ObjectiveTo develop traditional Chinese medicine （TCM） formulae for the treatment of nonsevere coronavirus disease 2019 （COVID-19） and to explore its anti-inflammatory mechanism. MethodsThe dysregulated signaling pathways were determined in macrophages from bronchoalveolar lavage fluid of COVID-19 patients and in lung epithelial cells infected with SARS-CoV-2 in vitro based on transcriptome analysis. A total of 102 TCM formulae for the clinical treatment of nonsevere COVID-19 were collected through literature. The pathway-reversing rates of these formulae in macrophages and lung epithelial cells were evaluated based on signature signaling pathways， and the basic formula was determined in conjunction with TCM theory. The commonly used Chinese materia medica for nonsevere COVID-19 were summarized from the 102 TCM formulae as abovementioned. And together with the screening results from the Pharmacopoeia of the People's Republic of China， a “Chinese materia medica pool” was esta-blished for the development of TCM formulae for COVID-19. The regulatory effects of each herb on signaling pathways were obtained based on targeted transcriptome analysis. Oriented at reversing dysregulated signaling pathways of COVID-19， the calculation was carried out， and the artificial intelligent methods for compositing formulae， that are exhaustive method and parallel computing， were used to obtain candidate compound formulas. Finally， with reference to professional experience， an innovative formula for the treatment of nonsevere COVID-19 was developed. The ethanol extract of the formula was evaluated for its anti-inflammatory effects by detecting the mRNA expression of interleukin 1b （Il1b）， C-X-C motif chemokine ligand 2 （Cxcl2）， C-X-C motif chemokine ligand 10 （Cxcl10）， C-C motif chemokine ligand 2 （Ccl2）， nitric oxide synthase 2 （Nos2）， and prostaglandin-endoperoxide synthase 2 （Ptgs2） using reverse transcription-quantitative polymerase chain reaction （RT-qPCR） in RAW264.7 cells treated with lipopolysaccharide （LPS）. ResultsIn macrophages and lung epithelial cells， 34 dysregulated signaling pathways associated with COVID-19 were identified respectively. The effects of the 102 formulae for clinical treatment of nonsevere COVID-19 were evaluated based on the dysregulated signaling pathways and targeted transcriptome， and the result showed that Yinqiao Powder and Pingwei Powder （银翘散合平胃散， YQPWP） ranked first， reversing 91.18% of the dysregulated signaling pathways in macrophages and 100% of the dysregulated signaling pathways in lung epithelial cells. Additionally， YQPWP had the function of scattering wind and clearing heat， resolving toxins and removing dampness in accordance with the pathogenesis of wind-heat with dampness in COVID-19. It was selected as the basic formula， and was further modified and optimized to develop an innovative fomula Qiaobang Zhupi Yin （翘蒡术皮饮， QBZPY） based on expert experience and artificial intelligence in composing formulae. QBZPY can reverse all the dysregulated signaling pathways associated with COVID-19 in macrophages and lung epithelial cells， with the reversing rates of 100%. The chief medicinal of QBZPY， including Lianqiao （Fructus Forsythiae）， Xixiancao （Herba Siegesbeckiae） and Niubangzi （Fructus Arctii）， can down-regulate multiple signaling pathways related with virus infection， immune response， and epithelial damage. RT-qPCR results indicated that compared with the model group， the QBZPY group down-regulated the mRNA expression of Il1b， tumor necrosis factor （Tnf）， Cxcl2， Cxcl10， Ccl2， Nos2 and Ptgs2 induced by LPS in RAW264.7 cells （P＜0.05 or P＜0.01）. ConclusionBased on targeted transcriptome analysis， expert experience in TCM and artificial intelligence， QBZPY has been developed for the treatment of nonsevere COVID-19. The ethanol extract of QBZPY has been found to inhibit mRNA expression of several pro-inflammatory genes in a cellular inflammation model.

Acute respiratory distress syndrome is one of the common complications of sepsis syndrome, belonging to the "Chuan syndrome", "Baochuan", and "Chuantuo" in the TCM field, and the disease is mainly located in the lung. The main etiology and pathogenesis of sepsis syndrome is deficient healthy qi and blood stasis with toxin blocking collaterals. Blood stasis and toxin invade the lung, causing heat and toxin to burn the body fluid in the blood. Blood viscosity and poor circulation lead to the accumulation of blood stasis and toxin in the lung. Acute deficiency syndrome, heat toxin damaging qi, heat toxin burning body fluid deficiency with little ability to dissipate qi, resulting in deficiency of healthy qi, inability to regulate breathing, inability to consolidate body fluid, inability to promote blood circulation, causing phlegm, dampness, and blood stasis blocking the lung. This disease is characterized by blood stasis with toxin blocking collaterals, deficient lung qi, and obstruction of lung qi caused by phlegm, water, dampness, and blood stasis. Therefore, blood stasis with toxin blocking collaterals, as well as deficient healthy qi are TCM pathogenesis of ARDS with sepsis syndrome.

Objective:To verify the therapeutic effect of Astragalus on mice with acute respiratory distress syndrome with sepsis and to explore its mechanism.Methods:Seventy SPF-grade C57 mice were divided into astragalus group ( n=30), control group ( n=30) and sham surgery group ( n=10) according to random number table method, and CLP surgery was performed on Astragalus group and control group to induce sepsis acute respiratory distress syndrome, and CLP sham surgery was performed in the sham surgery group. After surgery, the astragalus group was treated with astragalus decoction for gastric gavage, the sham surgery group and the control group were gavaged with normal saline, and the mice were sacrificed 12 hours and 24 hours after the operation, and the lung histopathology was observed, the ratio of dry to wet weight of lung tissue, the protein concentration of alveolar lavage fluid was determined, the alveolar lavage fluid and serum were analyzed proteomics, and the differential proteins were enriched and analyzed. Results:Astragalus reduced the total protein concentration of BALF in ARDS mice, reduced the dry-to-wet ratio of ARDS mice, and HE staining of lung tissues showed that Astragalus decoction improved acute alveolar injury in ARDS mice. Proteomic analysis of serum samples and BALF samples showed that there were certain differential proteins between astragalus group and control group, and enrichment analysis showed that it was mainly enriched in the pathway of inflammatory factors, confirming that astragalus decoction may play a role by inhibiting the activation and release of inflammatory factors.Conclusions:Astragalus decoction can effectively reduce the inflammatory exudation of lung tissue in acute respiratory distress syndrome of sepsis, and its mechanism of action may be to inhibit the expression of inflammatory factors.

Discipline construction is the power source to realize the high quality development of public hospitals,and high quality scientific research management is the inevitable path to realize the connotative development of public hospitals.The quality improvement of scientific research project process management is step-by-step,and mid-term inspection is a representative work.This paper applies PDCA cycle theory to the mid-term inspection of scientific research projects,analyzes the problems encountered in the mid-term inspection of scientific research projects from the four stages of plan,implementation,check and act,and develops effective intervention measures.The mid-term inspection mode,which combines publicity activities of scientific research norms with self-examination by researchers and on-the-spot inspection by the scientific research department,should be carried out to standardize the process of mid-term inspection of scientific research projects and promote the high-quality development of scientific research in hospitals.

Cognitive dysfunction refers to dysfunction of individual perception,memory,understanding,learning,creation and other dysfunctions caused by abnormal brain function and structure.Based on the fact that the spleen can't regulate transportation and transformation,govern blood and send up essential substance,combined with the microbiota-gut-brain axis,this article discussed the etiology and pathogenesis of intestinal flora imbalance affecting cognitive dysfunction in TCM.It was proposed that the spleen in TCM and intestinal flora are connected in physiology and pathology:the spleen regulates spirit and governs cognition,when the spleen fails to function normally that it can't dominate transportation and transformation,govern blood and send up essential substance will cause that the brain spirit can not be nourished;intestinal flora is closely related to the spleen in TCM,and affects brain function through the nervous system,endocrine,immune and metabolic mechanisms.This article can provide explore new ideas for the clinical research and treatment of cognitive dysfunction of traditional Chinese and Western medicine.

Objective To explore the effect mechanism of lipophagy in diabetic nephropathy model rats based on intervention of Dangui Hongqi ultrafiltration in diabetic nephropathy model rats.Methods Fifty male Wistar rats of SPF grade were randomly selected 7 rats as the blank group,and the other 43 rats were given a one-time high-dose intraperitoneal injection of streptozotocin combined with high-fat and high-sugar diet to prepare diabetes nephropathy model.The modeling rats were randomly divided into model group,irbesartan group(17.9 mg/kg),and TCM low-,medium-,and high-dosage groups(1.5,3,6 g/kg).The rats were continuously gavaged by corresponding drugs for 12 weeks.Randomized blood glucose,body mass,and 24 h urine protein content were detected;biochemical tests were used for GSP,SCr,BUN,TG,TC,HDL-C,LDL-C,FFA content;HE staining was used to observe morphology changes in renal tissue,Masson staining was used to observe fibrosis changes in renal tissue,renal tissue microstructure changes were observed under transmisson electron microscopy,RT-qPCR was used to detect the mRNA expressions of mTOR and LC3B in renal tissue,and Western blot was used to detect the protein expressions of mTOR,TFEB,p-TFEB,and LC3B in renal tissue.Results Compared with the blank group,the model group rats showed a significant increase in randomized blood glucose(P<0.01),a significant decrease in body mass(P<0.01),a significant increase in 24 h urine protein content(P<0.01),a significant increase in GSP,SCr,BUN,TG,TC,LDL-C,FFA content(P<0.01),and a significant decrease in HDL-C content(P<0.01);renal tubular epithelial cells underwent vacuolar degeneration,cytoplasmic vacuolization,and extensive infiltration of inflammatory cells,collagen fibers increased and were distributed randomly,the number of lipid droplets increased,and autophagosomes decreased;the mTOR mRNA expressions in renal tissue significantly increased(P<0.01),the LC3B mRNA expressions significantly decreased(P<0.01),the mTOR and p-TFEB protein expressions significantly increased(P<0.01),the expression of TFEB,LC3BⅡ protein significantly decreased(P<0.01).Compared with the model group,the randomized blood glucose and 24 h urine protein content of rats in each treatment group were significantly reduced,the body mass significantly increased,and the contents of GSP,SCr,BUN,TG,TC,LDL-C,FFA decreased at 12 week of treatment,while the content of HDL-C increased;the inflammatory cell infiltration,fibrosis,and lipid droplet deposition in renal tissue alleviated to varying degrees;the expressions of mTOR mRNA decreased,the expressions of LC3B mRNA increased,the expressions of mTOR and p-TFEB protein decreased,while the expression of TFEB and LC3BⅡ protein increased.There was a statistically significant difference in the irbesartan group and TCM high-dosage group(P<0.01,P<0.05).Conclusion Dangui Hongqi ultrafiltration can improve the disorder of glucose and lipid metabolism,antagonize heterotopic lipid deposition in the kidney,promote lipid phagocytosis,and delay the process of diabetic nephropathy in model rats.The mechanism may be related to mTOR/TFEB signaling pathway.

Objective Using cochlear metabolomics to study the mechanisms underlying age-related hearing loss in rat.Methods A total of 30 rats with 2-month-old(young group)and 14-month-old(old group)were select-ed,with 15 rats in each group.The auditory function in each group was detected by auditory brainstem response(ABR),the morphology of cochlear tissue in both groups was observed using HE staining,and the oxidative stress status of cochlear tissue was detected by flow cytometry.Five rats/groups were selected for metabolomic examina-tion of cochlear tissue by untargeted ultra-high performance liquid chromatography-mass spectroscopy(LC-MS/MS)to analyze the metabolic differences in the aging cochlea.Results Compared with young group,ABR detection of tone burst at 8,16,and 32 kHz and click response thresholds were significantly higher in old group(P＜0.05),HE staining showed cochlear senescence-related vascular stripe atrophy(P＜0.05),and flow cytometric techniques suggested significantly higher levels of oxidative stress in old group(P＜0.05).Metabolomics detection revealed that a total of 124 differential metabolites were identified in the cochlea of the old group,of which 16 metabolites in-cluding sphingosine,all-trans-retinoic acid,and oleamide were significantly upregulated,while the levels of 108 me-tabolites such as purine,taurine,thiamine,and proline and its derivatives were significantly decreased.The results suggested that physiopathological mechanisms such as protein synthesis and catabolism,sphingolipid metabolism,purine metabolism,oxidative stress-related signaling,cell death,and coenzyme biosynthesis may be involved in co-chlear aging.Conclusion Cellular senescence and cochlear metabolic dysfunction may be important mechanisms of age-related hearing loss.

Sensory nerves belong to the afferent nerve part of the peripheral nervous system.Their role is to accept the stimuli inside and outside the body and transmit them to the center nerve system to form sensations or reflexes.Sensory nerve damage can be caused by trauma,tumor invasion,surgical injury,etc.Sensory nerve injury may cause decline or loss of some sensory organs function in patients.Damage of important sensory nerves such as optic nerves and auditory nerves can bring profound troubles to patients'lives.So far,the main clinical method to repair sensory nerves is autologous nerve transplantation.However,its application is limited by various factors,and the recovery effect of nerve function is often limited.Stem cells have the potential of multi-directional differentiation,which can differentiate into Schwann cells,and then secrete neurotrophic factors to promote axonal growth and myelin regeneration.Schwann cells directionally proliferate and form Bungner zones which guide nerve regeneration.Stem cells can also differentiate into neurons and construct nerve defect repair materials,which is an ideal choice for nerve repair.At present,the tissue engineering technology based on stem cells,combined with several key biotechnology,such as the use of biopolymerized or artificial surface micro-patterning nerve conduit to bridge nerve defects,and the use of microspheres to achieve the controlled release of extracellular matrix proteins and neurotrophic factors,is being widely studied and has achieved certain research results.This article reviews the research progress of stem cells in the repair of several major sensory nerves,such as optic nerves,olfactory nerves,cochlear nerves and sensory nerve fibers of sciatic nerve,expecting to provide a new perspective for neural repair of stem cells,broaden the preclinical research in nerve repair,and provide reference for follow-up clinical application.

Objective : To investigate the effects of miR⁃26a⁃3p on rat myocardial cell ( H9c2) injury induced by hypoxia/reoxygenation (H/R) and its mechanism . Methods : H9c2 cardiomyocytes in logarithmic growth phase were subjected to hypoxia (1% O2 ) for 6 h , and reoxygenated at different times (2 , 4 , 8 , 12 h) to establish H/R model cell . Normoxia group was also set up , and cell proliferation activity was detected by cell counting kit⁃8 (CCK⁃8) . The level of lactic dehydrogenase (LDH) in cell supernatant was determined by colorimetry . The expression levels of miR⁃26a⁃3p and Survivin mRNA were detected by real⁃time fluorescence quantitative PCR (qRT⁃PCR) . The expression level of Survivin protein in the cells was detected by Western blot . H9c2 cells were transfected with miR⁃26a⁃3p inhibitor and negative control inhibitor NC , Survivin gene siRNA interference plasmid ( si⁃Survivin) and negative control si⁃NC , followed by H/R intervention . CCK⁃8 was used to detect cell proliferation in each group . The activity of superoxide dismutase (SOD) and the content of malonaldehyde (MDA) in cell and the level of LDH in supernatant were determined by colorimetry . The apoptosis level of each group was detected by flow cytometry . The protein expression levels of Bcl⁃2 associated X protein ( Bax) , B ⁃cell lymphoma⁃2 ( Bcl⁃2 ) , cleaved caspase⁃3 and Survivin were detected by Western blot . Targeting relationship between miR⁃26a⁃3p and Survivin gene was determined by dual luciferase . Results : Compared with the normoxia group , proliferative activity , mRNA and protein expression levels of Survivin in H9c2 cells gradually decreased with the extension of reoxygen ation time (P < 0. 05) , while LDH and expression level of miR⁃26a⁃3p gradually increased ( P < 0. 05) . Downregulating the expression of miR⁃26a⁃3p increased proliferative activity , SOD activity , and expression level of Bcl⁃2 protein in H9c2 cells exposed to H/R ( P < 0. 05) , while MDA content , LDH release amount , apoptosis rate , expression levels of Bax and cleaved caspase⁃3 protein decreased (P < 0. 05) . Survivin deficiency reversed the protective effect of miR⁃26a⁃3p inhibitor on H9c2 cells induced by H/R . Dual luciferase reporter gene assay confirmed that Survivin was the target gene of miR⁃93 ⁃5p . Conclusion miR⁃26a⁃3p is highly expressed in cardiomyocyte injury induced by H/R . Inhibition of miR⁃26a⁃3p expression can inhibit H/R⁃induced cardiomyocyte apoptosis and oxidative stress by targeted up⁃regulation of Survivin expression .

Objective:To evaluate the safety of double and a half layered esophagojejunal anastomosis in radical gastrectomy.Methods:This prospective, multi-center, single-arm study was initiated by the Affiliated Cancer Hospital of Zhengzhou University in June 2021 (CRAFT Study, NCT05282563). Participating institutions included Nanyang Central Hospital, Zhumadian Central Hospital, Luoyang Central Hospital, First Affiliated Hospital of Henan Polytechnic University, First Affiliated Hospital of Henan University, Luohe Central Hospital, the People's Hospital of Hebi, First People's Hospital of Shangqiu, Anyang Tumor Hospital, First People's Hospital of Pingdingshan, and Zhengzhou Central Hospital Affiliated to Zhengzhou University. Inclusion criteria were as follows: (1) gastric adenocarcinoma confirmed by preoperative gastroscopy;(2) preoperative imaging assessment indicated that R0 resection was feasible; (3) preoperative assessment showed no contraindications to surgery;(4) esophagojejunostomy planned during the procedure; (5) patients volunteered to participate in this study and gave their written informed consent; (6) ECOG score 0–1; and (7) ASA score I–III. Exclusion criteria were as follows: (1) history of upper abdominal surgery (except laparoscopic cholecystectomy);(2) history of gastric surgery (except endoscopic submucosal dissection and endoscopic mucosal resection); (3) pregnancy or lactation;(4) emergency surgery for gastric cancer-related complications (perforation, hemorrhage, obstruction); (5) other malignant tumors within 5 years or coexisting malignant tumors;(6) arterial embolism within 6 months, such as angina pectoris, myocardial infarction, and cerebrovascular accident; and (7) comorbidities or mental health abnormalities that could affect patients' participation in the study. Patients were eliminated from the study if: (1) radical gastrectomy could not be completed; (2) end-to-side esophagojejunal anastomosis was not performed during the procedure; or (3) esophagojejunal anastomosis reinforcement was not possible. Double and a half layered esophagojejunal anastomosis was performed as follows: (1) Open surgery: the full thickness of the anastomosis is continuously sutured, followed by embedding the seromuscular layer with barbed or 3-0 absorbable sutures. The anastomosis is sutured with an average of six to eight stitches. (2) Laparoscopic surgery: the anastomosis is strengthened by counterclockwise full-layer sutures. Once the anastomosis has been sutured to the right posterior aspect of the anastomosis, the jejunum stump is pulled to the right and the anastomosis turned over to continue to complete reinforcement of the posterior wall. The suture interval is approximately 5 mm. After completing the full-thickness suture, the anastomosis is embedded in the seromuscular layer. Relevant data of patients who had undergone radical gastrectomy in the above 12 centers from June 2021 were collected and analyzed. The primary outcome was safety (e.g., postoperative complications, and treatment). Other studied variables included details of surgery (e.g., surgery time, intraoperative bleeding), postoperative recovery (postoperative time to passing flatus and oral intake, length of hospital stay), and follow-up conditions (quality of life as assessed by Visick scores).Result:[1] From June 2021 to September 2022,457 patients were enrolled, including 355 men and 102 women of median age 60.8±10.1 years and BMI 23.7±3.2 kg/m2. The tumors were located in the upper stomach in 294 patients, mid stomach in 139; and lower stomach in 24. The surgical procedures comprised 48 proximal gastrectomies and 409 total gastrectomies. Neoadjuvant chemotherapy was administered to 85 patients. Other organs were resected in 85 patients. The maximum tumor diameter was 4.3±2.2 cm, number of excised lymph nodes 28.3±15.2, and number of positive lymph nodes five (range one to four. As to pathological stage,83 patients had Stage I disease, 128 Stage II, 237 Stage III, and nine Stage IV. [2] The studied surgery-related variables were as follows: The operation was successfully completed in all patients, 352 via a transabdominal approach, 25 via a transhiatus approach, and 80 via a transthoracoabdominal approach. The whole procedure was performed laparoscopically in 53 patients (11.6%), 189 (41.4%) underwent laparoscopic-assisted surgery, and 215 (47.0%) underwent open surgery. The median intraoperative blood loss was 200 (range, 10–1 350) mL, and the operating time 215.6±66.7 minutes. The anastomotic reinforcement time was 2 (7.3±3.9) minutes for laparoscopic-assisted surgery, 17.6±1.7 minutes for total laparoscopy, and 6.0±1.2 minutes for open surgery. [3] The studied postoperative variables were as follows: The median time to postoperative passage of flatus was 3.1±1.1 days and the postoperative gastrointestinal angiography time 6 (range, 4–13) days. The median time to postoperative oral intake was 7 (range, 2–14) days, and the postoperative hospitalization time 15.8±6.7 days. [4] The safety-related variables were as follows: In total, there were 184 (40.3%) postoperative complications. These comprised esophagojejunal anastomosis complications in 10 patients (2.2%), four (0.9%) being anastomotic leakage (including two cases of subclinical leakage and two of clinical leakage; all resolved with conservative treatment); and six patients (1.3%) with anastomotic stenosis (two who underwent endoscopic balloon dilation 21 and 46 days after surgery, the others improved after a change in diet). There was no anastomotic bleeding. Non-anastomotic complications occurred in 174 patients (38.1%). All patients attended for follow-up at least once, the median follow-up time being 10 (3–18) months. Visick grades were as follows: Class I, 89.1% (407/457); Class II, 7.9% (36/457); Class III, 2.6% (12/457); and Class IV 0.4% (2/457).Conclusion:Double and a half layered esophagojejunal anastomosis in radical gastrectomy is safe and feasible.