Objective: To explore the changes of mechanosensitive channels Piezos (Piezo 1 and Piezo 2) in neurogenic bladder (NB) of young rats and their effects，so as to provide reference for clinical search of new therapeutic targets. Methods: A total of 30 female young SD rats were divided into 5 groups based on random number table method：sham operation group (sham)，2-week nerve transection group (NB-2W)，6-week nerve transection group (NB-6W)，2-week nerve transection + Piezos inhibitor group (NB-P-2W) and 6-week nerve transection + Piezos inhibitor group (NB-P-6W)，with 6 rats in each group.The NB models were constructed by transecting the L6 and S1 spinal nerves of young rats.The NB-2W and NB-6W groups were not intervened after modeling，while the NB-P-2W and NB-P-6W groups were intraperitoneally injected with Piezos inhibitor GsMTx4 (10 mg/kg) every 2 days after modeling.Bladder cystometry and ultrasound were performed after 2 and 6 weeks of transection.The expressions of Piezos and fibrosis-related indexes (Collagen Ⅰ and α-smooth muscle actin) were detected in bladder tissues. Results: The results of bladder cystometry showed that the basal bladder pressure in NB-2W group was significantly increased，while it was slightly decreased but was still higher in NB-6W group than in the sham group (P<0.05).Basal bladder pressure was lower in NB-P-2W group than in NB-2W group，but was higher than that in the sham group; basal bladder pressure was lower in NB-P-6W group than in NB-6W group，but higher than that in the sham group (P<0.05).Compared with the sham group，the NB-2W and NB-6W groups had firstly increased and then decreased maximum cystometric capacity (MCC) (P<0.05).Compared with NB-2W group，NB-P-2W group had lower bladder leakage point pressure (BLPP)，but higher MCC and bladder compliance (BC) (P<0.05).Compared with NB-6W group，NB-P-6W group had significantly lower BLPP but higher MCC and BC (P<0.05).HE and MASSON staining and ultrasound results showed that，with the extension of nerve transection time，bladder fibrosis gradually worsened，the bladder wall became rough and thickened，calculi were visible inside，and hydronephrosis gradually appeared; the degree of fibrosis in NB-P-2W and NB-P-6W groups was less than that in NB-2W and NB-6W groups，and no hydronephrosis was observed in the upper urinary tract.In addition，Western blotting and immunohistochemical results showed that NB-2W and NB-6W groups had significantly higher relative expression levels of Piezos，Collagen Ⅰ and α-SMA than the sham group (P<0.01)，while NB-P-2W and NB-P-6W groups had lower relative expression levels of Piezos,Collagen Ⅰ and α-SMA than NB-2W and NB-6W groups (P<0.01). Conclusion: The increased expressions of mechanosensitive channels Piezos in NB young rats may be involved in the progression of bladder fibrosis，but its mechanism needs further study.

Aromatic traditional Chinese medicine(TCM) has played an important role against epidemics and viruses, and volatile components are the main components that exert the pharmacological effects of aromatic TCM. By screening the related monomer components in aromatic TCM against epidemic and viruses and analyzing and endowing TCM with medicinal properties based on its clinical application and pharmacological research according to the theoretical thinking of TCM, the key technical issues of compatibility of TCM monomer components were solved from a theoretical perspective, providing new ideas and methods for screening raw materials and formulas for the development of new TCM drugs. Based on the conditions of antiviral activity, clinical application foundation, definite therapeutic effect, and high safety, a gradient screening of aromatic TCM was carried out. Firstly, 30 aromatic TCM were screened from anti-epidemic literature and clinical trial formulas, and seven volatile monomers were further screened from them. Then, four monomer components with significant effects, namely patchouli alcohol, carvacrol, p-cymene, and eucalyptol were screened. By adopting the "four-step method for a systematic study of TCM properties", the four monomer components were endowed with medicinal properties, and compatibility and combination studies were conducted to explore the theoretical basis of monomer formulas and form monomer formulas guided by TCM theory. The screening results of volatile monomers in aromatic TCM against viral pneumonia included patchouli alcohol, carvacrol, p-cymene, and eucalyptol. The medicinal properties and compatibility theory of volatile monomer components in TCM were explored. Patchouli alcohol was the main herb, with a cool and pungent nature. It entered the lung meridian to dispel evil Qi and has the effects of aromatization, detoxification, and epidemic prevention. Carvacrol was a minister drug with a cool and pungent taste. It had the effects of aromatizing, moistening, and dissolving the exterior, as well as strengthening the spleen and stomach. p-Cymene was an adjunctive medicine with a mild and pungent nature. It entered the lungs and kidneys and had the effects of aromatic purification, cough relief, and asthma relief. Eucalyptol was also an adjunctive medicine with a pungent and warm taste. It had the functions of aromatic purification, cough relief, phlegm reduction, and pain relief. The combination of the four medicines had the effects of aromatizing, moistening, detoxifying, and epidemic prevention, as well as relieving cough and asthma and strengthening the spleen and stomach. They were used to treat viral pneumonia caused by upper respiratory tract viral infections, with symptoms such as chest tightness, cough, wheezing, fatigue, nasal congestion, runny nose, nausea, and vomiting. This study has laid a literature and theoretical foundation for further drug efficacy verification experiments, compatibility efficacy experiments, and subsequent product development and clinical applications, and it serves as an innovative practice that combines literature research, theoretical research, experimental research, and clinical practice to develop new products.
Drugs, Chinese Herbal/therapeutic use* ; Antiviral Agents/pharmacology* ; Humans ; Pneumonia, Viral/virology* ; Medicine, Chinese Traditional ; Volatile Organic Compounds/pharmacology* ; Animals

Objective To compare the long-term prognosis differences between surgical radical resection and endoscopic resection for early gastric cancer patients based on the SEER database. Methods A total of 1 437 patients with stage Tis to T_1b gastric adenocarcinoma were selected from the SEER database from January 1, 2004 to December 31, 2013. They were divided into a surgery group (n=1 257) and an endoscope group (n=180) according to the treatment method. Kaplan-Meier survival curve and Cox regression model were used to analyze survival outcomes. Results The patients in the surgery group were younger than those in the endoscope group ([67.63±12.97] years old vs [71.29±10.82] years old), with higher rates of T₁ stage (97.45% vs 87.78%) and lymph node metastasis (19.73% vs 5.00%, all P＜0.001). The median follow-up time for all patients was 37 (15, 66) months, and the mortality rate of gastric cancer in the endoscope group was lower than that in the surgery group (23.33% vs 27.13%, P＜0.001). Univariate Cox analysis showed that treatment modality, age, sex, T stage, lymph node metastasis were all associated with early gastric cancer mortality (all P＜0.05), and the risk of death in the endoscope group was 43% of that in the surgery group (HR=0.43, P=0.015). After adjusting for multiple factors, there was no statistically significant difference in mortality risk between the two groups (P=0.067), but after excluding lymph node positive patients, the mortality risk in the endoscope group was 46% of that in the surgery group (HR=0.46, P=0.048). Conclusions For early gastric cancer patients with negative lymph nodes, endoscopic resection may provide better survival benefits than surgical procedures, suggesting that it can be the preferred treatment strategy for patients with low risk of lymph node metastasis.

Microwave thermotherapy(MWTT),as a treatment for tumors,lacks specificity and requires sensitizers.Most reported microwave sensitizers are single metal-organic frameworks(MOFs),which must be loaded with ionic liquids to enhance the performance in MWTT.Meanwhile,MWTT is rarely combined with other treatment modalities.Here,we synthesized a novel Fe-Cu bimetallic organic framework FeCuMOF(FCM)by applying a hydrothermal method and further modified it with methyl polyethylene glycol(mPEG).The obtained FCM@PEG(FCMP)showed remarkable heating performance under low-power microwave irradiation;it also acted as a novel nanospheres enzyme to catalyze H2O2 decompo-sition,producing abundant reactive oxygen species(ROS)to deplete glutathione(GSH)and prevent ROS clearance from tumor cells during chemodynamic treatment.The FCMP was biodegradable and demonstrated excellent biocompatibility,allowing it to be readily metabolized without causing toxic effects.Finally,it was shown to act as a suitable agent for T2 magnetic resonance imaging(MRI)in vitro and in vivo.This new bimetallic nanostructure could successfully realize two tumor treatment modalities(MWTTand chemodynamic therapy)and dual imaging modes(T2 MRI and microwave thermal imaging).Our findings represent a breakthrough for integrating the diagnosis and treatment of tumors and pro-vides a reference for developing new microwave sensitizers.

BACKGROUND: Repair of long-distance peripheral nerve defects remains an important clinical problem. Nerve grafts incorporated with extracellular vesicles (EVs) from various cell types have been developed to bridge peripheral nerve defects. In our previous research, EVs obtained from skin-derived precursor Schwann cells (SKP-SC-EVs) were demonstrated to promote neurite outgrowth in cultured cells and facilitate nerve regeneration in animal studies. METHODS: To further assess the functions of SKP-SC-EVs in nerve repair, we incorporated SKP-SC-EVs and Matrigel into chitosan nerve conduits (EV-NG) for repairing a 15-mm long-distance sciatic nerve defect in a rat model. Behavioral analysis, electrophysiological recording, histological investigation, molecular analysis, and morphometric assessment were carried out. RESULTS: The results revealed EV-NG significantly improved motor and sensory function recovery compared with nerve conduits (NG) without EVs incorporation. The outgrowth and myelination of regenerated axons were improved, while the atrophy of target muscles induced by denervation was alleviated after EVs addition. CONCLUSION Our data indicated SKP-SC-EVs incorporation into nerve grafts represents a promising method for extended peripheral nerve damage repair.

Objective To investigate effect of plasma ammonia on β-amyloid(Aβ)of CSF and cognitive function in mild Alzheimer's disease(AD).Methods A total of 108 mild AD patients admitted to our hospital and 47 volunteers(HC group)were studied,the cognitive function were measured and plasma ammonia were detected.The mild AD patients were divided into normal ammonia group(ADA-group)and hyperammonemia group(ADA + group)by the plasma ammonia level.The level of Aβ42,Aβ40,total tau and phosphorylated tau protein in CSF of AD patients were detected,and the results were compared.Results Compared with HC group,the MMSE and Montreal Cognitive Assessment(MoCA)in the ADA-group and ADA + group were significantly lower(all P＜0.001).The MoCA of ADA + group was significantly lower than that of ADA-group(P＜0.001).The plasma ammonia of ADA + group were significantly higher than those of ADA-group and HC group(all P＜0.001).The levels of Aβ42 and Aβ40 in ADA + group were significantly lower than those of ADA-group(t =2.29,P =0.024;t =2.72,P =0.008).In ADA + group,the plasma ammonia level was negatively correlated with the MoCA score(r =-0.47,P＜0.001)and level of Aβ42 in CSF(r =-0.63,P＜0.001).The level of Aβ42 played a partial mediating role between the plasma ammonia level and cognitive function,and mediating effect accounted for 45.94%of the total effect.Conclusion The plasma ammonia level is elevated in some AD patients,high plasma ammonia level may reduce the Aβ42 level in CSF,contributes to Aβ42 deposition which forms the amyloid plaques,ultimately aggravates cognitive impairment.

SARS-CoV-2 infection causes complicated clinical manifestations with variable multi-organ injuries, however, the underlying mechanism, in particular immune responses in different organs, remains elusive. In this study, comprehensive transcriptomic alterations of 14 tissues from rhesus macaque infected with SARS-CoV-2 were analyzed. Compared to normal controls, SARS-CoV-2 infection resulted in dysregulation of genes involving diverse functions in various examined tissues/organs, with drastic transcriptomic changes in cerebral cortex and right ventricle. Intriguingly, cerebral cortex exhibited a hyperinflammatory state evidenced by significant upregulation of inflammation response-related genes. Meanwhile, expressions of coagulation, angiogenesis and fibrosis factors were also up-regulated in cerebral cortex. Based on our findings, neuropilin 1 (NRP1), a receptor of SARS-CoV-2, was significantly elevated in cerebral cortex post infection, accompanied by active immune response releasing inflammatory factors and signal transmission among tissues, which enhanced infection of the central nervous system (CNS) in a positive feedback way, leading to viral encephalitis. Overall, our study depicts a multi-tissue/organ transcriptomic landscapes of rhesus macaque with early infection of SARS-CoV-2, and provides important insights into the mechanistic basis for COVID-19-associated clinical complications.
Animals ; COVID-19/genetics* ; Macaca mulatta ; SARS-CoV-2/genetics* ; Transcriptome

Objective:To investigate the function of glutamatergic neuron of the parasubiculum in spatial memory.Methods:Sixteen adult male C57BL/6 mice aged 6-8 weeks were divided into two groups randomly, 0.4 μl AAV5-CaMKⅡα-eNpHR3.0-eYFP was injected into the bilateral parasubiculum respectively in experimental group, equal dose AAV5-CaMKⅡα-eYFP for control group.The optic fiber was implanted 6 weeks after virus injection.The novel object place recognition test was performed one week after optic fiber implantation, continuous yellow light was delivered during the behavioral test to inhibit the function of glutamatergic neuron in the parasubiculum.The standard memory index (D2) was used to evaluate the spatial memory function.SPSS 20.0 software was used to process the data, and the independent-samples t-test and paired-samples t-test were used for data analysis. Results:In the novel object place recognition experiment, the mice showed no preference for either object in both control group(new object: 0.51±0.06, familiar object: 0.49±0.04, t=1.21, P>0.05) and experimental group(new object: 0.49±0.05, familiar object: 0.50±0.04, t=-0.78, P>0.05). Compared with the control group (0.55±0.06), the D2 score of the experimental group (0.26±0.07) was significantly lower ( t=-2.96, P<0.05), and the number of c-fos positive neuron in experimental group (96.33±7.13) was also significantly less than that in control group (127.67±5.24, t=-3.54, P<0.05). Conclusion:Inhibiting glutamatergic neuronal activity in the parasubiculum impairs spatial memory in mice, suggesting that glutamatergic neurons of the parasubiculum play an important role in spatial memory.

【Objective】 To analyze the HIV-, HCV- and HBV- NAT yield rate in different areas of Henan province, so as to provide the basis for disease prevention and control as well as the establishment of a unified quality control standard for nucleic acid testing(NAT) in the Henan province. 【Methods】 The number and prevalence of NAT yielding samples with isolated infectious virus, namely HIV, HCV and HBV, in 18 blood stations in Henan province from 2017~2019, as well as the trends were analyzed. The NAT quality of each laboratory and each testing system was analyzed according to the ratio of reactive individual donation(ID) results to reactive minipools(MP). 【Results】 The HBV, HCV and HIV ID-NAT yield numbers in 3 501 251 blood donations were HBV 2 606(74/100 000), HCV 21 (0.63/100 000), and HIV 34(1.00/100 000). The HBV ID-NAT yield rate showed an upward trend in the whole province from 2017 to 2019, while the prevalence of HIV and HCV ID-NAT yield didn′t differ significantly during three years. 5 kinds of NAT detection systems were applied in 18 blood centers. among which Ⅰ, Ⅱ, Ⅳ and Ⅴ were triplex detection systems. 2661 ID-reactive samples were implicated in 5 595 MP-reactive samples, with a resolution rate of 47.56%. The resolution rate of triplex NAT system Ⅰ, Ⅱ, Ⅳ and Ⅳ was 39.63%~47.95%, 40.43%~54.36%, 51.61% and 70.00%~45.45%, respectively. An upward trend in triplex NAT resolution rate was observed in 8 laboratories, i. e.B, D, E, F, I, K, L and Q, and an descending trend in A and C. The NAT system Ⅲ, a ID-NAT system, was used only by laboratory C, presenting a NAT-yield rate of 0.19% (282/145 474) and resolution rate of 46.45% (131/282). 【Conclusion】 The majority of NAT-yield of one infectious virus in Henan province is HBV, presenting annual increasing trend. The quality management of NAT laboratories should be strengthened as the divergence was seen in the performance of different NAT laboratories.

【Objective】 To analyze the cause of single-ELISA reactive of four blood screening items in 18 blood stations in Henan, so as to provide the basis for improving the quality of blood screening. 【Methods】 The single-ELISA reactive rate of HBsAg, anti-HCV, HIV Ag/Ab and anti-TP of 18 blood station laboratories in Henan throughout 2019 was calculated, and the causes were analyzed according to different ELISA reagent combinations and gray area settings in each laboratory. 【Results】 The overall single-ELISA reactive rates of HBsAg, anti-HCV, HIV Ag/Ab and anti-TP were 1.740(2 154/1 237 789), 0.564‰(698/1 237 789), 1.421‰(1 759/1 237 789) and 1.561‰(1 932/1 237 789), respectively, showing significant differences by detection items (P <0.05). Person correlation analysis showed that the single-ELISA reactive rate was independent of the gray area settings.but dependent on laboratories and reagent combinations. The single-ELISA reactive rate of HBsAg, anti-HCV, HIV Ag/Ab and anti-TP in D laboratory was the highest and higher than that in other labs using the same reagent.The laboratories with high HBsAg single-ELISA reactive rate were mostly those using a combination of imported reagents and domestic reagents, including the top 6 laboratories. The laboratories with high anti-HCV single-ELISA reactive rate were mostly those using certain domestic reagents. No obvious rules was noticed by single-ELISA reactive for anti-HIV. Laboratories with high anti-TP single-ELISA reactive rate were mostly those using combination 4. 【Conclusion】 The HBsAg single-ELISA reactive rate was the highest in the four blood screening items of blood station laboratories in Henan. The single-ELISA reactive rate is related to the laboratory itself and the reagent manufacturer, suggesting that laboratory quality control should be strengthened and proper reagent combination should be selected to reduce the waste of blood.