Related factors of treatment zone diameter after Paragon CRT orthokeratology / 国际眼科杂志(Guoji Yanke Zazhi)

AIM:To explore the influence factors of the treatment zone diameter(TZD)and its correlation with axial length growth(ALG)after Paragon CRT orthokeratology.METHODS: Retrospective clinical study. The data of 226 myopic patients(226 eyes)wearing Paragon CRT orthokeratology from April 2020 to September 2022 were collect. The correlated factors of TZD after wearing lens for 1mo, and the relationship between the overlapping treatment zone/ pupil area ratio and the ALG after wearing lens for 1a were analyzed.RESULTS: After wearing lens for 1mo, the TZD was negatively correlated with central corneal thickness(CCT)and positively correlated with the flat corneal eccentricity. After wearing lens for 1a, the ALG of the small TZD group(0.25±0.18mm)was significantly smaller than that of the large TZD group(0.34±0.24mm, P=0.002), and the ALG of the small area ratio group(0.24±0.19mm)was significantly smaller than that of the large area ratio group(0.35±0.23mm,P<0.001). Age and overlapping treatment zone area/pupil area ratio were significantly associated with the ALG in multivariate linear regression(all P<0.05).CONCLUSION: The wearers with thicker CCT and smaller flat corneal eccentricity usually had smaller TZD, and both the TZD and the overlapping treatment zone area/pupil area ratio were correlated with the ALG.

PAFR/Stat3 axis maintains the symbiotic ecosystem between tumor and stroma to facilitate tumor malignancy

Stroma surrounding the tumor cells plays crucial roles for tumor progression. However, little is known about the factors that maintain the symbiosis between stroma and tumor cells. In this study, we found that the transcriptional regulator-signal transducer and activator of transcription 3 (Stat3) was frequently activated in cancer-associated fibroblasts (CAFs), which was a potent facilitator of tumor malignancy, and formed forward feedback loop with platelet-activating factor receptor (PAFR) both in CAFs and tumor cells. Importantly, PAFR/Stat3 axis connected intercellular signaling crosstalk between CAFs and cancer cells and drove mutual transcriptional programming of these two types of cells. Two central Stat3-related cytokine signaling molecules-interleukin 6 (IL-6) and IL-11 played the critical role in the process of PAFR/Stat3 axis-mediated communication between tumor and CAFs. Pharmacological inhibition of PAFR and Stat3 activities effectively reduced tumor progression using CAFs/tumor co-culture xenograft model. Our study reveals that PAFR/Stat3 axis enhances the interaction between tumor and its associated stroma and suggests that targeting this axis can be an effective therapeutic strategy against tumor malignancy.

Marsdenia tenacissima injection induces the apoptosis of prostate cancer by regulating the AKT/GSK3β/STAT3 signaling axis / 中国天然药物

Marsdenia tenacissima injection, a standard Marsdenia tenacissima extract (MTE), has been approved as an adjuvant therapeutic agent for various cancers. Our previous study showed that MTE inhibited the proliferation and metastasis of prostate cancer (PCa) cells. However, the underlying mechanisms and active ingredients of MTE against PCa were not completely understood. This study revealed that MTE induced significant decreases in cell viability and clonal growth in PCa cells. In addition, MTE induced the apoptosis of DU145 cells by reducing the mitochondrial membrane potential and increasing the expression of Cleaved Caspase 3/7, Cyt c, and Bax. In vivo, DU145 xenografted NOD-SCID mice treated with MTE showed significantly decreased tumor size. TUNEL staining and Western blot confirmed the pro-apoptotic effects of MTE. Network pharmacology analysis collected 196 ingredients of MTE linked to 655 potential targets, and 709 PCa-associated targets were retrieved, from which 149 overlapped targets were screened out. Pathway enrichment analysis showed that the HIF-1, PI3K-AKT, and ErbB signaling pathways were closely related to tumor apoptosis. Western blot results confirmed that MTE increased the expression of p-AKTSer473 and p-GSK3βSer9, and decreased the expression of p-STAT3Tyr705in vitro and in vivo. A total of 13 compounds in MTE were identified by HPLC-CAD-QTOF-MS/MS and UPLC-QTOF-MS/MS. Molecular docking analysis indicated that six compounds may interact with AKT, GSK3β, and STAT3. In conclusion, MTE induces the endogenous mitochondrial apoptosis of PCa by regulating the AKT/GSK3β/STAT3 signaling axis, resulting in inhibition of PCa growth in vitro and in vivo.

PPAR-γ activation promotes xenogenic bioroot regeneration by attenuating the xenograft induced-oxidative stress / 国际口腔科学杂志·英文版

Xenogenic organ transplantation has been considered the most promising strategy in providing possible substitutes with the physiological function of the failing organs as well as solving the problem of insufficient donor sources. However, the xenograft, suffered from immune rejection and ischemia-reperfusion injury (IRI), causes massive reactive oxygen species (ROS) expression and the subsequent cell apoptosis, leading to the xenograft failure. Our previous study found a positive role of PPAR-γ in anti-inflammation through its immunomodulation effects, which inspires us to apply PPAR-γ agonist rosiglitazone (RSG) to address survival issue of xenograft with the potential to eliminate the excessive ROS. In this study, xenogenic bioroot was constructed by wrapping the dental follicle cells (DFC) with porcine extracellular matrix (pECM). The hydrogen peroxide (H2O2)-induced DFC was pretreated with RSG to observe its protection on the damaged biological function. Immunoflourescence staining and transmission electron microscope were used to detect the intracellular ROS level. SD rat orthotopic transplantation model and superoxide dismutase 1 (SOD1) knockout mice subcutaneous transplantation model were applied to explore the regenerative outcome of the xenograft. It showed that RSG pretreatment significantly reduced the adverse effects of H2O2 on DFC with decreased intracellular ROS expression and alleviated mitochondrial damage. In vivo results confirmed RSG administration substantially enhanced the host's antioxidant capacity with reduced osteoclasts formation and increased periodontal ligament-like tissue regeneration efficiency, maximumly maintaining the xenograft function. We considered that RSG preconditioning could preserve the biological properties of the transplanted stem cells under oxidative stress (OS) microenvironment and promote organ regeneration by attenuating the inflammatory reaction and OS injury.

Re-discussion on the comprehensive treatment strategy of complex ventral hernia from the perspective of intraperitoneal pressure / 中华外科杂志

Complex ventral hernia refers to a large hernia that is complicated by a series of concurrent conditions. Change in intra-abdominal pressure is one of the main pathways through which various factors exert an impact on perioperative risk and postoperative recurrence. Taking abdominal pressure reconstruction as the core, the treatment strategy for complex abdominal hernia can be formulated from three aspects: improving patients' tolerance, expanding abdominal cavity volume, and reducing the volume of abdominal contents. Improving patients' tolerance includes abdominal wall compliance training and progressive preoperative pneumoperitoneum. To expand the volume of the abdominal cavity, implanting hernia repair materials, component separation technique, autologous tissue transplantation, component expend technique, and chemical component separation can be used. Initiative content reduction surgery and temporary abdominal closure may be performed to reduce the volume of abdominal contents. For different cases of complex ventral hernia, personalized treatment measures can be safely and feasibly adopted depending on the condition of the patients and the intra-abdominal pressure situation.

Analysis and evaluation of bioactive constituents from different parts of Epimedium brevicornum / 中国中药杂志

A comprehensive analytical method based on ultra-fast liquid chromatography coupled with triple quadrupole/linear ion trap tandem mass spectrometry(UFLC-QTRAP-MS/MS) was established for simultaneous determination of the content of 45 bioactive constituents including flavonoids, alkaloids, amino acids, phenolic acids, and nucleosides in Epimedium brevicornum. The multiple bioactive constituents in leaves, petioles, stems and rhizomes of E. brevicornum were analyzed. The gradient elution was performed at 30 ℃ in an XBridge~® C_(18) column(4.6 mm×100 mm, 3.5 μm) with 0.4% formic acid aqueous solution-acetonitrile as the mobile phase at a flow rate of 0.8 mL·min~(-1). Single factor experiment and response surface methodology were employed to optimize the extraction conditions. Multivariate statistical analyses including systematic cluster analysis(SCA), principal component analysis(PCA), partial least squares discriminant analysis(PLS-DA), and one-way analysis of variance(One-way ANOVA) were carried out to classify the samples from different parts and identify different constituents. Grey relation analysis(GRA) and entropy weight-TOPSIS analysis were performed to build a multi-index comprehensive evaluation model for different parts of E. brevicornum. The results showed that there was a good relationship between the mass concentrations of 45 constituents and the corresponding peak areas, with the correlation coefficients(r) not less than 0.999 0. The precision, repeatability, and stability of the established method were good for all the target constituents in this study, with the relative standard deviations(RSDs) less than 5.0%(0.62%-4.9%) and the average recovery of 94.51%-105.7%. The above results indicated that the bioactive constituents varied in different parts of E. brevicornum, and the overall quality followed the trend of leaves > petioles > rhizomes > stems. This study verified the rationality of the Chinese Pharmacopoeia(2020 edition) stipulating that the medicinal part of E. brevicornum is the leaf. Moreover, our study indicated that the rhizome had the potential for medicinal development. The established method was accurate and reliable, which can be used to comprehensive evaluate and control the quality of E. brevicornum. This study provides data reference for clarifying the medicinal parts and rationally utilizing the resources of E. brevicornum.

Research advances in role of angiogenesis in diabetic ulcer and traditional Chinese medicine intervention / 中国中药杂志

Diabetic ulcer(DU) is one of the common complications of diabetes often occurring in the peripheral blood vessels of lower limbs or feet with a certain degree of damage. It has high morbidity and mortality, a long treatment cycle, and high cost. DU is often clinically manifested as skin ulcers or infections in the lower limbs or feet. In severe cases, it can ulcerate to the surface of tendons, bones or joint capsules, and even bone marrow. Without timely and correct treatment, most of the patients will have ulceration and blackening of the extremities. These patients will not be able to preserve the affected limbs through conservative treatment, and amputation must be performed. The etiology and pathogenesis of DU patients with the above condition are complex, which involves blood circulation interruption of DU wound, poor nutrition supply, and failure in discharge of metabolic waste. Relevant studies have also confirmed that promoting DU wound angiogenesis and restoring blood supply can effectively delay the occurrence and development of wound ulcers and provide nutritional support for wound healing, which is of great significance in the treatment of DU. There are many factors related to angiogenesis, including pro-angiogenic factors and anti-angiogenic factors. The dynamic balance between them plays a key role in angiogenesis. Meanwhile, previous studies have also confirmed that traditional Chinese medicine can enhance pro-angiogenic factors and down-regulate anti-angiogenic factors to promote angiogenesis. In addition, many experts and scholars have proposed that traditional Chinese medicine regulation of DU wound angiogenesis in the treatment of DU has broad prospects. Therefore, by consulting a large number of studies available, this paper expounded on the role of angiogenesis in DU wound and summarized the research advance in traditional Chinese medicine intervention in promoting the expression of angiogenic factors [vascular endothelial growth factor(VEGF), fibroblast growth factor(FGF), and angiopoietin(Ang)] which played a major role in promoting wound angiogenesis in the treatment of DU to provide ideas for further research and new methods for clinical treatment of DU.

Research progress in role of autophagy in diabetic wound healing and traditional Chinese medicine intervention / 中国中药杂志

Diabetic ulcer(DU) is a chronic and refractory ulcer which often occurs in the foot or lower limbs. It is a diabetic complication with high morbidity and mortality. The pathogenesis of DU is complex, and the therapies(such as debridement, flap transplantation, and application of antibiotics) are also complex and have long cycles. DU patients suffer from great economic and psychological pressure while enduring pain. Therefore, it is particularly important to promote rapid wound healing, reduce disability and mortality, protect limb function, and improve the quality of life of DU patients. By reviewing the relevant literatures, we have found that autophagy can remove DU wound pathogens, reduce wound inflammation, and accelerate ulcer wound healing and tissue repair. The main autophagy-related factors microtubule-binding light chain protein 3(LC3), autophagy-specific gene Beclin-1, and ubiquitin-binding protein p62 mediate autophagy. The traditional Chinese medicine(TCM) treatment of DU mitigates clinical symptoms, accelerates ulcer wound healing, reduces ulcer recurrence, and delays further deterioration of DU. Furthermore, under the guidance of syndrome differentiation and treatment and the overall concept, TCM treatment harmonizes yin and yang, ameliorates TCM syndrome, and treats underlying diseases, thereby curing DU from the root. Therefore, this article reviews the role of autophagy and major related factors LC3, Beclin-1, and p62 in the healing of DU wounds and the intervention of TCM, aiming to provide reference for the clinical treatment of DU wounds and subsequent in-depth studies.

Research on the driving mechanism of residents′ willingness to participate in tiered medical care based on harmonious management theory / 中华医院管理杂志

Objective:To construct and validate a theoretical model of residents′ willingness to participate in tiered medical care based on harmonious management theory, providing reference for promoting the tiered medical care system and aiding governmental decision-making.Methods:Based on the harmonious management theory and literature review, a model capturing residents′ propensity to engage in tiered medical care was formulated. Using convenience sampling method, a questionnaire survey was conducted on 2 067 residents from 24 communities in Zhejiang province from April to May 2022. Descriptive statistical analysis was conducted on the survey results, and multilevel linear regression and structural equation modeling were used to analyze the driving mechanism of residents′ willingness to participate in tiered medical care.Results:The willingness rate of residents to participate in tiered medical care was 69.7%, which was at an average level. Regression insights highlighted the positive influence of policy support perception ( β=0.170, P<0.01), awareness of management mechanisms ( β=0.093, P<0.01), cognitive attitudes ( β=0.102, P<0.01), and trust levels ( β=0.244, P<0.01) on residents′ participation willingness. In contrast, resource allocation perceptions lacked a significant effect ( β=0.065, P>0.05). The structural equation model revealed that cognitive attitudes played a mediating role in the " policy system perception → participation willingness" and " management mechanism perception → participation willingness" pathways, with effect sizes of 0.030 and 0.039, respectively. Trust levels also mediated these paths, with effect sizes of 0.039 and 0.045, and entirely mediated the " resource allocation perception → participation willingness" path, registering an effect size of 0.053. Conclusions:The harmonious management theory can be used to explain the formation mechanism of residents′ willingness to participate in tiered medical care. The government and medical institutions urgently need to further improve residents′ awareness of tiered medical care, focus on enhancing residents′ trust, and further improve policies and management measures such as financial investment, medical insurance reimbursement, and referral systems.

Theoretical exploration and research pathways of the harmonious symbiotic mechanism in the tiered medical treatment system / 中华医院管理杂志

The tiered medical treatment system stands as a cornerstone in the deepening reforms of China′s medical and health sectors, playing a crucial role in building a healthy China. Exploring the harmonious coexistence mechanism of multiple entities on the supply and demand sides of the tiered diagnosis and treatment system, and promoting the formation of a scientific and reasonable tiered diagnosis and treatment order, has become an urgent public proposition that needs to be answered and has significant social impact. Addressing the challenges in China′s tiered medical treatment system, particularly its need for a more systematic, comprehensive, and collaborative approach, this study is informed by a thorough literature review. Based on the harmonious management and symbiosis theories, the authors proposed a theoretical concept and future research path for the formation of a harmonious symbiotic mechanism in the tiered diagnosis and treatment system, in order to pave the way for exploring the harmonious symbiotic mechanism in the tiered diagnosis and treatment system.

Tendon manipulation based on meridian tendon theory can improve the treatment of knee osteoarthritis / 中华物理医学与康复杂志

Objective:To observe any effect of tendon manipulation on the joint pain, joint motion and gait of persons with knee osteoarthritis (KOA).Methods:Sixty-one KOA patients were randomly divided into an observation group ( n=31) and a control group ( n=30). Both groups received ultrasonic physiotherapy and exercise trai-ning (including quadriceps femoris training and heel raising training), while the observation group was additionally provided with daily tendon manipulation, five times a week for 3 weeks. Before and after the treatment, knee pain (using a visual analog scale (VAS)), motor function (using the Western Ontario and McMaster University (WOMAC) osteoarthritis index scale), step length, gait speed and the double support phase ratio were evaluated in both groups using three-dimensional gait analysis equipment. Results:After the treatment the average VAS scores, as well as the joint pain, stiffness and dysfunction and the total WOMAC scores of both groups had decreased significantly. There was significant improvement in the average stride length, walking speed and the proportion of double support phase among the observation group, and the latter two measurements had also improved significantly in the control group. After the intervention, the average pain, WOMAC scores and gait descriptors of the observation group were significantly superior to the control group′s results.Conclusion:Tendon manipulation can usefully supplement routine rehabilitation in the treatment of KOA, improving walking efficiency and thus life quality.

Paclitaxel drug-coated balloons combined with bare metal stents vs. bare metal stents for the treatment of superficial femoral atherosclerosis obliterans / 中华普通外科杂志

Objective:To compare the efficacy and safety of drug-coated balloons (DCB) combined with bare metal stents (BMS) and BMS only for superficial femoral atherosclerosis obliterans.Methods:The clinical and follow-up data of 80 patients (82 limbs) who received combined treatment or BMS implantation at Cardiovascular Surgery Department of China Japan Friendship Hospital from Jan 2017 to Aug 2022 were retrospectively analyzed.Results:43 patients (43 limbs) were included in combined treatment group. 37 patients (39 limbs) were in BMS only. The average lesion length of combined group was longer than BMS group (19.54±7.04 cm vs. 16.25±6.43 cm, P=0.031). The primary patency rate of combined group at 36 months was not statistically different with BMS only group (56.9% vs. 38.5%, P=0.171). The subgroup analysis of superficial femoral artery TASC C/D (Trans-Atlantic Inter-Society Consensus) and CTO (chronic total occlusion) lesions indicated that efficacy of the combined group was superior to BMS only group. The patency rates of the combined group compared with the BMS group at 36 months were 57.6% vs. 23.8%, P=0.046, 60.2% vs. 31.4%, P=0.028, respectively. There was no significant difference in the FCD-TLR (free from clinical driven target lesion revascularization) between the two groups at 36 months (72.6% vs. 66.5%, P=0.706). There was no significant difference in major adverse events between the two groups ( P>0.05). Conclusion:Paclitaxel drug-coated balloon combined with bare metal stent is a safe and effective treatment for superficial femoral atherosclerosis obliterans, which is superior to bare metal stent, especially in TASC C/D and chronic total occlusive lesions.

Carotid endarterectomy for symptomatic carotid artery near-occlusion / 中华普通外科杂志

Objective:To investigate the effect of carotid endarterectomy(CEA) in the treatment of symptomatic carotid artery near-occlusion(CNO).Methods:Clinical symptoms, imaging examination, treatment and prognosis of 122 symptomatic CNO patients admitted to China-Japan Friendship Hospital from Jan 2014 to Jan 2020 undergoing CEA were retrospectively analyzed. Patients were divided into two groups based on the collapse condition,full collapse group(54 cases) and non-full collapse group(68 cases).Results:The difference was insignificant between the two groups at the 30-day and 12-month occurrence rate of primary endpoints(1.85% vs. 4.41%, P=0.629;7.41% vs. 4.41%, P=0.698).Postoperative re-stenosis occurred in one case in the non-full collapse group 8 months after CEA. Conclusions:CEA can achieve good curative effect for patients with CNO with recurrent symptoms, irrelevant to the existence of distal full collapse. The shunt can prevent intraoperative hypoperfusion and postoperative hyperperfusion.

Management of mesh infection after tension-free repair of inguinal hernia / 中华普通外科杂志

Objective:To investigate the characteristics and surgical management of mesh infection after tension-free repair of inguinal hernia.Methods:The clinical and follow-up data of 87 patients with mesh infection after tension-free repair of inguinal hernia at the Department of Hernia and Abdominal Wall Surgery,Beijing Chaoyang Hospital from 2018 to 2020 were retrospectively analyzed.Results:The most frequent type of repair was plug implantation, accounting for 57.5% of the procedures. The most common clinical presentation was a chronic sinus. 79.3% patients had a >3-month history of chronic infection. Staphylococcus aureus was the most common bacteria. All patients underwent open debridement. Fifty-one patients had a complete removal of the infected mesh, and 36 had partial removal. All patients were followed up for 18.7-54.2 months. There was no significant difference in the incidence of wound infection, seroma, hematoma, inguinal hernia recurrence, and chronic pain between those with complete removal and that partial removal (all P>0.05). Seventeen cases suffered recurrent sinus in the partial mesh removal group, and the incidence was significantly higher than that in the complete mesh removal group ( P<0.001). Conclusion:Infected mesh removal is an effective treatment for mesh infection after tension-free repair of inguinal hernia and should be removed as completely as possible.

Correlation between metabolic syndrome and hyperuricemia in perimenopausal women / 中华内分泌代谢杂志

Objective:To assess the prevalence of metabolic syndrome(MS) and its relationship with hyperuricemia(HUA) in perimenopausal women in Anning city, Yunnan province.Methods:This is a cross-sectional survey. In May 2021, a multi-stage stratified sampling method was used to collect demographics and clinical data [ethnicity, living community, height, weight, waist circumference, blood pressure, fasting plasma glucose, triglycerides(TG), serum uric acid, high density lipoprotein-cholesterol(HDL-C), alanine transaminase(ALT), etc] in a total of 6 721 perimenopausal women aged 45-60 years.Results:A total of 6 721 perimenopausal women were included in this study. The prevalences of MS and HUA were 14.05%(95% CI 13.22%-14.88%) and 6.46%(95% CI 5.88%-7.07%), respectively. The average age, HDL-C, urea, direct bilirubin, and albumin levels in the perimenstrual HUA population were lower than those in the non-HUA population while the levels of TG, ALT, heart rate, body mass index(BMI), and creatinine were higher(all P<0.05). The prevalence of HUA in perimenopausal women with ethnic minorities and family history of chronic diseases was higher than that in Han nationality and without family history of chronic diseases. The prevalence of MS in perimenopausal women was increased with the increase of serum uric acid( Z=-15.313 8, P<0.001). Multivariate logistic regression model showed that HUA was positively correlated with MS( OR=1.526, 95% CI 1.192-1.954) after adjusting for covariates such as BMI and ethnicity, and the incidence of MS in perimenopausal women in HUA group was 1.526 folds higher than that in non-hyperuricemia group. Conclusion:HUA is highly positively correlated with MS in perimenopausal women. The management of uric acid level in perimenopausal women should be strengthened.

Research progress on the role and mechanism of premature cellular senescence on wound healing in radiation-induced skin injury / 中华放射医学与防护杂志

Radiation skin injury can be induced by medical exposure, occupational exposure, and emergency exposure. Many relevant studies focused on the prevention and treatment of radiation-induced skin injury, but the underlying molecular mechanisms have not been fully clarified. It has been demonstrated that radiation-induced premature cellular senescence is involved in radiation skin injury. To discuss the relationship between radiation-induced premature cellular senescence and radiation-induced skin injury, this paper reviewed the mechanism of radiation-induced skin injury, the promotion of premature cellular senescence and related signal pathways, and the role of premature cellular senescence in wound healing.

Minimally invasive repair of acute closed Achilles tendon rupture with two-way needle suture technique / 中华创伤骨科杂志

Objective:To investigate the efficacy of two-way needle suture technique (TNST) in the minimally invasive repair of acute closed Achilles tendon rupture.Methods:From June 2019 to June 2021, 26 patients with acute closed Achilles tendon rupture were treated at Zhengzhou Orthopedic Hospital. They were 20 males and 6 females, with a mean age of 28 (23, 31) years. The rupture end was (4.2±1.3) cm away from the calcaneal insertion, and the interval from injury to operation 4.3 (2.0, 5.0) d. Preoperative MRI examinations revealed in all the patients closed Achilles tendon rupture which was to be repaired by TNST. The operation time, incision length, incidence of complications, ankle dorsiflexion and plantar flexion were recorded. The Arner-Lindholm scoring was used to evaluate the clinical efficacy.Results:The operation time was (20.0±5.0) min and the incision length (2.5±0.4) cm. Postoperatively, all incisions healed by the first stage, with no complications like incision infection, skin edge necrosis, deep vein thrombosis at lower limbs, injury to the sural nerve, or re-rupture of the Achilles tendon. All patients were followed up for (12.0±6.0) months. At the last follow-up, the patients walked normally, their incisions healed well, the continuity of the Achilles tendon was good by palpation, their heel lift was strong, and all their activities were restored to the levels before rupture of the Achilles tendon. The ankle dorsiflexion was 22.6°±3.7° and the plantar flexion 25.3°±3.7°, According to the Arner-Lindholm evaluation, the clinical efficacy was rated as excellent in 25 cases and as good in 1 case, giving an excellent and good rate of 100% (26/26).Conclusion:In the minimally invasive repair of acute closed Achilles tendon rupture, TNST shows the advantages of limited surgical invasion, a low incidence of postoperative complications, and reliable curative effects.

Establishment and application of hepatic organoid model of hepatitis B virus infection / 中华传染病杂志

Objective:To establish the hepatic organoid of hepatitis B virus (HBV) infection on the basis of induced pluripotent stem cells (iPSC) and an inverted colloidal crystal polyethylene glycol scaffold (ICC), and to evaluate the antiviral effect of nucleoside drugs.Methods:iPSC was differentiated into hepatocyte-like cells (HLC), and inoculated into ICC to construct a hepatic organoid. The relative mRNA expressions of Nanog homeobox (NANOG), sex determining region Y-box (SOX) 2, SOX17, forkhead box protein A2 (FOXA2), alpha fetoprotein (AFP) and albumin (ALB) were detected by real time quantitative polymerase chain reaction (RT-qPCR). Confocal laser microscopy was used to photograph the three-dimension (3D) structure of organs. The expression of sodium taurocholate cotransporting polypeptide (NTCP) in HLC was analyzed by Western blot and immunofluorescence. HepG2.2.15 cells were used to extract HBV virus particles to infect hepatic organoid. The relative expression of HBV pregenome RNA (pgRNA) in cells was detected by RT-qPCR. The expressions of hepatitis B core antigen (HBcAg) and hepatitis B surface antigen (HBsAg) in cytoplasm were observed under confocal laser microscopy. A total of 0.5 μmol/L entecavir and 0.5 μmol/L lamivudine were used to treat the infected cells respectively. The relative expression of HBV pgRNA in infected and uninfected cells was detected by RT-qPCR. Independent sample t test and one-way analysis of variance were used for statistical analysis. Results:Within 21 days of iPSC differentiation, the mRNA expressions of NANOG and SOX2 in stem cells markers decreased ( F=158.90 and 8.31, respectivley; P<0.001 and P=0.002, respectively), while the mRNA expressions of SOX17 and FOXA2 in the endoderm increased first and then decreased ( F=37.23 and 82.57, respectively, both P<0.001). In the later stage of differentiation, the mRNA expressions of AFP and ALB in liver cells increased ( F=4.65 and 34.64, respectively, P=0.012 and P<0.001, respectively), and all differences were statistically significant. NTCP was highly expressed in differentiated cells detected by Western blot and fluorescence microscopy, the protein expression level was 0.803±0.099. Confocal laser microscopy confirmed that the differentiated cells expressed ALB and presented spherical structure in ICC. The expression of HBV pgRNA and the immunostaining of HBsAg and HBcAg confirmed that HBV successfully infected hepatic organoid. Three days after the application of entecavir and lamivudine, the HBV pgRNA level decreased significantly both in entecavir group (0.665±0.220) and lamivudine group (0.503±0.117) compared to the uninfected cells (3.347±0.454), and the differences were both statistically significant ( t=10.53 and 12.72, respectively, both P<0.001). Conclusions:HLC display hepatic specific genes ALB and NTCP. Hepatic organoids constructed with iPSC and ICC have human liver function and can be infected by HBV. Entecavir and lamivudine could effectively inhibit the replication of HBV in hepatic organoids.

High-throughput transcriptional profiling of perturbations by Panax ginseng saponins and Panax notoginseng saponins using TCM-seq / 药物分析学报

Panax ginseng(PG)and Panax notoginseng(PN)are highly valuable Chinese medicines(CM).Although both CMs have similar active constituents,their clinical applications are clearly different.Over the past decade,RNA sequencing(RNA-seq)analysis has been employed to investigate the molecular mechanisms of extracts or monomers.However,owing to the limited number of samples in standard RNA-seq,few studies have systematically compared the effects of PG and PN spanning multiple conditions at the transcriptomic level.Here,we developed an approach that simultaneously profiles transcriptome changes for multiplexed samples using RNA-seq(TCM-seq),a high-throughput,low-cost workflow to molecularly evaluate CM perturbations.A species-mixing experiment was conducted to illustrate the accuracy of sample multiplexing in TCM-seq.Transcriptomes from repeated samples were used to verify the robustness of TCM-seq.We then focused on the primary active components,Panax notoginseng sa-ponins(PNS)and Panax ginseng saponins(PGS)extracted from PN and PG,respectively.We also char-acterized the transcriptome changes of 10 cell lines,treated with four different doses of PNS and PGS,using TCM-seq to compare the differences in their perturbing effects on genes,functional pathways,gene modules,and molecular networks.The results of transcriptional data analysis showed that the tran-scriptional patterns of various cell lines were significantly distinct.PGS exhibited a stronger regulatory effect on genes involved in cardiovascular disease,whereas PNS resulted in a greater coagulation effect on vascular endothelial cells.This study proposes a paradigm to comprehensively explore the differences in mechanisms of action between CMs based on transcriptome readouts.

Correlation of serum immunoglobulins levels with disease severity and nutritional indexes in elderly patients with heart failure / 中国医师进修杂志

Objective:To observe the correlation between serum immunoglobulins levels with the disease severity and nutritional indexes in elderly patients with heart failure.Methods:The clinical data of 53 elderly patients with heart failure (observation group) from October 2020 to January 2022 in the Affiliated Hospital of Ningbo University Medical College were retrospectively analyzed, and 53 cases of health examination at the same time were selected as the control group. The disease severity was assessed by a 6-minute walk test (6MWT), and nutritional status was assessed by nutritional index. The serum levels of IgA, IgM and IgG were measured by PUZS-300 fully automated biochemical analyzer; the serum nutrient indexes were measured by enzyme linked immunosorbent assay, including total protein, albumin and proalbumin. Pearson method was used for correlation test; the value of IgA, IgM and IgG in predicting disease severity in elderly patients with heart failure was analyzed by the receiver operating characteristic (ROC) curve.Results:The IgA, IgM and IgG in observed group were significantly higher than those in control group: (4.31 ± 1.50) g/L vs. (1.63 ± 0.71) g/L, (18.50 ± 3.93) g/L vs. (11.33 ± 1.12) g/L and (4.58 ± 1.26) g/L vs. (1.96 ± 0.36) g/L, and there were statistical differences ( P<0.01). The 6MWT result showed that 23 cases were with mild status, 18 cases moderate, and 12 cases severe. The IgA, IgM and IgG in moderate and severe patients were significantly higher than those in mild patients: (4.34 ± 0.78) and (6.38 ± 0.91) g/L vs. (3.23 ± 0.94) g/L, (18.90 ± 2.09) and (23.81 ± 2.78) g/L vs. (15.44 ± 2.03) g/L, (4.77 ± 0.56) and (6.47 ± 0.34) g/L vs. (3.45 ± 0.44) g/L, the indexes in severe patients were significantly higher than those in moderate patients, and there were statistical differences ( P<0.05). Pearson correlation analysis result showed that IgA, IgM and IgG were positively correlated with disease severity in elderly patients with heart failure ( r = 0.801, 0.830 and 0.925; P<0.01). The nutritional index result showed that malnutrition was in 25 cases, and normal nutrition in 28 cases. The IgA, IgM and IgG in patients with malnutrition were significantly higher than those in patients with normal nutrition: (4.89 ± 0.80) g/L vs. (1.98 ± 0.69) g/L, (19.45 ± 2.01) g/L vs. (12.01 ± 1.28) g/L and (4.88 ± 0.59) g/L vs. (2.01 ± 0.47) g/L, the nutritional index, total protein, albumin and proalbumin were significantly lower than those in patients with normal nutrition: (49.44 ± 6.98) scores vs. (58.34 ± 8.12) scores, (62.87 ± 5.20) g/L vs. (66.74 ± 4.54) g/L, (33.21 ± 2.64) g/L vs. (39.12 ± 3.11) g/L and (185.55 ± 16.72) mg/L vs. (196.33 ± 18.90) mg/L, and there were statistical differences ( P<0.01 or <0.05). Pearson correlation analysis result showed that the IgA and IgM were negatively correlated with nutritional index, total protein, albumin and proalbumin in elderly patients with heart failure (IgA: r = - 0.456, - 0.353, -0.620 and -0.281; IgM: r = -0.445, -0.327, -0.611 and -0.321; P<0.01 or <0.05); IgG was negatively correlated with nutritional index, total protein and albumin ( r = - 0.425, - 0.359 and - 0.646; P<0.01), and it had no correlation with proalbumin ( P>0.05). ROC curve analysis result showed that the areas under the curve of IgA, IgM and IgG in predicting disease severity in elderly patients with heart failure were 0.891, 0.943 and 0.838, sensitivity of 76.70%, 90.00% and 73.33%, and specificity of 87.00%, 87.00% and 100.00%. Conclusions:The serum levels of IgA, IgM and IgG increased significantly in elderly patients with heart failure, who were also with abnormal immune function and decreased nutritional status. The serum levels of IgA, IgM and IgG correlate with disease severity and nutritional indexes.