Hyperuricemic nephropathy （HN）， a secondary renal damage common in clinical practice， is characterized by early concealing and continuous progression. The understanding of HN in traditional Chinese medicine （TCM） is from a macroscopic perspective. According to the TCM theory， HN is caused by the combination of external pathogens and internal injuries， with the main pathogenesis being root deficiency combined with superficial excess and deficiency-excess in complexity. In western medicine， the understanding of HN is from the microscopic perspective， which holds that the occurrence of HN is the result of inflammation， oxidative stress， renin-angiotensin-aldosterone system （RAAS） activation， and metabolic abnormalities. The TCM syndromes of HN include internal dampness and heat， obstruction in dampness and turbidity， deficiency of spleen and kidney， and deficiency of kidney yin. Accordingly， the prescriptions should clear heat and dampness， remove dampness and turbidity， tonify spleen and kidney， and nourish kidney yin， respectively. In addition to TCM prescriptions， single herbal medicines and their extracts， Chinese patent medicines， and external applications of Chinese medicines have played a significant role in the treatment of HN， promoting the application of TCM in the treatment of HN. Moreover， the integrated traditional Chinese and western medicine has also played a role in the treatment of HN， enriching the treatment schemes of HN. Different from common kidney diseases such as acute and chronic glomerulonephritis and nephrotic syndrome， HN with particularity should be carefully differentiated in clinical practice. This article systematically summarizes the research progress in the treatment of traditional Chinese medicine and integrated traditional Chinese and western medicine on hyperuricemic nephropathy with TCM and integrated traditional Chinese and western medicine， aiming to enrich the system and theory of HN treatment and further guide the clinical practice.

BACKGROUND: Coronavirus disease 2019 (Covid-19) remains a serious health threat worldwide. We aimed to investigate whether low molecular weight heparin (LMWH) can promote organ function recovery in moderate Covid-19 pneumonia patients. METHODS: We initiated an LMWH protocol in Covid-19 patients with increased D-dimer, body mass index >30 kg/m2 or a history of diabetes from January 18, 2020 at Shanghai Public Health Clinical Center. In this retrospective study, we assigned moderate Covid- 19 pneumonia patients admitted between January 18th and April 18, 2020 receiving the LMWH protocol to the LMWH group. Moderate patients who met the inclusion criteria but did not receive LMWH protocol were included in the control group by 1:2 propensity score matching. General clinical information, indicators for renal function, arterial blood gas analyses, arterial blood lactic acid content (mmol/L), and coagulation indexes at 0 day, 3 days, 7 days, and 11 days after admission were recorded and compared between the two groups. RESULTS: There were 41 patients in the LMWH group and 82 patients in the control group. General information in both groups were similar. Compared to the control group, the arterial blood lactic acid content (mmol/L) at day 11 (1.3 [1.1, 1.7] vs. 1.2 [0.9, 1.3], P = 0.016) was reduced in the LMWH group. The estimated glomerular filtration rate (eGFR) in the LMWH group was higher than that in the control group at day 7 (108.54 [89.11, 128.17] vs. 116.85 [103.39, 133.47], P = 0.039) and day 11 (113.74 [94.49, 126.34] vs. 128.31 [112.75, 144, 12], P  = 0.003). The serum creatinine levels (Scr) in the LMWH group were lower than that in the control group at day 7 (62.13 [51.47, 77.64] vs. 55.49 [49.50, 65.75], P = 0.038) and day 11 (63.35 [50.17, 75.73] vs. 51.62 [44.62, 61.24], P = 0.005). CONCLUSIONS: LMWH treatment can reduce arterial blood lactic acid levels and improve eGFR in moderate Covid-19 pneumonia patients. Randomized controlled trials are warranted to further investigate this issue. TRIAL REGISTRATION ChiCTR.org.cn, ChiCTR2000034796.
COVID-19 ; China ; Glomerular Filtration Rate ; Heparin, Low-Molecular-Weight/therapeutic use* ; Humans ; Lactic Acid ; Retrospective Studies

Objective To analyze the clinical features of patients with coronavirus disease 2019 (COVID-19) in Shanghai and to investigate the risk factors for disease progression to severe cases. Methods The clinical data of 292 adult patients with COVID-19 hospitalized in Shanghai Public Health Clinical Center from January 20, 2020 to February 10, 2020 were retrospectively analyzed, including 21 severe patients and 271 mild patients. The demographic characteristics, epidemiological history, history of underlying diseases and laboratory examinations were compared between the two groups. Measurement data were compared using t test or Mann-Whitney U test. The count data were compared using hi-square test. The binary logistic regression equation was used to analyze the risk factors for the progression of patients to severe cases. Results Among the 292 patients, 21 were severe cases with the rate of 7.2% (21/292). One patient died, and the mortality rate was 4.8% in severe patients. The severe patients aged (65.0±15.7) years old, 19 (90.5%) were male, 11 (52.4%) had underlying diseases, 7 (33.3%) had close relatives diagnosed with COVID-19. The mild patients aged (48.7±15.7) years old, 135 (49.8%) were male, 74 (27.3%) had underlying diseases, 36 (13.3%) had close relatives diagnosed with COVID-19. The differences between two groups were all significant statistically ( t =-4.730, χ 2 =12.930, 5.938 and 4.744, respectively, all P <0.05). Compared with the mild patients, the levels of absolute numbers of neutrophils, alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, creatinine, serum cystatin C, C reactive protein (CRP), procalcitonin , D -dimer, pro-B-type natriuretic peptide (proBNP), serum myoglobin, creatine kinase (CK), creatine kinase isoenzyme (CK-MB), serum troponin I (cTnI) in severe patients were all significantly higher ( U =2 091.5, 1 928.0, 1 215.5, 729.0, 1 580.5, 1 375.5, 917.5, 789.5, 1 209.0, 1 434.0, 638.0, 964.5, 1 258.0 and 1 747.5, respectively, all P <0.05), while the levels of lymphocyte count, albumin, transferrin, CD3 + T lymphocyte count, CD8 + T lymphocyte count and CD4 + T lymphocyte count in severe patients were all significantly lower ( U =1 263.5, t =4.716, U =1 214.0, 962.0, 1 167.5 and 988.0, respectively, all P <0.05). Further logistic regression analysis showed that the albumin (odds ratio ( OR )=0.806, 95% CI 0.675-0.961), CRP ( OR =1.016, 95% CI 1.000-1.032), serum myoglobin ( OR =1.010, 95% CI 1.004-1.016), CD3 + T lymphocyte count ( OR =0.996, 95% CI 0.991-1.000) and CD8 + T lymphocyte count ( OR =1.006, 95% CI 1.001-1.010) at admission were independent risk factors for the progression of COVID-19 patients to severe illness (all P <0.05). Conclusions Severe cases of patients with COVID-19 in Shanghai are predominantly elderly men with underlying diseases. Albumin, CRP, serum myoglobin, CD3 + T lymphocyte count and CD8 + T lymphocyte count could be used as early warning indicators for severe cases, which deserve more clinical attention.

Objective:To investigate the clinical value of high intensity focused ultrasound (HIFU) ablation combined with levonorgestrel releasing in uterine system (LNG-IUS) in the treatment of adenomyosis.Methods:From January 2015 to January 2018, patients with adenomyosis diagnosed and treated in Obstetrics and Gynecology of our hospital were selected as the research objects. According to the wishes and treatment methods of the patients, the patients were divided into two groups: the combined treatment group was treated with HIFU combined with LNG-IUS, and the HIFU group was only treated with HIFU; the lesion volume and uterine volume reduction rate, hemoglobin, carbohydrate antigen 125 (CA125) and verbal rating scale (VRS) scores were compared between the two groups before and after treatment, and adverse reactions after treatment the scores were recorded.Results:Cases were followed up for 12 months after treatment: the lesion volume reduction rate and uterine volume reduction rate in the combined treatment group were better than those in the HIFU group [(58.8±14.1)% vs (49.3±17.2)%, (37.4±6.2)% vs (32.9±5.0)%, P<0.05]; the hemoglobin level was higher than that in the control group [(113.4±12.8)g/L vs (107.5±10.6)g/L, P<0.05]. In addition, the VRS score of dysmenorrhea in the combined treatment group was also better than that in the HIFU group, with statistically significant difference ( P<0.05). Conclusions:Compared with HIFU ablation alone, patients performed in HIFU combined with LNG-IUS achieved better lesion volume reduction rate and uterine volume reduction rate, and hemoglobin level and dysmenorrhea symptoms improved better in patients with adenomyosis.

Objective:To investigate the role of ineffective esophageal motility (IEM) in the diagnosis of non-erosive reflux disease (NERD) and its relationship with acid exposure.Methods:From March 2013 to May 2019, in First Hospital Affiliated to Jilin University, patients who underwent gastroendoscopy exam, esophageal high-resolution manometry (HRM), 24-h pH monitoring and had gastroesophageal reflux symptoms, and without mucosal or structural abnormal changes under gastroendoscopy were retrospectively selected. Based on Rome Ⅳ criteria, the patients were reevaluated and the diagnostic types were NERD, reflux hypersensitivity (RH) and functional heartburn (FH). The changes of esophageal HRM metrics and acid reflux-related parameters of patients with IEM were analyzed and compared. Independent sample t-test, nonparametric test and chi-square test were used for statistical analysis. Results:The data of 228 patients were collected. Thirty-seven cases with esophageal gastric junction (EGJ) outflow obstruction and severe esophageal motility disorder (8 cases of achalasia, 9 cases of EGJ outflow obstruction, 4 cases of distal esophageal spasm, 14 cases of absent contractility and 2 cases of hypercontractile esophagus) and fifty-three cases with endoscopic reflux esophagitis under endoscopy (20 cases of Los Angeles grade A, 15 cases of grade B, 13 cases of grade C, and 5 cases of grade D) were excluded. In the end 138 patients were enrolled, including 60 males and 78 females, with a mean age of (50.1±14.1) years, including 36 cases of NERD, 44 cases of RH and 58 cases of FH. According to esophageal HRM Chicago classification standard, 138 patients with gastroesophageal reflux symptoms were divided into IEM group (46 cases, including 15 cases of NERD, 12 cases of RH, and 19 cases of FH) and normal manometry group (92 cases, including 21 cases of NERD, 32 cases of RH, and 39 cases of FH). There was no statistically significant difference in the proportion of patients diagnosed as NERD, RH and FH between the two groups ( P> 0.05). The length of lower esophageal sphincter (LES) (2.70 cm, 2.40 to 3.00 cm vs. 3.00 cm, 2.70 to 3.20 cm), the average value of LES resting breathing pressure (16.55 mmHg, 7.98 to 22.95 mmHg vs. 19.10 mmHg, 14.15 to 25.68 mmHg, 1 mmHg=0.133 kPa), the distal contractile integral (DCI)(417.90 mmHg·s·cm, 279.08 to 584.45 mmHg·s·cm vs. 1 429.40 mmHg·s·cm , 994.38 to 1 852.80 mmHg·s·cm) and EGJ contractile integral (37.86 mmHg·cm, 26.97 to 46.78 mmHg·cm vs. 45.19 mmHg·cm, 35.39 to 58.20 mmHg·cm) of IEM group were all lower than those of normal manometry group, ( Z=3.33, 2.09, 8.09, and 2.90, all P<0.05). There were no statistically significant differences in LES resting pressure at the end of the breath, 4 s-intergrated reloxation pressure, distal latency, upper esophageal sphincter (UES) resting pressure (UESP), UES residual pressure, UES baseline relaxation time, UES recovery time, EGJ type, acid reflux related parameters (total acid exposure time (AET), AET in upright position, AET in supine position, and Demeester score) between the two groups (all P>0.05). The 36 NERD patients were divided into IEM group (15 cases) and normal manometry group (21 cases). The distal contractile integral was lower in IEM group than that in normal manometry group (401.10 mmHg·s·cm, 276.60 to 555.60 mmHg·s·cm vs. 1 135.00 mmHg·s·cm, 903.20 to 1 537.65 mmHg·s·cm), the difference was statistically significant ( Z=3.93, P<0.01). There was no statistically significant difference in EGJ type, other HRM parameters or acid reflux-related parameters between IEM group and normal manometry group (all P>0.05). Conclusions:IEM is not related with the diagnosis of NERD. In patients with gastroscopy-negative gastroesophageal reflux symptoms or NERD with IEM, except for weakened peristaltic function, the EGJ morphological evaluation of the anti-reflux barrier function has nothing to do with IEM. In NERD patients, the relationship between IEM and acid exposure needs further study.

Objective To explore the protective effect of ETaR siRNA on renal ischemia reperfusion injury (IRI) by changing the immuno-microenvironment in rats .Methods A total of 40 male Sprague-Dawley (SD) rats were randomized into four groups of sham ,IR ,negative siRNA and ETaR siRNA .A renal IRI model was generated by clamping left renal artery .ETaR siRNA was delivered into kidney through renal vein by a retrograde 'hydrodynamic' injection .Blood samples were collected for detecting renal function and kidney tissue harvested for Hematoxylin & Eosin (HE) staining , TdT-mediated dUTP Nick-End Labeling (TUNEL) staining ,polymerase chain reaction (PCR) and Western blot at 48 h post-reperfusion .Results Serum creatinine ,blood urea nitrogen and renal apoptotic cells increased and renal tissue was injured after IR . The changes were inhibited by ETaR siRNA . PCR showed that ETaR siRNA treatment significantly down-regulated the expressions of inflammatory factors TNF-α , IFN-γ and IL-6 and transcription factor NF-κB induced by IR .Conclusions ETaR siRNA can effectively improve the immunomicroenvironment and thereby alleviate renal ischemia reperfusion injury .

Objective To explore the efficacy of renal transplantation plus hematopoietic stem cell transplantation on inducing immune tolerance and summarize its long-term follow-up outcomes . Methods From 2009 to 2018 ,a total of 11 cases of living related donor kidney transplantation plus hematopoietic stem cell transplantation were performed .Two of them were HLA-matched and the remainder were mismatched for one HLA haplotype . The donor hematopoietic stem cells were mobilized using granulocyte colony-stimulating factor at 5 days pre-transplantation and collected at 1 day pre-operation .The recipients received total lymphoid irradiation for 3 days pre-transplantation and received anti-thymocyte globulin induction during transplantation .The donor hematopoietic stem cells were infused at 2 ,4 and 6 postoperative day .Postoperative regulatory T cells ,chimerism ,B cell activating factor and mixed lymphocyte culture and other parameters were detected and long-term follow-up outcomes tracked .Results The immune tolerance-inducible recipients had a significant increase in activated Treg .One HLA-matched recipient achieved 30％-50％ of chimerism and lost after 6 months .However ,other recipients did not achieve mixed chimerism .The BAFF of recipient spiked sharply after transplantation .Mixed lymphocyte culture indicated that a donor-specific low response was induced .The recipients were followed up for 717 to 3612 days .The first recipient lost renal function and another ten recipients had stable renal function . None of the recipients had myelosuppression or graft-versus-host disease .Allograft biopsy confirmed only one case of mild acute rejection . The dose of immunosuppressive agents was lowered in 5 patients .Conclusions Hematopoietic stem cell transplantation for inducing tolerance is safe during renal transplantation . And chimerism is essential for inducing immune tolerance .

PURPOSE: Rituximab with cyclophosphamide, doxorubicin, vincristine, and prednisone administered every 3 weeks (R-CHOP-21) is the standard care for diffuse large B-cell lymphoma (DLBCL). It is unknown whether the dose-dense R-CHOP (R-CHOP-14) could improve the outcome of the disease in Asian population. MATERIALS AND METHODS: Newly diagnosed DLBCL patients were centrally, randomly assigned (1:1) to receive R-CHOP-14 or R-CHOP-21. R-CHOP-14 was administered every 2 weeks, and R-CHOP-21 was administered every 3 weeks. Primary end point was disease-free survival (DFS). Secondary end points included overall survival (OS), progression-free survival (PFS), response rate and toxicities. RESULTS: Seven hundred and two patients were randomly assigned to receive R-CHOP-14 (n=349) or R-CHOP-21 (n=353). With a median follow-up of 45.6 months, the two groups did not differ significantly in 3-year DFS (79.6% for R-CHOP-14 vs. 83.2% for R-CHOP-21, p=0.311), 3-year OS (77.5% for R-CHOP-14 vs. 77.6% for R-CHOP-21, p=0.903), or 3-year PFS (63.2% for R-CHOP-14 vs. 66.1% for R-CHOP-21, p=0.447). Patients with an International Prognostic Index (IPI) score ≥ 2 had a poorer prognosis compared to those with an IPI score < 2. Grade 3/4 hematologic and non-hematologic toxicities were manageable and similar between R-CHOP-14 and R-CHOP-21. CONCLUSION: R-CHOP-14 did not improve the outcome of DLBCL compared to R-CHOP-21 in Asian population. With manageable and similar toxicities, both of the two regimens were suitable for Asian DLBCL patients. For high-risk patients with IPI ≥ 2, new combination regimens based on R-CHOP deserve further investigation to improve efficacy.
Asian Continental Ancestry Group ; B-Lymphocytes ; Cyclophosphamide ; Disease-Free Survival ; Doxorubicin ; Follow-Up Studies ; Humans ; Lymphoma, B-Cell ; Prednisone ; Prognosis ; Rituximab ; Vincristine

Objective To investigate the clinical and pathologic features of patients with gastric neuroendocrine neoplasms (g-NENs).Methods A total of 50 cases of g-NENs diagnosed by pathology in the First Hospital of Jilin University from May 2012 to January 2016 were retrospective analyzed to summarize the clinical manifestations and pathological features.The location of lesion,gross morphology,maximum diameter,lymph node metastasis rate,distant metastasis rate,and survival time between patients with neuroendocrine tumors and neuroendocrine carcinomas were compared.Results Among the 50 patients,34 were males and 16 were females with a male to female ratio of 2.125 ∶ 1.Their age ranged from 33 to 77 years with an mean age of 60± 11 years.There were 13 cases (26％) of neuroendocrine tumors,31 (62％) neuroendocrine carcinomas,and 6 (12％) mixed adenoneuroendocrine carcinomas.The maximum diameter of lesion was less than 2 cm in 8 cases (16％),and equal or greater than 2 cm in 42 cases (84％).There was single lesion in 48 cases (96％) and multiple lesions in 2 cases (4％).There were 19 cases (38％) located in gastric antrum,16 (32％) in gastric body,11 (22％) in gastric fundus or cardia,3 (6％) in gastric angle,and 1 (2％) in the junction of gastric antrum and body.Thirty-two patients (64％) had metastasis,including 20 cases of lymph node metastasis and 12 cases of distant metastasis.The clinical symptoms of the patients were different,mainly were digestive system symptoms and tumor occupying symptoms,and no carcinoid syndrome was reported.The gross morphology (x2 =24.446.P =0.000).maximum diameter (t =-4.044,P =0.001),lymph node metastasis rate (x2=4.435,P =0.035),and survival time (t =2.925,P =0.000) were significantly differences between 13 cases of neuroendocrine tumors and 37 cases of neuroendocrine carcinoma.But the location of lesion (x2 =6.921,P=0.082) and distant metastasis rate (x2 =0.715,P =0.389) were no statistically different between the two groups.Conclusion Gastric neuroendocrine neoplasms can occur in any part of stomach,majority of tumor is single lesion and lack of specific clinical manifestations.The mostly gross morphology of gastric neuroendocrine carcinoma and mixed adenoneuro-endocrine carcinoma are ulcer type with a large diameter and poor prognosis.

This study is to evaluate the therapeutic effect of fibroblast growth factor 21 (FGF21) on type 2 diabetic mice model and to provide mechanistic insights into its therapeutic effect. Type 2 diabetic animal model was established with high calorie fat diet and low dose streptozotocin (STZ) injection. Mice were then randomized into 5 groups: model control, FGF21 0.25 and 0.05 μmol x kg(-1) x d(-1) groups, insulin treatment group. Ten age-matched normal KM mouse administered with saline were used as normal controls. Serum glucose, insulin, lipid products and the change of serum and liver tissue inflammation factor levels between five groups of mouse were determined. The results showed that blood glucose, insulin, free fatty acids (FFAs), triglycerides, and inflammatory factor average FGF-21 of type 2 diabetes model group and normal control group were significantly higher (P < 0.01), while compared with insulin group, no difference was significant. Average blood glucose, insulin, blood lipid and inflammatory factor of FGF-21 treatment group compared with type 2 diabetes group was significantly lower (P < 0.01) and insulin group has no difference with the model control group. The results of OGTT and HOMA-IR showed that insulin resistance state was significantly relieved in a dose-dependent manner. Thus, this study demonstrates that FGF-21 significantly remits type 2 diabetic mice model's insulin resistance state and participates in the regulation of inflammatory factor levels and type 2 diabetes metabolic disorders.