ObjectiveTo observe the effect of Dahuang Xiezhuo prescription on the clinical symptoms， blood uric acid， and renal tubular function of patients with immunoglobulin A （IgA） nephropathy in stages 1-2 of chronic kidney disease （CKD） complicated with hyperuricemia （HUA）. MethodSixty patients with IgA nephropathy in stages 1-2 of CKD complicated with HUA of spleen and kidney deficiency and combined turbidity and blood stasis syndromes were randomly divided into an observation group and a control group， with 30 cases in each group. The patients in the control group received basic treatment， i.e.， losartan potassium tablets 50-100 mg/time， once per day， and sodium bicarbonate tablets 0.5 g/time， three times per day by oral administration， combined with low-salt， low-fat， and low-purine diet. The patients in the observation group received Dahuang Xiezhuo prescription on the basis of basic treatment， one dose per day， twice a day in the morning and evening with warm water. Both groups were treated for two months. The total scores of traditional Chinese medicine（TCM）syndrome， blood pressure， 24 h urinary protein （24 h UTP）， blood urea nitrogen （BUN）， serum creatinine （SCr） ［glomerular filtration rate （eGFR） was calculated by CKD-epidemiology collaboration （CKD-EPI） formula］， serum uric acid （SUA）， and renal tubular function indexes ［urinary α₁-microglobulin （α₁-MG）， urinary β₂-microglobulin （β₂-MG）， urinary kidney injury molecule-1 （KIM-1）， and neutrophil gelatinase-associated lipocalin （NGAL）］ of the two groups before treatment and two months after treatment were recorded. The clinical efficacy of the two groups was evaluated two months after treatment. ResultAfter 2 months of treatment，the total effective rate in the observation group was 81.48%（22/27），higher than 50.00%（14/28） in the control group（χ² =6.661，P<0.05）. The total scores of TCM syndrome， 24 h UTP， and SUA in the observation group and the observation group were lower than those before treatment （P<0.05）， and compared with the control group after treatment， the observation group decreased more significantly （P<0.05）. After treatment， the blood pressure in the observation group and the observation group was lower than that before treatment （P<0.05）， and there was no significant difference in blood pressure between the two groups after treatment. After treatment， the levels of urinary α₁-MG， β₂-MG， KIM-1， and NGAL in the two groups were lower than those before treatment （P<0.05）， and the observation group was lower than the control group after treatment （P<0.05）. There were no significant inter-group and intra-group differences in BUN， SCr， and eGFR levels before and after treatment. There were no obvious abnormalities in blood routine， liver function， and electrolytes before and after treatment in the two groups， and no adverse reactions such as allergies occurred. ConclusionDahuang Xiezhuo prescription can effectively improve the clinical symptoms of IgA nephropathy with HUA （CKD1-2） patients with spleen and kidney deficiency and combined turbidity and blood stasis syndromes， reduce blood uric acid level， alleviate renal tubular injury， and protect the kidney. The curative effect is better than that of basic treatment.

Objective:To study the efficacy and safety of EndoClot polysaccharide hemostatic system (EndoClot PHS) for heparinized arterial hemorrhage of upper digestive tract (Forrest Ⅰa) in animal model.Methods:Twelve experimental pigs were randomly divided into the test group ( n=6) and the control group ( n=6) by simple random grouping method. Gastric arterial hemorrhage models were established. Endoclot PHS and Hemospray were used to spray on the wound to stop bleeding in the test group and the control group respectively. The time of effective hemostasis, the amount of hemostatic particles used, and the blockage of the powder feeding tube and its replacement were compared between the two groups. The survival and complications of experimental pigs were observed after the operation. In 10 days after the operation, the experimental pigs were euthanized for pathological dissection. Results:Spurting or pulsatile bleeding was achieved in all experimental pigs. There were significant differences in the time of effective hemostasis (8.75±0.84 min VS 9.83±0.62 min, t=-2.53, P=0.030) and the amount of hemostatic particles used to achieve effective hemostasis (6.71±0.39 g VS 14.10±1.62 g, t=-10.86, P<0.001) between the test group and the control group. There was no significant difference in the occurence of clogging or the replacement of powder feeding pipes between the two groups (0.64±0.02 times VS 0.67±0.04 times, t=-1.64, P=0.131). In addition, the gas source of the test group was stable, and the visual field under the endoscope was clear. Neither the test group nor the control group had gastric lesions, perforation, or embolism. The blood glucose, blood routine, and liver and kidney functions were normal, and no thrombosis or embolism of the main organs occurred in either group. Conclusion:EndoClot PHS is safe and effective for heparinized upper gastrointestinal arterial hemorrhage (Forrest Ⅰa) in animal models.

Background: Co-infections of the porcine reproductive and respiratory syndrome virus (PRRSV) and the Haemophilus parasuis (HPS) are severe in Chinese pigs, but the immune response genes against co-infected with 2 pathogens in the lungs have not been reported. Objectives: To understand the effect of PRRSV and/or HPS infection on the genes expression associated with lung immune function. Methods: The expression of the immune-related genes was analyzed using RNA-sequencing and bioinformatics. Differentially expressed genes (DEGs) were detected and identified by quantitative real-time polymerase chain reaction (qRT-PCR), immunohistochemistry (IHC) and western blotting assays. Results: All experimental pigs showed clinical symptoms and lung lesions. RNA-seq analysis showed that 922 DEGs in co-challenged pigs were more than in the HPS group (709 DEGs) and the PRRSV group (676 DEGs). Eleven DEGs validated by qRT-PCR were consistent with the RNA sequencing results. Eleven common Kyoto Encyclopedia of Genes and Genomes pathways related to infection and immune were found in single-infected and co-challenged pigs, including autophagy, cytokine-cytokine receptor interaction, and antigen processing and presentation, involving different DEGs. A model of immune response to infection with PRRSV and HPS was predicted among the DEGs in the co-challenged pigs. Dual oxidase 1 (DUOX1) and interleukin-21 (IL21) were detected by IHC and western blot and showed significant differences between the co-challenged pigs and the controls. Conclusions These findings elucidated the transcriptome changes in the lungs after PRRSV and/or HPS infections, providing ideas for further study to inhibit ROS production and promote pulmonary fibrosis caused by co-challenging with PRRSV and HPS.

BACKGROUND: Since the outbreak of coronavirus disease 2019 (COVID-19), human mobility restriction measures have raised controversies, partly because of the inconsistent findings. An empirical study is promptly needed to reliably assess the causal effects of the mobility restriction. The purpose of this study was to quantify the causal effects of human mobility restriction on the spread of COVID-19. METHODS: Our study applied the difference-in-difference (DID) model to assess the declines of population mobility at the city level, and used the log-log regression model to examine the effects of population mobility declines on the disease spread measured by cumulative or new cases of COVID-19 over time after adjusting for confounders. RESULTS: The DID model showed that a continual expansion of the relative declines over time in 2020. After 4 weeks, population mobility declined by -54.81% (interquartile range, -65.50% to -43.56%). The accrued population mobility declines were associated with the significant reduction of cumulative COVID-19 cases throughout 6 weeks (ie, 1% decline of population mobility was associated with 0.72% [95% CI: 0.50%-0.93%] reduction of cumulative cases for 1 week, 1.42% 2 weeks, 1.69% 3 weeks, 1.72% 4 weeks, 1.64% 5 weeks, and 1.52% 6 weeks). The impact on the weekly new cases seemed greater in the first 4 weeks but faded thereafter. The effects on cumulative cases differed by cities of different population sizes, with greater effects seen in larger cities. CONCLUSIONS Persistent population mobility restrictions are well deserved. Implementation of mobility restrictions in major cities with large population sizes may be even more important.
COVID-19 ; China/epidemiology* ; Cities ; Humans ; SARS-CoV-2

Objective:To study the effect of Bushen Huatan prescription on helper T cell 17 （Th17）/T regulatory cells （Treg） balance of immune T cell subsets in the prevention and treatment of postmenopausal osteoporosis. Method:Sixty 6-month-old female SD rats were randomly divided into sham operation group， model group， estradiol valerate group （0.184 mg·kg^-1） and Bushen Huatan prescription low， medium and high groups （4.7， 9.4， 18.8 g·kg^-1） according to the random number table. All the groups except the sham operation group received ovariectomy to make postmenopausal osteoporosis model. Intragastric administration was started 1 week after operation， and the rats in model group and sham operation group received equal volume of normal saline， once a day for 12 weeks. Microcomputed tomography （Micro CT） was then used to detect bone mass and microstructure of rats， the contents of Forkhead box protein （Foxp3） and retinoic acid related nuclear orphan receptor （RORγt） in serum were detected by enzyme-linked immunosorbent assay （ELISA）， the mRNA expression levels of Foxp3 and RORγt in bone tissues were detected by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot was used to detect the protein expression of Foxp3 and RORγt in bone tissues， the number of Th17 and Treg cells in each group was analyzed and compared by flow cytometry. Result:Compared with the sham operation group， the bone mass and trabeculae of the model group decreased （P<0.01）， the bone microstructure was destroyed， the concentration of Foxp3 in serum decreased， the concentration of RORγt increased （P<0.01）， the mRNA and protein expression levels of Foxp3 in bone tissues decreased， RORγt increased， the number of Treg cells in bone tissues decreased， number of Th17 cells increased （P<0.01）， and Th17/Treg ratio increased （P<0.01） in model group. Compared with the model group， the bone mass in each treatment group increased （P<0.05， P<0.01）， Foxp3 concentration in serum increased， RORγt concentration decreased （P<0.01）， the mRNA and protein expression levels of Foxp3 in bone tissues increased significantly （P<0.05， P<0.01）， but no statistical difference was shown in mRNA expression between low dose group and the model group. In addition， the mRNA and protein expression of RORγt decreased （P<0.05， P<0.01）， number of Treg cells increased， number of Th17 cells decreased （P<0.05， P<0.01）， and Th17/Treg ratio decreased in treatment groups （P<0.01）. Conclusion:Bushen Huatan prescription can increase bone mass， improve bone microstructure， increase the number of Treg cells and decrease the number of Th17 cells in ovariectomized rats. It is concluded that Bushen Huatan prescription may play a role in preventing and treating postmenopausal osteoporosis by regulating Th17/Treg balance.

Objective:To explore the effect of Bushen Huatan prescription on serum lipopolysaccharide （LPS） and Toll-like receptor 4 （TLR4）/ myeloid cell differentiation protein 88 （MyD88）/nuclear transcription factor-κB （NF-κB） signaling pathway in rats with ovariectomy-induced osteoporosis. Method:Sixty SPF 6-month-old female rats were randomly divided into sham operation group， model group， estradiol valerate group and Bushen Huatan prescription low， medium and high dose groups.One week after modeling by bilateral ovariectomy， 8 rats in each group were selected to receive intragastric administration.The estradiol valerate group was given 0.184 mg·kg^-1 by gavage， and Bushen Huatan prescription low， middle and high dose groups were given 4.7， 9.4 and 18.8 g·kg^-1 by gavage， sham operation group and model group were given 0.9% saline 4 mL by gavage respectively.After 12 weeks of intervention， the rats were sacrificed for detection.Serum LPS was detected by enzyme linked immunosorbent assay （ELISA）， while protein expressions of TLR4， MyD88 and phosphorylated （p）-NF-κB p65 in bone tissue were detected by Western blot， and the mRNA expressions of TLR4， MyD88， NF-κB p65， IL-1β， and IL-6 in bone tissue were detected by quantitative real-time polymerase chain reaction（PCR）. Result:Compared with sham operation group， the serum LPS level as well as protein expression of TLR4， MyD88， p-NF-κB p65 and mRNA expression of TLR4， MyD88， NF-κB p65， IL-1β， and IL-6 significantly increased in model group（P<0.05）.Compared with the model group， serum LPS level， protein expression of TLR4， MyD88， and p-NF-κB p65， mRNA levels of TLR4， MyD88， and NF-κB p65 in bone tissues as well as downstream inflammatory factors IL-1β， IL-6 mRNA expression decreased to different degrees in estradiol valerate group and Bushen Huatan prescription high dose group（P<0.05）. Conclusion:Bushen Huatan prescription can reduce serum LPS content， regulate mRNA and protein expression of TLR4， MyD88， NF-κB p65 and p-NF-κB p65 in TLR4/MyD88/NF-κB pathway， and down-regulate mRNA levels of IL-1β and IL-6 in bone tissues to improve bone microstructure and inhibit the development of postmenopausal osteoporosis （PMOP）.

Objective:To study the clinical characteristics and classification of gastric neuroendocrine neoplasm(NEN) and prognostic factors of mixed adenoneuroendocrine carcinoma (MANEC) and gastric neuroendocrine carcinoma(NEC).Methods:A total of 148 gastric NENs were divided into type Ⅰ, type Ⅱ and type Ⅲ based on the classification of European Neuroendocrine Tumor Society (ENETS). Kaplan-Meier test and Cox regression model were used in univariate and multivariate survival analysis in 108 cases with pathological G3 gastric NEN.Results:In this study, the percentages of type Ⅰ, type Ⅱ and type Ⅲ were 25.0%(37), 3.4%(5) and 71.6%(106) respectively. Among type Ⅰ patients, 28(75.7%) lesions were located in gastric fundus or body, 29(78.4%) had bumps. Lymph node involvement was found in 4 (10.8%) patients. Twenty-six (70.3%) patients received endoscopic treatment and 11 (29.7%) with surgery. All 5 type Ⅱ patients presented lesions in gastric fundus or body, including 4 with ulcers, who were all treated by endoscope. Three type Ⅱ patients had gastrinoma, and 2 combined with multiple endocrine neoplasmⅠ. In type Ⅲ patients, 56(52.8%) showed ulcerative lesions. The majority of patients (102, 96.2%) had a single lesion, 94(88.7%) with lymph node or other organ metastasis. In this study, no deaths were reported in gastric NEN with a pathological grade of G1 or G2. The mortality rate was 38.9%(42/108) in patients with G3 NEN. Survival analysis suggested that age, metastasis of tumor were associated with poor prognosis ( P=0.041, 0.025). Conclusions:Patients with gastric NEN have heterogenous clinical presentations according to gender, age, endoscopic features, infiltration and metastasis, and pathological grade. Aging and metastasis are negative prognostic factors of G3 gastric NEN.

Given that increased thermogenesis in white adipose tissue, also known as browning, promotes energy expenditure, significant efforts have been invested to determine the molecular factors involved in this process. Here we show that HOXC10, a homeobox domain-containing transcription factor expressed in subcutaneous white adipose tissue, is a suppressor of genes involved in browning white adipose tissue. Ectopic expression of HOXC10 in adipocytes suppresses brown fat genes, whereas the depletion of HOXC10 in adipocytes and myoblasts increases the expression of brown fat genes. The protein level of HOXC10 inversely correlates with brown fat genes in subcutaneous white adipose tissue of cold-exposed mice. Expression of HOXC10 in mice suppresses cold-induced browning in subcutaneous white adipose tissue and abolishes the beneficial effect of cold exposure on glucose clearance. HOXC10 exerts its effect, at least in part, by suppressing PRDM16 expression. The results support that HOXC10 is a key negative regulator of the process of browning in white adipose tissue.
Adipocytes ; Adipose Tissue, Brown ; Adipose Tissue, White ; Animals ; Ectopic Gene Expression ; Energy Metabolism ; Genes, Homeobox ; Glucose ; Mice ; Myoblasts ; Thermogenesis ; Transcription Factors

Objective To evaluate and compare the clinical efficacy and safety of intense pulsed light (IPL) versus 595-nm pulsed dye laser (PDL) for the treatment of post-acne erythema.Methods A randomized split-face clinical trial was conducted.A total of 20 patients with post-acne erythema were enrolled,and randomized to receive treatment with IPL on one half of the face and 595-nm PDL on the other facial side once every 4 weeks for 3 sessions.Digital photographs were taken using the VISIA,and erythema index was recorded before each treatment and one month after the last treatment.The severity of bilateral facial erythema was evaluated based on a 4-point grading scale before the first treatment and after the last treatment.Pain scores and adverse reactions were recorded using a visual analogue scale (VAS) after each treatment,and a patient satisfaction survey was conducted by questionnaire at the last follow-up.Results The mean erythema index on the IPL side before and after treatment was 472.25 ± 86.02 and 357.15 ±82.71 respectively,and that on the PDL side before and after treatment was 476.40 ± 74.25 and 360.05 ± 64.83 respectively.Repeated measures analysis of variance (ANOVA) showed that the erythema indices on both treated sides significantly decreased over time (F =197.666,P ＜ 0.001),and the efficacy of IPL was better than that of PDL (F =1 173.909,P ＜ 0.001).Erythema severity grades on the IPL side as well as on the PDL side significantly differed between before and after treatment (Z =28.735,31.450,respectively,both P ＜ 0.001).As VAS showed,the pain score on the PDL side was significantly lower than that on the IPL side (t =2.468,P ＜ 0.05).Among the 20 patients,17 and 15 assessed their improvement as good or excellent after PDL and IPL treatment respectively,but there was no significant difference between the two groups (Z =2.696,P ＞ 0.05).The adverse reactions included erythema,burning sensation,tense sensation,blistering and hyperpigmentation on IPL-treated side,and erythema and purpuric reactions on the PDL-treated side,which all disappeared in a few hours to several days.Conclusions Both IPL and 595-nm PDL are effective and safe for the treatment of post-acne erythema,and are worthy of clinical promotion and application.IPL shows superiority in the efficacy,but elicits higher pain sensation compared with PDL.

BACKGROUNDIn order to improve the clinical treatment level of urinary system injury, it is necessary to build up an animal model of urinary system wound, which is not only analogous to real clinical practice, but also simple and practical.

METHODSWe have developed the third generation of firearm fragment wound generator based on the first and the second producer. The best explosive charge of the blank cartridge was selected by gradient powder loading experiments. The firearm fragment injuries were made to the bulbous urethra of 10 New Zealand male rabbits. One week preoperatively and 2, 4 and 8 weeks postoperatively, all the animals underwent urethroscopy and urethrography. At 2, 4 and 8 weeks postoperatively, two animals were randomly selected and killed, and the urethra was cut off for pathological examination.

RESULTSThe shooting distance of the third generation of firearm fragment wound generator is 2 cm. The best explosive charge of the blank cartridge is 1 g of nitrocotton. All rabbits survived the procedures and stayed alive until they were killed. Injuries were limited to bulbous urethra and distal urethra. Round damaged areas, 1-1.5 cm in length, on the ventral wall were observed. Ureteroscopy results showed that canal diameter gradually shrank by over 50% in 9 rabbits. The rate of success was 90%. Urethrography result noted that a 1-1.3 cm stricture was formed at the bulbous urethra. Histology results of injured stricture urethra showed that fibrous connective tissue hyperplasia and hyaline degeneration caused further stricture in the canal.

CONCLUSIONSThe third generation of firearm fragment wound generator imitates the bullet firing process and is more accurate and repeatable. The corresponding rabbit model of traumatic complex urethral stricture simulates the real complex clinical conditions. This animal model provides a standardized platform for clinical researches on treating traumatic injuries to the urinary system.

Animals ; Disease Models, Animal ; Male ; Penis ; surgery ; Rabbits ; Urethra ; surgery ; Urethral Stricture ; surgery