Rhegmatogenous retinal detachment(RRD)is a common blinding ophthalmic disease that has always received significant attention in clinical treatment. The foldable capsular buckle(FCB), as a new method for extraocular treatment of RRD, offers“Five Noes” advantages over traditional treatments such as scleral buckling(SB), pars plana vitrectomy(PPV), and pneumatic retinopexy(PR), including no retrobulbar anesthesia, no muscle traction, no scleral fluid release, no intraoperative positioning, and no cryotherapy. This effectively reduces postoperative complications in RRD patients and shortens the operation time. This review aims to investigate the development process and treatment principle of FCB, and focus on its therapeutic advantages, indication selection, efficacy and safety for RRD. It is expected to play a more important role in the treatment of a variety of retinal diseases through technological innovation and application field expansion.

Objective To analyze the detrimental effects of exposure to environmental noise alone and combined with carbon monoxide(CO)on spermatogenesis in male rats,investigate the underlying mechanisms involved in such damage,and evaluate the protective role of pterostilbene(PTE)against these adverse effects.Methods Sixty male SD rats(6～8 weeks old,weighing 200±10 g)were randomly divided normal control group(standard housing),sham-exposure control group(restraint stress only),noise exposure(85 dB),CO exposure(460 mg/m3),combined exposure(simultaneous exposure),and PTE intervention(80 mg/kg pretreatment),with 10 animals in each group.The rats were exposed daily for 2 h via a nose-only inhalation exposure system within a multifactorial environmental simulation chamber for 60 consecutive days.Sperm count and viability were measured after exposure.Histopathological changes of testicular tissues were observed with HE staining.qRT-PCR was used to measure stage-specific mRNA levels in germ cells.Serum sex hormone levels and adenosine triphosphate(ATP)concentrations in testes and sperm were detected.Transmission electron microscopy(TEM)was applied to observe the ultrastructural damage in the spermatocytes.Additionally,transcriptome sequencing was performed on testicular tissue,followed by bioinformatics analysis.Results Compared with the negative control group,the combined exposure group exhibited significant reductions in sperm viability and count(P<0.05),and developmental arrest of immature germ cells in the testicular tissue,with obviously less spermatogonia,spermatocytes,and round/elongated spermatids(P<0.01).Additionally,significantly reduced levels of reproductive-related hormones,such as gonadotropin-releasing hormone,follicle-stimulating hormone,luteinizing hormone and testosterone,and ATP levels in testes and sperm were observed in the mice after combined exposure(P<0.01),accompanied by mitochondrial rupture and cristae disruption in spermatocytes.Conversely,the PTE intervention group showed marked alleviation of these impairments,with parameters recovering almost to normal levels.Transcriptome sequencing identified biological processes related to reproductive development and ATP-dependent pathways as potential contributors to testicular injury induced by noise and CO exposure,with key genes including Nppa,Adm,Gnrh1,Ptafr,Atp13a5,Atp8b1,and LOC102555469.Conclusion Noise and CO exposure induce spermatogenic damage in rats,which may be related with energy metabolism and hormonal regulation,while PTE demonstrates significant protective effects against such reproductive impairments.

Objective:Based on the specific cleavage and non-specific "trans-cleavage" activities of the clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated protein(CRISPR/Cas13), we established a visually amplification-free rapid detection technique of 2019-nCoV nucleic acid. This technique is easily processed with a low detection limit and good specificity.Methods:According to the 2019-nCoV gene sequence, specific CRISPR RNAs were screened and designed by bioinformatics analysis, and then synthesized as universal signal-strained RNA transcription targets in vitro to establish and optimize the reaction system. Moreover, the 2019-nCoV pseudoviral nucleic acid was used as a standard substance to evaluate the detection limit. A total of 65 positive samples were collected from various 2019-nCoV variants, while 48 negative samples included other clinically common respiratory pathogens, such as influenza A virus, influenza B virus, human parainfluenza virus, Klebsiella pneumonia, etc. All samples were tested by quantitative PCR (qPCR), digital PCR, and the method established in this study. The sensitivity and specificity of the newly established method were analyzed and evaluated. Results:With the newly established technique, the detection time for 2019-nCoV nucleic acid could be minimized to 6 minutes. In addition, the detection limit was 14 copies/μl when assisted by the displaying instrument, whereas it increased to 28 copies/μl with the naked eye. This technique had a sensitivity and specificity of 98.5% (66/67) and 100% (46/46) respectively, showing no statistically significant difference compared to the gold standard qPCR( P=1). Conclusions:This study has successfully established a CRISPR/Cas13a-based visually rapid detection technique for 2019-nCoV nucleic acid. This technique offers the advantages of a simple process, convenient operation, low environmental operating requirements, a detection limit close to qPCR, and a strong potential for on-site testing applications.

BACKGROUND: Intensive systolic blood pressure (SBP) control improved outcomes in the Strategy of Blood Pressure Intervention in the Elderly Hypertensive Patients (STEP) trial. Whether baseline serum lipid parameters influence the benefits of intensive SBP control is unclear. METHODS: The STEP trial was a randomized controlled trial that compared the effects of intensive (SBP target of 110 to <130 mmHg) and standard (SBP target of 130 to <150 mmHg) SBP control in Chinese patients aged 60 to 80 years with hypertension. The primary outcome was a composite of cardiovascular disease events. A total of 8283 participants from the STEP study were included in this post hoc analysis to examine whether the effects of the SBP intervention differed by baseline low-density lipoprotein cholesterol (LDL-C) and non-high-density lipoprotein cholesterol (non-HDL-C) concentrations. RESULTS: Regardless of the randomized SBP intervention, baseline LDL-C and non-HDL-C concentrations had a J-shaped association with the hazard of the primary outcome. However, the effects of the intensive SBP intervention on the primary outcome were not influenced by baseline LDL-C level ( P for interaction = 0.80) and non-HDL-C level ( P for interaction = 0.95). Adjusted subgroup analysis using tertiles in LDL-C1 (hazard ratio [HR], 0.77; 95% confidence interval [CI], 0.52-1.13; P = 0.18), LDL-C2 (HR, 0.81; 95% CI, 0.55-1.20; P = 0.29), and LDL-C3 (HR, 0.68; 95% CI, 0.47-0.98; P = 0.04) was provided, with an interaction P value of 0.49. Similar results were showed in non-HDL-C1 (HR, 0.87; 95% CI, 0.59-1.29; P = 0.49), non-HDL-C2 (HR, 0.70; 95% CI, 0.48-1.04; P = 0.08), and non-HDL-C3 (HR, 0.67; 95% CI, 0.47-0.95; P = 0.03), with an interaction P -value of 0.47. CONCLUSION: High baseline serum LDL-C and non-HDL-C concentrations were associated with increased risk of primary cardiovascular disease outcome, but there was no evidence that the benefit of the intensive SBP control differed by baseline LDL-C and non-HDL-C concentrations. CLINICAL TRIAL REGISTRATION ClinicalTrials.gov, NCT03015311.
Aged ; Humans ; Cardiovascular Diseases ; Blood Pressure/physiology* ; Cholesterol, LDL ; Hypertension ; Cholesterol ; Risk Factors

Objective:To explore the effect of Internet + technical liaison service mode on the postoperative continuing nursing of elderly patients with osteoporotic hip fractures.Methods:A total of 92 elderly patients with osteoporotic hip fractures who were admitted into in Orthopaedics Department of the First Affiliated Hospital of Soochow University from July 2018 to December 2019 were selected, and randomly divided into intervention group and control group by random number table method, with 46 cases in each group. The control group was given routine follow-up outside hospital, while the intervention group was given the continuing nursing led by the orthopedic specialist nurses based on the Internet + Technology home orthopedic care platform. All patients were followed up to 6 months after operation, and the differences of Harris Hip Score (Harris), Numeric Rating Scales (NRS), Barthel Index, Short Form 36-item Health Survey (SF-36) between the two groups were compared.Results:The Harris scores were 49.74 ± 4.28, 76.59 ± 4.33 and 90.78 ± 2.61 in the intervention group, and 46.17 ± 3.85, 74.26 ± 4.24 and 88.65 ± 2.17 in the control group in 1, 3 and 6 months after operation, respectively. The differences were statistically significant ( t=-4.20, -2.60, -4.26, all P<0.05). The NRS scores in the intervention group were 1.33 ± 0.47, 0.83 ± 0.38 and 0.76±0.43 in 1, 3 and 6 months after operation respectively, while the NRS scores in the control group were 1.61 ± 0.54, 0.96 ± 0.42 and 0.84 ± 0.38, respectively. The difference in pain scores between the two groups was statistically significant only at 1 month after operation ( t=2.68, P<0.05). The Barthel Index in the intervention group were 61.74 ± 8.90, 93.80 ± 5.29 and 98.26 ± 2.83 in 1, 3 and 6 months after operation respectively, while those of the control group were 60.33 ± 5.81, 91.09 ± 7.52 and 97.83 ± 3.10, respectively. The difference in Barthel Index between the two groups was statistically significant only in 3 months after operation ( t=-2.00, P<0.05). The scores of SF-36 in the intervention group were 93.73 ± 3.89, 100.26 ± 3.77 and 107.50 ± 3.56 at 1, 3 and 6 months after operation respectively, while those of the control group were 92.67±3.42, 97.71±2.67 and 103.68±2.83, respectively. The difference in SF-36 scores between the two groups was statistically significant only at 3 and 6 months after operation ( t=-3.74, -5.71, P<0.05). Conclusions:The continuing nursing based on multi-disciplinary team cooperation in hospital + Internet + Technology home orthopaedic nursing platform led by orthopaedic specialist nurses can improve joint function, relieve pain and improve quality of life of elderly patients with osteoporotic hip fractures after operation.

SIRT6 belongs to the conserved NAD⁺-dependent deacetylase superfamily and mediates multiple biological and pathological processes. Targeting SIRT6 by allosteric modulators represents a novel direction for therapeutics, which can overcome the selectivity problem caused by the structural similarity of orthosteric sites among deacetylases. Here, developing a reversed allosteric strategy AlloReverse, we identified a cryptic allosteric site, Pocket Z, which was only induced by the bi-directional allosteric signal triggered upon orthosteric binding of NAD⁺. Based on Pocket Z, we discovered an SIRT6 allosteric inhibitor named JYQ-42. JYQ-42 selectively targets SIRT6 among other histone deacetylases and effectively inhibits SIRT6 deacetylation, with an IC₅₀ of 2.33 μmol/L. JYQ-42 significantly suppresses SIRT6-mediated cancer cell migration and pro-inflammatory cytokine production. JYQ-42, to our knowledge, is the most potent and selective allosteric SIRT6 inhibitor. This study provides a novel strategy for allosteric drug design and will help in the challenging development of therapeutic agents that can selectively bind SIRT6.

Objective · To design and synthesize a series of benzenesulfonamide derivatives, test their inhibitory activity to CDK2-cyclinA2 kinase, and investigate the structure-activity relationship. Methods · Virtual screening was executed via computer-aided drug design according to the ATP binding site in CDK2-cyclinA2 protein crystal. A series of benzenesulfonamide derivatives were designed and synthesized on the basis of the interaction modes between the lead compound and the CDK2-cyclinA2. The biological evaluation of compounds was made through the CDK2-cyclinA2 in-vitro kinase activity detection system. Results · Twenty-nine new benzenesulfonamide compounds were prepared, and their inhibitory activity to CDK2-cyclinA2 was elicited. WZ-026 had the highest inhibitory parameter, which half maximal inhibitory concentration (IC50) was 3.81 μmol/L. Conclusion · By multipurpose utilization of virtual screening, chemical synthesis, and biological activity test, a benzenesulfonamide compound WZ-026 was found, which has great inhibitory activity towards CDK2-cyclinA2. Preliminary structure-activity relationship of compounds was obtained.

Molecular imprinting technique is a novel technology for preparing polymers with specific binding properties tosome specific molecules, and received widely attention in recent years.The article that was reviewed the applications of microcalorimetry in the molecular imprinting technique.The basic principle of microcalorimetry,characteristics and its advanced applications on evaluating imprinting effects of the molecularly imprinted polymers, screening of the monomers and the cross-linking agents, optimizing reaction conditions etc.were introduced.

Objective To observe the long-term relationship between body mass index (BMI) and cardiovascular events in male elderly hypertensive patients.Methods A total of 839 male elderly (＞ 65 years old) hypertensive patients were included in this prospective study.Baseline data were obtained on January 2004 and participants were followed up yearly till January 2014.Patients were divided into 3 groups according to their BMI:normal weight group (18.5 kg/m2 ≤BMI ＜24.0 kg/m2),overweight group (24.0 kg/m2 ≤ BMI ＜ 28.0 kg/m2),obese group (BMI ≥ 28.0 kg/m2).All-cause death and cardiovascular events were compared.Results The average age of all 839 hypertension men was (75.4 ± 4.8) years at baseline.Baseline systolic blood pressure was (133.7 ± 14.6) mmHg(1 mmHg =0.133 kPa),diastolic blood pressure was (74.3 ± 9.3) mmHg.Baseline systolic and diastolic blood pressure was similar among the three groups.All 839 patients completed follow-up.There were 178 all-cause deaths,54 cardiovascular deaths,51 new/recurrent myocardial infarctions and 105 new/recurrent strokes during follow up.Incidence of all-cause mortality in overweight group (16.74％,72/430) was significantly lower than in normal weight group (27.01％ (74/274),P ＜ 0.05).Kaplan-Meier curves showed the all-cause mortality and cardiovascular mortality were higher in normal weight group than in the other two groups.According to the Cox proportional hazards regression model,the risk of all-cause mortality (RR =0.867,95％ CI:0.792-0.949) and cardiovascular death (RR =0.179,95 ％ CI:0.05-0.645) in patients with a BMI ≥ 24.0 kg/m2 were lower than in the group with BMI ＜ 24.0 kg/m2.Conclusion Obesity paradox phenomenon is observed in elderly male hypertensive patients in that higher BMI is associated with lower mortality risks in elderly male hypertensive patients during the 10 years follow-up.

Objective To examine the therapeutic effect of C Ⅱ TA inhibition in collagen-induced arthritis(CIA),using a delivery system tailored to target C ⅡTA gene by small interfering RNA (siRNA).Methods Mice with collagen-induced arthritis were injected intravenously with C Ⅱ TA siRNA.The clinical score was monitored for up to 4 weeks after treatment.The severity of inflammation of mouse joint was evaluated by histological examination.Real-time PCR was used to determine the cytokine mRNA expression.Cytokine production was measured by ELISA from serum.T cell proliferation was examined by MTT method.Results IFN-γ and IL-17 were elevated in CIA mice,but were iuhibited significantly by C Ⅱ TA siRNA either prevention or intervention of autoimmune arthritis.Collagen specific T cell proliferation was significantly suppressed.Increased level of IL-4 by T cells was observed in C Ⅱ TA siRNA treated group compared with that of control group.Conclusion Our findings indicate that systemic RNAi-mediated C Ⅱ TA gene silencing is effective in the treatment of CIA and regulateds the balance of Th1/Th2 differentiation.