Study on the correlation between retinal microvascular density and damage to visual field in patients with sellar region tumor / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To evaluate the changes of retinal microvascular density in patients with sellar region tumor, and its correlation with the damage to visual field, and to explore its application value in evaluating optic nerve injury of those patients.METHODS: Cross-sectional study. A total of 157 patients(292 eyes)with sellar region tumor, including 82 cases(152 eyes)of pituitary adenoma and 75 cases(140 eyes)of craniopharyngioma, were selected from neurosurgery department and ophthalmology department of Beijing Tiantan Hospital, Capital Medical University between October 2018 and May 2022. A total of 90 people(180 eyes)during the same period, including the family members of patients, students and staff in Beijing Tiantan Hospital, Capital Medical University were collected as control group. All participants underwent optical coherence tomography angiography(OCTA)examination. The changes of retinal microvascular density and its correlation with visual field parameters were compared between the two groups.RESULTS: In patients with sellar region tumor, the radial peripapillary capillary(RPC)and superficial retinal capillary plexus(SRCP)density were significantly lower than that in the control group [50.81%(46.49%, 53.49%)vs. 52.78%(50.73%, 54.51%)and 50.57%(48.13%, 52.73%)vs. 51.63%(49.78%, 53.02%), all P<0.05]. The RPC density in the craniopharyngioma group was lower than that in the pituitary adenoma group [49.71%(44.33%, 53.14%)vs. 51.37%(47.42%, 53.95%), P<0.05]. The MD, PSD and VFI of the sellar region tumor group were -4.33(-12.22, -1.85)dB, 3.37(1.91, 8.82)dB and 92%(65%, 97%)respectively. RPC density of patients with sellar region tumor was positively correlated with MD and VFI, and was negatively correlated with PSD. The SRCP density of each quadrant was positively correlated with MD, and was positively correlated with VFI except Para-T and it was negatively correlated with PSD(all P<0.05).CONCLUSION: Retinal microvascular changes were present in patients with sellar region tumor. Lower vessel density indicates more severe damage to visual field. In the clinic, visual field examinations combined with OCTA were helpful to find the optic nerve injury of patients.

Application and prospect of gene therapy for fundus vascular diseases / 国际眼科杂志(Guoji Yanke Zazhi)

Fundus vascular diseases, including neovascular age-related macular degeneration(nAMD)and diabetic retinopathy(DR), are the leading causes of visual impairment worldwide. With the accelerated aging and increased incidence of diabetes, the prevalence of these two fundus diseases will continue to rise. Currently, intraocular injection of anti-vascular endothelial growth factor(anti-VEGF)remains the first-line treatment for fundus vascular diseases, but disadvantages exist, such as frequent intraocular injections, high cost and poor compliance, thus more durable and effective therapeutic strategies need to be explored. The successful application of gene therapy in inherited retinal diseases(IRDs)provides a new idea for the treatment of fundus vascular diseases. With the ongoing of several clinical trials, gene therapy for fundus vascular diseases is expected to be employed in the clinical setting. But there still remain some concerns, including the optimal therapeutic targets selection, administration route and safety issues. This review focuses on the application and prospect of gene augmentation and gene editing-mediated anti-VEGF therapy for the treatment of nAMD and DR.

Diagnosis and treatment of adult diaphragmatic hernia / 中华消化外科杂志

The etiology of diaphragmatic hernia in adults is mainly congenital and traumatic, its overall incidence in adults is low, and adult diaphragmatic hernia is easily misdiagnosed and missed diagnosis because of lacking specificity in clinical presentation. There is no clinical guidelines or consensus for the diagnosis and treatment of diaphragmatic hernia in adults. The authors inquire into the diagnosis and treatment of diaphragmatic hernia in adults by summarizing relevant litera-tures and combining with clinical practice, and recommend that multi-slice spiral computed tomo-graphy should be promptly refined for suspected cases, especially focusing on sagittal images. The symptomatic patients should be repaired promptly, with a preference for laparoscopic surgery, and mesh augmentation is recommended in those with larger defects.

Rational application of breast oncoplastic surgery techniques / 中华内分泌外科杂志

Breast oncoplastic surgery technique is a new technique in the surgical treatment of breast cancer. For tumors in different quadrants, volume displacement or volume replacement techniques can be used to obtain tumor safety while effectively reducing the occurrence of breast deformity and maximizing the aesthetic appearance of the breast. This article provides a comprehensive introduction of breast-conserving surgery for breast tumors, which can provide guidance and direction for breast surgeons to perform this technique in a more standardized and rational way in clinical practice, and ultimately allow patients to obtain satisfactory treatment results.

Long-term efficacy of endoscopic transluminal drainage for acute pancreatitis complicated with walled-off necrosis or pancreatic pseudocyst / 中华消化内镜杂志

Objective:To evaluate the long-term efficacy of endoscopic transluminal drainage(ETD) for acute pancreatitis complicated with walled-off necrosis (WON) or pancreatic pseudocyst (PPC).Methods:A total of 79 patients who were diagnosed as having WON or PPC by abdominal CT or ultrasound and treated with ETD in Nanjing Drum Tower Hospital were enrolled. Past medical records and follow-up by phone call after discharge were analyzed for long-term outcomes including endocrine and exocrine functions and long-term quality of life.Results:A total of 50 patients were enrolled, including 31 patients with infected WON/PPC and 19 patients with uninfected WON/PPC. Seventeen patients (54.84%) in the infected WON/PPC group and 11 patients (57.89%) in the uninfected WON/PPC group lost 5% or more of their weight. There were no significant differences in the proportion of cases of weight loss of 5% or more ( P=0.833), or the weight loss between the two groups (12.59±8.89 kg VS 10.91±2.47 kg, P=0.522). Only one patient in the infected WON/PPC group had chronic abdominal pain. There was no significant difference in the Izbicki score between the two groups (23.79±6.74 VS 22.03±3.21, P=0.295). None of the patients developed steatorrhea after discharge. Five patients (16.67%, 5/30) in the infected WON/PPC group and 6 patients (40.00%, 6/15) in the uninfected WON/PPC group developed endocrine insufficiency with no significant difference ( P=0.140). Greater risk of secondary diabetes resulted from higher low-density lipoprotein cholesterol ( HR=1.9, 95% CI: 1.0-3.4, P=0.044)and triglycerides ( HR=1.2, 95% CI: 1.0-1.3, P =0.029). Conclusion:ETD is safe and effective for WON and PPC. But there is possibility that patients develop secondary diabetes. Additionally, greater risk of secondary diabetes results from higher low-density lipoprotein cholesterol and triglycerides.

Short-term clinical study of vitrectomy combined with intraoperative slow-release dexamethasone implantation in the treatment of severe idiopathic macular epiretinal membrane / 中华眼底病杂志

Objective:To observe the efficacy of dexamethasone intravitreal implant (DEX) combined with pars plana vitrectomy (PPV) in eyes with severe idiopathic epimacular membrane (IMEM).Methods:A prospective clinical case study. From December 2018 to May 2021, 24 patients with 25 eyes of severe IMEM diagnosed in Tianjin Medical University Eye Hospital were included in the study. Among them, 7 males had 7 eyes, 17 females had 18 eyes. Age was 57 to 84 years old. The IMEM stage was 3 to 4 examined by spectral domain optical coherence tomography (SD-OCT). All eyes were performed best corrected visual acuity (BCVA) and central macular thickness (CMT) by SD-OCT. The patients were randomly divided into PPV group (11 eyes) and PPV+DEX group (14 eyes). Standard PPV by three-channel 25G was performed. Phacoemulsification, membrane stripping and intraocular lens implantation were combined during the operation. Patients received vitreous injection of 0.7 mg DEX in PPV+DEX group at the end of the operation. At 1 week, 1 month, 3 months and 6 months after operation, the same equipments and methods were used to perform relevant examinations. The changes of BCVA and CMT were compared between the two groups by t test. Results:Compared with before operation, at 1, 3 and 6 months after operation, the BCVA of the eyes in the PPV+DEX group was significantly improved ( t=3.974, 4.639, 4.453), CMT was significantly decreased ( t=2.955, 3.722, 4.364), the differences were statistically significant ( P<0.05); at 3 and 6 months after surgery, the BCVA of the eyes in the PPV group was significantly improved ( t=2.983, 4.436), CMT was significantly decreased ( t=2.983, 3.461), the differences were statistically significant ( P<0.05). Conclusion:In the treatment of severe IMEM, DEX can accelerate the early postoperative visual recovery and reduce CMT.

Development of bioprinting technology and its application in bone tissue engineering / 中华骨科杂志

In recent decades, bone tissue engineering has made great progress in the treatment of large bone defects, among which bioprinting is one of the most important technologies. 3D bioprinting achieves precise control of the spatial structure of bone tissue engineering scaffold manufacturing by adding different materials in layers, and cells are placed into the scaffolds based on hydrogel materials to solve the uniform distribution of cells in the scaffolds. However, most biomedical materials used for 3D bioprinting are static and cannot be changed with the dynamics of the body's internal environment. 4D bioprinting combines the concept of time with 3D bioprinting and uses stimulus-responsive materials to change their shape under various stimuli to create dynamic 3D biological structures. It offers unprecedented potential for bone tissue engineering. The shape memory properties of printed structures meet the needs of personalized bone defect repair, and functional maturation procedures promote osteogenic differentiation of stem cells. In this paper, we review the commonly used 3D bioprinting methods and the mechanism of functional and morphological transformation in 3D bioprinting developed into 4D bioprinting technology by summarizing the research on bioprinting and tissue engineering at home and abroad in recent years. What's more, we introduce the application of bioprinting in the treatment of bone defects in bone tissue engineering as well as the current challenges and future prospects.

Anti-tumor activity of yeast vesicle biomimetic nanomedicine with the ability of active tumor penetration / 药学学报

The dense extracellular matrix (ECM) of the tumor severely limits the deep penetration of nanomedicine and weakens its anti-tumor effect. Based on this, the yeast vesicle biomimetic nanomedicine with active deep penetration ability of tumor tissue was designed and developed for enhanced tumor therapy. Results of characterization showed that the yeast cell vesicles (YCV) displayed a spherical morphology with diameter of around 100 nm and was well dispersed. Then the chemotherapeutic drug doxorubicin (DOX) was selected as a model drug, and DOX was loaded into YCV to obtain YCV/DOX through electrostatic interaction, the encapsulation efficiencies of DOX were calculated as 82.5%. The drug release profile of YCV/DOX implied that DOX release showed a manner of pH-dependent, it may be that pH has affected the electrostatic effect of YCV and DOX. Compared with liposomes (Lipo), in vitro cell experiments showed that YCV from natural sources had stronger permeability in three-dimensional multicellular spheres. It is speculated that the mechanism may be good deformation capacity of YCV. A 4T1 xenograft tumor model was established to evaluate the therapeutic efficacy of YCV/DOX. The results suggested that YCV/DOX has stronger tumor tissue penetration ability and could effectively inhibit the tumor growth. All animal experiments were performed in line with national regulations and approved by the Animal Experiments Ethical Committee of Zhengzhou University. This study brings new ideas for the development of biomimetic nanomedicine to overcome the ECM of solid tumors.

The role of TNF-α/TNFR1 inhibiting autophagy of M1-type Kupffer cells in liver injury in trichloroethylene-sensitized mice / 中华劳动卫生职业病杂志

Objective: To detect the expression levels of M1-type polarization and autophagy-related indicators in the liver of trichloroethylene (TCE) -sensitized mice, and to explore the role of liver tumor necrosis factor-α (TNF-α) and tumor necrosis factor receptor 1 (TNFR1) in regulating M1-type Kupffer cells autophagy in liver injury in TCE-sensitized mice. Methods: In November 2019, according to simple random grouping, 45 SPF grade BALB/c female mice (6-8 weeks old) were divided into 4 groups: blank control group (n=5) , solvent control group (n=5) , TCE treatment group (n=18) , TCE+R7050 (inhibitor) treatment group (n=17) . Transdermally sensitized mice, 24 h after the last challenge, the mice were divided into TCE sensitized group and TCE non-sensitized group according to the skin reaction score. The livers of mice were harvested, and the pathological changes of the livers were observed under light and electron microscopes. Western blotting was used to detect the expressions of TNF-α, TNFR1 and autophagy-related indexes. The expression of inducible nitric oxide synthase (iNOS) , a marker of M1-type Kupffer cells, was detected by immunohistochemistry, and the occurrence of autophagy in M1-type Kupffer cells was detected by immunofluorescence double-labeling method. Results: The sensitization rate of TCE treatment group was 38.9% (7/18) , and TCE+R7050 treatment group was 35.3% (6/17) , with no significant difference between the two groups (P=1.000) . Compared with the blank control group, mice in the TCE sensitized group had abnormal liver ocytes, obvious liver injury, reduced mitochondria and broken endoplasmic reticulum. Western blotting results showed that the expressions of TNF-α and TNFR1 protein in the liver of the mice in the TCE sensitized group increased, the expression of iNOS protein in M1-type Kupffer cells increased, and the expressions of autophagic microtubule-associated protein 1 light-chain 3 (LC3B) and Beclin1 protein were decreased (P<0.05) . The results of immunohistochemistry showed that iNOS was not significantly expressed in the blank control group and solvent control group, and a small amount of expression was found in the TCE non-sensitized group, the positive staining area was obvious in TCE sensitized group, and the expression of iNOS was significantly increased (P<0.05) . Immunofluorescence results showed that the iNOS protein levels in the blank control group, solvent control group and TCE non-sensitized group were lower, and only partially colocalized with P62; the colocalization of iNOS with P62 in the TCE sensitized group was significantly increased. Conclusion: TNF-α/TNFR1 signaling pathway may promote liver injury in TCE-sensitized mice by inhibiting autophagy of M1-type Kupffer cells.

Oligometastatic and oligoprogressive esophageal squamous cell carcinoma:clarifying conceptions and surgery perspectives / 中华外科杂志

The oligometastatic and oligoprogressive state has been a hot issue in cancer research. Its indolent tumor behavior, representing a novel therapeutic opportunity, has been identified as a clinical subtype in several malignancies. However, the clinical implications of the oligometastatic and oligoprogressive state in esophageal squamous cell carcinoma (ESCC) have not been thoroughly elucidated. There are still controversies regarding the existence of the oligometastatic state in ESCC, if the solitary regional lymph node metastasis should be viewed as oligoprogressive disease after esophagectomy, and the role of surgery and radiotherapy in ESCC oligometastatic disease. Despite many exciting contributions to the literature on these, further exploration is warranted. Thus, fostering the advance of research and scientific knowledge on the biological and prognostic characteristics scrupulously would facilitate personalizing treatment strategy for better outcomes.

M1 macrophages promote non-alcoholic steatohepatitis / 中华消化杂志

Objective:To investigate the function, mechanism and therapeutic potential of macrophages in non-alcoholic steatohepatitis (NASH).Methods:Eight-week-old male foz/ foz (Alms mutant) mice were fed with a high fat diet (HFD) for 6, 8 and 10 weeks and 8-week-old male C57BL/6 mice were fed with a methionine and choline-deficient (MCD) diet for 7 d, 3 weeks and 4 weeks to establish NASH models. The mice of control group were fed with normal diet or MCD control diet. The expression of F4/80 mRNA level in the livers of mice of NASH model group and control group was detected by fluorescence quantitative polymerase chain reaction. Macrophages in the livers of mice of NASH group and control group were determined by immunofluorescence staining. After transgenic lysM-Cre/DTR mice were fed with MCD diet for 5 weeks, they were divided into transgenic experimental group (ablation of macrophages induced by diphtheria-toxin (DTox) injection) and transgenic control group (phosphate buffer saline injection). The levels of triglyceride and lipid peroxide in the livers of transgenic experimental group and transgenic control group were detected, and the inflammation of the livers of the mice was scored. The mechanism of macrophages regulating inflammation in NASH was investigated by cytokine profiliny analysis and Western blotting. The interaction between hepatocytes and macrophages were determined by co-culturing the conditional medium of hepatocytes AML-12 and macrophages RAW264.7. Macrophages of mice of control group and NASH model group were depleted by liposomal clodronate to confirm its value in NASH prevention. Independent sample t-test was used for statistical analysis. Results:F4/80 mRNA level in the livers of NASH model foz/ foz mice fed with HFD for 6 weeks, 8 weeks and 10 weeks was higher than that of control group (1.49±0.19, 1.70±0.15 and 1.93±0.04 vs.1.05±0.22), and the differences were statistically significant ( t=3.06, 4.92 and 7.92, all P<0.05). The expression of F4/80 mRNA level of the livers of NASH model mice fed with MCD for 7 d and 3 weeks was higher than that of control group (2.70±0.99 and 3.08±1.71 vs.1.00±0.83), and the differences were statistically significant ( t=3.43 and 3.54, both P<0.01). The results of immunofluorescence demonstrated that compared with that of control group, the number of F4/80 + inducible nitric oxide synthase (iNOS) + M1 macrophages were significantly increased, while F4/80 + CD206 + M2 macrophages were significantly decreased in the livers of NASH model mice fed with MCD for 4 weeks. After macrophages depletion, the inflammation score, the levels of triglyceride and lipid peroxide in the liver of transgenic experimental mice were all lower than those of transgenic control mice (0.69±0.32 vs. 1.95±0.74, (43.97±13.24) g/mg vs. (63.09±14.85) g/mg, (24.84±6.21) nmol/mg vs.(37.91±8.91) nmol/mg), and the differences were statistically significant ( t =3.14, 2.72 and 2.41, all P<0.05). The results of cytokine profiling analysis showed that macrophage depletion could lower the levels of interleukin (IL)-12 and macrophages inflammatory protein-1α (the difference between multiples: -3.98, -2.74, both P<0.05). CCAAT/enhancer binding protein β was defected in the nuclear of transgenetic experimental mice. In vitro study showed that RAW264.7 macrophages conditional medium could promote lipid accumulation in AML-12 hepatocytes, while conditional medium from MCD medium-treated AML-12 hepatocytes could promote RAW264.7 macrophages to M1 polarization. After treated with liposomal clodronate, the levels of triglyceride and lipid peroxidation in the liver of control mice were both lower than those of MCD-induced NASH model mice((45.33±14.59) g/mg vs. (63.10±16.02) g/mg, (2.11±0.48) nmol/mg vs. (2.73±0.17) nmol/mg), and the differences were statistically significant ( t=2.84 and 2.73, both P<0.05). The results of Western blotting indicated that after treating with liposomal clodronate, the relative content of phosphorylated protein kinase R-like endoplasmic reticulum kinase, inositol requiring enzyme-1α, protein disulfide isomerase, glucose regulatory protein 78, phosphorylated eukaryotic initiation factor 2α in the liver of NASH model mice were all lower than those of NASH model mice without liposomal clodronate treatment (1.84±0.36 vs. 3.05±0.83, 1.50±0.84 vs. 6.65±1.47, 0.87±0.12 vs. 2.28±0.52, 1.68±0.43 vs. 4.76±1.13, 1.42±0.19 vs. 2.75±0.79), and the differences were statistically significant( t=2.32, 5.28, 4.56, 4.41 and 2.85, all P<0.05). Conclusions:Macrophages are polarized into M1 phenotype in NASH. M1 macrophages contributed to NASH progression by interacting with hepatocyets to promote the secretion of inflammatory cytokines, up-regulation of lipogenic factors, oxidative stress and endoplasmic reticulum stress, resulting in the progression of NASH. Macrophages depletion by liposomal clodronate is a potential noval approach for NASH prevention.

Biomarkers of zinc deficiency in left-behind children under 1 year old in Zunyi area / 中华实用儿科临床杂志

Objective:To analyze the urine of normal healthy left-behind children under 1 year old and left-behind children with zinc deficiency under 1 year old in Zunyi area using hydrogen nuclear magnetic resonance ( 1HNMR), thus providing a new biomarker for the early diagnosis of zinc deficiency. Methods:From January to August 2018, a total of 40 normal healthy left-behind children under 1 year old in Zunyi area(healthy control group)[22 males and 18 females, average age of (7.78±3.62) months, average height of (65.01±2.67) cm and average body mass of (7.15±1.59) kg] and 40 age-matched left-behind children with zinc deficiency in the same region(zinc deficiency group)[19 males and 21 females, average age of (7.89±3.57) months, average height of (64.25±2.95) cm and average body mass of (7.02±1.68) kg] were included for a cross-sectional study by stratified sampling.The urine 1HNMR spectra of children in the 2 groups were measured, and the age, height, body mass and serum zinc content of children in the 2 groups were compared.The metabolites of the 2 groups were compared by metabono-mics technology combined with multivariate statistical analysis, and the differential metabolites of children with zinc deficiency were screened out. Results:There were no significant differences in age, height and body mass between the 2 groups (all P>0.05). The serum zinc level of healthy control group was significantly higher than that of zinc deficiency group [(54.3±3.06) mmol/L vs.(39.2±3.77) mmol/L, t=22.65, P<0.05]. Urine 1HNMR spectrogram results showed that compared with healthy controls, 4-hydroxyphenylpyruvic acid, phenyl acetyl glycine, and hippuric acid salt water were significantly lower in zinc deficiency group ( r=-0.620, -0.689, and -0.721, respectively, all | r|>0.602, all P<0.05). Conclusions:Zinc deficiency in left-behind children under 1 year old in Zunyi area is mainly manifested by decreased metabolites of 4-hydroxyphenylpyruvic acid, phenylacetyl glycine and horse-urate, suggesting metabolic disorder of intestinal flora.Differentially expressed metabolites have a potential application value in the early diagnosis of zinc deficiency.

Characteristics of sepsis in the emergency department of a tertiary hospital in Tianjin: A 4-year retrospective analysis / 中华急诊医学杂志

Objective:Taking emergency department (ED) as a starting point, to analyze the epidemiological characteristics and mortality risk factors of sepsis, and to provide evidences for ED to carry out the strategy of "three early and two lower" for sepsis.Methods:Based on the ED and inpatient medical record management information platform of Tianjin Medical University Gernal Hospital, adult ED patients with sepsis from January 1, 2017 to December 31, 2020 were included according to the third international consensus definitions for sepsis and septic shock in 2016 and the consensus of Chinese experts on early prevention and blocking of sepsis in 2020. The epidemiological characteristics of patients were retrospectively analyzed. Chi-square test was used to compare the difference of age, sex, hospitalization times, length of stay, hospitalization cost and infection location between dead patients and survival patients, and a stepwise logistic regression model was used to analyze the influencing factors of mortality in hospitalized patients with ED sepsis.Results:A total of 7 494 patients with sepsis in ED were included in this study, and the annual and monthly component ratios varied from 3.8‰ to 6.1‰ and 2.0‰ to 9.0‰, respectively. The main characteristics of patients with sepsis in ED were as follows: 40-69 years old (46.0%), male (59.0%), mostly diagnosed with sepsis (96.8%), mainly treated with urban health insurance (59.6%), and ED diagnosis and treatment fees of 2 000-8 000 Yuan (51.1%). The mortality of hospitalized patients with ED sepsis was 24.4% and that of hospitalized patients with septic shock was 28.8%. The main characteristics of hospitalized patients with ED sepsis were as follows: most of them were male (56.2%) patients over 70 years old (56.0%), most of them were diagnosed with sepsis (94.0%) and hospitalized for the first time (76.0%), the median hospitalization time was 15 d, most of them were hospitalized under urban health insurance (65.2%), and the median hospitalization fees was 47 000 Yuan. The risk factors of death were influenced by age and length of stay. Patients aged 70 years or older had a higher risk of death than those aged from 18 to 39 years, and patients with a length of stay of more than 7 d had a lower risk of death than those with a length of stay of shorter than 7 d. The primary infection focus were mainly respiratory and urinary systems, while the death rate of patients with hematological and abdominal infections was relatively high, and the difference was statistically significant ( P<0.01). Respiratory and abdominal infections were risk factors for death in patients with ED sepsis. Conclusions:The composition ratio of sepsis in ED patients is not regular in time, so vigilance of sepsis in elderly men and patients with respiratory system, blood system, urinary system and abdominal infections should be constantly raised. Patients with sepsis who are older, hospitalized more frequently, hospitalized for a shorter time, and infected in the respiratory system or abdomen have a higher risk of death.

A Neural Circuit Mechanism Controlling Breathing by Leptin in the Nucleus Tractus Solitarii / 神经科学通报·英文版

Leptin, an adipocyte-derived peptide hormone, has been shown to facilitate breathing. However, the central sites and circuit mechanisms underlying the respiratory effects of leptin remain incompletely understood. The present study aimed to address whether neurons expressing leptin receptor b (LepRb) in the nucleus tractus solitarii (NTS) contribute to respiratory control. Both chemogenetic and optogenetic stimulation of LepRb-expressing NTS (NTSLepRb) neurons notably activated breathing. Moreover, stimulation of NTSLepRb neurons projecting to the lateral parabrachial nucleus (LPBN) not only remarkably increased basal ventilation to a level similar to that of the stimulation of all NTSLepRb neurons, but also activated LPBN neurons projecting to the preBötzinger complex (preBötC). By contrast, ablation of NTSLepRb neurons projecting to the LPBN notably eliminated the enhanced respiratory effect induced by NTSLepRb neuron stimulation. In brainstem slices, bath application of leptin rapidly depolarized the membrane potential, increased the spontaneous firing rate, and accelerated the Ca2+ transients in most NTSLepRb neurons. Therefore, leptin potentiates breathing in the NTS most likely via an NTS-LPBN-preBötC circuit.

Butyl alcohol extract of Baitouweng Decoction alleviates vulvovaginal candidiasis in mice by downregulating NLRP3 inflammasome and related signal pathways / 中国中药杂志

This study aims to explore the effect of butyl alcohol extract of Baitouweng Decoction(BAEB) on vulvovaginal candidiasis(VVC) in mice and to clarify the mechanism from Toll-like receptors(TLRs)/MyD88 and Dectin-1/Syk signal pathways and NLRP3 inflammasome. To be specific, female KM mice were randomized into control group(i.g., normal saline), model group, fluco-nazole group(i.g., 20 mg·kg~(-1)), and low-dose, medium-dose, and high-dose BAEB groups(i.g., 20, 40, and 80 mg·kg~(-1), respectively). VVC was induced in mice except the control group. After the modeling, administration began and lasted 7 days. The ge-neral conditions and body weight of mice were recorded every day. On the 1 st, 3 rd, 7 th, and 14 th after vaginal infection by Candida albicans, the fungal load in the vaginal lavage fluid of the mice was measured with the plate method, and the morphology of C. albicans in vaginal lavage fluid was observed based on Gram staining. After the mice were killed, vaginal tissues were subjected to hematoxylin-eosin(HE) staining and periodic acid-Schiff(PAS) staining for vaginal histopathological analysis. The content of cytokines in vaginal lavage fluid, such as interleukin(IL)-1β, IL-18, tumor necrosis factor-α(TNF-α), IL-6, and S100 a8, was determined by enzyme-linked immunosorbent assay(ELISA), and content of reactive oxygen species(ROS) in vaginal tissues by tissue ROS detection kit. The protein expression of NLRP3, ASC, caspase-1, Dectin-1, Syk, MyD88, TLR2, TLR4, and nuclear factor-κB(NF-κB) in vaginal tissues was detected by Western blot, and the levels and distribution of NLRP3, Dectin-1, Syk, MyD88, TLR2, and TLR4 in vaginal tissues were determined with the immunohistochemical method. The results show that BAEB can improve the general conditions of VVC mice, reduce the fungal load and C. albicans hyphae in vaginal secretion, decrease ROS content in vaginal tissues and content of cytokines in vaginal lavage fluid, and down-regulate the expression of NLRP3, ASC, caspase-1, Dectin-1, Syk, MyD88, TLR2, TLR4, and NF-κB in vaginal tissues. The above results indicate that BAEB exerts therapeutic effect on VVC mice by down-regulating the key proteins in the TLRs/MyD88 and Dectin-1/Syk signal pathways and NLRP3 inflammasome.

Anti-nociceptive effects of dual neuropeptide antagonist therapy in mouse model of neuropathic and inflammatory pain

Background@#Neurokinin-1 (NK1) and calcitonin gene-related peptide (CGRP) play a vital role in pain pathogenesis, and these proteins’ antagonists have attracted attention as promising pharmaceutical candidates. The authors investigated the antinociceptive effect of co-administration of the CGRP antagonist and an NK1 antagonist on pain models compared to conventional single regimens. @*Methods@#C57Bl/6J mice underwent sciatic nerve ligation for the neuropathic pain model and were injected with 4% formalin into the hind paw for the inflammatory pain model. Each model was divided into four groups: vehicle, NK1 antagonist, CGRP antagonist, and combination treatment groups. The NK1 antagonist aprepitant (BIBN4096, 1 mg/kg) or the CGRP antagonist olcegepant (MK-0869, 10 mg/ kg) was injected intraperitoneally. Mechanical allodynia, thermal hypersensitivity, and anxiety-related behaviors were assessed using the von Frey, hot plate, and elevated plus-maze tests. The flinching and licking responses were also evaluated after formalin injection. @*Results@#Co-administration of aprepitant and olcegepant more significantly alleviated pain behaviors than administration of single agents or vehicle, increasing the mechanical threshold and improving the response latency. Anxiety-related behaviors were also markedly improved after dual treatment compared with either naive mice or the neuropathic pain model in the dual treatment group. Flinching frequency and licking response after formalin injection decreased significantly in the dual treatment group. Isobolographic analysis showed a meaningful additive effect between the two compounds. @*Conclusions@#A combination pharmacological therapy comprised of multiple neuropeptide antagonists could be a more effective therapeutic strategy for alleviating neuropathic or inflammatory pain.

Advances in drugs on targeting SMN2 for the treatment of spinal muscular atrophy / 药学学报

As one of the most serious hereditary neuromuscular disease, spinal muscular atrophy (SMA) is caused by the loss or mutation of survival motor neuron 1 (SMN1) gene. It leads to a decrease in the level of SMN protein and a consequent loss of alpha neurons and progressive muscle atrophy resulting in the progressive muscle weakness, the significant disability and the shortened lifespan. Up till now, only three drugs have been approved for SMA, including the gene therapy drug onasemnogene abeparvovec. The antisense oligonucleotide drug nusinersen and and the small molecule chemical drug risdiplam were briefly introduced. Some representative samples of the small molecule chemical drugs and antisense oligonucleotide drugs targeting SMN2 in the clinical trial or preclinical research phases were also reviewed.

Emerging targets and drugs of inflammatory bowel disease / 药学学报

Inflammatory bowel disease (IBD) is a chronic, repeated intestinal inflammatory disease. Clinically commonly used therapeutic drugs have some disadvantages, such as poor efficacy and many adverse reactions after long-term application. Although new biological therapies such as anti-tumor necrosis factor agents, overcome common adverse reactions, also have problems such as high price, difficult storage, drug resistance and recurrence after application. In recent years, many new therapeutic methods for inflammatory bowel disease have emerged, for example, modulators that inhibit lymphocyte migration (integrin inhibitors and sphingosine 1-phosphate receptor agonists) have been introduced into the clinical treatment of inflammatory bowel disease, inflammatory cytokine inhibitors (interleukin-23 inhibitors, Janus kinase inhibitors, phosphodiesterase inhibitors, etc.) and inhibitors targeting fibrosis and intestinal tissue degradation and remodeling (matrix metalloproteinase inhibitors) are also being evaluated in clinical trials of IBD. Based on the mechanisms of action, this paper intends to outline the current mainstream IBD therapies and some emerging drugs, and briefly introduce their targets to provide reference for IBD drug design and development.

Respiratory virus infection and risk factors in children with bronchial asthma / 公共卫生与预防医学

Objective To understand the etiological characteristics and risk factors of respiratory virus infection in children with bronchial asthma, and to provide theoretical basis for the prevention and treatment of respiratory virus infection in children with bronchial asthma. Methods A total of 374 children with bronchial asthma who were treated in Jianyang People's Hospital from December 2018 to December 2020 were enrolled. Pharyngeal swabs were collected from the outpatient children on the day of treatment, and 2 mL of nasopharyngeal secretions were collected from the hospitalized children within 24 hours by negative pressure aspirator. Seven viral antigens including RSV, ADV, IVA, IVB, PIVI, PIV II, and PIV III were detected. According to whether the virus test results were positive or not, they were divided into the experimental group (n=191) and the control group (n=183). Logistic regression analysis was used to screen the risk factors of respiratory virus infection in children with bronchial asthma. Results Among the 374 samples, the virus positive rate was 51.07% (191/374), and the top 3 virus species in the positive samples were RSV, ADV, and PIV III, accounting for 41.36% (79/191), 30.36% (58/191), and 9.42% (18/191), respectively. In addition, IVA accounted for 5.24% (10/191), PIV II accounted for 5.24% (10/191), PIVI accounted for 3.66% (7/191), and IVB accounted for 1.57% (3 /191). The positive rates of virus were 47.96% (94/196) and 54.49% (97/178) in male and female children, respectively, with no significant difference (χ2=1.597，P>0.05). The positive rate of 1~3 years old children was significantly higher than that of >3 years old group (χ2=6.412，P3 times, intravenous glucocorticoid application and onset season were independent risk factors for respiratory virus infection in children with bronchial asthma (P<0.05). Conclusion The infection season of acute respiratory tract infection in children with asthma is mainly concentrated in autumn and winter, with RSV as the main viral pathogen. Targeted preventive measures should be given to children with bronchial asthma who have more than 3 asthma attacks and intravenous glucocorticoid application, which can reduce respiratory virus infection in children with asthma.

The MAPK signaling pathway: A new target for the treatment of hepatic echinococcosis / 临床肝胆病杂志

The MAPK signaling pathway can mediate a variety of cytokines to participate in the processes of inflammation, cancer, immune disorder, and neurodegenerative diseases, and it also plays an important role in the development and progression of hepatic echinococcosis. This article reviews the structure and regulation of the MAPK signaling pathway and elaborates on the role of the MAPK signaling pathway in hepatic echinococcosis. It is pointed out that the MAPK signaling pathway can activate both the cyst and the host in hepatic echinococcosis, participate in the development and progression of the disease, and exert an impact on its treatment. Drug therapy targeting the MAPK signaling pathway is expected to become a new strategy for the treatment of hepatic echinococcosis.