ObjectiveTo observe the clinical efficacy and safety of Tangning Tongluo tablets in the treatment of nonproliferative diabetic retinopathy （DR）. MethodsFourteen research centers participated in this study， which spanned a time interval from September 2021 to May 2023. A total of 240 patients with nonproliferative DR were included and randomly assigned into an observation group （120 cases） and a control group （120 cases）. The observation group was treated with Tangning Tongluo tablets， and the control group with calcium dobesilate capsules. Both groups were treated for 24 consecutive weeks. The vision， DR progression rate， retinal microhemangioma， hemorrhage area， exudation area， glycosylated hemoglobin （HbA1c） level， and TCM syndrome score were assessed before and after treatment， and the safety was observed. ResultsThe vision changed in both groups after treatment （P<0.05）， and the observation group showed higher best corrected visual acuity （BCVA） than the control group （P<0.05）. The DR progression was slow with similar rates in the two groups. The fundus hemorrhage area and exudation area did not change significantly after treatment in both groups， while the observation group outperformed the control group in reducing the fundus hemorrhage area and exudation area. There was no significant difference in the number of microhemangiomas between the two groups before treatment. After treatment， the number of microhemangiomas decreased in both the observation group （Z=-1.437， P<0.05） and the control group （Z=-2.238， P<0.05）， and it showed no significant difference between the two groups. As the treatment time prolonged， the number of microhemangiomas gradually decreased in both groups. There was no significant difference in the HbA1c level between the two groups before treatment. After treatment， the decline in the HbA1c level showed no significant difference between the two groups. The TCM syndrome score did not have a statistically significant difference between the two groups before treatment. After treatment， neither the TCM syndrome score nor the response rate had significant difference between the two groups. With the extension of the treatment time， both groups showed amelioration of TCM syndrome compared with the baseline. ConclusionTangning Tongluo tablets are safe and effective in the treatment of nonproliferative DR， being capable of improving vision and reducing hemorrhage and exudation in the fundus.

Objective To analyze the postoperative therapeutic effect of prokinetic agents in patients after tricuspid valve replacement （TVR） under cardiopulmonary bypass. Methods Patients received TVR under cardiopulmonary bypass （during June 2010 to December 2021） in the department of Cardiovascular Surgery of the First Affiliated Hospital of Naval Medical University were selected as the subjects of our study. The data of basic characteristics, first postoperative defecation time and postoperative recovery condition were collected and retrospectively analyzed in the patients taking prokinetic agents within three days after surgery （prevention group） and patients not taking prokinetic agents within three days after surgery （control group）. Results A total of 184 patients were selected, including 101 in the prevention group and 83 in the control group. The first defecation time of patients in the prevention group was significantly earlier than that in the control group （P<0.05）. The incidences of abdominal distension and pulmonary infection in the prevention group were significantly lower than that in the control group. The length of time in ICU, postoperative mechanical ventilation and nasogastric tube decompression in the prevention group were significantly shorter than that in the control group （P<0.05）. Conclusion Taking prokinetic agents within three days after TVR under cardiopulmonary bypass could effectively improve the prognosis of patients.

Objective To investigate the modulatory effect of Yulian Pills(composed of Coptidis Rhizoma and Euodiae Fructus)on splenic memory follicular T helper cell(mTfh)in mice with dextran sodium sulfate(DSS)-induced ulcerative colitis.Methods Forty BALB/c mice were randomly divided into normal group,model group,Yulian Pills group(0.5 g·kg-1)and Mesalazine group(0.3 g·kg-1),10 mice in each group.The mouse model of ulcerative colitis was induced by ad libitum drinking 3%DSS solution for 7 days.During the experiment,the mental state,faecal characteristics,blood in stool and body mass of the mice were recorded daily,and the length and mass of the colon were measured and the colon mass index was calculated;HE staining was used to observe the pathological and morphological changes of the colon tissue;ELISA was used to determine the expression levels of interleukin(IL)-6 and IL-15 in the colon tissues;flow cytometry was used to determine the mTfh cell subpopulation in the spleen tissue expression;Western Blot was used to determine the protein expression levels of Roquin-1,AMPK-α,p-AMPK-α in colon tissues.Results Compared with the normal group,the mice in the model group showed a significant decrease in body mass(P＜0.01),a significant shortening of colon length(P＜0.01),significant increase in colon mass(P＜0.05)and colon mass index(P＜0.01),and severe pathological damage to colon tissues;the expression levels of the pro-inflammatory cytokines IL-6 and IL-15 in the colon tissues were significantly increased(P＜0.01);cell expression levels of CD4+CCR7-CXCR5+CD62L+,CD4+CCR7+CXCR5+ GL7+,CD4+CCR7-CXCR5+GL7+ were significantly increased in spleen tissues(P＜0.01),whereas the expression level of CD4+CCR7+CXCR5+CD62L+ cell was significantly decreased(P＜0.01);and protein expression levels of Roquin-1,AMPK-α,p-AMPK-α were significantly reduced in the colonic tissues(P＜0.05).Compared with the model group,mice in the Yulian Pills group and Mesalazine group showed a significant increase in body mass(P＜0.05),a significant extension of colon length(P＜0.01),a significant reduction in colon mass(P＜0.05),a significant decrease in the colon mass index(P＜0.01),and a more obvious improvement in pathological damage of the colon tissues;a significant decrease in the expression levels of IL-6 and IL-15 in the colon tissues(P＜0.01);cell expression levels of CD4+CCR7-CXCR5+CD62L+,CD4+CCR7+CXCR5+GL7+,CD4+CCR7-CXCR5+GL7+ in splenic tissues was significantly reduced(P＜0.01),whereas the expression level of CD4+CCR7+CXCR5+CD62L+ cell was significantly increased(P＜0.01);the protein expression levels of Roquin-1,AMPK-α,and p-AMPK-α were significantly increased in colon tissues(P＜0.05,P＜0.01).Conclusion The therapeutic effect of Yulian Pills on DSS-induced ulcerative colitis mice can ameliorate the histopathological damage of colon,which may be related to the activation of the Roquin-1/MPK-α signalling pathway,the down-regulation of the expressions of inflammatory cytokines IL-6 and IL-15,and the modulation of the homeostasis of the mTfh cell subpopulation.

ObjectiveThe human angiotensin converting enzyme2 （hACE2） transgenic mouse model was used to clarify the antiviral efficacy of BD-77 against a novel coronavirus SARS-CoV-2 and explore the action mechanism of BD-77 against SARS-CoV-2. MethodSARS-CoV-2 Omicron and Delta variant strains-infected VeroE6 cell models were established and administered with BD-77 to observe the antiviral effect of BD-77 in vitro. A kit was used to detect the effect of BD-77 in vitro on the binding of spike S protein of SARS-CoV-2 virus （Delta/Omicron） to angiotensin converting enzyme2 （ACE2）. Chromatography was adopted to detect the binding of BD-77 to the S protein and N protein of the novel coronavirus. hACE2 transgenic C57BL/6 mice were divided into a blank control group， SARS-CoV-2 infection group， BD-77 administration groups of 37.5 mg·kg^-1 and 75 mg·kg^-1， with eight mice in each group. The pneumonia model of SARS-CoV-2-infected hACE2 transgenic mice was built to observe the survival of the mice， detect the virus titer of the lung tissue of the mice， and observe the lesions in the lung tissue. ResultBD-77 had a certain inhibitory effect on Omicron and Delta variant strains in vitro， with median inhibitory concentration （IC₅₀） of 526.3 mg·L^-1 and 653.0 mg·L^-1， respectively. BD-77 had no significant inhibitory effect on the binding of the S protein of WT， Omicron， and Delta variant strains of SARS-CoV-2 to ACE2 and had no binding effect with the S protein and N protein of the novel coronavirus. No mice in the blank group died， while the mortality rate of SARS-CoV-2-infected mice was 75%. There was a large amount of virus replication in the lung tissue of the mice and large areas of inflammatory infiltration in the lung tissue and interstitium. Compared with the model group， BD-77 administration groups of 37.5 mg·kg^-1 and 75 mg·kg^-1 could reduce the mortality of mice， significantly lower the virus titer in the lung tissue of mice （P<0.05）， and improve lung lesions. ConclusionBD-77 demonstrated significant inhibitory effects against SARS-CoV-2 virus in vitro and in vivo. However， its mechanism of action did not involve direct inhibition of the virus itself or intervention in the virus-host binding process. This finding suggests that the mechanism of action of BD-77 needs to be thoroughly investigated and elucidated by further experiments.

Objective:To explore the clinical features and diagnostic methods of primary ciliary dyskinesia (PCD).Methods:A case of PCD diagnosed by Kunming Children's Hospital was analyzed retrospectively (including general information, clinical characteristics, auxiliary examination results), and the literature was reviewed.Results:The patient, an 8-year-old female, went to hospital for repeated cough and suffered from pneumonia and sinusitis repeatedly in the past. The electron microscope of cilia biopsy showed that the number of cilia was reduced. The mutation of c.7615T>C (p.W2539R) in DNA H5 gene located in chr5-13,809,290 was detected by gene test, so the patient was diagnosed as PCD.The mutation site was a new mutation site.Conclusion:PCD is a rare disease in children. Electron microscopy and genetic examination are helpful to the diagnosis of PCD. Children with recurrent respiratory tract infection and wet cough should be alert to the possibility of PCD.

Objective:To investigate Helicobactor pylori (H. pylori) infection status and interfamilial transmission pattern in Zhengzhou area. Methods:A cross-sectional study was conducted from September 2020 to march 2021, among 731 individual from 266 families randomly selected from 9 communities of Zhengzhou area. H. pylori infection status was determined by serum antibody tests, and 13C-urea breath test was performed in the previously eradicated population to clarify the current infection status. The individual and familial infection rate, infection status for couples and children and adolescent were analyzed. Results:Among 731 individuals from 266 families, 397 of them were H. pylori positive. The individual infection rate was 54.31% (397/731); among infected individuals 77.83% (307/397) were infected with type Ⅰ strain, 22.67% (90/397) were infected by type Ⅱ strain. Annual household income ( χ2=0.419, 0.410, 0.213, all P>0.05), smoking history (χ 2=0.071, P>0.05), drinking history ( χ2=0.071, P>0.05), dining place ( χ2=0.009, P>0.05), gastrointestinal symptoms ( χ2=0.047, P>0.05), family history of gastric disease ( χ2=0.069, P>0.05), and history of gastric cancer ( χ2=0.004, P>0.05) had no significant differences between H. pylori-positive and -negative groups, but the infection rate in individuals with higher education level was lower ( χ2=4.449, P<0.05). The infection rate was significantly higher in≥18 age groups compared with<18 age groups ( χ2=6.531, 23.362, 20.671, 24.244, 37.948, 14.597 and 5.170, all P<0.05). The familial H. pylori infection rate was 87.59% (233/266), and in 61 families all member were infected (26.18%, 61/233). The positive rate was 23.08% (6/26) in 50 families with children under 18 years when both parents were infected. Among 231 coupled families, both couples were infected in 78 families (33.76%), one couple was infected in 113 families (48.92%), and both couples were not infected in 40 (17.32%). With the increase of marriage time, the infection rate of both spouses increased significantly ( χ2=7.775, 12.662, 15.487, all P<0.05). Conclusions:The distribution of H. pylori infection presents a family cluster pattern, and intrafamilial infection is an important transmission rout of H. pylori. The type I strain of H. pylori is the dominate strain in this area.

A randomized, double-blind, placebo-controlled, multi-center phase Ⅱ clinical trial design was used in this study to recruit subjects who were in line with the syndrome of excess heat and fire toxin, and were diagnosed as recurrent oral ulcers, gingivitis, and acute pharyngitis. A total of 240 cases were included and randomly divided into a placebo group and a Huanglian Jiedu Pills group. The clinical efficacy of Huanglian Jiedu Pills in treating the syndrome of excess heat and fire toxin was evaluated by using the traditional Chinese medicine(TCM) syndrome scale. Enzyme-linked immunosorbent assay(ELISA) was used to determine and evaluate the levels of adenosine triphosphate(ATP), 4-hydroxynonenal(4-HNE), and adrenocorticotropic hormone(ACTH) in plasma of the two groups before and after administration and to predict their application value as clinical biomarkers. The results showed that the disappearance rate of main symptoms in the Huanglian Jiedu Pills group was 69.17%, and that in the placebo group was 50.83%. The comparison between the Huanglian Jiedu Pills group and the placebo group showed that 4-HNE before and after administration was statistically significant(P<0.05). The content of 4-HNE in the Huanglian Jiedu Pills group decreased significantly after administration(P<0.05), but that in the placebo group had no statistical significance and showed an upward trend. After administration, the content of ATP in both Huanglian Jiedu Pills group and placebo group decreased significantly(P<0.05), indicating that the energy metabolism disorder was significantly improved after administration of Huanglian Jiedu Pills and the body's self-healing ability also alleviated the increase in ATP level caused by the syndrome of excess heat and fire toxin to a certain extent. ACTH in both Huanglian Jiedu Pills group and placebo group decreased significantly after administration(P<0.05). It is concluded that Huanglian Jiedu Pills has a significant clinical effect, and can significantly improve the abnormal levels of ATP and 4-HNE in plasma caused by the syndrome of excess heat and fire toxin, which are speculated to be the effective clinical biomarkers for Huanglian Jiedu Pills to treat the syndrome of excess heat and fire toxin.
Humans ; Adrenocorticotropic Hormone ; Hot Temperature ; Medicine, Chinese Traditional ; Adenosine Triphosphate

The clinical data of a child with anaplastic lymphoma kinase positive histiocytosis (ALK+ H) diagnosed in April 2020 by Kunming Children′s Hospital were retrospectively analyzed.The male child was 4 months and 29 days old and had multiple nodules throughout the body since 1 week after birth.Skin sarcoidosis examination showed non-Langerhans cell histiocytosis, and immunohistochemistry showed ALK (+ ), CD1a (-), and CD 163(+ ). Therefore, this patient was diagnosed as ALK+ H, which was very rare in clinical practice.Previously reported cases mainly showed soft tissue nodules or thrombocytopenia with anemia.In addition to multiple nodules throughout the body, this patient also had elevated platelets, neutropenia, and abnormal liver function, which was different from previous reports.Hence, this case could be used as a supplement to the disease database.

Objective:To investigate the efficacy and safety of fecal microbiota transplantation (FMT) in the treatment of irritable bowel syndrome (IBS), and to explore the effects of FMT on the gut microbiota of IBS patients.Methods:From September 2016 to August 2017, at Guangzhou First People′s Hospital, 28 hospitalized IBS patients who underwent FMT treatment were enrolled. Before FMT, four and 12 weeks after FMT, all the IBS patients completed the irritable bowel syndrome quality of life scale (IBS-QOL), irritable bowel syndrome severity scoring system (IBS-SSS) and gastrointestinal symptom rating scale (GSRS). 16S rDNA sequencing was performed before FMT and four weeks after FMT. The effects of FMT on gut microbiota diversity and microbiota structure of IBS patients were analyzed respectively from the level of phylum, family and genus, and linear discriminant analysis effect size (LEfSe) was further used to screen the different bacteria. Paired t test and paired rank sum test were used for statistical analysis. Results:Twelve weeks after FMT, the scores of the six dimensions of IBS-QOL including dysthymia, behavioral disorder, auto imagery, health concerns, eating avoidance, and relationship expansion were all lower than those before FMT (43.750, 22.656 to 56.250 vs. 48.438, 32.031 to 60.938; 37.500, 18.750 to 56.250 vs. 46.429, 21.429 to 62.500; 31.250, 14.063 to 42.188 vs. 31.250, 18.750 to 50.000; 41.667, 27.083 to 56.250 vs. 50.000, 41.667 to 66.667; 54.167, 43.750 to 72.917 vs. 66.667, 58.333 to 83.333; 8.333, 0.000 to 33.333 vs. 16.667, 8.333 to 33.333, respectively), and the differences were statistically significant ( Z=-2.157, -3.429, -2.274, -3.197, -3.042 and -2.329, all P<0.05). Twelve weeks after FMT, the scores of the two dimensions of IBS-QOL including behavioral disorder and relationship expansion were both lower than those of four weeks after FMT (37.500, 18.750 to 56.250 vs. 39.286, 19.643 to 62.500 and 8.333, 0.000 to 33.333 vs. 16.670, 2.083 to 41.667, respectively), and the differences were statistically significant ( Z=-1.998 and -2.110, both P<0.05). Four and 12 weeks after FMT, the scores of IBS-SSS and GSRS were both lower than those before FMT ((190.32±106.51), (201.43±102.48) vs. (245.93±86.10) and 5.50, 4.00 to 9.00 and 5.50, 4.00 to 8.75 vs. 7.00, 6.00 to 9.75), and the differences were statistically significant ( t=4.402 and 3.848, Z=-3.081 and -3.609; all P<0.01). No serious adverse reactions occurred in the patients after FMT. At the phylum level, after FMT the abundance of Verrucomicrobia in the feces of IBS patients was richer than that before FMT (6.74% vs. 0.37%); at the family level, after FMT the abundance of Verrucomicrobiaceae in the feces of IBS patients was richer than that before FMT (6.74% vs. 0.37%); at the genus level, after FMT the abundance of Akkermansia was richer than that before FMT (6.74% vs. 0.37%); and the differences were statistically significant (all Z=-2.589, all P=0.010). The results of LEfSe method indicated that four weeks after FMT the abundance of Akkermansia in the gut microbiota of IBS patients was richer than that before FMT (6.74% vs. 0.37%), and the difference was statistically significant (linear discriminant analysis value=4.5, P=0.049). Conclusions:FMT is safe and effective in the treatment of IBS. The mechanism may be through upregulating the diversity of gut microbiota and changing the structure of gut microbiota of IBS patients.

OBJECTIVE: To carry out mutation analysis and prenatal diagnosis for a family affected with primary carnitine deficiency. METHODS: Genomic DNA of the proband was extracted from peripheral blood sample 10 days after birth. The 10 exons and intron/exon boundaries of the SLC22A5 gene were subjected to PCR amplification and Sanger sequencing. The proband's mother was pregnant again two years after his birth. Fetal DNA was extracted from amniocytes and subjected to PCR and Sanger sequencing. RESULTS: Tandem mass spectrometric analysis of the proband revealed low level of plasma-free carnitine whilst organic acids in urine was normal. Compound heterozygous SLC22A5 mutations c.1195C>T (inherited from his father) and c.517delC (inherited from his mother) were detected in the proband. Prenatal diagnosis has detected no mutation in the fetus. The plasma-free carnitine was normal after birth. CONCLUSION Appropriate genetic testing and prenatal diagnosis can prevent further child with carnitine deficiency. The identification of c.517delC, a novel mutation, enriched the spectrum of SLC22A5 mutations.
Cardiomyopathies ; genetics ; Carnitine ; deficiency ; genetics ; Child, Preschool ; DNA Mutational Analysis ; Female ; Humans ; Hyperammonemia ; genetics ; Muscular Diseases ; genetics ; Mutation ; Pregnancy ; Prenatal Diagnosis ; Solute Carrier Family 22 Member 5 ; genetics