ObjectiveTo evaluate the clinical efficacy and safety of Tongluo Mingmu capsules in the treatment of diabetic retinopathy with blood stasis， collateral obstruction， and Qi and Yin deficiency syndrome. MethodA randomized， double-blind， positive-control， and multi-center clinical trial design method was used. 416 patients with diabetic retinopathy with blood stasis， collateral obstruction， and Qi and Yin deficiency syndrome in four test centers were included （the ratio of the treatment group to the control group was 3∶1）. On the basis of standardized hypoglycemic treatment， the treatment group was given both four Tongluo Mingmu capsules and two Calcium Dobesilate capsule agents three times a day， while the control group were given both two Calcium Dobesilate capsules and four Tongluo Mingmu capsule agents three times a day. The course of treatment was 12 weeks. The curative effect of Tongluo Mingmu capsules was evaluated by comparing the comprehensive curative effect of diabetic retinopathy， traditional Chinese medicine（TCM） syndrome score， corrected visual acuity， fundus changes， fundus fluorescence angiography， and other curative effect indexes before and after treatment in the two groups. At the same time， general examination， laboratory examination， and adverse events were performed to evaluate the safety of the drug. ResultThe baseline demographic data and disease characteristics of the treatment group and the control group were balanced and comparable， with the difference not statistically significant. After 12 weeks of treatment， the total effective rate of the comprehensive curative effect of diabetic retinopathy in the treatment group （61.0%， 189/310） was better than that in the control group （44.1%， 45/102）， and the difference was statistically significant （χ²=8.880， P<0.01）. The total effective rate of TCM syndromes in the treatment group （88.4%， 259/293） was better than that in the control group （69.9%， 65/93）， and the difference was statistically significant （χ²=17.927， P<0.01）. The disappearance rate of dry eyes （χ²=8.305）， dull complexion （χ²=4.053）， lassitude （χ²=10.267）， shortness of breath （χ²=8.494）， and dry stool （χ²=8.657） in the treatment group was higher than that in the control group， and the difference between the groups was statistically significant （P<0.05， P<0.01）. In terms of improving corrected visual acuity （χ²=8.382）， fundus changes （χ²=6.026） ， the treatment group was significantly better than the control group （P<0.05）. During the trial， the incidence of adverse events in the treatment group and the control group was 1.3% and 2.9%， respectively. There was no significant difference between the two groups. In addition， there were no serious adverse events and adverse events leading to withdrawal in both groups. ConclusionTongluo Mingmu capsules can improve the comprehensive curative effect of diabetic retinopathy and enhance the efficacy of TCM syndromes， visual acuity， fundus changes， and fundus fluorescein angiography， with great safety. Therefore， it can provide a new alternative therapeutic drug for patients with diabetic retinopathy.

Objective:To explore the clinical efficacy and safety analysis of a novel laser localization technology assisted percutaneous puncture of trigeminal nerve microsphere capsule compression surgery for the treatment of primary trigeminal neuralgia.Methods:A retrospective selection was conducted on 63 patients with primary trigeminal neuralgia who underwent percutaneous puncture of the trigeminal nerve microsphere capsule compression surgery at the First Hospital of Hunan University of Chinese Medicine from January 2020 to December 2021. According to different surgical methods, they were divided into a new laser localization assisted puncture group (observation group) of 32 cases and a traditional barehanded localization puncture group (control group) of 31 cases. An analysis was conducted on the surgical time, puncture time, puncture frequency, intraoperative exposure to radiation, number of cases of poor balloon formation, and clinical efficacy within 6 months after surgery for two groups of patients. The prognosis of the patients was followed up at 6 months after surgery.Results:The surgical time, puncture time, puncture frequency, and intraoperative exposure of the observation group were all less than those of the control group, and the differences were statistically significant (all P<0.05). There was no statistically significant difference ( P>0.05) in the number of cases of poor balloon angioplasty between the observation group and the control group, as well as the pain score grading of the Barlow Neurological Institute (BNI) on the first day after surgery. Within 6 months after surgery, there was no statistically significant difference in the incidence of facial numbness, diplopia, masseter weakness, perilabial herpes, and recurrent pain between the two groups of patients (all P>0.05). Conclusions:Laser positioning technology can assist in precise puncture of the foramen ovale and accurate placement of balloons based on surgical experience, which helps to improve surgical safety, reduce postoperative complications and intraoperative radiation dose, and achieve satisfactory short-term follow-up results.

Objective:To summarize the clinical phenotype and genetic characteristics of deficiency in ELF4 gene X-linked (DEX).Methods:A case series study was conducted to retrospectively analyze the clinical data and genetic testing results of 2 cases of DEX treated at Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and the First Hospital of Jilin University from January 2023 to April 2024. And literature up to April 2024 was searched from the PubMed database, as well as CNKI and Wanfang databases, using keywords such as "ELF4 deficiency" "deficiency in ELF4, X-linked""ELF4 gene". The main clinical manifestations and genotypes of DEX were summarized.Results:Both patients were male, with onset ages of 3 months and 3 years, respectively. Both patients presented with recurrent oral ulcers and abdominal pain. And the laboratory examination showed a significant increase in inflammatory markers. Intestinal examinations showed multiple intestinal ulcers, and both patients developed intestinal fistulas. Whole exome sequencing found ELF4 c.799C>T, p Arg267Trp and ELF4 c. 248-7G>A, both maternal variants. Based on clinical and genetic results, DEX were diagnosed. In terms of treatment, both patients underwent surgical treatment during the acute phase of the disease and received anti-tumor necrosis factor α therapy, but recurrent gastrointestinal symptoms were still observed in Patient 1, while the clinical effect in Patient 2 was still acceptable. However, the inflammatory markers in both patients were not normal even after treatment. Literature review found 18 patients including 2 patients in this study, reported in 5 English articles and no Chinese reports. Thirteen patients had disease onset age before 5. The main clinical manifestations were fever (12/17), oral ulcers (14/18), abdominal pain (8/18), diarrhea (6/18), perianal ulcers (5/17), ileum ulcers (6/16), colon ulcers (7/16), skin involvement (7/17) and recurrent infections (7/18); laboratory examinations found increased erythrocyte sedimentation rate (13/15) as well as C-reactive protein (9/9), and anemia (13/15); in terms of immunological function, there is a decrease in natural killer cells (9/15) as well as a decrease in class switching memory B cells (8/9). The main types of gene variantions were missense variantions (6/18), nonsense variantions (4/18) or frameshift variantions (3/18).Conclusions:DEX should be considered when an early-onset male patient manifested with recurrent fever, oral ulcers or mucosal ulcers, with elevated inflammatory markers, with or without recurrent infection. It is recommended to perform lymphocyte subsets analysis, gastrointestinal endoscopy and genetic testing to support the diagnosis.

Humans ; Child ; SARS-CoV-2 ; Viral Load ; COVID-19 ; Parents

Objective:To investigate the clinical characteristics of children infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variants, and the impact factors of duration of cycle threshold (Ct) values turning to ≥35 detected by nucleotide test.Methods:Children aged 0 to 14 years with clinical symptoms of Omicron variants infection who admitted to designated hospital in Shanghai City (Renji Hospital, South Branch, Shanghai Jiao Tong University School of Medicine) from April 7 to June 2, 2022 were enrolled. The daily nasopharyngeal swab specimens were used for SARS-CoV-2 nucleic acid detecting by polymerase chain reaction and the results were expressed as Ct values. The T Ct≥ x was defined as from the symptom onset or first positive nucleic acid test results (the earlier data) to Ct≥ x of the open reading frame 1ab ( ORF1 ab) gene, which was the time duration from the initial to a specific Ct value.Clinical data were collected, including age, sex, vaccination and comorbidities.Cox model was performed to analyzed the impact factors of T Ct≥35. Results:A total of 871 pediatric cases with a median age of two years (ranging from one month to 14 years old) were included. Among them, 474 cases (54.4%) were male, and 89 cases (10.2%) had underlying diseases including congenital heart disease, solid tumors and epilepsy. There were 572(65.7%) mild cases, 298(34.2%) common cases, one (0.1%) severe case and no critical cases or deaths. The T Ct≥35 was 12(10, 14) days. Cox model indicated that compared to children aged one to 12 months, children aged 37 to 84 months and 85 to 168 months had shorter T Ct≥35 (hazard ratio ( HR)=1.55 and 1.84, respectively, both P<0.001). After adjusted with age, comparing to unvaccinated patients, patients with one or two shots vaccine had shorter T Ct≥35 (adjected hazard ratio (a HR)=1.49, P=0.011), and common patients had longer T Ct≥35 than mild patients (a HR=0.78, P=0.002), and patients with comorbidities had longer T Ct≥35than patients without comorbidities (a HR=0.38, P<0.001).The duration of T Ct≥28, T Ct≥30, T Ct≥33 and T Ct≥35 in children without underlying diseases were 7(6, 9) d, 9(7, 10) d, 10(8, 11) d and 12(10, 14) d, respectively. Conclusions:Age, vaccination, disease severity and underlying diseases could affect the duration of SARS-CoV-2 nucleotide turning to negative (Ct value≥35) in children infected with Omicron variants.

Objective:To study the changes in long non-coding RNA C2dat1 expression in kidney tissues of rats at different stages of diabetic kidney disease (DKD) and its relationship with renal interstitial fibrosis.Methods:Forty-eight male SD rats were randomly divided into two groups with 24 rats in each group: control group and DKD group. The rats in the control group were fed with ordinary diet, while those in the DKD group were fed with high-fat diet and drank water freely. After eight weeks of feeding, the rats were fasted for 12 h with free access to water. Then, the DKD group was given a one-time intrabitoneal injection of streptozotocin and the control group was given an equal dose of sodium citrate buffer. After 72 h, the random peripheral blood glucose concentration (≥ 16.7 mmol/L for three consecutive days) and urine sugar (positive) were tested to assess the establishment of the diabetes model. Urine, blood and kidney samples were collected at 3, 6, 9 and 12 weeks. The urinary protein excretion rate within 24 h, urinary creatinine and serum total cholesterol were measured by automatic biochemical apparatus. Pathological changes in kidney tissues were observed by HE staining. The expression of calcium/calmodulin-dependent protein kinase Ⅱ delta (CaMK2D), p65, p50, α-SMA and E-cardherin was detected by immunohistochemistry. Quantitative real-time PCR (qPCR) was used to detect the expression of lncRNA C2dat1 and CaMK2D. The relationship of lncRNA C2dat1 with α-SMA, E-cardherin and CaMK2D was analyzed by correlation analysis. In in vitro experiment, renal tubular epithelial cells HK-2 were induced by high glucose. The expression of lncRNA C2dat1 and CaMK2D in HK-2 cells was detected by qPCR after 24, 48 and 72 h of intervention. Results:The rats in the DKD group showed typical symptoms such as polydipsia, polyphagia, significant weight loss and increased blood glucose as compared with the rats in the control group. Results of the biochemical tests revealed that compared with the control group, the DKD group had increased 24 h excretion rate of urinary protein, decreased urinary creatinine and up-regulated total cholesterol. HE staining showed that the rats in the control group had intact glomeruli, normal basement membrane and no mesangial hyperplasia or inflammatory cell infiltration. However, enlarged glomeruli and evenly thickened basement membrane were observed in the DKD group. Immunohistochemistry indicated that the expression of CaMK2D, p50 and α-SMA was higher in the DKD group than in the control group, while the expression of E-cardherin was lower in the DKD group. qPCR results showed that the expression of lncRNA C2dat1 and CaMK2D at mRNA level was higher in the DKD group than in the control group. In in vitro experiment, the expression of lncRNA C2dat1 and CaMK2D at mRNA level was also higher in HK-2 cells induced by high glucose than in the control group. Correlation analysis indicated that lncRNA C2dat1 was positively correlated with α-SMA and CaMK2D, but negatively correlated with E-cardherin. Conclusions:During the progression of DKD, the high expression of lncRNA C2dat1 might promote diabetic renal interstitial fibrosis by regulating the expression of CaMK2D to activate the NF-κB signaling pathway.

Humans ; Aminoquinolines/therapeutic use* ; Carcinoma, Non-Small-Cell Lung/genetics* ; Lung Neoplasms/genetics* ; Mutation/genetics* ; Standard of Care

Objective:To investigate the clinicopathologic features and differential diagnosis of ureteral fibroepithelial polyps.Methods:The clinicopathologic features and prognosis of ureteral fibroepithelial polyps with complete data retrieved from the pathology database of the Institute of Urology, Peking University from January 2013 to December 2021 were collected and analyzed. All HE staining sections were reviewed by a senior urologic pathologist. Immunohistochemical analysis was done in some cases for differential diagnosis. The clinical, imaging and outcome data were collected, and discussed together with relevant literature.Results:There were 45 patients with complete clinicopathologic data, including 34 males and 11 females (male: female=3.1∶1.0), with a median age of 36 (range 13-80) years. Preoperative diagnosis included polyp in 23 cases, tumor in 19 cases and calculi in 3 cases. The main clinical symptoms were hematuria (13 cases), low back and abdominal pain (9 cases) and no symptoms (9 cases). There were 29 cases of multiple polyps, 16 cases of single polyp; 32 cases were on the left side, 13 cases were on the right side; 29 cases of upper polyps, 9 cases of middle polyps, and 6 cases of lower polyps. Twenty-seven patients had no related urologic history, 10 patients had history of urolithiasis, and the rest had history of stents, strictures or tumors. Local ureteral resection and anastomosis were the most common treatment (20 cases), followed by ureteroscopic polypectomy (12 cases). The patients were followed up from the pathological diagnosis to the cut-off time: 4 cases were lost to follow-up, and the remaining 34 cases were followed up for 3 to 85 (mean 60 months). One case had polyp recurrence after 3 months, and the other case had polyp recurrence after 2 years. Fibroepithelial polyps had a variety of gross manifestations, ranging from elongated polyps or small papillary and polypoid to large papillary masses. Microscopically, they were divided into type 1, type 2 and type 3, and the type 3 was the most common type (28 cases). In this study, there were 41 cases of simple fibroepithelial polyp, 2 cases of malignant transformation of polyps into urothelial carcinoma, one case of polyps with urothelial carcinoma, and one case of polyp with surface urothelial carcinoma in situ; the stroma showed myofibroblastic proliferation.Conclusions:The clinical manifestations and morphologic characteristics of ureteral fibroepithelial polyps are diverse. The three microscopic types are easily confused with many benign and malignant ureteral diseases, such as inflammatory polyps, adenocystitis, papilloma, etc. Awareness of the key differentiation points and judicious use of immunohistochemistry will be helpful for the diagnosis and differential diagnosis.

【Objective】 To genetically analyze the D^el sample from a blood donor in Jiangyin and make clear the molecular basis of the serological phenotype. 【Methods】 The EDTA anticoagulant blood were collected: buffy coat were used for nucleic acid extract and cDNA analysis; red blood cells for serological test. Tube method and microcolumn gel were used for serological test. Genotyping kit were used for exon analysis. Gene mutation was analyzed using the sequence analyzer. 【Results】 Serological analysis demonstrated the sample′s RhD phenotype was D^el. The phenotype of RhCE was CCEe. Real-time fluorescence quota PCR result demonstrated the existence of all exones. Weak D15 and RHD^* DEL1 [RHD(1227G>A)], which had a high frequency of occurrence in China, were excluded according to real-time fluorescence quota PCR result. Sequence analyzing result verified RHD(28C>T) SNP mutation in cDNA. The genotype of this sample was RHD^*01 W. 61[RHD(28C>T)]. 【Conclusion】 A weak D61 was found among blood donors in our city, Jiangyin.