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.

AIM:To investigate the effects of sodium hydrosulfide(NaHS)on hexokinase 2(HK2)-nucleo-tide-binding oligomerization domain-like receptor protein 3(NLRP3)-gasdermin D(GSDMD)pathway and pyroptosis in-duced by lung ischemia/reperfusion(I/R)in rats.METHODS:Male Sprague-Dawley rats were divided into 6 groups:control group,control+NaHS group,I/R group,low-dose NaHS+I/R(L+I/R)group,medium-dose NaHS+I/R(M+I/R)group,and high-dose NaHS+I/R(H+I/R)group,with 6 rats in each group.The NaHS was administered via intraperi-toneal injection at 1.5 mL,30 min before modeling.The left lung tissues were collected 30 min after ischemia and 1 h af-ter reperfusion,and the wet/dry weight ratio and total lung water content were recorded.Hematoxylin-eosin(HE)staining was used to examine lung tissue morphological changes.The levels of malondialdehyde(MDA),myeloperoxidase(MPO)and lactate in lung tissues were measured with test kits.ELISA was employed to determine the levels of interleukin-1β(IL-1β)and IL-18.The expression of glycolysis-and pyroptosis-related indicators was analyzed by Western blot,qRT-PCR and immunofluorescence staining.RESULTS:Compared with control group,the rats in NaHS group showed no signifi-cant differences in all laboratory tests(P>0.05).The rats in I/R group exhibited significant lung injury,oxidative stress,increased lactate level,and up-regulated glycolysis and pyroptosis(P<0.05 or P<0.01).Compared with I/R group,the indicators in L+I/R group showed a downward trend(P<0.01)or no difference(P>0.05),while those in M+I/R group dis-played a significant reduction(P<0.05 or P<0.01).However,the indexes in H+I/R group exhibited no significant dif-ferences in these tests(all P>0.05).CONCLUSION:A moderate dose(56 μmol·L-1·kg-1)of NaHS mitigated the oc-currence of pyroptosis by inhibiting the HK2-NLRP3-GSDMD pathway,thus contributing to the attenuation of lung I/R in-jury in rats.

Objective:To investigate the value of peripheral blood neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and serum lactate dehydrogenase (LDH) levels for predicting the occurrence of radiation pneumonia (RP) in small cell lung cancer.Methods:A total of 84 patients with small cell lung cancer who received image-guided radiotherapy in Xuzhou Cancer Hospital between September 2019 and September 2022 were retrospectively analyzed. They were divided into an RP group ( n = 25) and a non-RP group ( n = 59) according to whether RP occurred. Peripheral blood NLR and PLR and serum LDH levels were compared between the two groups before and after radiotherapy. The receiver operating characteristic curve (ROC curve) was used to analyze the value of peripheral blood NLR, PLR, and serum LDH levels for the diagnosis of RP in small cell lung cancer. Results:Before radiotherapy, there were no significant differences in peripheral blood NLR and PLR between the two groups (both P > 0.05). After radiotherapy, peripheral blood NLR and PLR in the RP group were (3.39 ± 0.81) and (129.06 ± 24.90), respectively, which were significantly higher than those in the non-RP group [(2.54 ± 0.71), (104.76 ± 26.26), t = 3.61, 3.83, both P < 0.05]. The NLR (2.86 ± 0.30) and PLR (110.07 ± 10.05) were the lowest in patients with grade 2 RP and they were highest in patients with grade 4 RP [(4.49 ± 0.63), (168.88 ± 14.11)]. The grade of RP was positively correlated with peripheral blood NLR and PLR. The sensitivity of peripheral blood NLR in the diagnosis of RP was 88.0%, the specificity was 66.1%, and the area under the curve (AUC) was 0.791. The sensitivity of PLR in the diagnosis of RP was 48.0%, the specificity was 94.9%, and the AUC was 0.735. The sensitivity of NLR combined with PLR in the diagnosis of RP was 92.0%, the specificity was 59.3%, and the AUC was 0.801. There was no significant difference in serum LDH levels between the two groups before and after radiotherapy (both P > 0.05). Logistic regression analysis showed that NLR and PLR were risk factors for RP in patients with small cell lung cancer ( OR = 2.309, 1.037; 95% CI: 1.061-5.024, 1.004-1.071). Conclusion:In patients with small cell lung cancer who develop RP, peripheral blood NLR, and PLR are markedly elevated compared with those in patients who do not develop RP, and combined detection of peripheral blood NLR and PLR has a high value for early diagnosis of RP in patients with small cell lung cancer.

AIM:To investigate the effect and mechanism of the exogenous hydrogen sulfide donor GYY4137 on hypoxia-induced proliferation of rat pulmonary artery smooth muscle cells(PASMCs).METHODS:Rat PASMCs in optimal growth condition were used.Once the cell density reached 60%～70%,the cells were serum starved for 24 h.The cells were then randomly divided into four groups:normal group,normal+GYY4137 group,hypoxia group,and hypoxia+GYY4137 group.A CCK-8 assay was used to determine the safe concentration range of GYY4137 that exerted no adverse effects on normal cells,and the optimal concentration of GYY4137 to inhibit hypoxia-induced proliferation of PASMCs was identified.EdU staining was employed to assess PASMCs proliferation in each group.Western blot analysis was conducted to evaluate the expression of proliferating cell nuclear antigen(PCNA)and proteins related to glycolysis and pyroptosis in PASMCs.Lactic acid content was quantified using a lactic acid assay kit.Immunofluorescence was used to detect the pro-tein expression of hexokinase 2(HK2)and nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)in PASMCs,and the levels of interleukin-1β(IL-1β)and IL-18 in PASMCs were measured using ELISA.RESULTS:The effective concentration of GYY4137 in inhibiting hypoxia-induced viability of PAMSCs was 100 μmol/L(P＜0.05).Com-pared with the hypoxia group,the hypoxia+GYY4137 group showed a significant decrease in PCNA protein expression(P＜0.05),reduced PAMSCs proliferation(P＜0.01),decreased HK2 and pyruvate kinase isozyme type M2(PKM2)protein expression(P＜0.05,P＜0.01),increased pyruvate dehydrogenase(PDH)protein expression(P＜0.05),and reduced lac-tic acid content(P＜0.01).Additionally,the expression of pyroptosis-related proteins was significantly decreased(P＜0.015,P＜0.01),and immunofluorescence revealed a significant decrease in HK2 and NLRP3 expression(P＜0.01).ELISA results showed that IL-1β and IL-18 protein levels were significantly decreased(P＜0.05,P＜0.01).CONCLU-SION:GYY4137 inhibits hypoxia-induced proliferation of rat PASMCs by regulating glycolysis and pyroptosis.

AIM:To investigate the effect and mechanism of the exogenous hydrogen sulfide donor GYY4137 on hypoxia-induced proliferation of rat pulmonary artery smooth muscle cells(PASMCs).METHODS:Rat PASMCs in optimal growth condition were used.Once the cell density reached 60%～70%,the cells were serum starved for 24 h.The cells were then randomly divided into four groups:normal group,normal+GYY4137 group,hypoxia group,and hypoxia+GYY4137 group.A CCK-8 assay was used to determine the safe concentration range of GYY4137 that exerted no adverse effects on normal cells,and the optimal concentration of GYY4137 to inhibit hypoxia-induced proliferation of PASMCs was identified.EdU staining was employed to assess PASMCs proliferation in each group.Western blot analysis was conducted to evaluate the expression of proliferating cell nuclear antigen(PCNA)and proteins related to glycolysis and pyroptosis in PASMCs.Lactic acid content was quantified using a lactic acid assay kit.Immunofluorescence was used to detect the pro-tein expression of hexokinase 2(HK2)and nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)in PASMCs,and the levels of interleukin-1β(IL-1β)and IL-18 in PASMCs were measured using ELISA.RESULTS:The effective concentration of GYY4137 in inhibiting hypoxia-induced viability of PAMSCs was 100 μmol/L(P＜0.05).Com-pared with the hypoxia group,the hypoxia+GYY4137 group showed a significant decrease in PCNA protein expression(P＜0.05),reduced PAMSCs proliferation(P＜0.01),decreased HK2 and pyruvate kinase isozyme type M2(PKM2)protein expression(P＜0.05,P＜0.01),increased pyruvate dehydrogenase(PDH)protein expression(P＜0.05),and reduced lac-tic acid content(P＜0.01).Additionally,the expression of pyroptosis-related proteins was significantly decreased(P＜0.015,P＜0.01),and immunofluorescence revealed a significant decrease in HK2 and NLRP3 expression(P＜0.01).ELISA results showed that IL-1β and IL-18 protein levels were significantly decreased(P＜0.05,P＜0.01).CONCLU-SION:GYY4137 inhibits hypoxia-induced proliferation of rat PASMCs by regulating glycolysis and pyroptosis.

OBJECTIVE: To explore the genetic basis for a child with mental retardation. METHODS: Whole exome sequencing was carried out for the child. Candidate variant was screened based on his clinical features and verified by Sanger sequencing. RESULTS: The child was found to harbor a c.995_1002delAGACAAAA(p.Asp332AlafsTer84) frameshift variant in the SYNGAP1 gene. Bioinformatic analysis suggested it to be pathogenic. The same variant was not detected in either parent. CONCLUSION The c.995_1002delAGACAAAA(p.Asp332AlafsTer84) frameshift variant of the SYNGAP1 gene probably underlay the mental retardation in this child. Above finding has expanded the spectrum of SYNGAP1 gene variants and provided a basis for the diagnosis and treatment for this child.
Child ; Humans ; Intellectual Disability/genetics* ; Frameshift Mutation ; High-Throughput Nucleotide Sequencing ; Computational Biology ; Heterozygote ; Mutation ; ras GTPase-Activating Proteins/genetics*

Premature ovarian insufficiency has become a major problem that plagues women of childbearing age. So far, there is no effective treatment method. Stem cells have the potential for self-renewal and multidirectional differentiation, and are increasingly being considered for the treatment of ovarian insufficiency. Stem cells extracted from bone marrow, umbilical cord, peripheral blood, and amniotic fluid can migrate to the ovary and proliferate, differentiate and mature in a specific ovarian environment, secrete related factors, promote ovarian function repair, and increase the quality of ovarian follicles and the number of granulosa cells at all levels. Improve endocrine function and restore fertility to a certain extent. This article reviews the research progress of various types of stem cells in the treatment of premature ovarian insufficiency.

Premature ovarian insufficiency has become a major problem that plagues women of childbearing age. So far, there is no effective treatment method. Stem cells have the potential for self-renewal and multidirectional differentiation, and are increasingly being considered for the treatment of ovarian insufficiency. Stem cells extracted from bone marrow, umbilical cord, peripheral blood, and amniotic fluid can migrate to the ovary and proliferate, differentiate and mature in a specific ovarian environment, secrete related factors, promote ovarian function repair, and increase the quality of ovarian follicles and the number of granulosa cells at all levels. Improve endocrine function and restore fertility to a certain extent. This article reviews the research progress of various types of stem cells in the treatment of premature ovarian insufficiency.

Objective: To investigate the short-term efficacy and toxicity of bevacizumab combined with DP or rh-endostatin（recombinant human vascular endostatin injection）combined with DP in locally advanced EGFR wild-type non-small cell lung cancer (NSCLC). Methods: Seventy-two patients with treatment of locally advanced EGFR wild-type NSCLC admitted to the Department of Respiratory Medicine of Zhongshan Hospital Affiliated to Guangdong Medical University from January 2014 to January 2017 were divided into bevacizumab group (34 cases) and rh-endostatin group (38 cases) according to the random number method. The former group was treated with bevacizumab combined with docetaxel and cisplatin, while the latter was treated with rh-endostatin combined with docetaxel and cisplatin. According to RECISIT 1.1 standard, the changes of lesion size before and after treatment in two groups were evaluated. Serum levels of vascular endothelial growth factor (VEGF), carcinoembryonic antigen (CEA), cytokeratin 21-1 fragment (CYFRA21-1), squamous cell carcinoma antigen (SCC) were measured. The adverse reactions during treatment were also evaluated. Results: In bevacizumab group, patients with CR, PR, SD, PD, DCR and ORR were 2 cases, 12 cases, 15 cases, 5 cases, 41.18% and 85.29%, respectively. In rh-endostatin group, patients with CR, PR, SD, PD, DCR, ORR were 2 cases, 16 cases, 14 cases, 6 cases, 47.37% and 84.21%, respectively. The DCR in rh-endostatin group was significantly higher than that in bevacizumab group (P<0.05).The serum levels of VEGF and CEAin rh-endostatin group decreased more obvious than those in bevacizumab group (all P<0.05). The incidence of gastrointestinal reaction, skin reaction and cardiac toxicity in rh-endostatin group was higher than that in bevacizumab group, while the incidence of bleeding in bevacizumab group was higher than that in rh-endostatin group (all P<0.05). Conclusion: In patients with locally advanced EGFR wild-type NSCLC, rh-endostatin combined with DP regimen is better than bevacizumab combined with DPregimen. In clinical practice, corresponding treatment regimen can be selected according to different characteristics of patients, so as to minimize the toxic reaction during treatment and avoid clinical risk.

Objective To evaluate the effect of sevoflurane anesthesia on cognitive impairment in rats with traumatic brain injury. Methods One hundred and and twenty healthy male Wistar rats, aged 2-3 months, weighing 190-220 g, were assigned into 4 groups ( n=30 each) using a random number table method: control group ( group C) , traumatic brain injury group ( group T) , sevoflurane anesthesia group ( group S) , and traumatic brain injury plus sevoflurane anesthesia group ( group T+S) . A 40 g hammer was freely dropped onto the left parietal bone window from a height of 20 cm to establish the traumatic brain inju-ry model in T and T+S groups. Twelve days later, S and T+S groups inhaled 3％ sevoflurane for 3 h, and C and T groups inhaled pure oxygen for 3 h. On 1 day before anesthesia and 3 and 7 days after anesthesia, 10 rats in each group were randomly selected for performing Morris water maze test. Rats were sacrificed af-ter the end of Morris water maze test, and the hippocampal tissues were obtained for determination of the apoptosis rate of hippocampal neurons, cytoplasmic calcium concentration [Ca2+]i (by flow cytometry), expression of glucose-regulated protein 78 ( GRP78) and CCAAT∕enhancer-binding protein homologous pro-tein ( CHOP ) ( by immunohistochemistry ) , and expression of caspase-3 and caspase-12 ( by Western blot) . Results Compared with group C, the escape latency was significantly prolonged, the number of crossing platform was decreased, the apoptosis rate of hippocampal neurons and [ Ca2+] i were increased, and the expression of caspase-3, caspase-12, GRP78 and CHOP in hippocampal tissues was up-regulated in S, T and T+S groups ( P<0. 05) . Compared with T and S groups, the escape latency was significantly prolonged, the number of crossing platform was decreased, the apoptosis rate of hippocampal neurons and [ Ca2+] i were increased, and the expression of caspase-3, caspase-12, GRP78 and CHOP in hippocampal tissues was up-regulated in group T+S ( P<0. 05 ) . Conclusion Sevoflurane anesthesia can accentuate cognitive impairment in rats with traumatic brain injury, and the mechanism may be related to aggravating the degree of endoplasmic reticulum stress-induced calcium overload and increasing the apoptosis rate of hip-pocampal neurons.