Application of mesenchymal stem cell therapy in kidney transplantation: a continued story / 器官移植

Immunosuppressant is one of the main preventive measures for rejection after organ transplantation, whereas it may reduce the host response capability to pathogens and increase the risk of infection. In recent years, the application of mesenchymal stem cell (MSC) therapy in the field of solid organ transplantation has attracted widespread attention. Preclinical studies have shown that MSC therapy may prolong the survival time of transplant kidney, induce immune tolerance, accelerate the repair of acute kidney injury and promote the recovery of renal function. Clinical trials have confirmed the safety, tolerance and effectiveness of MSC therapy. Consequently, general characteristics, immunomodulation and tissue repair function of MSC, and the application of MSC in clinical trials of kidney transplantation were reviewed, the unresolved issues were briefly discussed and the prospects for subsequent research were predicted, aiming to provide reference for promoting the application of MSC therapy in clinical kidney transplantation.

Lethal mitochondrial trifunctional protein deficiency: a case report and literature review / 中国新生儿科杂志

Objective:To explore the clinical phenotype, diagnosis, treatment and genetic characteristics of infants with lethal mitochondrial trifunctional protein deficiency (MTPD).Methods:The clinical data of one patient with lethal MTPD admitted to the neonatal department of Guilin Maternal and Child Health Hospital were retrospectively analyzed. Relevant literature published up to July 2023 were retrieved from the Chinese Science and Technology Journal database, CNKI, Wanfang Database, Chinese Medical Journal Full-text Database, Chinese Biomedical Journal Literature Database, China Biomedical Literature Database, PubMed, Elsevier ScienceDirect, Embase and BIOSIS Previews with the terms of "mitochondrial trifunctional protein deficiency", "mitochondrial trifunctional protein", "HADHA", "HADHB", "newborn", "infant" and "lethal". Then the characteristics of clinical phenotypes and genetic variations about MTPD infants were summarized.Results:This patient was a 33 +3 week premature male infant who developed symptoms 9 d after birth. The main manifestations were metabolic acidosis, recurrent apnea, shock, cardiomyopathy and heart failure. Blood tandem mass spectrometry reported an increased levels of multiple acylcarnitines, and genetic testing indicated that the patient's HADHB gene had maternal c.527C>G missense mutation and de novo c.1148C>T missense mutation. The infant was diagnosed with lethal MTPD and died 12 d after birth after his family gave up the treatment. There were 29 cases in the total 13 publications that were retrieved. Together with this case, there were 30 cases involved. Among the 16 cases with relatively complete data, 10 cases were male and 15 cases developed symptoms in neonatal period. The main clinical phenotypes were cardiomyopathy, abnormal myocardial enzyme spectrum, heart failure and lactic acidosis or metabolic acidosis. Among the 15 cases with clear age of death, 14 died within 3 months of life. Of the reported patients, only one survived at 8 years of age. 29 cases were confirmed through genetic test, 10 infants had HADHA gene variations and 19 had HADHB gene variations. Only one patient was confirmed by pathological detection and mass spectrometry analysis. Conclusions:MTPD is a rare autosomal recessive genetic disease. Lethal MTPD has an early onset with high mortality. Severe acidosis and heart failure are the most common symptoms in neonatal period. Early detection of acylcarnitine and HADHB, HADHA gene should be performed in highly suspected infants to help early genetic diagnosis and intervention.

Analysis of work-related injury medical expenses and influencing factors in Kunshan City from 2016 to 2021 / 中国职业医学

ObjectiveTo understand the influencing factors of work-related injury medical expenses in Kunshan City. Methods The work-related injury data of Kunshan City from 2016 to 2021 were collected from the “Jiangsu Human Resources and Social Security Integration Handling Platform” of Kunshan Municipal Human Resources and Social Security Bureau, and the influencing factors of work-related injury medical expenses were analyzed using quantile regression. Results The median (interquartile range) of per capita work-related injury medical expenses in Kunshan City from 2016 to 2021 was 1 025.6(7 199.1) yuan. The result of 0.50 quantile regression analysis showed that the work-related injury medical expenses of male workers were higher than that of female workers (P<0.01), the work-related injury medical expenses of workers aged 46 and above were higher than those aged 16-<26 (P<0.01), the work-related injury medical expenses of veteran workers were lower than those of new workers (P<0.01), the work-related injury medical expenses of workers in the third, fourth, fifth, and sixth major risk industries were higher than that in the first major risk industry (all P<0.05), the work-related injury medical expenses on lower limb, head and neck, trunk, and multiple injured areas were lower than upper limb injuries (all P<0.01), the work-related injury medical expenses of workers with death, grades 5 to 6, grades 7 to 10, failure to reach grade, and ungraded injuries were lower than those of workers with grades 1 to 4 injuries (all P<0.01), the medical expenses for work-related injuries such as scalds, burns, and scorch were higher than cuts, abrasions, and stabs injuries (P<0.01). Conclusion The influencing factors of the workers' medical expenses for work-related injuries are age, gender, and injured body part. It is necessary to further strengthen the prevention of work-related injuries for males, new workers, workers in the third to sixth major risk industries, and those aged 46 and above. Meanwhile, it is needed to prevent workers from suffering scalds, burns, scorch injuries, upper limb injuries, and high disability grades injuries, to reduce the economic burden on workers and the society.

Development of a national health standard: Guideline for pediatric transfusion / 中国输血杂志

Children and adults differ significantly in physiology, biochemistry and immune function, which leads to significant differences in blood transfusion strategies between children and adults. To guide the clinical transfusion practice of pediatric patients and improve the prognosis of children, the National Health Commission organized the formulation and release of the health industry standard Guideline for Pediatric Transfusion (WS/T 795-2022).This paper will briefly introduce some concepts that help understand of the Standard and the preparation process of the Standard, and explain and interpret the preparation of the " scope", " general provisions" and " factors to consider" of the Standard, hoping to contribute to the understanding and implementation of the Standard.

Impact of subjective vertical perception impairment on function in stroke patients: a retrospective study / 中国康复理论与实践

ObjectiveTo explore the impact of subjective vertical perception impairment after stroke on visuospatial cognition, balance, walking and activities of daily living, to investigate the mediating role of visuospatial cognition and lateropulsion. MethodsFrom February to December, 2023, 96 stroke patients were selected from the Rehabilitation Medicine Center of the First Affiliated Hospital of Nanjing Medical University. They were divided into vertical perception impairment group (n = 53) and non-vertical perception impairment group (n = 43). They were assessed with National Institutes of Health Stroke Scale (NIHSS), the Scale for Contraversive Pushing (SCP), Burke Lateropulsion Scale (BLS), Line Bisection Test (LBT), Line Cancellation Test (LCT), Star Cancellation Test (SCT), Subjective Visual Vertical (SVV), Berg Balance Scale (BBS), Holden Functional Ambulation Categories (FAC) and Barthel Index (BI). ResultsScores of SVV orientation, SVV uncertainty, NIHSS, SCT, SCP, BLS, BBS, FAC and BI were worse in the vertical perception impairment group than in the non-vertical perception impairment group (|t| > 2.414, Z = -3.481, P < 0.05). Scores of SVV were correlated with SCT, BLS and BBS (|r| ≥ 0.273, P < 0.05). After controlling for age and gender, SVV orientation score did not directly impact BBS score (β = -0.011, P = 0.920). However, it exerted a partial mediating effect through BLS (effect = -0.173, 95%CI -0.278 to -0.076) and a chain-mediated effect through SCT and BLS (effect = -0.073, 95%CI -0.137 to -0.027), impacting BBS score. ConclusionSubjective vertical perception impairment results in poorer visuospatial cognition, balance, walking and activities of daily living in stroke patients. This influence on balance function is mediated through the mediating effects of visuospatial cognition and lateropulsion.

Effect of modified Baduanjin exercise on cardiopulmonary function, motor function and activities of daily living for stroke patients / 中国康复理论与实践

ObjectiveTo investigate the effect of modified Baduanjin exercise, as an rehabilitation exercise, on cardiopulmonary function, motor function and activities of daily living in patients with stroke. MethodsFrom January to September, 2023, 42 stroke patients in the Nanjing Qixia District Hospital were randomly divided into control group (n = 21) and experimental group (n = 21). The control group received routine rehabilitation, and the experimental group received modified Baduanjin exercise in addition, for four weeks. They were assessed with peak oxygen uptake (VO2peak), anaerobic threshold (AT), peak oxygen pulse (VO2peak/HR), forced vital capacity (FVC), forced expiratory volume in the first second (FEV1), peak expiratory flow (PEF), Fugl-Meyer Assessment-upper extremities (FMA-UE), Berg Balance Scale (BBS) and modified Barthel Index (MBI) before and after intervention. ResultsVO2peak, AT, and the scores of FMA-UE, BBS and MBI improved in the control group after intervention (|t| > 2.256, |Z| > 2.936, P < 0.05); while VO2peak, AT, VO2peak/HR, FVC, FEV1, PEF, and the scores of FMA-UE, BBS and MBI improved in the experimental group (|t| > 4.390, |Z| > 3.451, P < 0.001); and all the indexes were better in the experimental group than in the control group (|t| > 4.136，|Z| > 2.751，P < 0.01), except the scores of BBS and MBI. ConclusionModified Baduanjin exercise can improve the cardiopulmonary function and upper limb motor function for stroke patients.

Effect of galvanic vestibular stimulation on stroke patients with lateropulsion / 中国康复理论与实践

ObjectiveTo investigate the effect of galvanic vestibular stimulation on stroke patients with lateropulsion. MethodsFrom February to October, 2023, 30 stroke patients with lateropulsion in the First Affiliated Hospital of Nanjing Medical University were divided into control group (n = 15) and experimental group (n = 15) randomly. The control group received routine rehabilitation and sham galvanic vestibular stimulation, and the experimental group received routine rehabilitation and true galvanic vestibular stimulation, for two weeks. They were assessed with Scale for Contraversive Pushing (SCP), subjective visual vertical (SVV), Line Cancellation Test (LCT), Star Cancellation Test (SCT), Berg Balance Scale (BBS), Holden Functional Ambulation Category (FAC) and Barthel Index (BI) before and after treatment. ResultsAll the indexes improved in both groups after intervention (|t| > 2.461, Z > 3.000, P < 0.05), except the SVV orientation, SVV certainty and SCT in the control group; while the SCP, SVV certainty, LCT and FAC were better in the experimental group than in the control group (|t| > 2.189, Z = -2.862, P < 0.05), and the differences before and after intervention were better in the experimental group than in the control group (|t| > 2.382, P < 0.05), except LCT. SCP was correlated with SVV orientation, SVV certainty, SCT, BBS, BI and FAC (|r| > 0.381, P < 0.05). ConclusionGalvanic vestibular stimulation can improve the lateropulsion, balance, walking function and activities of daily living in stroke patients, which may be related to improvement for spatial cognitive function, especially vertical perception.

Burden of coronary heart disease for adult patients and its correlation with sociodemographic index / 公共卫生与预防医学

Objective To analyze the burden of disease attributable to coronary heart disease in adult patients in 2020, to compare the disease burden of patients with coronary heart disease among different sociodemographic indexes (SDI) , and to explore the correlation between the two to provide theoretical guidance for coronary heart disease prevention. Methods The data of 881 adult patients with coronary heart disease in our Hospital in 2020 were collected, and the data, such as illness, morbidity, mortality and disability-adjusted life years (DALY) of adult patients with coronary heart disease were analyzed. Pearson correlation was used to analyze the association between disease burden and sociodemographic index in adult patients with coronary heart disease. Results The prevalence and incidence of adult patients with coronary heart disease were higher in women than in men, while the mortality rate and DALY rate were mainly higher in men than in women. The prevalence, morbidity and mortality rates increased in different age groups, and increased rapidly in the age group of 45 years and beyond. The prevalence of DALY in adult patients with coronary heart disease in different age groups also showed an upward trend, and increased rapidly in the age group of 35 years and beyond. The SDI value of adult patients with coronary heart disease was (0.52±0.16), of which the low SDI value was (0.13±0.05), the medium and low SDI value was (0.34±0.17), the medium SDI value was (0.50±0.14), the medium and high SDI value was (0.82±0.25), and the high SDI value was (0.93±0.13). The chi-square results showed that there were differences in mortality (χ2=12.358, P=0.020) and DALY rate (χ2 =14.557, P=0.011) of adult patients with coronary heart disease between different grades of SDI groups, and the differences were statistically significant. Pearson-related results showed that SDI and DALY rate were negatively correlated in adult patients with coronary heart disease (r=-0.374, P=0.022), and there were gender differences. SDI was negatively correlated with DALY rate in male patients with coronary heart disease (r=-0.489, P=0.017), and SDI was negatively correlated with mortality (r=-0.290, P=0.040) and DALY rate in female patients with coronary heart disease (r=-0.392, P=0.006）. Conclusion Burden of disease attributed to coronary heart disease in adult patients varies by sex and it has a negative correlation with SDI, and the improvement of national welfare and education level, that is, the increase of SDI may have a certain effect on reducing the burden of coronary heart disease.

Characterization and correlation analysis of lung flora in rats with silica-induced acute lung injury / 中国病理生理杂志

AIM:To elucidate the possible biological mechanism of silica-induced acute lung injury in rats.METHODS:Sixteen Male Sprague-Dawley rats were divided into control and acute silicosis model groups,and instilled intratracheally with 1 mL of normal saline and 50 g/L silica suspension,respectively.After 7 d,the rats were sacrificed for collection of lung tissue and serum.The serum levels of interleukin-1β(IL-1β),IL-18 and tumor necrosis factor-α(TNF-α)were measured by using ELISA.The protein expression levels of nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)and gasdermin D(GSDMD)were measured by immunohistochemistry.Bacterial DNA was ex-tracted from the lung tissue for 16S ribosomal RNA gene sequencing to characterize changes in the composition of lung flo-ra.The differences in the structure of bacterial flora between control and model groups were analyzed by bioinformatic analy-ses.RESULTS:Immunohistochemical analysis showed that the protein expression levels of NLRP3 and GSDMD were higher in the lungs of the rats in model group.In addition,serum cytokine profiling showed that IL-1β,IL-18 and TNF-α levels were significantly higher in model group.The most abundant bacterial genera in the lung flora of the rats in model group were Bifidobacterium,Clostridium sensu stricto 1,and Parasutterella.The NLRP3 and GSDMD levels in the lung tissue and IL-1β and TNF-α levels in serum were positively correlated with the abundance of Parasutterella.CONCLU-SION:The alterations in lung flora structure and increased inflammation levels may be the actual biological mechanisms underlying silica-induced acute lung injury.The modulation of lung flora may provide a basis for the prevention and treat-ment of silica-induced acute lung injury.

Astrocytes in Chronic Pain: Cellular and Molecular Mechanisms / 神经科学通报·英文版

Chronic pain is challenging to treat due to the limited therapeutic options and adverse side-effects of therapies. Astrocytes are the most abundant glial cells in the central nervous system and play important roles in different pathological conditions, including chronic pain. Astrocytes regulate nociceptive synaptic transmission and network function via neuron-glia and glia-glia interactions to exaggerate pain signals under chronic pain conditions. It is also becoming clear that astrocytes play active roles in brain regions important for the emotional and memory-related aspects of chronic pain. Therefore, this review presents our current understanding of the roles of astrocytes in chronic pain, how they regulate nociceptive responses, and their cellular and molecular mechanisms of action.

Meta-analysis of the efficacy of small incision lenticule extraction for astigmatism correction after cyclotorsion compensation / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To compare the efficacy of and without small incision lenticule extraction(SMILE)with cyclotorsion compensation for astigmatism correction.METHODS: PubMed, Web of Science, EMBASE, Cochrane and CNKI, VIP, CBM, and Wan Fang Data were searched for clinically controlled studies from January 2010 to August 2022, including an experimental group with cyclotorsion compensation during SMILE and a control group without cyclotorsion compensation during SMILE. After literature screening, quality evaluation, and data extraction by two researchers independently, the Meta-analysis of uncorrected distance visual acuity(UDVA), residual astigmatism, vector analysis indicators for measuring the astigmatism correction including absolute value of angle of error(|AE|)and magnitude error(ME), and post-operative total higher order aberrations, spherical aberration and coma was carried out with Stata 16.0 software.RESULTS: Seven studies with a total of 846 eyes(442 in the experimental group, 404 in the control group)were finally included. The Meta-analysis showed that there were significant differences in the percentage of eyes with residual astigmatism ≥1.00D(OR=0.17, 95%CI: 0.06～0.49, P&#x003C;0.01), |AE|(WMD=-1.56, 95%CI: -2.68～-0.45, P&#x003C;0.01), the coma(WMD=0.06, 95%CI: -0.08～-0.04, P&#x003C;0.01), and the total higher order aberrations(WMD=-0.04, 95%CI: -0.06～-0.02, P&#x003C;0.01). However, there were no differences in the postoperative UDVA(WMD=0.00, 95%CI: -0.02～0.01, P=0.54), residual astigmatism(WMD=0.08, 95%CI: -0.02～0.18, P=0.10), ME(WMD=-0.01, 95%CI: -0.14～0.12, P=0.85), and the spherical aberration(WMD=0.03, 95%CI: -0.07～0.13, P=0.52).CONCLUSION: Cyclotorsion compensation in SMILE can reduce the angular error caused by eye rotation during astigmatism correction. It also decreases postoperative residual astigmatism. Overall, the SMILE with cyclotorsion compensation is superior in clinical efficacy of the precise correction of astigmatism.

Changes of corneal densitometry after small incision lenticule extraction and femtosecond laser in situ keratomileusis / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To compare the changes in corneal densitometry after small incision lenticule extraction(SMILE)and femtosecond laser in situ keratomileusis(FS-LASIK)and investigate the effect of corneal interface haze on vision after SMILE.METHODS: Prospective cohort study. A total of 93 patients(186 eyes)who were scheduled to undergo refractive surgery at the Ophthalmic Refractive Surgery Center of the Affiliated Hospital of Nantong University from May 2020 to October 2021 were included in the study, and there were 48 patients(96 eyes)in the SMILE group and 45 patients(90 eyes)in the FS-LASIK group. The changes in corneal densitometry, spherical equivalent(SE), and uncorrected visual acuity(UCVA)were observed and compared between the two groups before and at 1d, 1wk, 1, 3 and 6mo after surgery.RESULTS: The 93 patients all successfully completed the surgery, and there were no related complications during and after the surgery, and there were no lost cases. The UCVA of FS-LASIK group was 0.044±0.064 and -0.001±0.065 respectively at 1d and 1wk after surgery, which was better than that of SMILE group(0.102±0.077 and 0.023±0.064; all P&#x003C;0.05). There was no statistical difference in the SE between the two groups at the postoperative follow-ups(P&#x003E;0.05). The corneal densitometry values at 0-2 and 2-6 mm from corneal vertex and total corneal densitometry at 1d postoperatively in the FS-LASIK group were 18.0(17.5, 18.6), 16.2(15.6, 16.7)and 16.7(16.1, 17.3), which were lower than those of SMILE group [18.6(18.1, 19.3), 16.8(16.4, 17.4), 17.2(16.6, 17.8)](all P&#x003C;0.05); The corneal densitometry values at 0-2 and 2-6 mm from corneal vertex and total corneal densitometry at 1wk postoperatively in the FS-LASIK group were 17.2(16.7, 17.6), 15.5(15.0, 15.9)and 15.9(15.3, 16.7), which were lower than those of SMILE group [17.6(17.1, 18.3), 16.0(15.6, 16.5), 16.6(15.9, 17.1)](all P&#x003C;0.05).CONCLUSIONS: The transient interface haze after SMILE is responsible for the early higher corneal densitometry than FS-LASIK. The presence of interface haze is probably a factor for the quality of vision.

Research progress on the relationship between gut microbiota and male infertility / 现代泌尿外科杂志

With the decline in male fertility in recent years, infertility has become an urgent global problem to be solved. Existing evidence shows that gut microbiota has an important impact on male reproductive health, and gut microbiota disorder can affect spermatogenesis by inducing inflammation, metabolic disorder and endocrine disruption. This paper systematically reviews the relevant research progress in this field, focusing on the impact of gut microbiota disorder on male reproductive ability from the aspects of gut microbiota and spermatogenesis, gut microbiota and sex hormone metabolism, effects of fecal microbiota transplantation and dietary regulation on male reproductive function, and discusses the future research directions of gut micro-biota and male infertility.

Current status and new progress of drug therapy for premature ejaculation / 现代泌尿外科杂志

Premature ejaculation (PE) is the most common male sexual dysfunction with a high incidence, which seriously affects the relationship between a husband and wife and family harmony. Drug therapy is a first-line treatment for PE patients with premature ejaculation, and has achieved good efficacy, but the clinically available drugs are single and the abandonment rate is high. Coupled with the ineffective treatment of some patients, new drug research and development is imminent. This paper systematically reviews the current status of drug treatment for premature ejaculation, focusing on the research and development of new drugs and research progress in order to provide a reference for clinicians.

Efficacy of decitabine combined with low dose chemotherapy on children with acute myeloid leukemia / 中华儿科杂志

Objective: To evaluate the efficacy of decitabine combined with low dose chemotherapy (LDC) in the treatment of high-risk, refractory and relapsed pediatric acute myeloid leukemia (AML). Methods: Clinical data of 19 AML children treated with decitabine combined with LDC in the Department of Hematology, Children's Hospital of Soochow University from April 2017 to November 2019 were analyzed retrospectively. The therapeutic response, adverse effects and survival status were analyzed,and the outcomes of patients were followed up. Results: Among 19 AML cases, there were 10 males and 9 females. Five cases were high-risk AML, 7 cases were refractory AML, and 7 cases were relapsed AML. After one course of decitabine+LDC treatment, 15 cases achieved complete remission, 3 cases got partial remission, and only 1 case didn't get remission. All patients received allogeneic hematopoietic stem cell transplantation as consolidation therapy. The follow-up time of all cases was 46 (37, 58) months, 14 children had survived. The cumulative three-year overall survival rate was (79±9) %, events free survival rates was (68±11) %, and recurrence free survival rate was (81±10) %. The most common adverse effects related to the induction treatment were cytopenia (19 cases) and infection (16 cases).There were no treatment-related death during the therapy. Conclusion: Decitabine combined with LDC is a safe and effective option for high-risk, refractory and relapsed AML children, which provides an opportunity for HSCT.

Evaluation and treatment strategy of limb length discrepancy after total hip arthroplasty / 中华外科杂志

Limb length discrepancy(LLD) is a common complication after total hip arthroplasty (THA). Good positioning of the prosthesis and suitable soft tissue tension are essential to ensure hip joint stability. Patients will be more satisfied if almost the same length of both lower extremities is achieved. Preoperative comprehensive evaluation of patients is helpful to prevent the occurrence of LLD after surgery. Therefore, the pelvic spine conditions, as well as type and cause of LLD should be analyzed in detail before surgery. During operation, limb length should be adjusted by touching the position of patella, Kirschner's wires positioning and referring to the relationship between the center of femoral head and the tip of greater trochanter. After surgery, it is necessary to clearly distinguish true LLD from functional LLD, and make a reasonable therapeutic plan according to patient's symptoms and the range of differences in limb length. This article reviews the latest literatures based on clinical practice experience and summarizes the research status of LLD after THA, which helps joint surgeons to have an in-depth understanding of this postoperative complication.

Mechanism of total flavonoids of Rhododendra simsii in alleviating ischemic brain injury / 中国中药杂志

This study explores the effect of total flavonoids of Rhododendra simsii(TFR) on middle cerebral artery occlusion(MCAO)-induced cerebral injury in rats and oxygen-glucose deprivation/reoxygenation(OGD/R) injury in PC12 cells and the underlying mechanism. The MCAO method was used to induce focal ischemic cerebral injury in rats. Male SD rats were randomized into sham group, model group, and TFR group. After MCAO, TFR(60 mg·kg~(-1)) was administered for 3 days. The content of tumor necrosis factor-α(TNF-α), interleukin-1(IL-1), and interleukin-6(IL-6) in serum was detected by enzyme-linked immunosorbent assay(ELISA). The pathological changes of brain tissue and cerebral infarction were observed based on hematoxylin and eosin(HE) staining and 2,3,5-triphenyltetrazolium chloride(TTC) staining. RT-qPCR and Western blot were used to detect the mRNA and protein levels of calcium release-activated calcium channel modulator 1(ORAI1), stromal interaction molecule 1(STIM1), stromal intera-ction molecule 2(STIM2), protein kinase B(PKB), and cysteinyl aspartate specific proteinase 3(caspase-3) in brain tissues. The OGD/R method was employed to induce injury in PC12 cells. Cells were randomized into the normal group, model group, gene silencing group, TFR(30 μg·mL~(-1)) group, and TFR(30 μg·mL~(-1))+gene overexpression plasmid group. Intracellular Ca~(2+) concentration and apoptosis rate of PC12 cells were measured by laser scanning confocal microscopy and flow cytometry. The effect of STIM-ORAI-regulated store-operated calcium entry(SOCE) pathway on TFR was explored based on gene silencing and gene overexpression techniques. The results showed that TFR significantly alleviated the histopathological damage of brains in MCAO rats after 3 days of admini-stration, reduced the contents of TNF-α, IL-1, and IL-6 in the serum, down-regulated the expression of ORAI1, STIM1, STIM2, and caspase-3 genes, and up-regulated the expression of PKB gene in brain tissues of MCAO rats. TFR significantly decreased OGD/R induced Ca~(2+) overload and apoptosis in PC12 cells. However, it induced TFR-like effect by ORAI1, STIM1 and STIM2 genes silencing. However, overexpression of these genes significantly blocked the effect of TFR in reducing Ca~(2+) overload and apoptosis in PC12 cells. In summary, in the early stage of focal cerebral ischemia-reperfusion injury and OGD/R-induced injury in PC12 cells TFR attenuates ischemic brain injury by inhibiting the STIM-ORAI-regulated SOCE pathway and reducing Ca~(2+) overload and inflammatory factor expression, and apoptosis.

Methyl ferulic acid ameliorates ethanol-induced L02 cell steatosis through microRNA-378b-mediated CaMKK2-AMPK pathway / 中国中药杂志

Alcoholic liver disease(ALD), with its increasing morbidity and mortality, has seriously and extensively affected the health of people worldwide. Methyl ferulic acid(MFA) has been proven to significantly inhibit alcohol-induced lipid production in L02 cells through the AMP-activated protein kinase(AMPK) pathway, but its in-depth mechanism remains unclear. This study aimed to further clarify the mechanism of MFA in improving lipid accumulation in L02 cells through the microRNA-378b(miR-378b)-mediated calcium/calmodulin-dependent protein kinase kinase 2(CaMKK2)-AMPK signaling pathway based on existing researches. L02 cells were induced by 100 mmol·L~(-1) ethanol for 48 h to establish the model of ALD in vitro, and 100, 50, and 25 μmol·L~(-1) concentration of MFA was treated. MiR-378b plasmids(containing the overexpression plasmid-miR-378b mimics, silence plasmid-miR-378b inhibitor, and their respective negative control-miR-378b NCs) were transfected into L02 cells by electroporation to up-regulate or down-regulate the levels of miR-378b in L02 cells. The levels of total cholesterol(TC) and triglyceride(TG) in cells were detected by commercial diagnostic kits and automatic biochemical analyzers. The expression levels of miR-378b in L02 cells were detected by real-time quantitative polymerase chain reaction(qRT-PCR). CaMKK2 mRNA levels were detected by PCR, and protein expressions of related factors involved in lipid synthesis, decomposition, and transport in lipid metabolism were detected by Western blot. The results displayed that ethanol significantly increased TG and TC levels in L02 cells, while MFA decreased TG and TC levels. Ethanol up-regulated the miR-378b level, while MFA effectively inhibited the miR-378b level. The overexpression of miR-378b led to lipid accumulation in ethanol-induced L02 cells, while the silence of miR-378b improved the lipid deposition induced by ethanol. MFA activated the CaMKK2-AMPK signaling pathway by lowering miR-378b, thus improving lipid synthesis, decomposition, and transport, which improved lipid deposition in L02 cells. This study shows that MFA improves lipid deposition in L02 cells by regulating the CaMKK2-AMPK pathway through miR-378b.

Clinicopathological Features of Primary Small Cell Neuroendocrine Carcinoma of the Bladder / 中国医学科学院学报

Objective To investigate the clinicopathological features,immunohistochemical features,diagnosis,and relationship with sporadic prostate cancer in primary small cell neuroendocrine carcinoma of the bladder. Methods We retrospectively analyzed the clinical characteristics of 12 patients with primary small cell neuroendocrine carcinoma of the bladder diagnosed at Beijing Chao-Yang Hospital affiliated to Capital Medical University from January 2013 to September 2022.The histological features of primary small cell neuroendocrine carcinoma of the bladder were re-evaluated by two pathologists according to the 2022 revision of the World Health Organization Classification of Tumors of the Urinary System and Male Genital Organs.Electronic medical records were retrieved,and telephone follow-up was conducted from the time of histopathological diagnosis to the death or the end of the last follow-up until January 31,2023. Results The 12 patients include 7 patients in pT3 stage and 1 patient in pT4 stage.Eight patients were complicated with other types of tumors,such as high-grade urothelial carcinoma of the bladder and squamous cell carcinoma.Five patients had sporadic prostate cancer.Immunohistochemical staining showed that 12 (100.0%),10 (83.3%),and 8 (66.7%) patients were tested positive for CD56,Syn,and CgA,respectively.The Ki67 proliferation index ranged from 80% to 90%.Five patients with urothelial carcinoma were tested positive for CK20,GATA3,and CK7.P504S was positive in all the 5 patients with prostate cancer,while P63 and 34βE12 were negative.The follow-up of the 12 patients lasted for 3-60 months.Eight of these patients died during follow-up,with the median survival of 15.5 months.Four patients survived. Conclusions Primary small cell neuroendocrine carcinoma of the bladder is a rare urological tumor with high aggressiveness and poor prognosis.In male patients with bladder prostatectomy,all prostate tissue should be sampled.If prostate cancer is detected,the prostate-specific antigen level should be monitored.

Therapeutic effect of ursodeoxycholic acid-berberine supramolecular nanoparticles on ulcerative colitis based on supramolecular system induced by weak bond / 中国中药杂志

Ulcerative colitis(UC) is a recurrent, intractable inflammatory bowel disease. Coptidis Rhizoma and Bovis Calculus, serving as heat-clearing and toxin-removing drugs, have long been used in the treatment of UC. Berberine(BBR) and ursodeoxycholic acid(UDCA), the main active components of Coptidis Rhizoma and Bovis Calculus, respectively, were employed to obtain UDCA-BBR supramolecular nanoparticles by stimulated co-decocting process for enhancing the therapeutic effect on UC. As revealed by the characterization of supramolecular nanoparticles by field emission scanning electron microscopy(FE-SEM) and dynamic light scattering(DLS), the supramolecular nanoparticles were tetrahedral nanoparticles with an average particle size of 180 nm. The molecular structure was described by ultraviolet spectroscopy, fluorescence spectroscopy, infrared spectroscopy, high-resolution mass spectrometry, and hydrogen-nuclear magnetic resonance(H-NMR) spectroscopy. The results showed that the formation of the supramolecular nano-particle was attributed to the mutual electrostatic attraction and hydrophobic interaction between BBR and UDCA. Additionally, supramolecular nanoparticles were also characterized by sustained release and pH sensitivity. The acute UC model was induced by dextran sulfate sodium(DSS) in mice. It was found that supramolecular nanoparticles could effectively improve body mass reduction and colon shortening in mice with UC(P<0.001) and decrease disease activity index(DAI)(P<0.01). There were statistically significant differences between the supramolecular nanoparticles group and the mechanical mixture group(P<0.001, P<0.05). Enzyme-linked immunosorbent assay(ELISA) was used to detect the serum levels of tumor necrosis factor-α(TNF-α) and interleukin-6(IL-6), and the results showed that supramolecular nanoparticles could reduce serum TNF-α and IL-6 levels(P<0.001) and exhibited an obvious difference with the mechanical mixture group(P<0.01, P<0.05). Flow cytometry indicated that supramolecular nanoparticles could reduce the recruitment of neutrophils in the lamina propria of the colon(P<0.05), which was significantly different from the mechanical mixture group(P<0.05). These findings suggested that as compared with the mechanical mixture, the supramolecular nanoparticles could effectively improve the symptoms of acute UC in mice. The study provides a new research idea for the poor absorption of small molecules and the unsatisfactory therapeutic effect of traditional Chinese medicine and lays a foundation for the research on the nano-drug delivery system of traditional Chinese medicine.