To explore the application value of whole exome sequencing (WES) in the diagnosis of prenatal and postnatal neurodevelopmental disorders (NDDs). A total of 70 patients diagnosed with NDDs who underwent WES at the Medical Genetics Center of the Maternal and Child Health Hospital of Hubei Province between June 2020 and July 2021 were retrospectively analyzed. Genomic DNA was extracted from peripheral blood samples and amniotic fluid. WES-based copy number variant (CNV) analysis was integrated into the routine WES data analysis pipeline. The results showed that a molecular diagnosis rate could be made in 21/70 (30%) cases. Of 21 positive cases, 14 (23%) cases were detected by single-nucleotide variant/small insertion/deletion (SNV/Indel) analysis, of which 12 variants were novel, 6 (9.8%) cases were detected by WES-based CNV analysis, and 1 (1.6%) case was detected by a combination of both. The diagnostic yield of WES combined with CNV analysis was higher than that of SNV/Indel analysis alone (30%, 21/70 vs. 20%, 14/70). Of the 28 prenatally diagnosed cases, 6 cases were found to have inherited parental variation for NDDs, 10 cases were found not to have the same pathogenic variation as the proband, and the remaining 12 cases were found to have no pathogenic or likely pathogenic variation that could explain the NDDs phenotype. Clinical follow-up showed that 5 families opted for abortion and the remaining had no current abnormalities. In conclusion, WES may be an effective method to clarify the genetic etiology and prenatal diagnosis of NDDs, which is helpful in assessing the prognosis to aid clinical management and reproductive guidance.
Pregnancy ; Humans ; Female ; Exome Sequencing ; Retrospective Studies ; Prenatal Diagnosis ; Amniotic Fluid ; Phenotype

Abstract: Objective　To investigate the distribution characteristics of HCV genotypes and subtypes in patients with HIV (human immunodeficiency virus, HIV)/HCV co-infection in Kunming based on the nucleocapsid protein gene sequence of HCV (hepatitis C virus). Methods　Serum was collected from HIV/HCV co-infected patients with household registration in 14 county-level cities, districts and counties under the jurisdiction of Kunming, who admitted to Yunnan Provincial Infectious Disease Hospital from March to August 2019. The viral RNA was extracted from the serum, reverse transcribed to synthesize cDNA, and the HCV nucleocapsid protein gene-specific primers were used for nested PCR amplification. The positive amplification products were sequenced, bioinformatics software such as DNAstar and MEGAX were used for sequence analysis. Results　A total of 64 samples from co-infected patients with clinical diagnosis of suspected HIV/HCV were collected and amplified by HCV nucleocapsid protein gene-specific primers, of which 17 samples were amplified positively. The results of sequence analysis showed that the sequences of 9 cases were located in the same evolutionary branch as the HCV 3b subtype sequence, and the nucleotide homology was 93.3%-95.2%; the sequences of 5 cases were located in the same evolutionary branch as the HCV 1b subtype sequence, and the nucleotide homology was 96.8%-97.6%; the sequence of one case and the subtype sequence of HCV 3a gene were located in the same evolutionary branch, and the nucleotide homology was 95.2%; the sequence of one case and HCV 6n gene subtype sequence were located in the same evolutionary branch, and the nucleotide homology was 97.9%; One case was located in the same evolutionary branch as the HCV 6u gene subtype sequence, and the nucleotide homology was 98.4%. Conclusions　HCV 1b, HCV 3a, HCV 3b, HCV 6n and HCV 6u genotypes or subtypes of HCV are prevalent in Kunming, and HCV 3b is the most prevalent genotype.

Diabetic retinopathy(DR)is the most prevalent and severe ocular complication in people with diabetes, and it is one of the leading causes of blindness in adults. In recent years, drug therapy represented by anti-vascular endothelial growth factor(VEGF)agents has become the first-line therapy in DR treatment, but it cannot reverse retinal non-perfusion areas, microaneurysms and abnormal teleangiectatic capillaries, those who cannot be treated on time are at risk of disease progression. Laser photocoagulation has been widely applied for more than 40 years, it can effectively reduce the rate of blindness by eliminating the non-perfusion areas of capillaries, and panretinal photocoagulation(PRP)has been the primary treatment for DR. With the continuing innovations in laser technology, on the basis of maintaining the curative effect, the aim of minimizing retinal damage and adverse side effects has been realized. A combination of laser photocoagulation and anti-VEGF agents can achieve complementary advantages and better efficacy. Deepening the clinical research on laser therapy and laser therapy combined with anti-VEGF agents in the treatment of DR may help to establish the personalized treatment corresponds with our national conditions. This article briefly reviews the latest application progress of laser therapy in DR treatment in the era of anti-VEGF agents.

Diabetic macular edema(DME)and age-related macular degeneration(ARMD)are the leading causes of visual impairment and blindness worldwide, and their common pathological features are increased vascular permeability and abnormal neovascularization, in which cytokines such as vascular endothelial growth factor(VEGF)and angiopoietin-2(Ang-2)play an important role. Intravitreal injection of anti-VEGF agents significantly changed the clinical management of DME and ARMD, but limitations such as the non-responsive cases, the treatment burden and risks caused by frequent injections need to be overcome. Faricimab, a novel bispecific monoclonal antibody that simultaneously targets VEGF-A and Ang-2, can effectively reduce vascular permeability, decrease the number of neovascularization and alleviate retinal edema. Registered clinical studies have shown that Faricimab is effective in improving vision and reducing retinal edema, which is non-inferior to Aflibercept and Ranibizumab, maintains a long dosing interval, and has a high safety profile. This article reviews the latest advances in the treatment of DME and ARMD with Faricimab.

The present study investigated the effect of extract of Poria cocos polysaccharides(PCP) on cytochrome P450 2 E1(CYP2 E1) and nuclear factor κB(NF-κB) inflammatory signaling pathways in alcoholic liver disease(ALD) mice and explored its protective effect and mechanism. Sixty male C57 BL/6 N mice of SPF grade were randomly divided into a control group, a model group, a positive drug group(bifendate, 200 mg·kg~(-1)), and high-(200 mg·kg~(-1)) and low-dose(50 mg·kg~(-1)) PCP groups. Gao-binge mo-del was induced and the mice in each group were treated correspondingly. Liver morphological and pathological changes were observed and organ index was calculated. Serum levels of alanine aminotransferase(ALT) and aspartate aminotransferase(AST) were detected. Malondialdehyde(MDA) and superoxide dismutase(SOD) in liver tissues were detected by assay kits. The levels of interleukin-6(IL-6) and tumor necrosis factor-α(TNF-α) were detected by ELISA. The activation of macrophages was observed by immunofluorescence staining and protein expression of CYP2 E1, Toll-like receptor 4(TLR4), NF-κB p65, and phosphorylated NF-κB p65(p-NF-κB p65) were analyzed by Western blot. The ALD model was properly induced. Compared with the model group, the PCP groups significantly improved the pathological injury of liver tissues. Immunofluorescence staining revealed that compared with the model group, the groups with drug intervention showed decreased macrophages in liver tissues. Additionally, the PCP groups showed reduced ALT, AST, MDA, IL-6, and TNF-α(P<0.05), and potentiated activity of SOD(P<0.01). PCP extract has the protective effect against alcoholic liver injury in mice, and the underlying mechanism may be related to the regulation of the expression of CYP2 E1 and inhibition of TLR4/NF-κB inflammatory signaling pathway to reduce oxidative stress and inflammatory injury, thereby inhibiting the development of ALD.
Animals ; Cytochrome P-450 CYP2E1/pharmacology* ; Liver ; Liver Diseases, Alcoholic/pathology* ; Male ; Mice ; NF-kappa B/metabolism* ; Plant Extracts/pharmacology* ; Polysaccharides/pharmacology* ; Wolfiporia

Diabetic macular edema(DME)has become the leading cause of vision loss in patients with diabetes. Currently, intravitreal injection of anti-vascular endothelial growth factor(VEGF)therapy is the first-line treatment for DME. However, the economic burden and related complications brought by frequent injections should not be ignored. Therefore, the drugs with longer-lasting effects and longer injection intervals must be explored. Brolucizumab is a single-chain antibody fragment(scFv)with a high affinity for VEGF. Compared with other available anti-VEGFs, it has the characteristics of smaller molecular weight, higher tissue permeability and durable therapeutic effect. Clinical studies and real-world evidences showed that Brolucizumab is non-inferior to aflibercept in improving visual acuity in patients with DME. And Brolucizumab is more effective in regressing intra-retinal fluid and reducing central foveal thickness(CSFT)with longer injection interval. At the same time, Brolucizumab has a low incidence of adverse events and favourable safety after intraocular injection. This article reviews the latest progress of Brolucizumab in the treatment of DME.

Diabetic macular edema(DME)is the main cause of vision loss in patients with diabetes. Hyperglycemia leads to disruption of the blood-retinal barrier by triggering a pro-inflammatory and pro-angiogenic cascade, leading to intraretinal or subretinal fluid accumulation in the macula. Intravitreal administration of steroids represents an alternative for DME, while injection-related complications include endophthalmitis, vitreous hemorrhage, and retinal detachment. In order to reduce the risks and complications, dexamethasone intravitreal implant(DEX implant; Ozurdex®)were developed. DEX implant is a novel, artificially degradable sustained-release implant, with the advantages of reasonable release profile, strong anti-inflammatory, rapid improvement of macular edema, good bioavailability and safety. DEX implant provides a new choice for the treatment of patients with DME and has been recommended by several guidelines. This article reviews the latest research progress of DEX implant in the clinical treatment of DME.

PURPOSE: Posttraumatic stress disorder (PTSD) is a significant global mental health concern, especially in the military. This study aims to estimate the efficacy of mindfulness meditation in the treatment of military-related PTSD, by synthesizing evidences from randomized controlled trials. METHODS: Five electronic databases (Pubmed, EBSCO Medline, Embase, PsychINFO and Cochrane Library) were searched for randomized controlled trials focusing on the treatment effect of mindfulness meditation on military-related PTSD. The selection of eligible studies was based on identical inclusion and exclusion criteria. Information about study characteristics, participant characteristics, intervention details, PTSD outcomes, as well as potential adverse effects was extracted from the included studies. Risk of bias of all the included studies was critically assessed using the Cochrane Collaboration's tool. R Statistical software was performed for data analysis. RESULTS: A total of 1902 records were initially identified and screened. After duplicates removal and title & abstract review, finally, 19 articles in English language with 1326 participants were included through strict inclusion and exclusion criteria. The results revealed that mindfulness meditation had a significantly larger effect on alleviating military-related PTSD symptoms compared with control conditions, such as treatment as usual, present-centered group therapy and PTSD health education (standardized mean difference (SMD) = -0.33; 95% CI [-0.45, -0.21]; p < 0.0001). Mindfulness interventions with different control conditions (active or non-active control, SMD = -0.33, 95% CI [-0.46, -0.19]; SMD = -0.49, 95% CI [-0.88, -0.10], respectively), formats of delivery (group-based or individual-based, SMD = -0.30, 95% CI [-0.42, -0.17], SMD = -0.49, 95% CI [-0.90, -0.08], respectively) and intervention durations (short-term or standard duration, SMD = -0.27, 95% CI [-0.46, -0.08], SMD = -0.40, 95% CI [-0.58, -0.21], respectively) were equally effective in improving military-related PTSD symptoms. CONCLUSION Findings from this meta-analysis consolidate the efficacy and feasibility of mindfulness meditation in the treatment of military-related PTSD. Further evidence with higher quality and more rigorous design is needed in the future.

Although there is guidance from different regulatory agencies, there are opportunities to bring greater consistency and stronger applicability to address the practical issues of establishing and operating a data monitoring committee (DMC) for clinical studies of Chinese medicine. We names it as a Chinese Medicine Data Monitoring Committee (CMDMC). A panel composed of clinical and statistical experts shared their experience and thoughts on the important aspects of CMDMCs. Subsequently, a community standard on CMDMCs (T/CACM 1323-2019) was issued by the China Association of Chinese Medicine on September 12, 2019. This paper summarizes the key content of this standard to help the sponsors of clinical studies establish and operate CMDMCs, which will further develop the scientific integrity and quality of clinical studies.

OBJECTIVE: To observe the clinical effect of high suspension and low incision (HSLI) surgery on mixed haemorrhoids, compared with Milligan-Morgan haemorrhoidectomy. METHODS: A multi-centre, randomized, single-blind, non-inferiority clinical trial was performed. Participants with mixed haemorrhoids from Xiyuan Hospital of China Academy of Chinese Medical Sciences, Beijing Rectum Hospital, Air Force Medical Center of People's Liberation Army of China, and Puyang Hospital of Traditional Chinese Medicine were enrolled from September 2016 to March 2018. By using a blocked randomization scheme, participants were assigned to two groups. The experimental group was treated with HSLI, while the control group was treated with Milligan-Morgan haemorrhoidectomy. The primary outcome was the clinical effect evaluated at 12 weeks after operation. The secondary outcomes included the number of haemorrhoids treated during the operation, pain scores, use of analgesics, postoperative oedema, wound healing, incidence of anal stenosis, anorectal manometry after operation, as well as surgical duration, length of stay and total hospitalization expenses. A safety evaluation was also conducted. RESULTS: In total, 246 eligible participants were enrolled, with 123 cases in each group. There was no significant difference in the clinical effect between the two groups (100.00% vs. 99.19%, P>0.05). Compared with the control group, the number of external haemorrhoids treated during the operation and the pain scores after operation were significantly reduced in the experimental group (P<0.05 or P<0.01); the patient number with wound healing at 2 weeks after operation and the functional length of anal canal at 12 weeks after operation were significantly increased in the experimental group (P<0.05). There was no significant difference in the incidence of anal stenosis, the numbers of patients using analgesics and patients with postoperative oedema between the two groups after operation (P>0.05). The surgical duration and length of stay in the experimental group were significantly longer than those in the control group, and the total hospitalization expense was significantly higher than that in the control group (all P<0.05). No adverse events were reported in either group during the whole trial or follow-up period. CONCLUSION HSLI had the advantages of preserving the skin of anal canal completely, alleviating postsurgical pain and promoting rapid recovery after operation. (Registration No. ChiCTR1900022883).