Debates persist regarding the efficacy and safety of azvudine, particularly its real-world outcomes. This study involved patients aged ≥60 years who were admitted to 25 hospitals in mainland China with confirmed SARS-CoV-2 infection between December 1, 2022, and February 28, 2023. Efficacy outcomes were all-cause mortality during hospitalization, the proportion of patients discharged with recovery, time to nucleic acid-negative conversion (T _NANC), time to symptom improvement (T _SI), and time of hospital stay (T _HS). Safety was also assessed. Among the 5884 participants identified, 1999 received azvudine, and 1999 matched controls were included after exclusion and propensity score matching. Azvudine recipients exhibited lower all-cause mortality compared with controls in the overall population (13.3% vs. 17.1%, RR, 0.78; 95% CI, 0.67-0.90; P = 0.001) and in the severe subgroup (25.7% vs. 33.7%; RR, 0.76; 95% CI, 0.66-0.88; P < 0.001). A higher proportion of patients discharged with recovery, and a shorter T _NANC were associated with azvudine recipients, especially in the severe subgroup. The incidence of adverse events in azvudine recipients was comparable to that in the control group (2.3% vs. 1.7%, P = 0.170). In conclusion, azvudine showed efficacy and safety in older patients hospitalized with COVID-19 during the SARS-CoV-2 omicron wave in China.

OBJECTIVE To optimize the processing technology of Huechys sanguinea, and establish the quality standard of rice-fried Huechys sanguinea. METHODS Taking the exudates, scent, color, degree of crushing, and protein content as the evaluation indicators combining entropy weight method with analytic hierarchy process to establish a comprehensive evaluation method. The effects of frying time, temperature and the ratio of medicinal materials to excipients on the quality of rice-fried Huechys sanguinea were investigated, and an orthogonal test to optimize the best processing technology was established. Microscopic identification and thin-layer identification of rice-fried Huechys sanguinea, determination of its moisture, ash, extract and heavy metals, and establishment of quality standards. RESULTS The best processing process for Huechys sanguinea was after the rice with an excipient ratio of 1∶2 was frying and smoking, pour processed Huechys sanguinea, stir fry at 140 ℃ for 6 min. The extract content was 199 mg·g-1, the odor, color, and fragmentation scores were all 5, and the protein content was 136 mg·g-1. The moisture content of rice-fried Huechys sanguinea was 2.97%, the total ash content and acid insoluble ash content were 3.79% and 0.33% respectively, the contents of heavy metals lead, cadmium, arsenic, mercury and copper were 2.26, 1.91, 0.06, 0.13 and 38.14 mg·kg-1 respectively, and the aflatoxin B1, B2, G1 and G2 were all lower than the detection limit by 0.1 μg·kg-1, the content of extract was 20.10%. CONCLUSION The processing technology of Huechys sanguinea is reliable and stable, which provides a scientific basis for standardizing the processing technology and quality standards of Huechys sanguinea decoction pieces. It is suggested that the moisture content of rice-fried Huechys sanguinea is <3.56%, total ash and acid insoluble ash are <4.55% and 0.40% respectively, the content of heavy metal lead is <2.71 mg·kg-1, cadmium is < 2.29 mg·kg-1, arsenic is <0.07 mg·kg-1, mercury is <0.16 mg·kg-1, copper is <45.77 mg·kg-1, the content of extract is >16.08%, and aflatoxin B1, B2, G1, G2 are <0.1 μg·kg-1.

BACKGROUND/OBJECTIVES: Inonotus obliquus has been used as antidiabetic herb around the world, especially in the Russian and Scandinavian countries. Diabetes is widely believed to be a key factor in Alzheimer’s disease (AD), which is widely considered to be type III diabetes. To investigate whether I. obliquus can also ameliorate AD, it would be interesting to identify new clues for AD treatment. We tested the anti-AD effects of raw Inonotus obliquus polysaccharide (IOP) in a mouse model of AD (3×Tg-AD transgenic mice).MATERIALS/METHODS: SPF-grade 3×Tg-AD mice were randomly divided into three groups (Control, Metformin, and raw IOP groups, n = 5 per group). β-Amyloid deposition in the brain was analyzed using immunohistochemistry for AD characterization. Gene and protein expression of pertinent factors of the ubiquitin-proteasome system (UPS) was determined using real-time quantitative polymerase chain reaction and Western blotting. RESULTS: Raw IOP significantly reduced the accumulation of amyloid aggregates and facilitated UPS activity, resulting in a significant reduction in AD-related symptoms in an AD mouse model. The presence of raw IOP significantly enhanced the expression of ubiquitin, E1, and Parkin (E3) at both the mRNA and protein levels in the mouse hippocampus. The mRNA level of ubiquitin carboxyl-terminal hydrolase isozyme L1, a key factor involved in UPS activation, also increased by approximately 50%. CONCLUSIONS Raw IOP could contribute to AD amelioration via the UPS pathway, which could be considered as a new potential strategy for AD treatment, although we could not exclude other mechanisms involved in counteracting AD processing.

The growth plate (cartilage tissue) is the key to bone development and linear growth.However, as the adolescence proceeds, the proliferation capacity of the growth plate will be continuously consumed, and finally the growth plate will be closed.A variety of regulatory factors control chondrocyte proliferation and differentiation through different mechanisms.Endocrine regulators (including growth hormone, insulin-like growth factor, thyroxine, sex hormone, glucocorticoid, etc.) and transcription factors play an important role in regulating the development of growth plates through systematic modulation.In addition, such local regulatory factors as Indian hedgehog protein, parathyroid hormone-related peptide, bone morphogenetic protein and fibroblast growth factor also regulate the development of the growth plate.In this paper, the regulatory mechanism for chondrocyte proliferation and differentiation was summarized.

Objective:To evaluate the effectiveness and safety of ultrasound-guided hydrostatic reduction for pediatric acute intussusception.Methods:One thousand eight hundred and thirty patients with acute intussusception diagnosed by ultrasound in Shenzhen Children′s Hospital from September 2017 to July 2020 were treated with ultrasound-guided hydrostatic reduction method. The therapeutic effects, complications and ultrasonic features were observed.Results:Among 1 830 cases, 1 791 cases were diagnosed as primary intussusception, and 39 cases were secondary intussusception. The overall rate of successful ultrasound enema reduction were 1 780/1 830(93.7%) patients. All 50/1 830(2.7%) patients underwent surgery after unsuccessful enema reduction, including 42 cases of primary intussusception, and 8 cases of secondary intussusception. The complication of intestinal perforation occurred in 3 cases (0.16%), and there were no deaths.Conclusions:Ultrasound-guided enema reduction for pediatric acute intussusception is an effective and safe method without radiation exposure, and can be used as the preferred method for non-operative treatment of intussusception.

Objective:To explore the clinical characteristics of juvenile-onset ankylosing spondylitis.Methods:Clinical data of 350 cases of ankylosing spondylitis diagnosed in Beijing Jishuitan Hospital from January 2014 to December 2019 were collected. There were 75 cases with the symptom onset in age ≤16 years (juvenile-onset ankylosing spondylitis, JoAS), and 275 cases with the symptom onset in age>16 years (adult-onset ankylosing spondylitis, AoAS). The clinical characteristics of two groups were analyzed.Results:Compared with AoAS, JoAS had a higher proportion of males [98.7% (74/75) vs. 79.6% (219/275); χ 2=15.65, P<0.01] and longer course of disease [11(8,15) vs. 8(4,15) years; Z=-3.09, P<0.01]. Compared with AoAS, JoAS was more prone to have peripheral joint swelling and pain [45.3%(34/75) vs. 18.9%(52/275), χ 2=22.20, P<0.01], hip pain [26.7%(20/75) vs. 15.3%(42/275), χ 2=5.25, P=0.03] or heel pain [9.3%(7/75) vs. 2.9%(8/275), χ 2=5.93, P=0.02] as the first clinical manifestation. Compared with AoAS, JoAS had a higher incidence of radiological hip involvement [77.3%(58/75) vs. 43.3%(119/275), OR=4.71, Wald=25.60, P<0.01], lower bone mineral density than peers [34.7%(26/75) vs. 23.3%(64/275), OR=2.23, Wald=7.20, P<0.01], higher incidence of malnutrition [25.3%(19/75) vs. 13.8%(38/275), OR=2.16, Wald=5.84, P=0.02] and higher incidence of acute uveitis [17.3%(13/75) vs. 6.5%(18/275), OR=2.72, Wald=6.24, P=0.01] after adjusting the course of disease. Conclusion:Compared with adult-onset ankylosing spondylitis, juvenile-onset ankylosing spondylitis is more prone to have peripheral joint swelling or hip pain as the first clinical manifestation; the radiological hip involvement, lower bone mineral density than peers, malnutrition and uveitis are more likely to occur.

The main lysosomal protease cathepsin D (cathD) is essential for maintaining tissue homeostasis via its degradative function, and its loss leads to ceroid accumulation in the mammalian nervous system, which results in progressive neurodegeneration. Increasing evidence implies non-proteolytic roles of cathD in regulating various biological processes such as apoptosis, cell proliferation, and migration. Along these lines, we here showed that cathD is required for modulating dendritic architecture in the nervous system independent of its traditional degradative function. Upon cathD depletion, class I and class III arborization (da) neurons in Drosophila larvae exhibited aberrant dendritic morphology, including over-branching, aberrant turning, and elongation defects. Re-introduction of wild-type cathD or its proteolytically-inactive mutant dramatically abolished these morphological defects. Moreover, cathD knockdown also led to dendritic defects in the adult mushroom bodies, suggesting that cathD-mediated processes are required in both the peripheral and central nervous systems. Taken together, our results demonstrate a critical role of cathD in shaping dendritic architecture independent of its proteolytic function.

Objective To examine the expression profile of programmed death-ligand 1 (PD-L1) on lung endothelial or epithelial cells,and to determine the specific role of PD-L1 in mouse model of indirect acute lung injury (i-ALI).Methods Eighty male C57BL/6 mice were randomly divided into two parts (both n =40).The effects of different administration routes on the expression of PD-L1 were observed.The mice in each part were randomly divided into sham,i-ALI,i-ALI+small interfering RNA (siRNA) random sequence control,and i-ALI+PD-L1 siRNA which could specifically inhibit PD-L1 expression groups,with l0 mice in each group.i-ALI was reproduced in a mouse model of hemorrhagic shock in combination with a subsequent cecal ligation and puncture (CLP).In sham group,only bilateral femoral arteries were ligated without catheterization or bleeding,and only cecum was separated but perforation was not ligated.Intravenous or intratracheal delivery of PD-L1 siRNA was performed 2 hours following the resuscitation to suppress the expression of PD-L1 on lung endothelial or epithelial cells.The mice in i-ALI+siRNA random sequence control group were given siRNA random sequence without inhibition effect on PD-L1 expression,and those in sham group and i-ALI group were given 100 μL phosphate buffered saline (PBS).The mice were sacrificed at 24 hours after CLP,and samples of blood,lung tissue and bronchoalveolar lavage fluid (BALF) were harvested.Expressions of PD-L1 were determined with flow cytometry.Cytokines and chemokines in plasma,lung tissue and BALF were determined by enzyme linked immunosorbent assay (ELISA).The protein concentration in plasma and BALF and the activity of myeloperoxidase (MPO) in lung tissue were quantitatively measured.The pathological changes in lung tissue were observed under light microscope.Results ① Compared with sham group,PD-L1 expression on lung endothelial or epithelial cells were significantly elevated in i-ALI group [endothelial cells:(27.88 ± 1.53)％ vs.(19.64 ± 1.03)％,epithelial cells:(58.70 ± 8.21)％ vs.(29.23 ± 3.94)％,both P ＜ 0.05].② Mice received intravenous delivery of liposomal-encapsulated siRNA had significantly lower expression of PD-L1 on lung endothelial cells as compared with that of i-ALI group [(21.37 ± 0.76)％ vs.(27.88 ± 1.53)％,P ＜ 0.05].Intratracheal delivery of naked PD-L1 siRNA mainly inhibited the PD-L1 expression on epithelial cell as compared with that of i-ALI group [(31.23±4.71) ％ vs.(58.70±8.21) ％,P ＜ 0.05].The expression of PD-L1 in pulmonary microvascular endothelial cells or pulmonary epithelial cells of i-ALI mice was not affected by siRNA random sequence.③ PD-L1 silencing on pulmonary endothelial cells induced by intravenous delivery of PD-L1 siRNA led to a lower protein ratio of BALF/plasma [(4.48 ± 0.35) × 10-3 vs.(6.11 ± 0.56) × 10-3,P ＜ 0.05] and a decreased MPO activity in lung tissue (U · μg-1 · min-1:2.48 ± 0.47 vs.4.56 ± 0.52,P ＜ 0.05) as compared with that of i-ALI group.Moreover,inflammatory mediator levels such as interleukin-6 (IL-6),monocyte chemoattractant protein-1 (MCP-1),macrophage inflammatory protein-2 (MIP-2) and tumor necrosis factor-α (TNF-α) in lung tissue or plasma were significantly reduced following PD-L1 suppression on endothelial cells as compared with those of i-ALI group [IL-6 (ng/g):177.4±23.2 vs.287.9±57.3,MCP-1 (ng/g):839.6±91.7 vs.1 395.7±211.9,MIP-2 (ng/g):923.7± 107.3 vs.1 700.9±240.2 in lung tissue;IL-6 (ng/L):950.2±192.7 vs.1 828.2±243.6,TNF-α (ng/L):258.7±29.1 vs.443.0 ± 58.1,MCP-1 (ng/L):2 583.8±302.3 vs.4 328.1 ±416.4,MIP-2 (ng/L):1 512.9± 165.6 vs.2 005.9 ± 85.7 in plasma,all P ＜ 0.05],however,there was no significant change in the levels of inflammatory factors in BALF.It was shown in lung tissue histology that PD-L1 silencing on pulmonary endothelial cells induced by intravenous delivery of PD-L1 siRNA led to lessened pulmonary edema and reduced immune cells emigration.Intratracheal delivery of PD-L1 siRNA for PD-L1 suppression on epithelial cells had minimal effects on protein ratio of BALF/plasma,MPO activity,inflammatory mediator expressions in lung tissue,plasma,and BALF as well as lung tissue histology.Conclusion PD-L1 silencing on endothelial cells but not epithelial cells protected mice against hemorrhagic shock-sepsis induced i-ALI.

Objective: To investigate the risk factors of anastomotic leakage (AL) after laparoscopic surgery in rectal cancer patient with neoadjuvant therapy and construct a nomogram prediction model. Methods: This study was a retrospective case-control study that collected and reviewed the clinicopathological data of 359 patients who underwent laparoscopic surgery from January 2012 to January 2018, including 202 patients from the Department of General Surgery, Nanfang Hospital of Southern Medical University and 157 patients from the Department of Gastrointestinal Surgery of Fujian Provincial Cancer Hospital. Inclusion criteria: (1) age ≥ 18 years old; (2) diagnosis as rectal cancer by biopsy before treatment; (3) distance from tumor to anus within 12 cm; (4) locally advanced stage (T3-T4 or N+) diagnosed by imaging (CT, MRI, PET or ultrasound); (5) standardized neoadjuvant therapy followed by laparoscopic radical operation. Exclusion criteria: (1) previous history of colorectal cancer surgery; (2) short-term or incomplete standardized neoadjuvant therapy; (3) Miles, Hartmann, emergency surgery, palliative resection; (4) conversion to open surgery. Clinicopathological data, including age, gender, body mass index (BMI), preoperative albumin, distance from tumor to anus, operation hospital, American Society of Anesthesiologists score (ASA score), operation time, T stage, N stage, M stage, TNM stage, pathological complete response (pCR) were analyzed with univariate analysis to identify predictors for AL after laparoscopic surgery in rectal cancer patient with neoadjuvant therapy. Then, incorporated predictors of AL, which were screened by multivariate logistic regression, were plotted by the "rms" package in R software to establish a nomogram model. According to the scale of the nomogram of each risk factor, the total score could be obtained by adding each single score, then the corresponding probability of postoperative AL could be acquired. The area under ROC curve (AUC) was used to evaluate the predictive ability of each risk factor and nomogram on model. AUC > 0.75 indicated that the model had good predictive ability. The Bootstrap method (1000 bootstrapping resamples) was applied as internal verification to show the robustness of the model. The discrimination of the nomogram was determined by calculating the average consistency index (C-index) whose rage was 0.5 to 1.0. Higher C-index indicated better consistency with actual risk. The calibration curve was used to assess the calibration of prediction model. The Hosmer-Lemeshow test yielding a non-significant statistic (P>0.05) suggested no departure from the perfect fit. Results: Of 359 cases, 224 were male, 135 were female, 189 were ≥ 55 years old, 98 had a BMI > 24 kg/m², 176 had preoperative albumin ≤ 40 g/L, 128 had distance from tumor to anus ≤ 5 cm, 257 were TNM 0-II stage, 102 were TNM III-IV stage, and 84 achieved pCR after neoadjuvant therapy. The incidence of postoperative AL was 9.5% (34/359). Univariate analysis showed that gender, preoperative albumin and distance from tumor to the anus were associated with postoperative AL (All P<0.05). Multivariate logistic regression analysis revealed that male (OR=2.480, 95% CI: 1.012-6.077, P=0.047), preoperative albumin ≤40 g/L (OR=5.319, 95% CI: 2.106-13.433, P<0.001) and distance from tumor to anus ≤ 5 cm (OR=4.339, 95% CI: 1.990-9.458, P<0.001) were significant independent risk factors for postoperative AL. According to these results, a nomogram prediction model was constructed. The male was for 55 points, the preoperative albumin ≤ 40 g/L was for 100 points, and the distance from tumor to the anus ≤ 5 cm was for 88 points. Adding all the points of each risk factor, the corresponding probability of total score would indicated the morbidity of postoperative AL predicted by this nomogram modal. The AUC of the nomogram was 0.792 (95% CI: 0.729-0.856), and the C-index was 0.792 after internal verification. The calibration curve showed that the predictive results were well correlated with the actual results (P=0.562). Conclusions Male, preoperative albumin ≤ 40 g/L and distance from tumor to the anus ≤ 5 cm are independent risk factors for AL after laparoscopic surgery in rectal cancer patient with neoadjuvant therapy. The nomogram prediction model is helpful to predict the probability of AL after surgery.