblastic anemia accounted for 84.3%, bicytopenia for 51.0%, pancytopenia for 25.5%, and monocytopenia for 23.5%. The serologic test revealed no specific results. The first bone marrow aspiration were 38 patients and multi-site puncture were 7 patients. The diagnostic coincidence rate of bone marrow smear was 88.2%. Among 51 BMN patients, 41 patients received bone marrow biopsy, and the diagnostic coincidence rate of bone marrow biopsy was 75.6%. The abnormal signals were found in multiple vertebral bodies by spinal/pelvic MRI scan in 13 BMN patients; PET-CT scan revealed a diffuse pattern of low FDG uptake in the bone marrow in 16 patients, with a local increase in FDG uptake accompanied by bone marrow involvement. For 46 patients with BMN combined with malignancies, among which 35 patients died (76.1%) and the median survival time was 25 days. Among the 32 patients with hematologic tumors, early death occurred in 12 patients, BMN disappeared in 11 out of 20 patients received active chemotherapy for the primary disease, 9 patients died within 1 week to 3 months. Fourteen patients combined with bone marrow metastatic carcinoma died within 2 weeks to 3 months. Focal necrosis disappeared in 4 out of 5 BMN patients secondary to non-malignant diseases after symptomatic supportive treatment and still alived. Multiple logistic regression was performed to analyze factors affecting the prognosis of BMN patients, the result showed that the prognosis of BMN was closely related to the factors of primary disease (benign and malignant). The reasons for misdiagnosis and missed diagnosis were as follows: hidden onset of the primary disease, nonspecific symptoms, insufficient understanding and alertness of the physicians regarding the primary clinical characteristics and hematological abnormalities, and failure to receive multiple sites bone marrow punctures or bone marrow biopsies.@*CONCLUSION@#BMN usually occurs concomitantly to hematologic tumors and bone marrow metastases from solid tumors. Its prognosis is closely related to the nature and severity of the primary disease and its own severity. In the clinic, BMN should be suspected in patients with severe bone pain, fever, hepatosplenomegaly, hemocytopenia, lymphadenectasis and leukoerythroblastic anemia. Bone marrow puncture at multiple positions and bone marrow biopsy can compensate for each other in the diagnosis of BMN. The combined use of the two methods can improve the diagnostic coincidence rate of BMN, and the positive rate of the etiological diagnosis of BMN.

Development of 177Lu-EB-RGD molecular probe and its imaging and therapy in the patient-derived xenografts of non-small cell lung cancer / 中华核医学与分子影像杂志

Objective:To develop a novel α vβ 3-targeted theranostic agent 177Lu-Evans blue (EB)-Arg-Gly-Asp (RGD) and evaluate its value for SPECT imaging and targeted radionuclide therapy in the non-small cell lung cancer (NSCLC)-patient-derived xenografts (PDX). Methods:The α vβ 3-targeted molecule RGD was conjugated with the albumin binding moiety EB to obtain EB-RGD, and EB-RGD was further conjugated with the chelator 1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid (DOTA) for 177Lu radiolabeling. NSCLC-PDX mice models ( n=68) were established. 177Lu-EB-RGD SPECT imaging, biodistribution study were performed in 28 PDX mice models after being injected with 177Lu-EB-RGD or 177Lu-RGD. Targeted radionuclide therapy were subsequently performed in NSCLC-PDX mice models, saline group (group A), 18.5 MBq 177Lu-RGD group (group B), 18.5 MBq 177Lu-EB-RGD group (group C), 29.6 MBq 177Lu-EB-RGD group (group D), n=10 in each group; tumor volumes of PDX mice models in each group were observed within 50 d. Differences between 2 groups were compared using independent-sample t test. Results:177Lu-EB-RGD was radiolabeled at a specific activity of (55±14) GBq/μmol, with a radiochemical yield of more than 95% and a radiochemical purity of more than 95%. Regarding the SPECT imaging, tumors in NSCLC-PDX mice were clearly observed from 4 to 96 h post-injection and the tumor to muscle ratio (T/M) reached 7.34±0.67, 14.63±3.82, 15.69±3.58 and 15.99±5.42 at 4, 24, 72, 96 h post-injection, respectively. Biodistribution study further confirmed the findings from SPECT imaging, and the tumor uptake of 177Lu-EB-RGD were markedly increased compared to 177Lu-RGD 4 h post-injection ((10.15±1.17) vs (3.30±1.47) percent injection dose per gram (%ID/g); t=18.60, P<0.05). Regarding targeted radiotherapy, the tumor volumes were quickly increased within 50 d after treatment in group A and B, while the tumor volumes were decreased in group C and D, until the tumors in group C and D disappeared at the 28th day after initial treatment with no sign of recurrence during the observation period. Conclusions:177Lu-EB-RGD can target α vβ 3-positive NSCLC-PDX with intense tumor to background ratio and strong tumor inhibition efficacy. The preclinical data suggests that 177Lu-EB-RGD may be an effective new treatment option for advanced NSCLC patients with resistance or ineffective results for targeted therapy.

Enhancement of therapeutic efficacy by combination of integrin α vβ 3-targeted radiotherapy and anti-PD-L1 immunotherapy: a preclinical study / 中华核医学与分子影像杂志

Objective:To investigate the therapeutic efficacy and potential mechanisms of integrin α vβ 3-targeted radionuclide therapy (TRT) in combination with anti-programmed cell death protein ligand 1 (PD-L1) immunotherapy. Methods:Integrin α vβ 3-targeted molecule Arg-Gly-Asp (RGD) was conjugated with Evans blue (EB) and then labeled with 177Lu to obtain 177Lu-EB-RGD. The radioactivity and radiochemical purity were determined. MicroSPECT imaging, biodistribution, and in vivo therapeutic efficacy were subsequently performed in MC38 murine colon cancer models. Volume of tumor and body mass of mice were observed to assess the therapeutic efficacy and safety ( n=9 in each group). Flow cytometry was used to evaluate therapy response of saline-treated (control, group A), 18.5 MBq 177Lu-EB-RGD-treated (group B), 10 mg/kg PD-L1 antibody-treated (group C), TRT combined with immunotherapy-treated (group D, 18.5 MBq 177Lu-EB-RGD and 10 mg/kg PD-L1 antibody) mice and alterations in tumor microenvironment (PD-L1 + immune cells, CD8 + T cells and regulatory T cells). Independent-sample t test and repeated measures analysis of variance were used for data analysis. Results:The radioactivity of 177Lu-EB-RGD was (55.85±14.00) GBq/μmol. SPECT imaging clearly visualized the MC38 tumors in mice models with high uptake and long retention time, the tumor/muscle ratio reached 14.87±0.88 at 24 h postinjection, while less uptake and retention in normal tissues. Tumor uptake of 177Lu-EB-RGD was significantly higher than that of 177Lu-RGD 4 h post-injection ((12.00±1.60) vs (3.69±0.37) %ID/g; t=8.63, P<0.01). The efficacy results between each treatment group was significantly different ( F=7.32, P=0.03) at day 6 post-treatment. The combination therapy showed the most outstanding anti-tumor efficacy with 7/9 mice showed complete response. Flow cytometry results showed that TRT up-regulated the PD-L1 expression significantly, namely, PD-L1 + immune cells in group B and group A were significantly different (CD45 + /PD-L1: 2.34% vs 0.95%, CD11b + /PD-L1: 2.41% vs 0.66%; t values: 11.17 and 8.70, both P<0.01); immunotherapy and combination therapy dramatically stimulated the infiltration of CD8 + T cells (2.07% vs 0.26%, 2.71% vs 0.26%; t values: 4.10 and 6.03, both P<0.05). Conclusion:TRT in combination with immunotherapy synergistically enhance anti-tumor efficacy, which is expected to play a role in the treatment of patients with advanced tumor where TRT can be applied.

Mu-Opioid Receptors Expressed in Glutamatergic Neurons are Essential for Morphine Withdrawal / 神经科学通报·英文版

Although opioids still remain the most powerful pain-killers, the chronic use of opioid analgesics is largely limited by their numerous side-effects, including opioid dependence. However, the mechanism underlying this dependence is largely unknown. In this study, we used the withdrawal symptoms precipitated by naloxone to characterize opioid dependence in mice. We determined the functional role of mu-opioid receptors (MORs) expressed in different subpopulations of neurons in the development of morphine withdrawal. We found that conditional deletion of MORs from glutamatergic neurons expressing vesicular glutamate transporter 2 (Vglut2) largely eliminated the naloxone-precipitated withdrawal symptoms. In contrast, conditional deletion of MORs expressed in GABAergic neurons had a limited effect on morphine withdrawal. Consistently, mice with MORs deleted from Vglut2 glutamatergic neurons also showed no morphine-induced locomotor hyperactivity. Furthermore, morphine withdrawal and morphine-induced hyperactivity were not significantly affected by conditional knockout of MORs from dorsal spinal neurons. Taken together, our data indicate that the development of morphine withdrawal is largely mediated by MORs expressed in Vglut2 glutamatergic neurons.

Mu-Opioid Receptors Expressed in Glutamatergic Neurons are Essential for Morphine Withdrawal / 神经科学通报·英文版

Although opioids still remain the most powerful pain-killers, the chronic use of opioid analgesics is largely limited by their numerous side-effects, including opioid dependence. However, the mechanism underlying this dependence is largely unknown. In this study, we used the withdrawal symptoms precipitated by naloxone to characterize opioid dependence in mice. We determined the functional role of mu-opioid receptors (MORs) expressed in different subpopulations of neurons in the development of morphine withdrawal. We found that conditional deletion of MORs from glutamatergic neurons expressing vesicular glutamate transporter 2 (Vglut2) largely eliminated the naloxone-precipitated withdrawal symptoms. In contrast, conditional deletion of MORs expressed in GABAergic neurons had a limited effect on morphine withdrawal. Consistently, mice with MORs deleted from Vglut2 glutamatergic neurons also showed no morphine-induced locomotor hyperactivity. Furthermore, morphine withdrawal and morphine-induced hyperactivity were not significantly affected by conditional knockout of MORs from dorsal spinal neurons. Taken together, our data indicate that the development of morphine withdrawal is largely mediated by MORs expressed in Vglut2 glutamatergic neurons.

Investigation on iodine nutrition level of pregnant women and children of Xinjiang Uygur Autonomous Region in 2018 / 中华地方病学杂志

Objective:To estimate the iodine nutrition level of pregnant women and children in Xinjiang.Methods:Using cluster random sampling method, from March to September in 2018, in the whole district, county (city, district) was treated as a unit to conduct sampling; each county (city, district) was divided into five areas (east, west, south, north, middle), 40 children aged 8 - 10 and 20 pregnant women in each area were randomly selected, salt samples and urine samples were collected to measure iodine content, and B-ultrasound method was used to detect thyroid volume in children.Results:Among 94 counties (cities, districts), 18 859 salt samples were collected from children and 9 070 salt samples from pregnant women. The median salt iodine (interquartile range) for children was 26.65 (23.70, 29.80) mg/kg, and the median salt iodine (interquartile range) for pregnant women was 26.60 (23.80, 29.80) mg/kg. Totally 17 736 qualified iodized salt samples and 109 non-iodized salt samples consumed by children were tested, the coverage rate of iodized salt was 99.42% (18 750/18 859), qualified rate of iodized salt was 94.59% (17 736/18 750), the consumption rate of qualified iodized salt was 94.05% (17 736/18 859), and the non-iodized salt rate was 0.58% (109/18 859). Totally 8 533 qualified iodized salt samples and 57 non-iodized salt samples consumed by pregnant women were tested, the coverage rate of iodized salt was 99.37% (9 013/9 070), the qualified rate of iodized salt was 94.67% (8 533/9 013), the consumption rate of qualified iodized salt was 94.08% (8 533/9 070), and the non-iodized salt rate was 0.63% (57/9 070). Twelve counties (cities, districts) had a consumption rate of qualified iodized salt lower than 90% for children, and 14 counties (cities, districts) had a consumption rate of qualified iodized salt lower than 90% for pregnant women. Totally 18 862 8 - 10 years old children's urine samples were detected, median urinary iodine was 227.0 μg/L, no county (city, district) was found with median urinary iodine < 100 μg/L. A total of 9 070 pregnant women's urine samples were detected, median urinary iodine was 182.0 μg/L, and 23 counties (cities, districts) had a median urinary iodine less than 150 μg/L. B ultrasound was used to detect thyroid volume in 18 787 children aged 8 - 10 years, 231 children had goiter, and the goiter rate was 1.23%, ranged from 0 to 12.05%, and 2 counties (cities, districts) had goiter rate > 5%.Conclusions:There are still some areas in Xinjiang with the consumption rate of qualified iodized salt < 90%. Children's iodine nutrition is greater than the appropriate amount (200 - 299 μg/L), pregnant women's iodine nutrition is appropriate (150 - 249 μg/L), and children's goiter rate generally meets national elimination and control standards (< 5%). Monitoring of iodized salt should be strengthened, and iodine nutrition levels in children and pregnant women should be continuously monitored.

Analysis of iodine nutritional status of pregnant women in the early, middle and late pregnancy in different regions of Xinjiang Uyghur Autoromous Region in 2019 / 中华地方病学杂志

Objective:To understand the iodine nutritional status of pregnant women in the early, middle and late pregnancy in historical iodine deficiency areas (South Xinjiang) and non historical iodine deficiency areas (North Xinjiang) in Xinjiang, so as to provide scientific basis for the prevention and control of iodine deficiency disorders in pregnant women and the formulation of appropriate prevention and control measures.Methods:From March to June 2019, using cluster yandom sampling, each county (city, district, county for short) in the whole region was divided into five sampling areas according to the east, west, south, north and middle direction. Twenty pregnant women were selected from each area, and the iodine content was determined by taking household salt samples and random urine samples.Results:A total of 9 461 salt samples were collected from pregnant women's families in 96 counties, of which 9 099 were qualified iodized salts, 22 were non iodized salts, the rate of non iodized salt was 0.23%, the coverage rate of iodized salts was 99.77% (9 439/9 461), the consumption rate of qualified iodized salts was 96.17% (9 099/9 461), and the median of salt iodine was 27.42 mg/kg. A total of 9 456 urine samples of pregnant women were tested. The median of urinary iodine was 187.30 μg/L, ranging from 0.30 to 1 300.00 μg/L. The median of urinary iodine of pregnant women in 12 counties (North Xinjiang) was < 150 μg/L. The medians of urinary iodine of pregnant women in the early, middle and late pregnancy in historical iodine deficiency areas were 215.85, 208.10 and 196.60 μg/L, respectively, while that in the non historical iodine deficiency areas were 179.10, 180.70 and 179.15 μg/L, respectively, the differences were statistically significant ( P < 0.01). There was a significant difference in the urinary iodine content of pregnant women in the early, middle and late pregnancy in historical iodine deficiency areas ( H = 8.85, P < 0.05), but there was no significant difference in the non historical iodine deficiency areas ( H = 0.28, P > 0.05). Conclusions:Some pregnant women in North Xinjiang are in iodine deficiency. The contents of urinary iodine in the early, middle and late pregnancy in historical iodine deficiency areas are higher than those in non historical iodine deficiency areas. The distribution of urinary iodine in the early, middle and late pregnancy of pregnant women in the historical iodine deficiency areas is different.

Treatment and reflection of a case of complete rupture in an implanted intravenous infusion port under multidisciplinary cooperation / 中国实用护理杂志

Objective To explore the safety management of implantable venous infusion port, prevent and reduce the occurrence of catheter rupture and other related complications, and implement effective treatment measures after occurrence. Methods A patient with an implantable venous transfusion port suffered from complete rupture of the catheter outside the hospital. Under multidisciplinary consultation, the condition of the catheter inside the port was clarified, and a safe treatment plan was worked out. The multidisciplinary venous transfusion treatment team cooperated with each other to correctly implement the capture, catching and nursing in vivo. Results With the cooperation of multidisciplinary team, the broken port and catheter were successfully and safely removed without any discomfort. Conclusions Establishing a multi- disciplinary cooperation mechanism, standardizing the quality control of implantation in infusion port, popularizing the knowledge of post-implantation maintenance and implementing the safety management of infusion port can ensure the safe and long-term application of implanted intravenous infusion port.

Study on Mechanism of Dahuang Huanglian Xiexintang in Treatment of Type 2 Diabetes Mellitus Based on Network Pharmacology / 中国实验方剂学杂志

Objective: To explore the mechanism of Dahuang Huanglian Xiexintang in the treatment of type 2 diabetes mellitus based on network pharmacology. Method: Major chemical constituents, corresponding targets and target genes of Dahuang Huanglian Xiexintang were obtained by Traditional Chinese Medicine Systems Pharmacology(TCMSP), and target genes of type 2 diabetes mellitus were obtained by GeneCards. The target genes of drug and disease were mapped to predict target genes of Dahuang Huanglian Xiexintang for type 2 diabetes mellitus. Cytoscape3.7.1 software was used to construct the compound-target network and protein-protein interaction network (PPI) of traditional Chinese medicine. Gene ontology (GO) analysis of potential genes and enrichment analysis of gene encyclopedia kyoto encyclopedia of genes and genomes (KEGG) pathway were carried out using DAVID 6.8 online tool. Result: There were 17 active ingredients, 94 related targets, 17 key active ingredients and 16 key targets in Dahuang Huanglian Xiexintang on type 2 diabetes mellitus. GO analysis showed that the biological functions of potential genes of Dahuang Huanglian Xiexintang in the treatment of type 2 diabetes were mainly related to oxidative stress, apoptosis, protein binding, inflammatory reaction, et al. KEGG pathway enrichment results showed that the pathways of potential genes of Dahuang Huanglian Xiexintang in the treatment of type 2 diabetes mainly involved hypoxia inducible factor(HIF), tumor necrosis factor(TNF), phosphatidylinositol 3 kinase/protein kinase B(PI3K/Akt), nuclear transcription factor-кB(NF-кB), and vascular endothelial growth factor(VEGF) signaling pathways. Conclusion: Dahuang Huanglian Xiexintang is a complex process of multi-component, multi-target and multi-pathway in the treatment of type 2 diabetes mellitus. It plays an important role in the treatment of type 2 diabetes mellitus by participating in oxidative stress, apoptosis, protein binding and inflammatory reaction.

Treatment and reflection of a case of complete rupture in an implanted intravenous infusion port under multidisciplinary cooperation / 中国实用护理杂志

Objective@#To explore the safety management of implantable venous infusion port, prevent and reduce the occurrence of catheter rupture and other related complications, and implement effective treatment measures after occurrence.@*Methods@#A patient with an implantable venous transfusion port suffered from complete rupture of the catheter outside the hospital. Under multidisciplinary consultation, the condition of the catheter inside the port was clarified, and a safe treatment plan was worked out. The multidisciplinary venous transfusion treatment team cooperated with each other to correctly implement the capture, catching and nursing in vivo.@*Results@#With the cooperation of multidisciplinary team, the broken port and catheter were successfully and safely removed without any discomfort.@*Conclusions@#Establishing a multi-disciplinary cooperation mechanism, standardizing the quality control of implantation in infusion port, popularizing the knowledge of post-implantation maintenance and implementing the safety management of infusion port can ensure the safe and long-term application of implanted intravenous infusion port.

Research advances in frailty and osteoarthritis in the elderly / 中华老年医学杂志

Osteoarthritis (OA)is a chronic degenerative joint disease and one of the most common causes of pain and disability in the elderly.Frailty is a physiological state characterized by the deregulation of multiple physiologic systems in an aging organism,leading to the loss of homeostatic capacity that exposes the elderly to disability,disease,and eventual death.Prefrailty occurs at an earlier stage of the frailty spectrum and is closely associated with later development of frailty.A large number of studies,using various diagnostic criteria,have addressed the interrelationship between OA and frailty during their disease development processes.Identifying prefrailty and frailty is necessary for the choice of intervention measures and the prevention or delay of disability occurrence in elderly OA patients.Frailty can be considered as a new prognostic factor for mortality,especially in individuals with OA.