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.

The diagnosis of Parkinson's disease(PD)mainly relies on clinical appearance of patients,and the routine magnetic resonance scan has difficulty in finding the abnormality of that,which is not able to meet the requirement of early and precise quantification for the PD lesion area.Diffusion magnetic resonance imaging(dMRI)technique is a noninvasive method of examining the microstructure of living tissue.Diffusion weighted imaging(DWI)and diffusion tensor imaging(DTI)were the most widely used in clinical practice.However,the principles of them have limitation,which are not able to fully outline the microstructure of brain tissue.This paper discussed several new dMRI techniques that are able to make up conventional dMRI model,which included diffusion kurtosis imaging(DKI),neurite orientation dispersion and density imaging(NODDI)and diffusion tensor imaging index of perivascular space(DTI-ALPS).Moreover,this paper summarized the applications of above imaging technique in exploring the changes of the microstructure of brain tissue of PD patients,so as to provide more imaging information for the pathological changes of PD patients.

Objective:To investigate the characteristics and risk factors of local recurrence in resected pancreatic cancer.Methods:The clinicopathological data of 190 patients in whom recurrent sites can be identified after radical resection of pancreatic cancer from Sep 2013 to Aug 2020 at the Cangzhou Central Hospital were retrospectively analyzed. The survival time and clinicopathological characteristics of local recurrence were compared with those of other recurrence types. Cox risk regression model was used to analyze the risk factors of local recurrence.Results:The recurrence sites were local (49 cases, 25.8%), liver (53 cases, 27.9%), lung (35 cases, 18.4%), peritoneal (25 cases, 13.2%) and multiple sites (28 cases, 14.7%). Patients mRFS and mOS were 17.8 months and 30.9 months respectively. The clinicopathological features of patients with local recurrence were compared with those of other recurrence types [tumor diameter ( P=0.023), preoperative CA199 level ( P=0.021), peripancreatic nerve plexus invasion ( P=0.031), lymphovascular invasion ( P=0.004), surgical margin state ( P<0.001) and postoperative adjuvant chemotherapy ( P=0.038)]. Tumor diameter ( P=0.018), peripancreatic nerve plexus invasion ( P=0.002) and postoperative adjuvant chemotherapy ( P=0.004) were independent factors for local recurrence in resected pancreatic cancer, and only peripancreatic nerve plexus invasion was not associated with other recurrence types. Conclusions:Local recurrence in resected pancreatic cancer has important impact on the prognosis of patients. Peripancreatic nerve plexus invasion is an independent factor affecting local recurrence.

Objective:To study the changes the changes of cytokine expression the aqueous humor of patients with macular edema secondary to branch retinal vein occlusion (BRVO-ME) before and after intravitreal ranibizumab (IVR).Methods:A prospective clinical study. From June 2018 to June 2021, 31 eyes of 31 patients with non-ischemic BRVO-ME diagnosed by ophthalmic examination in Department of Ophthalmology, Beijing Hepingli Hospital were included in the study. Among them, 15 males had 15 eyes, and 16 females had 16 eyes. Age was 70 (65, 72) years; the course of disease was 10 (9, 15) days. All of them were first-time patients. All eyes were treated with IVR once a month for 3 consecutive months. At the end of each IVR treatment, 0.1 ml aqueous humor was extracted immediately. The concentrations of vascular endothelial growth factor (VEGF), interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in aqueous humor were detected by flow cytometry. The concentrations of cytokines in aqueous humor before and after treatment were compared by Kruskal-Wallis or Wilcoxon signed-rank test. Spearman correlation analysis was performed on the correlation between VEGF and MCP-1 expression level in aqueous humor before treatment.Results:The concentrations of VEGF and ICAM-1 in aqueous humor were significantly lower at 1 month after treatment compared with that before treatment, and at 2 months after treatment compared with that at 1 month after treatment ( Z=4.03, 3.25, 2.50, 3.48; P<0.05); the concentrations of IL-6 and VCAM-1 increased and the concentration of MCP-1 decreased, but there was no significant difference ( Z=-0.21, 1.42, 0.86, -0.53, 0.92, -1.57; P>0.05). Spearman correlation analysis showed that there was a strong positive correlation between VEGF and MCP-1 in aqueous humor before treatment ( r=0.78, P<0.001). Conclusion:The concentrations of VEGF and ICAM-1 in aqueous humor significantly decrease after IVR treatment in BRVO-ME; the concentrations of IL-6, MCP-1 and VCAM-1 do not obviously change.

Objective:To evaluate the efficacy and safety of compound anisodine (CA) injection for anterior ischemic optic neuropathy (AION).Methods:Studies, which were randomized controlled trials (RCT) of CA with routine treatment for AION from PubMed, The Cochrane Library, Web of Science, CNKI, Wanfang database, Chinese science and technology journals full-text database and CD-ROM database of Chinese Biology Medical disc published from January 1978 to June 2021 were searched.Included studies were screened by two researchers independently based on inclusion and exclusion criteria.After data collection and quality assessment, a meta-analysis of included studies was performed with Revman 5.3 software.Results:Thirteen RCT were included, involving 1 636 eyes, with 829 eyes in treatment group and 807 eyes in control group without CA treatment.It was found that the total effective rate of treatment group was higher than that of control group ( OR=3.25, 95% CI: 2.47-4.28, P<0.01), and the best corrected visual acuity of AION patients after CA treatment was significantly better than that of control group when articles with high heterogeneity were excluded (MD=0.14, 95% CI: 0.11-0.17, P<0.01) or not (MD=0.14, 95% CI: 0.12-0.16, P<0.01).The mean defect of visual field was significantly smaller and the mean sensitivity of visual field was higher in treatment group than control group (MD=-2.58, 95% CI: -3.98--1.19, P<0.01; MD=3.49, 95% CI: 3.07-3.91, P<0.01). Conclusions:CA shows good efficacy in the treatment of AION.It can improve visual acuity and mean sensitivity of visual field, decrease mean defect of visual field.

Objective:To analyze the characteristics and prognosis of visual field of Leber hereditary optic neuropathy (LHON) with G11778A mutation.Methods:A retrospective clinical study. Twenty-two (44 eyes) of LHON patients diagnosed with G11778A site mutation by mt-DNA examination from May 2008 to February 2018 in Ophthalmology Department of Dongfang Hospital of Beijing University of Chinese Medicine, were enrolled in this study. All patients underwent best corrected visual acuity (BCVA), visual field and optical coherence tomography (OCT). The BCVA examination was performed using the international standard visual acuity chart, which was converted into logarithm of the minimum angle of resolution (logMAR) BCVA for record. The thickness of the retinal nerve fiber layer (RNFL) in the 200μm×200μm annular region 1.73 mm outside the optic disc was measured by OCT. At least 7 visual field examinations were performed within one month before and after 2, 4, 8, 12, 18, 24 and 30 months of the course of disease by using Octopus 101 perimetry. Among 44 eyes, 27 eyes were detected with G2 procedure (G2 group) and 17 eyes were detected with LVC procedure (LVC group). The mean field defect (MD) and mean optical sensitivity (MS) were used as the main outcome indexes. According to the onset age, the patients were further divided into the ≤14 years old group and>14 years old group. There was a significant difference in initial logMAR BCVA between the G2 group and LVC group ( t=4.994, P=0.000), but there was no significant difference in gender ( χ2=1.896, P=0.169) and age ( t=0.337, P=0.708) between the two groups. Independent sample t test was used for comparison between groups, paired t test was used for comparison within groups, and one-way analysis of variance was used for comparison between groups. The statistical data were compared by χ2 test. Results:In the G2 group, the MD value of the subgroup of children (≤14 years old) decreased gradually during the follow-up period, and the MD value since 18 months after onset was significantly lower than the value of 2 months after onset ( t=3.813, 4.590, 5.033; P=0.002, 0.001, 0.000). No obvious visual field index changes were seen in other subgroups ( P>0.05). The central scotoma was the most common type of visual field defect in the early stage, and the diffuse defect was the most common type of visual field defect in the late stage. There was a significant difference in the types of visual field distribution between the early and late stage in G2 group ( χ2=17.414, P=0.015). There was no significant difference in the type of visual field distribution between the early and late stage in LVC group ( χ2=4.541, P=0.474). The MD value in the G2 group remained stable within 8 months after onset, but significantly improved after 18 months after onset ( t=2.100, 3.217, 3.566; P=0.046, 0.003, 0.001). The MS in the LVC group did not significantly improve during follow-up ( P>0.05). The average visual acuity of the G2 group was significantly improved from 12 months ( t=3.039, 3.678, 4.264, 5.078; P=0.008, 0.002, 0.001, 0.000). The visual acuity of the eyes in the G2 group was better than that of the LVC group during all follow-up periods ( P≤0.05). The RNFL thickness of all patients continued to decrease after onset, but the RNFL thickness was significantly higher at 4, 8, 18, 24, 30 months in the G2 group than those in the LVC group ( t=2.471, 2.269, 2.474, 2.509, 2.782; P=0.018, 0.028, 0.017, 0.016, 0.008). Conclusions:The main types of visual field defect of LHON with G11778A mutation are the central scotoma in the early stage, while the diffuse defect and central scotoma are both very common in the later stage. The visual field of LHON patients examined by G2 procedure is significantly improved during the follow-up, as well as the visual acuity improved significantly, and the visual field improvement in younger cases (≤14 years old) is better than that of older cases (>14 years old), but the visual field of the LVC procedure cases did not improve during follow-up.

Genetics ; Laboratories ; Technology ; standards ; United States

Intrahepatic cholangiocarcinomas (ICCA) are primary intrahepatic malignancies originating from biliary epithelia.While both hepatocellular cancer and ICCA can present as mass lesions within the liver,these cancers are distinct in their morphology,etiology,pathology,natural history and response to therapy.There is a need for accurate and sensitive molecular markers for the diagnosis of ICCA.Recent advances in elucidating molecular and genetic characteristics of ICCA offer the potential of molecular-based diagnosis of ICCA.Specific genetic mutations of IDH1/2,BAP1,p53,and KRAS,FGFR gene fusions and alterations in microRNA have all been described in ICCA.Although there are no accurate serum or biliary biomarkers currently available for diagnosis of ICCA,several potential candidates have been identified.Knowledge of specific genetic or molecular abnormalities offers potential for individualized approaches for the treatment of patients with ICCA in the future.

Objective To evaluate the clinical value of the real-time three-dimensional ultrasound in the diagnosis of the fistula-in-ano.Methods One hundred and eighteen fistula-in-ano patients were examined using conventional and three-dimensional ultrasound,the stereotaxis of interal opening and the shape of the fistula-in-ano were analyzed.Then the diagnosis results of ultrasound were compared with the surgery and pathology.Results In 1 1 8 patients,the accuracy of preoperative identifying internal opening by two-dimensional ultrasound was 85%,and 95% for three-dimensional ultrasound with statistically significant difference (χ2 =6.679,P <0.05).For complex anal fistula,the diagnostic accuracy rates of main fistula tract by three-dimensional ultrasound (100%,82/82 )was higher than that by two-dimensional ultrasound(95%,78/82),the difference was statistically significant (χ2 =4.100,P <0.05 ).In 82 cases of complex anal fistula,the diagnostic accuracy of branch fistula tract by two-dimensional ultrasound was 70%(57/82 ),the accuracy using three-dimensional ultrasound was 89% (73/82 ),there was statistically significance (χ2 =9.499,P < 0.05 ).Conclusions Three-dimensional ultrasound can accurately locate the interal opening of fistula-in-ano and determine the shape of fistula-in-ano,which provided the most intuitive information for clinical treatment and had high practical value.

OBJECTIVETo report on clinical, genetic and molecular characterization of two Chinese families with Leber's hereditary optic neuropathy.

METHODSOphthalmological examinations have revealed variable severity and age at onset of visual loss among the probands and other matrilineal relatives of both families. The entire mitochondrial genome of the two probands was amplified with PCR in 24 overlapping fragments using sets of oligonucleotide primers.

RESULTSThe ophthalmological examinations showed that penetrance was 12.5% and 30.0% respectively in the two families. Sequence analysis of the complete mitochondrial genomes in these pedigrees has identified unreported homoplasmic T8821G mutation in the ATPase 6 gene and distinct sets of polymorphisms belonging to haplogroups M10a. The T8821G mutation has occurred at the extremely conserved nucleotide (conventional position 99) of the ATPase6. Thus, this mutation may alter structural formation of ATPase6, thereby leading to failure in the synthesis of ATP involved in visual impairment.

CONCLUSIONAbove observations have suggested that the ATPase6 T8821G mutation may be involved in the pathogenesis of optic neuropathy in these families.

Adolescent ; Asian Continental Ancestry Group ; genetics ; Base Sequence ; China ; DNA, Mitochondrial ; genetics ; Female ; Humans ; Male ; Mitochondrial Proton-Translocating ATPases ; genetics ; Molecular Sequence Data ; Optic Atrophy, Hereditary, Leber ; enzymology ; genetics ; Pedigree ; Point Mutation ; Young Adult