OBJECTIVES: To investigate the protective effect of Yiqi Yangyin Huazhuo Tongluo Formula (YYHT) against high glucose-induced injury in mouse renal podocytes (MPC5 cells) and the possible mechanism. METHODS: Adult Wistar rats were treated with 19, 38, and 76 g/kg YYHT or saline via gavage for 7 days to prepare YYHT-medicated or blank sera for treatment of MPC5 cells cultured in high glucose (30 mmol/L) prior to transfection with a miR-21a-5p inhibitor or a miR-21a-5p mimic. The changes in miR-21a-5p expressions and the mRNA levels of FoxO1, PINK1, and Parkin in the treated cells were detected with qRT-PCR, and the protein levels of nephrin, podocin, FoxO1, PINK1, and Parkin were detected with Western blotting. Autophagic activity in the cells were evaluated with MDC staining. The effect of miR-21a-5p mimic on FoxO1 transcription and the binding of miR-21a-5p to FoxO1 were examined with luciferase reporter gene assay and radioimmunoprecipitation assay. RESULTS: MPC5 cells exposed to high glucose showed significantly increased miR-21a-5p expression, lowered expressions of FoxO1, PINK1, and Parkin1 mRNAs, and reduced levels of FoxO1, PINK1, parkin, nephrin, and podocin proteins and autophagic activity. Treatment of the exposed cells with YYHT-medicated sera and miR-21a-5p inhibitor both significantly enhanced the protein expressions of nephrin and podocin, inhibited the expression of miR-21a-5p, increased the mRNA and protein expressions of FoxO1, PINK1 and Parkin, and upregulated autophagic activity of the cells. Transfection with miR-21a-5p mimic effectively inhibited the transcription of FoxO1 and promoted the binding of miR-21a-5p to FoxO1 in MPC5 cells, and these effects were obviously attenuated by treatment with YYHT-medicated sera. CONCLUSIONS YYHT-medicated sera alleviate high glucose-induced injury in MPC5 cells by regulating miR-21a-5p/FoxO1/PINK1-mediated mitochondrial autophagy.
Animals ; MicroRNAs/genetics* ; Podocytes/pathology* ; Drugs, Chinese Herbal/pharmacology* ; Autophagy/drug effects* ; Rats, Wistar ; Protein Kinases/metabolism* ; Rats ; Forkhead Box Protein O1 ; Mice ; Mitochondria/drug effects* ; Ubiquitin-Protein Ligases/metabolism* ; Glucose ; Diabetic Nephropathies ; Male ; Membrane Proteins/metabolism* ; Intracellular Signaling Peptides and Proteins

Peganum harmala L. (P. harmala) is a significant economic and medicinal plant. The seeds of P. harmala have been extensively utilized in traditional Chinese medicine, Uighur medicine, and Mongolian medicine, as documented in the Drug Standard of the Ministry of Health of China. Twelve novel tryptamine-derived alkaloids (1-12) and eight known compounds (13-20) were isolated from P. harmala seeds. Compounds 1 and 2 represent the first reported instances of tryptamine-derived heteromers, comprising tryptamine and aniline fragments with previously undocumented C-3-N-1' linkage and C-3-C-4' connection, respectively. Compounds 3-5 were identified as indole-quinazoline heteromers, exhibiting a novel C-3 and NH-1' linkage between indole and quinazoline-derived fragments. Compound 6 demonstrates the dimerization pattern of C-C linked tryptamine-quinazoline dimer. Compound 8 represents a tryptamine-derived heterodimer with a distinctive carbon skeleton, featuring an unusual spiro-tricyclic ring (7) and conventional bicyclic tryptamine. Compounds 9-11 constitute novel 6/5/5/5 spiro-tetracyclic tryptamine-derived alkaloids presenting a unique ring system of tryptamine-spiro-pyrrolizine. Compounds 1-3 and 6-11 were identified as racemates. Compounds 2, 7, 9, 10, and 12 were confirmed via X-ray crystallographic analysis. All isolated compounds (1-20) exhibited varying degrees of antiviral efficacy against respiratory syncytial virus (RSV). Notably, the anti-RSV activity of compound 12 (IC₅₀ 5.01 ± 0.14 μmol·L^-1) surpassed that of the positive control (ribavirin, IC₅₀ 6.23 ± 0.95 μmol·L^-1), as validated through plaque reduction and immunofluorescence assays. The identification of anti-RSV compounds from P. harmala seeds may enhance the development and application of this plant in antiviral therapeutic products.
Antiviral Agents/isolation & purification* ; Tryptamines/isolation & purification* ; Peganum/chemistry* ; Seeds/chemistry* ; Alkaloids/isolation & purification* ; Molecular Structure ; Humans ; Respiratory Syncytial Viruses/drug effects* ; Plant Extracts/pharmacology* ; Drugs, Chinese Herbal/pharmacology*

Immune checkpoint inhibitors(ICIs)have become the most widely used drugs in tumor immunotherapy, with ipilimumab and nivolumab as their representatives.However, the use of immune checkpoint inhibitors has brought about many immune-related adverse events, of which myocarditis is one of the most fatal adverse reactions.The pathogenesis of immune checkpoint inhibitor-associated myocarditis is not fully understood, mainly involving autoimmune T lymphocyte infiltration, regulatory T-cell dysfunction, cytokines, autoantibody production, genetic factors, the gut microbiome, etc.The treatment and management of immune checkpoint inhibitor-associated myocarditis require concerted efforts of multidisciplinary experts.

Objective:To observe the clinical characteristics and surgical outcomes in patients with retinal detachment associated with atopic dermatitis (AD-RD).Methods:A retrospective case series. From January 2015 to April 2023, 8 patients (12 eyes) with AD-RD at Zhongshan Ophthalmic Center of Sun Yat-sen University were included. All patients underwent best-corrected visual acuity (BCVA), ultra-wide-field fundus photography, B-mode ultrasound, ultrasound biomicroscopy (UBM), and wide-field optical coherence tomography (OCT). BCVA was examined by standard logarithmic visual acuity chart and was converted into logarithm of the minimum angle of resolution (logMAR) visual acuity for statistical purposes. In the primary surgery, 9 eyes underwent scleral buckling; 1 eye underwent pars plana vitrectomy (PPV) combined with silicone oil tamponade; 1 eye underwent PPV combined with C 3F 8 tamponade; 1 eye underwent C 3F 8 tamponade combined with retinal laser photocoagulation. The follow-up time was (29.1±40.9) months. BCVA before and after surgery was compared using paired t test. Results:Among the 8 patients, 6 were male and 2 were female. The mean age was (23.38±7.95) years old. Among them, 4 patients had bilateral affliction while the remaining 4 had unilateral involvement. The logMAR BCVA was 0.86±0.86. All 12 eyes were with a history of uveitis. Among 8 eyes with bilateral involvement, 6 of them were misdiagnosed as uveitis with exudative retinal detachment; 11 eyes had anterior uveitis at presentation; 9 eyes had a history of cataract, with 4 eyes having concurrent cataract and 5 eyes with intraocular lens. All affected eyes displayed as focal retinal detachment. UBM revealed ciliary epithelial detachment in 9 eyes, and no definite ciliary epithelial break was found in any case. Retinal breaks were observed in only 2 eyes in the pre-surgery retina examination, while ciliary epithelial holes were discovered in other 10 eyes during surgery. The retina was successfully reattached in 10 eyes after one surgery, including 9 eyes received scleral buckling. During the final follow-up, the logMAR BCVA of the affected eye improved significantly to 0.30±0.25 compared to pre-surgery values ( t=2.43, P=0.03). Conclusions:AD-RD is a challenging complication of AD with a high rate of young onset, bilateral involvement, associated with concurrent cataracts, and shallow temporal retinal detachment associated with ciliary epithelial detachment. Scleral buckling is an effective treatment for AD-RD.

OBJECTIVE: To study the anatomical characteristics of blood vessels in the lateral segment of the vertebral body through the surgical approach of oblique lumbar interbody fusion (OLIF) using MRI imaging, and evaluate its potential vascular safety zone. METHODS: The lumbar MRI data of 107 patients with low back and leg pain who met the selection criteria between October 2019 and November 2022 were retrospectively analyzed. The vascular emanation angles, vascular travel angles, and the length of vessels in the lateral segments of the left vertebral body of L ₁-L ₅, as well as the distance between the segmental vessels in different Moro junctions of the vertebral body and their distances from the edges of the vertebrae in the same sequence (bottom marked as I, top as S) were measured. The gap between the large abdominal vessels and the lateral vessels of the vertebral body was set as the lateral vascular safe zones of the lumbar spine, and the extent of the safe zones (namely the area between the vessels) was measured. The anterior 1/3 of the lumbar intervertebral disc was taken as the simulated puncture center, and the area with a diameter of 22 mm around it as the simulated channel area. The proportion of vessels in the channel was further counted. In addition, the proportions of segmental vessels at L ₅ without a clear travel and with an emanation angel less than 90° were calculated. RESULTS: Except for the differences in the vascular emanation angles between L ₄ and L ₅, the vascular travel angles between L ₁, L ₂ and L ₄, L ₅, and the length of vessels in the lateral segments of the vertebral body among L ₁-L ₄ were not significant ( P>0.05), the differences in the vascular emanation angles, vascular travel angles, and the length of vessels between the rest segments were all significant ( P<0.05). There was no significant difference in the distance between vessels of L ₁, L ₂ and L ₂, L ₃ at Moro Ⅰ-Ⅳ junctions ( P>0.05), in L ₃, L ₄ and L ₄, L ₅ at Ⅱ and Ⅲ junction ( P>0.05). There was no significant difference in the vascular distance of L ₂, L ₃ between Ⅱ, Ⅲ junction and Ⅲ, Ⅳ junction, and the vascular distance of L ₃, L ₄ between Ⅰ, Ⅱ junction and Ⅲ, Ⅳ junction ( P>0.05). The vascular distance of the other adjacent vertebral bodies was significant different between different Moro junctions ( P<0.05). Except that there was no significant difference in the distance between L ₂I and L ₃S at Ⅰ, Ⅱ junction, L ₃I and L ₄S at Ⅱ, Ⅲ junction, and L ₂I and L ₃S at Ⅲ, Ⅳ junction ( P>0.05), there was significant difference of the vascular distance between the bottom of one segment and the top of the next in the other segments ( P<0.05). Comparison between junctions: Except for the L ₃S between Ⅰ, Ⅱ junction and Ⅱ, Ⅲ junction, and L ₅S between Ⅰ, Ⅱ junction and Ⅱ, Ⅲ and Ⅲ, Ⅳ junctions had no significant difference ( P>0.05), there were significant differences in the distance between the other segmental vessels and the vertebral edge of the same sequence in different Moro junctions ( P<0.05). The overall proportion of vessels in the simulated channels was 40.19% (43/107), and the proportion of vessels in L ₁ (41.12%, 44/107) and L ₅ (18.69%, 20/107) was higher than that in the other segments. The proportion of vessels in the channel of Moro zone Ⅰ (46.73%, 50/107) and zone Ⅱ (32.71%, 35/107) was higher than that in the zone Ⅲ, while no segmental vessels in L ₁ and L ₂ were found in the channel of zone Ⅲ ( χ ²=74.950, P<0.001). Moreover, 26.17% (28/107) of the segmental vessels of lateral L ₅ showed no movement, and 27.10% (29/107) vascular emanation angles of lateral L ₅ were less than 90°. CONCLUSION L ₁ and L ₅ segmental vessels are most likely to be injured in Moro zones Ⅰ and Ⅱ, and the placement of OLIF channels in L _{4, 5} at Ⅲ, Ⅳ junction should be avoided. It is usually safe to place fixation pins at the vertebral body edge on the cephalic side of the intervertebral space, but it is safer to place them on the caudal side in L _{1, 2} (Ⅰ, Ⅱ junction), L _{3, 4} (Ⅲ, Ⅳ junction), and L _{4, 5} (Ⅱ, Ⅲ, Ⅳ junctions).
Humans ; Retrospective Studies ; Spinal Puncture ; Magnetic Resonance Imaging ; Anticoagulants ; Bone Nails

Objective:To observe and analyze the clinical features, treatment methods and efficacy of patients with retinopathy associated with incontinentia pigmenti (IP).Methods:A retrospective case study. Twelve clinical confirmed IP patients (24 eyes) in Zhongshan Ophthalmic Center of Sun Yat-sen University from January 2015 to December 2018 were included in this study. The best corrected visual acuity and intraocular pressure examination were performed in patients (>4 years old). All patients were examined on the anterior segment, vitreous body, and fundus under topical anesthesia or general anesthesia. Eight cases underwent genetic testing. Patients with active disease should be given anti-vascular endothelial growth factor (VEGF) drug treatment, retinal laser photocoagulation or vitrectomy, those without active disease should be observed. All patients were followed up for 1 to 3 months, with an average follow-up time of 18.7 months.Results:All patients were all female, with an average age of 6.3±9.8 years old at the first ophthalmology visit. According to the recommendations of the pediatrician, 3 cases were actively screened for ophthalmology (referrals), with an average age of 0.4±0.5 years (median age: 2 months). A total of 9 cases were not recommended for referrals (non-referrals), including 3 cases of ophthalmology who were diagnosed for the first time due to visual impairment, and 6 cases of undiagnosed IP before the ophthalmology visit, the average age of their first visit was 8.2±10.8 years (medium age: 3 years old). The age of the first visit for non-referred patients was larger than that of referrals, and the difference was statistically significant ( Z=-2.141, P=0.036). Among the 24 eyes of 12 cases, there were no obvious fundus abnormalities in 1 case or 2 eyes, 11 cases of IP-related retinopathy in 22 eyes (91.7%, 22/24), 8 cases of binocular asymmetry (66.7%, 8/12). There were active lesions on the fundus in 7 eyes (29.2%, 7/24). Patients underwent simple retinal laser photocoagulation and/or anti-VEGF drug therapy. During the follow-up, retinal neovascularization recurred in 1 eye. Among the 8 cases that underwent genetic testing, 3 cases (37.5%, 3/8) were deleted in exons 4-10 of the IKBKG gene. Conclusions:IP is more common in women. IP-associated retinopathy is noted with early-onset, asymmetrical retinopathy, which is identified with retinal neovascularization and vitreous proliferation. Early detection and timely treatment are essential.

Objective:To analyze the related risk factors for vertebral artery tortuosity, and explore the mechanism of vertebral artery tortuosity.Methods:Two hundred and eighty-two patients accepted head/neck and MR angiography in our hospital from October 2016 to October 2017 were selected. The tortuosity degrees of vertebral artery were measured and calculated by PACS system. The differences of tortuosity degrees of vertebral arteries in different age groups were compared. Correlation analysis was performed to determine the correlation between vertebral artery tortuosity and both clinical data and and biochemical levels, and multivariate linear regression analysis was performed to determine the independent risk factors for vertebral artery tortuosity.Results:The tortuosity degrees of the left and right vertebral arteries in these patients ranged from 5.1% to 72.6%. The tortuosity degrees of vertebral arteries in patients aged 40-49 years were significantly higher than those in patients aged 20-29 years and 30-39 years ( P<0.05). Correlation analysis showed that the tortuosity degree of the right vertebral artery was positively correlated with age and triglyceride level ( r=0.232, P=0.000; r=0.172, P=0.004); the tortuosity degree of the left vertebral artery was positively correlated with triglyceride level ( r=0.123, P=0.043). Multivariate regression analysis showed that age ( 95%CI: 0.059-0.194, P=0.000) and triglyceride level ( 95%CI: 0.173-1.942, P=0.019) were independent risk factors for right vertebral artery tortuosity. Triglyceride level ( 95%CI: 0.041-2.559, P=0.043) was independent risk factor for left vertebral artery tortuosity. Conclusion:There are congenital developmental factors associated with vertebral artery tortuosity; some nurture factor, as triglyceride level, may promote its development.

Objective:To study the effect of spleen and marrow strengthening method combined with CAG regimen on the quality of life(QOL) of elderly patients with acute myeloid leukemia with spleen-kidney Yang deficiency syndrome.Methods:From June 2017 to October 2018, 50 elderly patients with acute myeloid leukemia with spleen-kidney Yang deficiency were randomly divided into treatment group and control group by random number table method, with 25 patients in each group.The patients in the control group were treated with CAG regimen(Ara-C+ Acla+ G-CSF), while the patients in the treatment group were treated with CAG regimen and leukemia prescription I, which was the empirical prescription for spleen and kidney Yang deficiency syndrome in elderly patients with acute myeloid leukemia.The patients were treated for two courses.The traditional Chinese medicine (TCM) syndromes and QOL scores of patients in two groups were compared and observed.Results:Before treatment, there was no statistically significant difference in the score of TCM syndromes between the two groups ( P>0.05). After treatment, the improvement of TCM syndromes in the treatment group had statistically significant difference compared with before treatment[before treatment (9.29±4.22)points, after treatment (5.04±3.83)points, t=3.656, P=0.001], but that in the control group had no statistically significant difference ( P>0.05). The treatment group was better than the control group ( t=-2.081, P=0.044). The total effective rate of the treatment group was 58.33% (14/24), which was significantly higher than that of the control group[26.32% (5/19)], and the difference was statistically significant (χ 2=5.831, P<0.05). Before treatment, there was no statistically significant difference in the total score of QOL between the two groups ( P>0.05). After treatment, the scores of QOL in both two groups were improved, the differences were statistically significant[the control group: (40.37±2.93)points vs.(38.21±2.76)points, t=2.337, P=0.025; the treatment group: (41.46±2.57)points vs.(36.54±2.34)points, t=6.929, P=0.000], and the QOL score of the treatment group was better than that of the control group ( t=-2.145, P=0.038). Conclusion:The improvement of TCM syndromes and QOL of elderly patients with acute myeloid leukemia with spleen-kidney Yang deficiency syndrome treated by spleen and marrow strengthening method combined with CAG regimen is better than that treated by CAG chemotherapy alone.

Objective:To observe the clinical characteristics of adult patients with ocular toxoplasmosis (OT).Methods:This study was a retrospective clinical trial. Among the 83 consecutive OT patients diagnosed in the Zhongshan Eye Center of Sun Yat-Sen University, 14 patients (16.9%, adult group) aged ≥18 years were included in the study from January 2017 to December 2019. A total of 14 OT patients (children group) aged less than 18 years who had consecutive visits from July to December 2019 were selected as controls. All patients underwent BCVA, slit lamp microscope, fundus color photography, and B-mode ultrasound examination. Eighteen cases underwent UBM examination, including 6 and 12 cases in the adult group and child group respectively; 23 cases underwent FFA examination, including 12 and 11 cases in the adult group and child group respectively. Snellen visual acuity chart was used for BCVA examination, which was converted into logMAR visual acuity in statistics. We compared the two groups of patients' residence (urban or rural), history of contact with dogs and cats, main symptoms, reasons for treatment, course of disease, and clinical and imaging characteristics and so on. For measurement data conforming to normal distribution, t-test was performed for comparison between groups; for Skewness distribution measurement data, rank sum test was performed for comparison between groups. Results:Compared with the adult group and the child group, there was no significant difference in the canine-cat contact history ( Z=2.661, P=0.257) and the time from first diagnosis to diagnosis ( t=-0.186, P=0.351); compared with the children group and the adult group, the patient's living environment was mainly urban, and the course of disease was significantly shorter ( Z=-2.005), and the difference was statistically significant ( P=0.047). The logMAR BCVA of the adult group and the child group were 0.81±1.08 and 2.08±1.30, respectively, and the difference was statistically significant ( Z=-2.811, P=0.004); compared with the child group, the adult group had lighter vitreous opacities, but the difference was statistical significance ( Z=7.847, P=0.048). FFA examination revealed 20 cases of "fern-like" leakage of retinal capillaries. Among them, the adult group and child group were 10 (83.3%, 10/12) and 10 (90.9%, 10/11) cases respectively. Conclusions:Adult patients account for 16.9% of OT patients. Compared with children, adult patients mostly live in towns or cities, have a short course of disease, good vision at first diagnosis, and mild inflammation or hyperplasia of the vitreous cavity. FFA is helpful for the diagnosis of adult OT.

Objective: To explore the effects of Yiqi Yangyin Liangxue method on platelets, interleukin-10(IL-10) and transforming growth factor beta (TGF-β) of immune thrombocytopenic purpura(ITP) model mice, and to analyze its curative effect and possible mechanism. Methods: A total of 100 ITP model mice were randomly divided into blank group, model group, single Chinese medicine group, single hormone group and Chinese medicine combined with hormone group.Drug intervention was started on the 8th day after the establishment of the model, and the drug was given for a total of 14 days.The blood of mice was collected and the levels of platelets, TGF-β and IL-10 in serum of mice in each group were detected. Results: There was no statistically significant difference in platelet count among all groups before modeling(F=0.556, P>0.05). Before administration, there was statistically significant difference between the model group and the blank group (t=28.207, P<0.01), there were no statistically significant differences between the model group and the traditional Chinese medicine group, hormone group, hormone+ traditional Chinese medicine group (t=-1.96, -0.464, -0.979, all P>0.05). After gastric administration, the platelet counts in the traditional Chinese medicine group[(710.45±124.52)×10⁹/L], hormone group[(768.10±127.42)×10⁹/L], hormone+ traditional Chinese medicine group[(908.05±89.66)×10⁹/L] were significantly higher than that in the model group[(413.55±38.84)×10⁹/L](t=-10.18, -11.90, -22.63, all P<0.01). After gastric administration, there was no statistically significant difference between the traditional Chinese medicine group and the hormone group(t=-1.447, P>0.05). After gastric administration, the platelet count of the hormone+ traditional Chinese medicine group was significantly higher than that of the hormone group and the traditional Chinese medicine group(t=-4.017, -5.759, all P<0.01). There was statistically significant difference in IL-10 level among groups after administration(F=32.20, P<0.01). IL-10 levels between the model group[(20.28±0.75)ng/L] and traditional Chinese medicine group[(21.41±1.40)ng/L], hormone group[(21.79±1.14)ng/L] and traditional Chinese medicine+ hormone group[(23.14±1.34)ng/L] had statistically significant differences (t=-3.18, -4.93, -8.33, all P<0.01). There was no statistically significant difference between the traditional Chinese medicine group and hormone group(t=-0.927, P>0.05). There were statistically significant differences between the traditional Chinese medicine+ hormone group and traditional Chinese medicine group, hormone group (t=-3.97, -3.43, all P<0.01). There was statistically significant difference in TGF-beta level among all groups after administration(F=31.16, P<0.01). The TGF-β levels between the model group[(82.32±3.42)ng/L] and Chinese medicine group[(88.10±8.51)ng/L], hormone group[(90.03±4.50)ng/L] and Chinese medicine combined with hormone group[(94.41±2.53)ng/L] had statistically significant differences (t=-2.82, -6.10, -12.70, all P<0.01). There was no significant difference in TGF-β level between the Chinese medicine group and hormone group(t=-0.90, P>0.05). There were statistically significant differences in in TGF-beta level between the traditional Chinese medicine+ hormone group and Chinese medicine group, hormone group (t=-3.18, -3.79, all P<0.01). Conclusion Yiqi Yangyin Liangxue method can reduce platelet destruction by regulating the levels of IL-10 and TGF-β and inhibiting immunity, and it has good therapeutic effect on ITP.