Objective:To investigate the ultra-long-term antihypertensive efficacy, safety, major adverse events, and survival benefits of renal denervation (RDN) in patients with resistant hypertension (rHTN) and mild chronic kidney disease (CKD).Methods:This real-world, single-center retrospective study enrolled patients with rHTN and mild CKD who underwent RDN at Tianjin First Central Hospital between October 2011 and June 2016. Office blood pressure, home self-measured blood pressure, 24-hour ambulatory blood pressure, serum creatinine, estimated glomerular filtration rate, and urine albumin-to-creatinine ratio were collected at baseline and at 1, 5, and 13 years post-RDN. The total daily defined dose of antihypertensive medications at 13 years post-RDN was recorded, along with endpoint events during follow-up, including cardiovascular death, all-cause death, hospitalization for heart failure, myocardial infarction, and stroke. Patients were stratified according to CKD stage (G1-G2 vs. G3a) and baseline systolic blood pressure (mild-to-moderate vs. severe hypertension), and follow-up data were compared across subgroups.Results:A total of 40 patients were included, aged (51±15) years, including 26 (65%) males. At the 13-year follow-up, office systolic blood pressure (SBP) and diastolic blood pressure (DBP) decreased by (-32±20) mmHg and (-15±14) mmHg (1 mmHg=0.133 kPa), respectively; reductions in home self-measured blood pressure (SBP: (-25±14) mmHg, DBP: (-10±11) mmHg) and 24-hour ambulatory blood pressure (SBP: (-16±9 mmHg, DBP: (-10±6) mmHg) were also observed, alongside a reduction in the total daily defined dose of antihypertensive medications by (1.1±0.9) compared to baseline. Renal function assessments showed no significant differences at 13 years versus baseline in serum creatinine ((105±51) μmol/L vs. (96±22) μmol/L), estimated glomerular filtration rate ((72±22) ml·min -1·1.73 m -2 vs. (78±17) ml·min -1·1.73 m -2), or urine albumin-to-creatinine ratio ((101±86) mg/g vs. (127±82) mg/g) (all P>0.05). All-cause and cardiovascular mortality rates during follow-up were 13% (5/40) and 8% (3/40), respectively. Subgroup analysis results showed that, although CKD G1-G2 patients had smaller reductions in office SBP ((-31±20) mmHg vs. (-34±19) mmHg) and DBP ((-13±10) mmHg vs. (-25±18) mmHg) compared to G3a patients at 13 years, intergroup differences were not significant (all P>0.05). In contrast, severe hypertension subgroup exhibited greater reductions in office SBP ((-55±13) mmHg vs. (-20±10) mmHg) and DBP ((-24±17) mmHg vs. (-13±10) mmHg) versus mild-to-moderate hypertension subgroup (all P<0.05). Conclusion:RDN demonstrates sustained antihypertensive efficacy with favorable renal safety in rHTN patients with mild CKD. Patients with higher baseline systolic blood pressure may exhibit better responsiveness to RDN.

Objective:To investigate the ultra-long-term antihypertensive efficacy, safety, major adverse events, and survival benefits of renal denervation (RDN) in patients with resistant hypertension (rHTN) and mild chronic kidney disease (CKD).Methods:This real-world, single-center retrospective study enrolled patients with rHTN and mild CKD who underwent RDN at Tianjin First Central Hospital between October 2011 and June 2016. Office blood pressure, home self-measured blood pressure, 24-hour ambulatory blood pressure, serum creatinine, estimated glomerular filtration rate, and urine albumin-to-creatinine ratio were collected at baseline and at 1, 5, and 13 years post-RDN. The total daily defined dose of antihypertensive medications at 13 years post-RDN was recorded, along with endpoint events during follow-up, including cardiovascular death, all-cause death, hospitalization for heart failure, myocardial infarction, and stroke. Patients were stratified according to CKD stage (G1-G2 vs. G3a) and baseline systolic blood pressure (mild-to-moderate vs. severe hypertension), and follow-up data were compared across subgroups.Results:A total of 40 patients were included, aged (51±15) years, including 26 (65%) males. At the 13-year follow-up, office systolic blood pressure (SBP) and diastolic blood pressure (DBP) decreased by (-32±20) mmHg and (-15±14) mmHg (1 mmHg=0.133 kPa), respectively; reductions in home self-measured blood pressure (SBP: (-25±14) mmHg, DBP: (-10±11) mmHg) and 24-hour ambulatory blood pressure (SBP: (-16±9 mmHg, DBP: (-10±6) mmHg) were also observed, alongside a reduction in the total daily defined dose of antihypertensive medications by (1.1±0.9) compared to baseline. Renal function assessments showed no significant differences at 13 years versus baseline in serum creatinine ((105±51) μmol/L vs. (96±22) μmol/L), estimated glomerular filtration rate ((72±22) ml·min -1·1.73 m -2 vs. (78±17) ml·min -1·1.73 m -2), or urine albumin-to-creatinine ratio ((101±86) mg/g vs. (127±82) mg/g) (all P>0.05). All-cause and cardiovascular mortality rates during follow-up were 13% (5/40) and 8% (3/40), respectively. Subgroup analysis results showed that, although CKD G1-G2 patients had smaller reductions in office SBP ((-31±20) mmHg vs. (-34±19) mmHg) and DBP ((-13±10) mmHg vs. (-25±18) mmHg) compared to G3a patients at 13 years, intergroup differences were not significant (all P>0.05). In contrast, severe hypertension subgroup exhibited greater reductions in office SBP ((-55±13) mmHg vs. (-20±10) mmHg) and DBP ((-24±17) mmHg vs. (-13±10) mmHg) versus mild-to-moderate hypertension subgroup (all P<0.05). Conclusion:RDN demonstrates sustained antihypertensive efficacy with favorable renal safety in rHTN patients with mild CKD. Patients with higher baseline systolic blood pressure may exhibit better responsiveness to RDN.

The polyfoliate perforator flap is a new type of flap that was developed on the basis of the traditional polyfoliate myocutaneous flap, polyfoliate fascial flap and perforator flap. It overturns the traditional idea that the deep fascial vascular network is the fundamental for a survival of the flap, and enables the flaps to achieve the best profile and function of the recipient areas with minimal damage to the donor area. In order to improve the understanding of the polyfoliate perforator flap and further standardise its clinical application, this paper forms a consensus on the definition, classification, indications, operative points and precautions of the polyfoliate perforator flap, so as to provide references in diagnosis and treatment process and practical application for the surgeons.

The polyfoliate perforator flap is a new type of flap that was developed on the basis of the traditional polyfoliate myocutaneous flap, polyfoliate fascial flap and perforator flap. It overturns the traditional idea that the deep fascial vascular network is the fundamental for a survival of the flap, and enables the flaps to achieve the best profile and function of the recipient areas with minimal damage to the donor area. In order to improve the understanding of the polyfoliate perforator flap and further standardise its clinical application, this paper forms a consensus on the definition, classification, indications, operative points and precautions of the polyfoliate perforator flap, so as to provide references in diagnosis and treatment process and practical application for the surgeons.

Protein self-assemblies at the micro- and nano-scale are of great interest because of their morphological diversity and good biocompatibility. High-throughput screening of protein self-assembly at different scales and morphologies using protein crystallization screening conditions is an emerging method. When using this method to screen protein self-assembly conditions, some apparently transparent droplets are often observed, in which it is not clear whether self-assembly occurs. We explored the interaction between β-lactoglobulin and the protein crystallization kit Index™ C10 and observed the presence of micro- and nano-scale protein self-assemblies in the transparent droplets. The diverse morphology of the micro- and nano-scale self-assemblies in the transparent droplets formed by mixing different initial concentrations of β-lactoglobulin and Index™ C10 was further investigated by scanning electron microscope. Self-assembly process of fluorescence-labelled β-lactoglobulin was monitored continuously by laser confocal microscope, allowing real-time observation of the liquid-liquid phase separation phenomenon and the morphology of the final self-assemblies. The internal structure of the self-assemblies was gradually ordered over time by in-situ X-ray diffraction. This indicates that the self-assembly phenomenon within transparent droplets, observed in protein self-assembly condition screening experiments, is worthy of further in-depth exploration.
Crystallization ; Lactoglobulins

Clinical studies have validated low-level viremia is associated with a variety of adverse outcomes in patients with chronic hepatitis B during the course of receiving nucleos(t)ide analogue antiviral therapy. With the advancement of PCR technology, the high sensitivity PCR detection of HBV DNA can reach the lower limit of detection of < 5-10 IU/mL. The standard criterion for judging among patients who have achieved complete virological response is HBV DNA levels < 20 IU/ml. The use of highly sensitive PCR tests can detect very low-level viremia (HBV DNA < 20 IU/ml, but > 5-10 IU/mL) in some patients. However, there are currently fewer relevant studies, and more research data needs to be accumulated to answer this clinical question of whether long-term very low-level viremia affects the clinical outcome of patients with chronic hepatitis B.

OBJECTIVETo investigate the effect of reverse saphenous nerve neurocutaneous flaps for skin defects of forefoot.

METHODSIn the anatomic study, 50 cadaveric feet were injected with red latex and the anastomosis, distribution and external diameters of medialtarsal artery, medial anterior malleolus artery, medial plantar artery, the superficial branch of the medial basal hallucal artery and saphenousnerve nutritional vessels were observed. Based on anatomic research results, we designed the reverse saphenous nerve neurocutaneous flaps for repairing skin defects of forefoot.

RESULTSThe blood supply of reverse saphenous nerve neurocutaneous flaps were based on the vasoganglion, which consist of arterial arch at the superior border of abductor hallucis and arterial network on the surface of abductor hallucis around the saphenous nerve and medial pedis flap. From Oct. 2006 to Oct. 2011, the reverse saphenous nerve neurocutaneous flaps were used to repair skin defects of forefoot in 11 cases. The flap size ranged from 2.5 cm x 3.5 cm to 7.5 cm x 8.5 cm. The wounds at donor site were covered with full-thickness skin graft. All flaps survived completely with no ulcer at the donor site. 11 cases were followed up for 6 to 18 months( mean, 10 months). The skin color and texture were satisfactory. The patients could walk very well.

CONCLUSIONSIt is reliable to repair the skin defects of forefoot with reverse saphenous nerve neurocutaneous flaps. It is easily performed with less morbidity. This flap should be considered as a preferential way to reconstruct skin defects of forefoot.

Arteries ; anatomy & histology ; Cadaver ; Female ; Foot ; blood supply ; innervation ; Forefoot, Human ; injuries ; surgery ; Humans ; Male ; Muscle, Skeletal ; anatomy & histology ; Reconstructive Surgical Procedures ; Skin Transplantation ; methods ; Surgical Flaps ; blood supply ; innervation ; Transplant Donor Site ; surgery

BACKGROUNDLowering intraocular pressure (IOP) is currently the only therapeutic approach in primary open-angle glaucoma. and the fixed-combination medications are needed to achieve sufficiently low target IOP. A multicenter prospective study in the Chinese population was needed to confirm the safety and efficacy of Bimatoprost/Timolol Fixed Combination Eye Drop in China. In this study, we evaluated the safety and efficacy of Bimatoprost/Timolol Fixed Combination with concurrent administration of its components in Chinese patients with open-angle glaucoma or ocular hypertension.

METHODSIn this multicenter, randomized, double-masked, parallel controlled study, patients with open-angle glaucoma or ocular hypertension who were insufficiently responsive to monotherapy with either topical β-blockers or prostaglandin analogues were randomized to one of two active treatment groups in a 1:1 ratio at 11 Chinese ophthalmic departments. Bimatoprost/timolol fixed combination treatment was a fixed combination of 0.03% bimatoprost and 0.5% timolol (followed by vehicle for masking) once daily at 19:00 P.M. and concurrent treatment was 0.03% bimatoprost followed by 0.5% timolol once daily at 19:00 P.M. The primary efficacy variable was change from baseline in mean diurnal intraocular pressure (IOP) at week 4 visit in the intent-to-treat (ITT) population. Primary analysis evaluated the non-inferiority of bimatoprost/ timolol fixed combination to concurrent with respect to the primary variable using a confidence interval (CI) approach. Bimatoprost/timolol fixed combination was to be considered non-inferior to concurrent if the upper limit of the 95% CI for the between-treatment (bimatoprost/timolol fixed combination minus concurrent) difference was ≤ 1.5 mmHg. Adverse events were collected and slit-lamp examinations were performed to assess safety. Between-group comparisons of the incidence of adverse events were performed using the Pearson chi-square test or Fisher's exact test.

RESULTSOf the enrolled 235 patients, 121 patients were randomized to receive bimatoprost/timolol fixed combination and, 114 patients were randomized to receive concurrent treatment. At baseline the mean value of mean diurnal IOP was (25.20 ± 3.06) mmHg in the bimatoprost/timolol fixed combination group and (24.87 ± 3.88) mmHg in the concurrent group. The difference between the treatment groups was not statistically significant. The mean change from baseline in mean diurnal IOP (± standard deviation) in the bimatoprost/timolol fixed combination group was (-9.38 ± 4.66) mmHg and it was (-8.93 ± 4.25) mmHg in the concurrent group (P < 0.01). The difference between the two treatment groups (bimatoprost/timolol fixed combination minus concurrent) in the change from baseline of mean diurnal IOP was -0.556 mmHg (95% CI: -1.68, 0.57, P = 0.330). The upper limit of the 95% CI was less than 1.5 mmHg, the predefined margin of non-inferiority. Adverse events occurred in 26.4% (32/121) of the bimatoprost/timolol fixed combination patients and 30.7% (35/114) of the concurrent patients. The most frequent adverse event was conjunctival hyperemia, which was reported as treatment related in 16.5% (20/121) in the bimatoprost/timolol fixed combination group and 18.4% (21/114) in the concurrent group (P > 0.05).

CONCLUSIONSBimatoprost/Timolol Fixed Combination administered in Chinese patients with open-angle glaucoma or ocular hypertension was not inferior to concurrent dosing with the individual components. Safety profiles were similar between the treatment groups.

Adolescent ; Adult ; Aged ; Amides ; administration & dosage ; adverse effects ; therapeutic use ; Bimatoprost ; Cloprostenol ; administration & dosage ; adverse effects ; analogs & derivatives ; therapeutic use ; Female ; Glaucoma, Open-Angle ; drug therapy ; Humans ; Male ; Middle Aged ; Ocular Hypertension ; drug therapy ; Timolol ; administration & dosage ; adverse effects ; therapeutic use ; Young Adult

Determination of protein 3-dimensional structure offers very important information in biology researches, especially for understanding protein functions and redundant drug design. The X-ray crystallography is still the main technique for protein structure determination. Obtaining protein crystals is an essential procedure after protein purification in this technique. However, there is only 42% of soluble purified proteins yield crystals by statistics. Experimental verification of protein crystallizability is relatively expensive and time-consuming. Thus it is desired to predict the protein crystallizability by a computational method before starting the experiment. In this paper, combined with our own efforts, some successful in silico methods to predict the protein crystallizability are reviewed.
Crystallization ; methods ; Crystallography, X-Ray ; Protein Structure, Tertiary ; Proteins ; chemistry

Objective To explore the methods of repairing great toe soft tissue defect with the reverse medial pedis island flap with transverse artery of great toe.Methods This study was made up of two parts:an anatomical study and clinical application.In the anatomical study,49 cadaveric feet were injected with red latex and then anostomosis,distribution and external diameters of transverse artery of great toe,the deep branches of the first plantar metatarsal arteries and the deep branches of medial plantar artery were observed.From September 2006 to December 2012,8 cases of soft-tissue defects with the retrograde-flow medial pedis island flaps were harvested to cover the soft tissue defects of great toe.Soft tissue defect was form 2.5 cm × 3.5 cm-3.5 × 4.5 cm.Results There was an arterial circle under the first metatarsophalangeal joint which consisted of transverse artery of great toe,tibial proper plantar digital artery of great toe,fibular proper plantar digital artery of great toe and the distal part of first plantar metatarsal artery.This arterial circle under the first metatarsophalangeal joint and arterial network on the surface of abductor hallucis was responsible for the blood supply of the flap of medial pedis.The diameter of the pedicle was great,and the length of the pedicle was longer than in previous reported.In terms of clinical application,all patients were followed up with the mean of 10 months (range fromn 6-24 months).All flaps survived totally without diabrosis and swelling.The walking and weight-bearing were normal and the blood supply of foot was good.Conclusion Using of arterial circle under the first metatarsophalangeal joint,the medial pedis island flap has a reliable retrograde blood supply.The reverse point of the reverse medial pedis flap moved forward to th interphalangeal joint.This flap should be considered as a preferential way to reconstruct soft-tissue defects of the great toe.