Functional study of the soybean stamen-preferentially expressed gene GmFLA22a in regulating male fertility.

China has a high dependence on soybean imports, yield increase at a faster rate is an urgent problem that need to be solved at present. The application of heterosis is one of the effective ways to significantly increase crop yield. In recent years, the development of an intelligent male sterility system based on recessive nuclear sterile genes has provided a potential solution for rapidly harnessing the heterosis in soybean. However, research on male sterility genes in soybean has been lagged behind. Based on transcriptome data of soybean floral organs in our research group, a soybean stamen-preferentially expressed gene GmFLA22a was identified. It encodes a fasciclin-like arabinogalactan protein with the FAS1 domain, and subcellular localization studies revealed that it may play roles in the endoplasmic reticulum. Take advantage of the gene editing technology, the Gmfla22a mutant was generated in this study. However, there was a significant reduction in the seed-setting rate in the mutant plants at the reproductive growth stage. The pollen viability and germination rate of Gmfla22a mutant plants showed no apparent abnormalities. Histological staining demonstrated that the release of pollen grains in the mutant plants was delayed and incomplete, which may due to the locule wall thickening in the anther development. This could be the reason of the reduced seed-setting rate in Gmfla22a mutants. In summary, our study has preliminarily revealed that GmFLA22a may be involved in regulating soybean male fertility. It provides crucial genetic materials for further uncovering its molecular function and gene resources and theoretical basis for the utilization of heterosis in soybean.

Research Progress of Traditional Chinese Medicine Intervention in Nrf2/HO-1 Signaling Pathway for Acute Pancreatitis： A Review / 中国实验方剂学杂志

Acute pancreatitis （AP） is a common clinical acute abdominal disease， which is characterized by acute onset， rapid development， severe disease， many complications， and high mortality rate. It can progress to severe AP （SAP） if not treated promptly in the early stage. The pathogenesis of AP is complex and involves multiple cellular and molecular levels. It is now clear that oxidative stress and reactive oxygen species （ROS） production are involved in the physiopathological process of AP， which is associated with a low quantity and activity of antioxidant enzymes in pancreatic cells. Nuclear factor E2-related factor 2 （Nrf2） serves as the ''golden key'' to maintain redox homeostasis in tissue cells and constitutes an important signaling pathway for antioxidant response and inflammation in vivo by collaborating with downstream antioxidant enzymes such as heme oxygenase-1 （HO-1）. Traditional Chinese medicine has unique efficacy in treating diseases due to its multi-component， multi-target， multi-drug delivery， and multi-formulation characteristics. Based on the concept of synergy between traditional Chinese and Western medicine， traditional Chinese medicine is becoming a new craze in the treatment of AP. The level of oxidative stress and Nrf2/HO-1 signaling pathway in AP pancreatic tissue are in a dynamic change process， and the intervention of traditional Chinese medicine can clean ROS production， affect the inflammatory pathway， and reduce oxidative stress damage， so as to protect against pancreatic injury. This suggests that this pathway plays an important role in AP. This article reviews the recent literature on the regulation of the Nrf2/HO-1 signaling pathway by traditional Chinese medicine for AP and summarizes that the monomers of traditional Chinese medicine targeting this pathway are mainly heat-clearing and detoxifying， blood-activating and blood-stasis-removing， and Qi benefiting and middle warming， and the compounds of traditional Chinese medicine include Yinchenhao Decoction and QingYi Ⅱ， so as to provide a new direction for the prevention and treatment of AP and further drug development.

PDMS-filled micro-spring Fabry-Perot cavity for temperature sensing.

A highly sensitive fiber-tipped temperature sensor based on polydimethylsiloxane (PDMS)-filled spring Fabry-Perot (FP) cavity has been proposed and experimentally demonstrated. The spring FP cavity is first fabricated on the fiber endface by the two-photon polymerization lithography. After that, PDMS is filled into the cavity to drive the elongation of the flexible spring and thus to functionalize high-performance temperature sensing. Benefiting from the large thermal expansion coefficient of PDMS, the proposed sensor exhibits a maximal temperature sensitivity of 704.3 pm/°C with excellent operating repeatability and stability. Besides, by selecting a proper spring constant k, the FP sensitivity can be precisely adjusted in the range of 100-700 pm/°C. Thanks to the advantages of high fabrication accuracy and designable property, the proposed sensor could promote numerous usages for customizable temperature sensing.

Washed microbiota transplantation for Clostridioides difficile infection: A national multicenter real-world study.

OBJECTIVES: Fecal microbiota transplantation (FMT) has been recommended for the treatment of recurrent Clostridioides difficile infection (CDI). We aimed to evaluate the therapeutic efficacy and safety of washed microbiota transplantation (WMT), a new method of FMT, for CDI across various medical settings. METHODS: This multicenter real-world cohort study included CDI patients undergoing WMT. The primary outcome was the clinical cure rate of CDI within 8 weeks after WMT. Secondary outcomes included the CDI recurrence rate and reduction in total abdominal symptom score (TASS) during the follow-up period. Adverse events related to WMT were recorded. RESULTS: Altogether 90.7% (49/54) of CDI patients achieved clinical cure after treated with WMT. The cure rate was 83.3% for cases with severe and complicated CDI (ScCDI) (n = 30) and 100% for non-ScCDI cases (n = 24) (P = 0.059). No difference was observed in the clinical cure rate between patients with first and recurrent CDI (91.9% vs 88.2%, P = 0.645). One week post-WMT, TASS showed a remarkable decrease compared to that at baseline (P < 0.001). Totally, 8.2% (4/49) of patients suffered CDI recurrence during the follow-up period. A WHO performance score of 4, age ≥65 years, higher TASS score, and higher Charlson comorbidity index score were potential risk factors for efficacy (P = 0.018, 0.03, 0.01, 0.034, respectively). Four (3.8%) transient adverse events related to WMT were observed. CONCLUSIONS: This study emphasizes the attractive value of WMT for CDI. Early WMT may be recommended for CDI, especially for those in serious condition or with complex comorbidities. TRIAL REGISTRATION: ClinicalTrials.gov, no. NCT03895593 (registered on 27 March 2019).

Treatment persistence of bictegravir/emtricitabine/tenofovir alafenamide and efavirenz + lamivudine + tenofovir disoproxil among HIV-1 patients newly starting treatment in Hunan Province in China.

BACKGROUND: Though bictegravir/emtricitabine/tenofovir (BIC/FTC/TAF) have been regulatory approved and included in the National Reimbursement Drug List in China, due to the affordability concern, generic version of efavirenz + lamivudine + tenofovir (EFV + 3TC + TDF) is still recommended as the first-line therapy in the clinical guideline and widely used in clinical practice. The aim of the study is to assess the persistence with first-line BIC/TAF/TAF and EFV + 3TC + TDF in newly treated HIV-1 patients in the real-world setting in Hunan Province in China. METHODS: A retrospective analysis of the medical records of HIV patients initiating first-line antiretroviral therapy in the First Hospital of Changsha in January 1st, 2021-July 31st, 2022 was conducted. Persistence was assessed as the number of days on the therapy from the index until treatment discontinuation or end of data availability. Kaplan-Meier Curves and Cox Proportional Hazard models were used to evaluate the discontinuation rates. Subgroup analysis was performed excluding BIC/FTC/TAF patients with treatment discontinuation due to economic reason, and EFV + 3TC + TDF patients with a viral load > 500,000 copies/mL. RESULTS: A total of 310 eligible patients were included in the study, with 244 and 66 patients in the BIC/FTC/TAF group and EFV + 3TC + TDF group, respectively. Compared with EFV + 3TC + TDF patients, BIC/FTC/TAF patients were older, more living in the capital city currently, and had significantly higher total cholesterol and low-density level (all p < 0.05). No significant difference was shown in the time to discontinuation between BIC/FTC/TAF patients and EFV + 3TC + TDF patients. After excluding BIC/FTC/TAF patients with treatment discontinuation due to economic reason, EFV + 3TC + TDF group were shown to have a significantly higher risk of discontinuation than BIC/FTC/TAF group (hazard ratio [HR] = 11.1, 95% confidence interval [CI] = 1.3-93.2). After further removing the EFV + 3TC + TDF patients with a viral load > 500,000 copies/mL, the analysis showed similar results (HR = 10.1, 95% CI = 1.2-84.1). 79.4% of the EFV + 3TC + TDF patients discontinued treatment due to clinical reasons, while 83.3% of the BIC/FTC/TAF patients discontinued treatment due to economic reasons. CONCLUSIONS: Compared with BIC/FTC/TAF, EFV + TDF + 3TC patients were significantly more likely to discontinue the first-line treatment in Hunan Province in China.

Radiobacillus kanasensis sp. nov., a halotolerant bacterium isolated from woodland soil.

A novel Gram-positive, aerobic, rod-shaped, non-motile, endospore-forming salt-tolerant bacterium strain (80T), was isolated from woodland soil collected near Kanas lake in the Altay region of Xinjiang, PR China. The strain grew at 15-45 °C, pH6.0-9.0 and with 0-14 % (w/v) NaCl. The complete genome size of the novel strain was 4 031 766 bp including a circle chromosome and a circle plasmid. The genomic DNA G+C content was 38.99 mol %. Phylogenetic analysis based on 16S rRNA gene sequence and genome showed that strain 80T has the highest similarity to Radiobacillus deserti TKL69T. However, the novel strain showed an average nucleotide identity value of 78.65 % (lower than 95 %) and a digital DNA-DNA hybridization value of 22.30 % with R. deserti TKL69T based on the genome sequences. The major fatty acids were anteiso-C15 : 0, iso-C15 : 0, anteiso-C17:0 and C16 : 1 ω7c alcohol. The only respiratory quinone was MK-7. The cell wall peptidoglycan was meso-diaminopimelic acid. Diphosphatidylglycerol, phosphatidylglycerol, one unidentified phospholipid, one unidentified aminophospholipid and two unidentified glycolipids were identified as the major polar lipids. The phylogenetic, phenotypic and chemotaxonomic analyses showed that strain 80T represents a novel species of the genus Radiobacillus and the name Radiobacillus kanasensis sp. nov. is proposed. The type strain is 80T (=GDMCC 1.2844T=JCM 35077T).

Characteristics of corneal stromal demarcation line after different cross-linking methods in keratoconus and its influence on the cross-linking effect / 中华实验眼科杂志

Objective:To compare the characteristics of corneal stromal demarcation line after different surgical methods of riboflavin/ultraviolet A corneal collagen cross-linking (CXL) in early keratoconus, and analyze the influence of the demarcation line on the cross-linking effect.Methods:A non-randomized controlled clinical study was conducted.Sixty-nine eyes of 69 patients treated with riboflavin/ultraviolet A CXL in the Eye Hospital of Shandong First Medical University from May 2019 to February 2021 were included.According to the cross-linking methods, the patients were divided into epithelium-on treatment group (21 eyes) and epithelium-off treatment group (48 eyes). There were 25 eyes in 5.4 J energy group and 44 eyes in 7.2 J energy group.The morphology and changes of corneal stromal cross-linking reaction (corneal stromal demarcation line) were observed at 2 weeks, 1, 3 and 4 months after operation.Changes in the thinnest corneal thickness (TCT), uncorrected visual acuity (UCVA, LogMAR), best corrected visual acuity (BCVA, LogMAR) and corneal maximum curvature (Kmax) were recorded.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Eye Hospital of Shandong First Medical University (No.2019.05). Written informed consent was obtained from each subject.Results:Of the 69 eyes after operation, 44 eyes (63.77%) had demarcation lines, and 25 eyes (36.23%) had no demarcation lines.The occurrence rate of demarcation lines in the epithelium-on treatment group was 79.17%(38/48), which was significantly higher than 28.57%(6/21) in the epithelium-off treatment group ( χ2=16.186, P<0.01). The occurrence rate of demarcation line in 5.4 J energy group was 72.00%(18/25), and the 7.2 J energy group was 56.80%(25/44), with no significant difference ( χ2=1.565, P=0.302). Slit lamp microscopy and anterior segment-optical coherence tomography showed that the demarcation line appeared at 1-2 weeks after operation, gradually converged and strengthened after 1 month, turned diffuse, blurred and faded by degrees after 2-3 months, and basically disappeared after 4 months.The depth of the demarcation line reached 141-423 μm, with an average depth of (263.44±84.22)μm.Scanning laser confocal microscopy showed that corneal stromal cells were activated and light reflection was enhanced after CXL.Collagen fibers extended vertically and horizontally, crisscrossed, and were in a reticular arrangement.The TCT decreased from preoperative (458.69±38.28)μm to (443.86±36.54)μm at 4 months after operation, showing a statistically significant difference ( t=6.705, P<0.001). There was no significant difference in the TCT reduction between groups with and without demarcation lines ( t=1.684, P=0.100). At 4 months postoperatively, the UCVA of all eyes increased from preoperative 0.74±0.37 to 0.69±0.38, and the difference was statistically significant ( t=2.109, P=0.039). There was no significant difference in BCVA between before and after operation ( t=1.006, P=0.319). There was no significant difference in change of UCVA and BCVA between groups with and without demarcation lines ( t=0.065, P=0.949; t=0.346, P=0.730). There was no significant difference in Kmax in all patients between before and after operation ( t=0.050, P=0.950). There was no significant difference in the Kmax change between groups with and without demarcation lines ( t=-0.739, P=0.464). The change in TCT in the epithelium-off treatment group was significantly greater than that in the epithelium-on treatment group ( t=2.815, P=0.008). There was no significant difference in UCVA, BCVA and Kmax changes between epithelium-on and epithelium-off treatment groups (all at P>0.05). There was no obvious corneal scarring, infectious keratitis, corneal endothelial decompensation or other complications. Conclusions:The demarcation line after CXL may be a sign of the depth of cross-linking reaction, which is more prone to occur after the epithelium-off operation method.Both the epithelium-on and epithelium-off operation methods have similar therapeutic effects.Demarcation line after different cross-linking methods has no significant influence on the cross-linking effect in keratoconus.

Application value of donor liver autologous portal venous blood rinse in orthotopic liver trans-plantation / 中华消化外科杂志

Objective:To investigate the application value of donor liver autologous portal venous blood rinse in orthotopic liver transplantation (OLT).Methods:The retrospective cohort study was conducted. The clinicopathological data of 35 pairs of donors and recipients who underwent OLT in the First Affiliated Hospital of University of Science and Technology of China from May 2018 to June 2019 were collected. Of the 35 donors, there were 31 males and 4 females, aged (48±9)years. Of the 35 recipients, there were 25 males and 10 females, aged (47±9)years. Of the 35 recipients, 16 recipients undergoing donor liver autologous portal venous blood rinse were allocated into the portal vein group, and 19 recipients undergoing donor liver albumin water rinse were allocated into the albumin group. Observation indicators: (1) surgical situations; (2) postoperative situations; (3) follow-up. Measurement data with normal distribution were represented as Mean± SD, and compari-son between groups was analyzed using the t test. Measurement data of skewed distribution were represented as M(range). Count data were descried as absolute numbers, and comparison between groups was analyzed using the Fisher exact probability. Results:(1) Surgical situations. The anhepatic phase time and arterial blood Ca 2+ concentration within 5 minutes after reperfusion of the recipients were (52±12)minutes and (0.99±0.10)mmol/L in the portal vein group, versus (64±12)minutes and (1.05±0.07)mmol/L in the albumin group, showing significant differences in the above indicators between the two groups ( t=2.94, 2.22, P<0.05). The mean arterial pressure, arterial blood K +concentration and arterial blood pH within 5 minutes after reperfusion of the recipients were (70±24)mmHg (1 mmHg=0.133 kPa), (4.7±1.3)mmol/L and 7.27±0.06 in the portal vein group, versus (71±28)mmHg, (4.6±1.1)mmol/L and 7.30±0.07 in the albumin group, showing no significant difference in the above indicators between the two groups ( t=0.14, 0.30, 1.22, P>0.05). (2) Post-operative situations. Cases with post-reperfusion syndrome (PRS), cases with severe PRS of cardiac arrest, cases with primary graft nonfunction of the recipients were 6, 0, 2 in the portal vein group, versus 8, 1, 1 in the albumin group, showing no significant difference in the above indicators between the two groups ( P>0.05). Total bilirubin on postoperative day 7 of the recipients was (90±52)μmol/L in the portal vein group, versus (166±112)μmol/L in the albumin group, showing a significant difference between the two groups ( t=2.66, P<0.05). International normalized ratio on postoperative day 7, the highest alanine aminotransferase and aspartate aminotransferase within 7 days after operation of the recipients were 2.1±2.0, (1 952±2 813)IU/L and (3 944±6 673)IU/L in the portal vein group, versus 1.8±0.6, (1 023±1 014) IU/L and (2 005±2 910)IU/L in the albumin group, showing no significant difference in the above indicators between the two groups ( t=0.66, 1.23, 1.08, P>0.05). Recipients with hepatic artery complication and biliary complication were 1 and 2 in the portal vein group, versus 0 and 4 in the albumin group, showing no significant difference in the above indicators between the two groups ( P>0.05). There were 3 cases and 2 cases died during the perioperative period in the portal vein group and the albumin group, respectively. (3) Follow-up. Of the 35 recipients, 30 recipients were followed up for 534(range, 28?776)days after operation. During the follow-up, there were 3 patients with postoperative complications in the portal vein group including 2 cases died and 1 case recovered after sympto-matic treatment. There were 5 patients with postoperative complications in the albumin group including 1 case died and 4 cases recovered after symptomatic treatment. Up to the follow-up date, 11 patients in the portal vein group and 16 patients in the albumin group were in good condition. Conclusion:Rinse of the donor liver with autologous portal venous blood during liver transplantation can shorten the time of anhepatic phase, without increasing the occurrence of post-reperfusion syndrome, ischemia re-perfusion injury and biliary tract complications.

Recent progress and future prospects of treatment for peritoneal metastasis in gastric cancer / 中华胃肠外科杂志

Peritoneal metastasis is one of the most frequent patterns of metastasis in gastric cancer, and remains a major unmet clinical problem. Thus, systemic chemotherapy remains the mainstay of treatment for gastric cancer with peritoneal metastasis. In well-selected patients, the reasonable combination of cytoreductive surgery, hyperthermic intraperitoneal chemotherapy (HIPEC), and neoadjuvant intraperitoneal chemotherapy with systemic chemotherapy will bring significant survival benefits to patients with gastric cancer peritoneal metastasis. In patients with high-risk factors, prophylactic therapy may reduce the risk of peritoneal recurrence, and improves survival after radical gastrectomy. However, high-quality randomized controlled trials will be needed to determine which modality is better. The safety and efficacy of intraoperative extensive intraperitoneal lavage as a preventive measure has not been proven. The safety of HIPEC also requires further evaluation. HIPEC and neoadjuvant intraperitoneal and systemic chemotherapy have achieved good results in conversion therapy, and it is necessary to find more efficient and low-toxicity therapeutic modalities and screen out the potential benefit population. The efficacy of CRS combined with HIPEC on peritoneal metastasis in gastric cancer has been preliminarily validated, and with the completion of clinical studies such as PERISCOPE II, more evidence will be available.

Prevalence of smoking in adults aged 40 years and above in China, 2019-2020 / 中华流行病学杂志

Objective: To understand the prevalence of smoking and its change in adults aged ≥40 years in China and provide evidence for the development of chronic obstructive pulmonary disease (COPD) prevention and control strategies. Methods: The data of this study were obtained from COPD surveillance in China during 2014-2015 and during 2019-2020. The surveillance covered 31 provinces (autonomous regions and municipalities). A multi-stage stratified cluster random sampling were used to select residents aged ≥40 years, and face-to-face interviews were conducted to collect the information about their tobacco use. After complex sampling weighting of the samples, the current smoking rate, average age to start smoking and average daily cigarette consumption of people with different characteristics during 2019-2020 were estimated, and the changes in the current smoking rate and average daily cigarette consumption were analyzed from 2014-2015 to 2019-2020. Results: During 2019-2020, the current smoking rate in adults aged ≥40 years was 27.2%, and the rate was much higher in men (52.1%) than in women (2.5%).The average age of the smokers to start smoking was 20.0 years old, and men usually started smoking at younger age (19.6 years) compared with women (27.9 years). The average daily cigarette consumption of daily smokers was 18.0 sticks, and the consumption of men (18.3 cigarettes) was higher than that of women (11.1 cigarettes). Compared with the surveillance results during 2014-2015, the current smoking rate had decreased by 2.8 percentage points in the general population, 4.1 percentage points in males, 1.6 percentage points in females, and the urban and rural areas fell by 3.1 percentage points and 2.5 percentage points, respectively. The average daily cigarette consumption decreased by 0.6 sticks. Conclusions: In recent years, the current smoking rate and average daily cigarette consumption in adults aged ≥40 years decreased in China, but smoking is still common in more than quarter of this population and more than half of men aged ≥40 years. It is necessary to take targeted tobacco control measures based on population and regional characteristics to further reduce the smoking level of the population.

Performance of pulmonary function test in people aged 40 years and above in China, 2019-2020 / 中华流行病学杂志

Objective: To understand the performance of pulmonary function tests in people aged ≥40 years and its changes in China, and provide evidence for the evaluation of the effect of chronic obstructive pulmonary disease (COPD) prevention and control in China. Methods: The subjects of the survey were from COPD surveillance during 2014-2015 and during 2019-2020, which covered 31 provinces (autonomous regions and municipalities) in China. The survey used multi-stage stratified cluster random sampling method, the trained investigators conducted face-to-face interview to know whether subjects had previous pulmonary function testing or not. Complex sampling weighting was used to estimate the rate of pulmonary function testing in people aged ≥40 years, and the pulmonary function testing rates of the two COPD surveillance periods were compared. Results: A total of 148 427 persons were included in the analysis, including 74 591 persons during 2014-2015 and 73 836 persons during 2019-2020. In 2019-2020, the pulmonary function testing rate in Chinese residents aged ≥40 years was 6.7% (95%CI: 5.2%-8.2%), the rate in men (8.1%, 95%CI: 6.7%-9.6%) was higher than that in women (5.4%, 95%CI: 3.7%- 7.0%), and the rate in urban residents (8.3%, 95%CI: 6.1%-10.5%) was higher than that in rural residents (4.4%, 95%CI: 3.8%-5.1%). The rate of pulmonary function testing increased with the increase of education level. During 2019-2020, the residents with history of chronic respiratory diseases had the highest rate of pulmonary function testing (21.2%, 95%CI: 16.8%-25.7%), followed by the residents with respiratory symptoms (15.1%, 95%CI: 11.8%-18.4%) , the pulmonary function testing rate in those who knew the name of chronic respiratory disease was higher than that in those who did not knew the name of respiratory disease, and the pulmonary function testing rate in former smokers was higher than that in current smokers and non-smokers. Those exposed to occupational dust and/or harmful gases had a higher rate of pulmonary function testing compared with those who were not exposed, and those who used polluted fuels indoors had a lower rate of pulmonary function testing than those who did not use polluted fuels indoors (all P<0.05). Compared with 2014-2015, the pulmonary function testing rate in residents aged ≥40 years in China increased by 1.9 percentage points during 2019-2020, and the rate of pulmonary function testing in groups with different characteristics all increased, and the rates of pulmonary function testing increased by 7.4 percentage points and 7.1 percentage points in residents with respiratory symptoms and in those with history of chronic respiratory diseases (all P<0.05). Conclusions: Compared with 2014-2015, the rate of pulmonary function testing increased in China during 2019-2020 and the increase in residents with history of chronic respiratory diseases and respiratory symptoms was relatively obvious, but the overall pulmonary function testing rate was still at a low level. Effective measures should be taken to further increase the rate of pulmonary function testing.

Clinical analysis of P2Y2 receptor agonist in the treatment of diabetic dry eye / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To evaluate the clinical efficacy of P2Y2 agonist diquafosol sodium(DQS)eye drops in the treatment of diabetic dry eye.METHODS: A total of 80 patients(160 eyes)with diabetic dry eye who admitted to our hospital from January 2022 to March 2022 were selected. They were randomly divided into study group and control group. A total of 40 patients(80 eyes)in the study group were treated with 3% DQS eye drops and 40 patients(80 eyes)in the control group were treated with 0.3% sodium hyaluronate eye drops. The ocular surface disease index(OSDI)score, non-invasive tear meniscus height(NITMH), first non-invasive tear film break-up time(NIBUTf), average non-invasive tear film break-up time(NIBUTav), tarsal gland loss score, lipid layer thickness grade and bulbar redness analysis(including conjunctival grade and ciliary grade), were examined before treatment and at 1wk, 1 and 3mo after treatment, respectively. Furthermore, corneal fluorescence staining and conjunctival lissamine green staining were analyzed based on the ocular surface staining score(OSS), and the conjunctival impression cytology and confocal microscopy were evaluated before and 3mo after treatment, respectively.RESULTS: There were no differences in OSDI score, tarsal gland loss score, conjunctival grade score and ciliary grade score between the two groups before and after treatment(P&#x0026;#x003E;0.05). OSS scores in the study group were lower than those in the control group, while NITMH, NIBUTf and NIBUTav were higher than those in the control group at 1 and 3mo after treatment(P&#x0026;#x003C;0.05). After 3mo of treatment, the density of conjunctival goblet cells increased and corneal dendritic cells decreased in the study group compared with the baseline(all P&#x0026;#x003C;0.05), while there were no significant changes in the control group compared with the baseline(all P&#x0026;#x003E;0.05).CONCLUSION: 3% DQS eye drops were effective in treating diabetic dry eye without serious complications.

Pancreatic melatonin enhances anti-tumor immunity in pancreatic adenocarcinoma through regulating tumor-associated neutrophils infiltration and NETosis

Tumor microenvironment contributes to poor prognosis of pancreatic adenocarcinoma (PAAD) patients. Proper regulation could improve survival. Melatonin is an endogenous hormone that delivers multiple bioactivities. Here we showed that pancreatic melatonin level is associated with patients' survival. In PAAD mice models, melatonin supplementation suppressed tumor growth, while blockade of melatonin pathway exacerbated tumor progression. This anti-tumor effect was independent of cytotoxicity but associated with tumor-associated neutrophils (TANs), and TANs depletion reversed effects of melatonin. Melatonin induced TANs infiltration and activation, therefore induced cell apoptosis of PAAD cells. Cytokine arrays revealed that melatonin had minimal impact on neutrophils but induced secretion of Cxcl2 from tumor cells. Knockdown of Cxcl2 in tumor cells abolished neutrophil migration and activation. Melatonin-induced neutrophils presented an N1-like anti-tumor phenotype, with increased neutrophil extracellular traps (NETs) causing tumor cell apoptosis through cell-to-cell contact. Proteomics analysis revealed that this reactive oxygen species (ROS)-mediated inhibition was fueled by fatty acid oxidation (FAO) in neutrophils, while FAO inhibitor abolished the anti-tumor effect. Analysis of PAAD patient specimens revealed that CXCL2 expression was associated with neutrophil infiltration. CXCL2, or TANs, combined with NET marker, can better predict patients' prognosis. Collectively, we discovered an anti-tumor mechanism of melatonin through recruiting N1-neutrophils and beneficial NET formation.

Deciphering suppressive effects of Lianhua Qingwen Capsule on COVID-19 and synergistic effects of its major botanical drug pairs / 中国天然药物

The COVID-19 pandemic has resulted in excess deaths worldwide. Conventional antiviral medicines have been used to relieve the symptoms, with limited therapeutic effect. In contrast, Lianhua Qingwen Capsule is reported to exert remarkable anti-COVID-19 effect. The current review aims to: 1) uncover the main pharmacological actions of Lianhua Qingwen Capsule for managing COVID-19; 2) verify the bioactive ingredients and pharmacological actions of Lianhua Qingwen Capsule by network analysis; 3) investigate the compatibility effect of major botanical drug pairs in Lianhua Qingwen Capsule; and 4) clarify the clinical evidence and safety of the combined therapy of Lianhua Qingwen Capsule and conventional drugs. Numerous bioactive ingredients in Lianhu Qingwen, such as quercetin, naringenin, β-sitosterol, luteolin, and stigmasterol, were identified to target host cytokines, and to regulate the immune defence in response to COVID-19. Genes including androgen receptor (AR), myeloperoxidase (MPO), epidermal growth factor receptor (EGFR), insulin (INS), and aryl hydrocarbon receptor (AHR) were found to be significantly involved in the pharmacological actions of Lianhua Qingwen Capsule against COVID-19. Four botanical drug pairs in Lianhua Qingwen Capsule were shown to have synergistic effect for the treatment of COVID-19. Clinical studies demonstrated the medicinal effect of the combined use of Lianhua Qingwen Capsule and conventional drugs against COVID-19. In conclusion, the four main pharmacological mechanisms of Lianhua Qingwen Capsule for managing COVID-19 are revealed. Therapeutic effect has been noted against COVID-19 in Lianhua Qingwen Capsule.

Thirty-day outcomes of in-hospital multi-vessel versus culprit-only revascularization strategy for ST-segment elevation myocardial infarction with multivessel coronary disease / 老年心脏病学杂志（英文版）

BACKGROUND@#Many studies have demonstrated the benefit of complete multivessel revascularization versus culprit-only intervention in patients of ST-segment elevation myocardial infarction (STEMI) and multivessel coronary artery disease. However, only a few single-center retrospective studies were performed on small Chinese cohorts. Our study aims to demonstrate the advantage of multivessel percutaneous intervention (PCI) strategy on 30-day in-hospital outcomes to patients with STEMI and multivessel disease in larger Chinese population.@*METHODS@#From the Improving Care for Cardiovascular Disease in China-Acute Coronary Syndrome (CCC-ACS) project, 5935 patients with STEMI and multivessel disease undergoing PCI and hospitalized for fewer than 30 days were analyzed. After 5: 1 propensity score matching, 3577 patients with culprit-only PCI and 877 with in-hospital multivessel PCI were included. The primary outcome was major adverse cardiovascular and cerebrovascular event (MACCE), defined as a composite of myocardial infarction, all-cause death, stent thrombosis, heart failure, and stroke.@*RESULTS@#Multivariable logistic regression analysis revealed that in-hospital multivessel PCI was associated with lower risk of 30-day MACCE (adjusted OR = 0.75, 95% CI: 0.57-0.98, P = 0.032) than culprit-only PCI and conferred no increased risk of all-cause death, myocardial infarction, stent thrombosis, stroke, or bleeding. Subgroup analysis showed that MACCE reduction was observed more often from patients with trans-femoral access (OR = 0.34, 95% CI: 0.15-0.74) than with trans-radial access (OR = 0.87, 95% CI: 0.66-1.16, P for interaction = 0.017).@*CONCLUSIONS@#The in-hospital multivessel PCI strategy was associated with a lower risk of 30-day MACCE than culprit-only PCI in patients with STEMI and multivessel coronary artery disease.

Expressions and Clinical Significance of Notch1 and Hes1 in Diffuse Large B-Cell Lymphoma / 中国实验血液学杂志

OBJECTIVE@#To investigate the expressions of Notch1 and Hes1 in diffuse large B-cell lymphoma (DLBCL), and their correlations with clinical features.@*METHODS@#Immunohistochemistry (IHC) was performed on DLBCL samples (54 cases) and lymphadenitis tissues (20 cases) to evaluate the expressions of Notch1 and Hes1, and analyze their correlations with clinical characteristics of patients. Based on Oncomine database, the expressions of Notch1 and Hes1 mRNA and DNA were also explored.@*RESULTS@#IHC result showed that the positive expression rates of Notch1 and Hes1 in DLBCL patients were significantly higher than those in the control group (P <0.05). In DLBCL patients, the expression of Notch1 was closely associated with B symptoms, Ann Arbor stage, lymphocyte count and the level of lactate dehydrogenase (P <0.05), while the expression level of Hes1 was significantly higher in patients with B symptoms (P <0.05). Notch+/Hes1+ expression was found in 21 DLBCL tissues (38.9%), and there was a correlation between Notch1 and Hes1 expression (r =0.296, P <0.05). Bioinformatics analysis (Oncomine database) showed that the mRNA expressions of Notch1 and Hes1 in the Brune dataset were significantly higher than those in the control tissues (P <0.05).@*CONCLUSION@#The expressions of Notch1 and Hes1 in DLBCL are significantly higher than those in lymphadenitis, and correlated with B symptoms and Ann Arbor stage, suggesting that Notch1 and Hes1 play important roles in the occurrence and development of DLBCL.

Omics Analysis of Ferroptosis and Establishment of Prognostic Model for multiple myeloma Patients / 中国实验血液学杂志

OBJECTIVE@#To explore the role of ferroptosis-related genes in multiple myeloma(MM) through TCGA database and FerrDb, and build a prognostic model of ferroptosis-related genes for MM patients.@*METHODS@#Using the TCGA database containing clinical information and gene expression profile data of 764 patients with MM and the FerrDb database including ferroptosis-related genes, the differentially expressed ferroptosis-related genes were screened by wilcox.test function. The prognostic model of ferroptosis-related genes was established by Lasso regression, and the Kaplan-Meier survival curve was drawn. Then COX regression analysis was used to screen independent prognostic factors. Finally, the differential genes between high-risk and low-risk patients were screened, and enrichment analysis was used to explore the mechanism of the relationship between ferroptosis and prognosis in MM.@*RESULTS@#36 differential genes related to ferroptosis were screened out from bone marrow samples of 764 MM patients and 4 normal people, including 12 up-regulated genes and 24 down-regulated genes. Six prognosis-related genes (GCLM, GLS2, SLC7A11, AIFM2, ACO1, G6PD) were screened out by Lasso regression and the prognostic model with ferroptosis-related genes of MM was established. Kaplan-Meier survival curve analysis showed that the survival rate between high risk group and low risk group was significantly different(P<0.01). Univariate COX regression analysis showed that age, sex, ISS stage and risk score were significantly correlated with overall survival of MM patients(P<0.05), while multivariate COX regression analysis showed that age, ISS stage and risk score were independent prognostic indicators for MM patients (P<0.05). GO and KEGG enrichment analysis showed that the ferroptosis-related genes was mainly related to neutrophil degranulation and migration, cytokine activity and regulation, cell component, antigen processing and presentation, complement and coagulation cascades, haematopoietic cell lineage and so on, which may affect the prognosis of patients.@*CONCLUSION@#Ferroptosis-related genes change significantly during the pathogenesis of MM. The prognostic model of ferroptosis-related genes can be used to predict the survival of MM patients, but the mechanism of the potential function of ferroptosis-related genes needs to be confirmed by further clinical studies.

Construction of a Prognostic Model of Multiple Myeloma Based on Metabolism-Related Genes / 中国实验血液学杂志

OBJECTIVE@#To screen the prognostic biomarkers of metabolic genes in patients with multiple myeloma (MM), and construct a prognostic model of metabolic genes.@*METHODS@#The histological database related to MM patients was searched. Data from MM patients and healthy controls with complete clinical information were selected for analysis.The second generation sequencing data and clinical information of bone marrow tissue of MM patients and healthy controls were collected from human protein atlas (HPA) and multiple myeloma research foundation (MMRF) databases. The gene set of metabolism-related pathways was extracted from Molecular Signatures Database (MSigDB) by Perl language. The biomarkers related to MM metabolism were screened by difference analysis, univariate Cox risk regression analysis and LASSO regression analysis, and the risk prognostic model and Nomogram were constructed. Risk curve and survival curve were used to verify the grouping effect of the model. Gene set enrichment analysis (GSEA) was used to study the difference of biological pathway enrichment between high risk group and low risk group. Multivariate Cox risk regression analysis was used to verify the independent prognostic ability of risk score.@*RESULTS@#A total of 8 mRNAs which were significantly related to the survival and prognosis of MM patients were obtained (P<0.01). As molecular markers, MM patients could be divided into high-risk group and low-risk group. Survival curve and risk curve showed that the overall survival time of patients in the low-risk group was significantly better than that in the high risk group (P<0.001). GSEA results showed that signal pathways related to basic metabolism, cell differentiation and cell cycle were significantly enriched in the high-risk group, while ribosome and N polysaccharide biosynthesis signaling pathway were more enriched in the low-risk group. Multivariate Cox regression analysis showed that the risk score composed of the eight metabolism-related genes could be used as an independent risk factor for the prognosis of MM patients, and receiver operating characteristic curve (ROC) showed that the molecular signatures of metabolism-related genes had the best predictive effect.@*CONCLUSION@#Metabolism-related pathways play an important role in the pathogenesis and prognosis of patients with MM. The clinical significance of the risk assessment model for patients with MM constructed based on eight metabolism-related core genes needs to be confirmed by further clinical studies.