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.

In line with the rising global incidence of cancer,tumor metastasis has become the leading cause of mortality among cancer patients.Formation of the pre-metastatic niche(PMN)creates an optimal microenvironment for tumor cell colonization and metastasis,thus facilitating tumor dissemination.In this context,cancer-associated fibroblasts(CAFs)have garnered significant attention as a result of their multifaceted roles in tumor progression.CAFs enhance the formation of the PMN and promote the invasive behavior of tumor cells by remodeling the extracellular matrix,inducing epithelial-mesenchymal transition,stimulating angiogenesis and modulating the tumor immune microenvironment.These processes not only expedite metastasis but also enable tumor immune evasion.This paper reviews the fundamental mechanisms and functions of CAFs in tumor metastasis,examines their potential applications in cancer research and therapy,and offers new perspectives and directions for the development of anti-tumor metastasis strategies.

Objective To analyze the correlation of cholecystectomy and changes in intestinal microbiota composition and function by observing functional characteristics of differential microbial communities.Methods A cross-sectional study was conducted on the patients(PC group,n=73)undergoing cholecystectomy in our hospital from 2020 to 2021.Another 56 healthy age-and gender-matched individuals(HC group)without a history of cholecystectomy were subjected and served as the control group.Fecal specimens were collected from the 2 groups.16S rRNA sequencing analysis was performed to examine the changes in composition and function of intestinal microbiota.Results There were no statistical differences between the 2 groups in baseline indicators,such as gender,age,BMI,smoking and drinking history,blood pressure,heart rate,and comorbidities,but significant difference was observed in total bilirubin(TBIL)between them(P<0.01).Alpha diversity analysis showed no significant difference in Chao1,Shannon,and Simpson indices between the 2 groups.Beta diversity analysis using the Bray-Curtis distance algorithm revealed a significant difference between the 2 groups at the class and genus levels(P<0.05).The analysis of microbiota relative abundance using LEFSE showed that Enterobacteriaceae,Lactobacillales,Citrobacter,Megasphaera,Lactobacillus,Enterococcus,Akkermansia,Streptococcus,Klebsiella,and Ruminococcus_gnavus were up-regulated in the PC group,and Lachnospiraceae,Sutterellaceae,Lachnospirales,Lachnospira,and Sutterella were down-regulated.Kyoto Encyclopedia of Genes and Genomes(KEGG)functional prediction analysis indicated that significant differences were seen between the 2 groups in metabolic pathways,including ascorbic acid(vitamin C)metabolism and aldonic acid metabolism(P<0.05),tricarboxylic acid cycle(TCA cycle)(P<0.05),glutathione metabolism(P<0.05),glutamic acid metabolism(P<0.05),secondary bile acid metabolism(P<0.05),and pentose phosphate pathway(P<0.01).Conclusion Cholecystectomy is closely associated with the structural alterations in the composition of intestinal microbiota.Variations in microbiota composition and function may induce perturbations in TCA cycle and glutathione metabolism,glutamate metabolism,secondary bile acid metabolism,and pentose phosphate pathways.

Purpose To explore the changes of brain function and network in primary insomnia(PI)patients using the percent amplitude of fluctuation(perAF)combined with functional connectivity(FC).Materials and Methods A total of 51 PI patients and 45 normal controls underwent resting functional magnetic resonance scans in Kunshan Traditional Chinese Medicine Hospital from November 2019 to December 2022,then the perAF value and FC in brain regions of different perAF value between the two groups was analyzed.Pearson correlation analysis was used to investigate the relationships between the altered perAF values and insomnia years,Pittsburgh sleep quality index and Montreal cognitive assessment.Results Compared with healthy group,PI patients had increased perAF values in the left prefrontal lobe(-42 9 45)and decreased perAF values in the right parahippocampal gyrus(27-12-27)[Gaussian random field(GRF)correction,voxel-wise P<0.001,cluster-level P<0.05].FC analysis showed that the right parahippocampal gyrus of PI patients exhibited significantly increased FC with the left middle temporal gyrus,inferior temporal gyrus(-57-15-33)and the left middle occipital gyrus(-30-78 27)(GRF corrected,voxel-wise P<0.001,cluster-level P<0.05).It was noteworthy that the perAF values of the right parahippocampal gyrus were positively correlated with Montreal cognitive assessment of PI patients(r=0.428,P=0.002).Conclusion Specific brain areas in PI patients may exhibit aberrant neuronal activity,mainly manifested as decreased perAF value in the right parahippocampal gyrus,which was increased FC with the left middle temporal gyrus,inferior temporal gyrus and the left middle occipital gyrus.These discoveries may be the core of the mechanism of impaired brain function in PI patients.

In line with the rising global incidence of cancer,tumor metastasis has become the leading cause of mortality among cancer patients.Formation of the pre-metastatic niche(PMN)creates an optimal microenvironment for tumor cell colonization and metastasis,thus facilitating tumor dissemination.In this context,cancer-associated fibroblasts(CAFs)have garnered significant attention as a result of their multifaceted roles in tumor progression.CAFs enhance the formation of the PMN and promote the invasive behavior of tumor cells by remodeling the extracellular matrix,inducing epithelial-mesenchymal transition,stimulating angiogenesis and modulating the tumor immune microenvironment.These processes not only expedite metastasis but also enable tumor immune evasion.This paper reviews the fundamental mechanisms and functions of CAFs in tumor metastasis,examines their potential applications in cancer research and therapy,and offers new perspectives and directions for the development of anti-tumor metastasis strategies.

Purpose To explore the changes of brain function and network in primary insomnia(PI)patients using the percent amplitude of fluctuation(perAF)combined with functional connectivity(FC).Materials and Methods A total of 51 PI patients and 45 normal controls underwent resting functional magnetic resonance scans in Kunshan Traditional Chinese Medicine Hospital from November 2019 to December 2022,then the perAF value and FC in brain regions of different perAF value between the two groups was analyzed.Pearson correlation analysis was used to investigate the relationships between the altered perAF values and insomnia years,Pittsburgh sleep quality index and Montreal cognitive assessment.Results Compared with healthy group,PI patients had increased perAF values in the left prefrontal lobe(-42 9 45)and decreased perAF values in the right parahippocampal gyrus(27-12-27)[Gaussian random field(GRF)correction,voxel-wise P<0.001,cluster-level P<0.05].FC analysis showed that the right parahippocampal gyrus of PI patients exhibited significantly increased FC with the left middle temporal gyrus,inferior temporal gyrus(-57-15-33)and the left middle occipital gyrus(-30-78 27)(GRF corrected,voxel-wise P<0.001,cluster-level P<0.05).It was noteworthy that the perAF values of the right parahippocampal gyrus were positively correlated with Montreal cognitive assessment of PI patients(r=0.428,P=0.002).Conclusion Specific brain areas in PI patients may exhibit aberrant neuronal activity,mainly manifested as decreased perAF value in the right parahippocampal gyrus,which was increased FC with the left middle temporal gyrus,inferior temporal gyrus and the left middle occipital gyrus.These discoveries may be the core of the mechanism of impaired brain function in PI patients.

Objective:To investigate the effect of microbubbles combined with gentamicin on the clearance of bacterial biofilms and the healing of diabetic foot ulcers under low-frequency ultrasound.Methods:From July 2021 to June 2022, 27 patients with chronic diabetic foot ulcers complicated with infection were prospectively selected from the Trauma Center of the Second Affiliated Hospital of Chongqing Medical University. The patients were divided into low-frequency ultrasound + microbubbles + gentamicin ointment group, low-frequency ultrasound + microbubbles group, and gentamicin ointment group by using a random number table, with 9 patients in each group. The three groups were all treated with simple debridement by the same surgeon.Afterward, in the low-frequency ultrasound+ microbubbles+ gentamicin ointment group, the wounds covered by 4% microbubble suspension were firstly irradiated with low-intensity focused ultrasound for 5 min, and then evenly applied with gentamicin ointment. In the low-frequency ultrasound + microbubbles group, the wounds covered by 4% microbubble suspension were irradiated with low-intensity focused ultrasound for 5 min. The gentamicin ointment group was treated with gentamicin ointment evenly. The treatment lasted for 2 weeks, and secretions and tissue specimens were collected during and 2 weeks after the treatment, respectively. The general indexes of wound surface (including ulcer depth score, secretion exudation score, fresh granulation tissue growth score, and total index score), ulcer area, ulcer healing rate, as well as negative rate of secretion culture were compared among the three groups after treatment. Additionally, the structural changes in bacterial biofilms under a scanning electron microscope and colony count under a laser confocal scanning microscope were compared among the three groups after treatment.Results:No significant differences were found in the general datas among the three groups (all P>0.05). After treatment for 2 weeks, the overall general indexes showed statistically and significant differences among the three groups (all P<0.05). Each index score in the low-frequency ultrasound + microbubbles + gentamicin ointment group was lower than that in the low-frequency ultrasound + microbubbles group and the gentamicin ointment group (all P<0.05). There were no significant differences in overall ulcer area among the three groups ( P>0.05). The overall ulcer healing rate presented significant differences among the three groups ( P<0.05). The healing rate in the low-frequency ultrasound + microbubbles + gentamicin ointment group was higher than that in the low-frequency ultrasound + microbubbles group and the gentamicin ointment group (all P<0.05). The overall negative rates of secretion culture among the three groups were significantly different ( P<0.05), the negative rate in the low-frequency ultrasound + microbubbles + gentamicin ointment group was higher than that in the low-frequency ultrasound + microbubbles group and the gentamicin ointment group (all P<0.05). Scanning electron microscopy confirmed bacterial biofilm infection in the three groups before treatment. After treatment for 2 weeks, the biofilm formation in the low-frequency ultrasound + microbubbles + gentamicin ointment group reduced significantly, while the low-frequency ultrasound + microbubbles group and the gentamicin ointment group had little change compared with that before treatment. Significant differences were detected in total colony count among the three groups under the confocal microscope ( P<0.05). The colony count in the low-frequency ultrasound + microbubbles + gentamicin ointment group was lower than that in the low-frequency ultrasound + microbubbles group and the gentamicin ointment group (both P<0.05). Conclusions:Ultrasound microbubbles combined with gentamicin can clear bacterial biofilms and promote the healing of diabetic foot ulcers.

BACKGROUND: Malignant pleural mesothelioma (MPM) is a highly aggressive disease arising from pleural mesothelial cells. Advanced pleural mesothelioma has a poor prognosis, with a median survival of no more than 15 months. First line standard chemotherapy regimen recommended is Pemetrexed based chemotherapy regimen, with or without bevacizumab. There is no consensus on whether patients who have received first-line standard chemotherapy can benefit from pemetrexed maintenance chemotherapy. The study aimed to investigate the efficacy and safety of pemetrexed maintenance therapy (PMT) after treatment with a pemetrexed and platinum regimen for patients with MPM. METHODS: A total of 40 MPM patients were collected from Cancer Hospital Chinese Academy of Medical Sciences from January 2013 to January 2018, eligible patients were unresectable MPM, without disease progression following 4 to 6 cycles of pemetrexed and platinum, including pemetrexed maintenance therapy group (22 cases) and observation group (18 cases). The last follow-up was conducted in January 2020. The primary endpoint were progression free survival (PFS), and the secondary end points were overall survival (OS), the efficacy, adverse reactions of PMT. RESULTS: The median PFS in the PMT arm was longer than that in the observation arm (8.5 mon vs 3 mon, P=0.008), but there was no significant difference in median OS (26.4 mon vs 15.7 mon, P=0.177). Objective response rate (ORR) of two group were 22.7% and 0%, respectively. The grade 3-4 toxicity in PMT group included grade 4 neutropenia in 1 patient (4.5%), grade 3 neutropenia in 1 patient (4.5%), grade 4 anemia in 1 patient (4.5%) and grade 3 nausea and anorexia in 1 patient (4.5%). CONCLUSIONS Pemetrexed maintenance therapy following initial pemetrexed and platinum chemotherapy improve PFS in patients with MPM, and is well tolerated.
Antineoplastic Combined Chemotherapy Protocols/adverse effects* ; Cisplatin/therapeutic use* ; Humans ; Lung Neoplasms/drug therapy* ; Mesothelioma/drug therapy* ; Mesothelioma, Malignant ; Neutropenia ; Pemetrexed/therapeutic use* ; Platinum/therapeutic use* ; Pleural Neoplasms/drug therapy*

Objective:To report embryonic testicular regression syndrome(ETRS) caused by DHX37 heterozygous variant for the first time in China and summarize the clinical manifestations of ETRS as to improve the understanding of doctors for this disease.Methods:The clinical data and whole exome sequencing results of five cases of ETRS from Shenzhen Children′s Hospital were collected. The reported cases of DHX37 heterozygous variant were reviewed.Results:Five patients with ETRS visited the doctors at the age of 2 months to 5 years and 5 months. Three patients raised as males came to hospital due to virilition and 2 female patients visited a doctor due to clitoral hypertrophy. No uterus was detected by ultrasound in all patients. The gonadal pathologies from 4 cases displayed no testicular tissue or gonadal dysgenesis, complicated with gonadoblastoma in one case. The genetic testing revealed that the heterozygous variant(c.923G>A, p. R308Q) in DHX37 was found in 2 cases, without variant in other 3 cases. According to the review, ETRS and 46, XY gonadal dysgenesis due to DHX37 herozygous variant was firstly reported in 2019. A total of 40 cases, including 21 cases of ETRS, presented with the virilition or female phenotype, with the disappearance of testicular tissue as the main pathologies. There is no report in China.Conclusion:The article summarized the clinical manifestations and whole exome sequencing results of 5 patients with ETRS, among which two cases were caused by DHX37 variants and one was complicated with gonadoblastoma.

Objective To study the clinical features, diagnosis and treatment of torsion of testes in newborn. Method Neonates who were diagnosed with neonatal testicular torsion and admitted to Shenzhen Children's Hospital from March 2008 to July 2018 were studied. The clinical data such as days in age, time of onset, clinical manifestations, time of ultrasound examination, characteristics of ultrasound examination, surgery time, surgical types, postoperative conditions, pathological findings, and follow-up results were retrospectively analyzed. Result A total of 12 infants with torsion of testes were enrolled. The average onset time was 2.9 d, ranged from 1～10 d. The time of onset was within 24 h after birth in six infants. The median duration from onset to seeing a doctor was 3.5 d, ranged from 2 h to 28 d. First manifestations being reported grammer were scrotal swelling or mass, including 7 cases on the left side and 5 cases on the right side. Among them, 9 cases were associated with redness or cyanosis of the scrotum. Ultrasound was characterized by the disappearance or significant reduction of testicular parenchymal blood flow signal, and the sensitivity of ultrasound was 100％. The average time from admission to operation was (2.1±1.1) h. All the 12 infants had orchiectomy,after necrosis of unilateral testicle was confirmed. Eight of them underwent contralateral test icular fixation. The average operation time was 46 min. There was no wound bleeding or infection postoperatively, and the average hospital stay was 6.4 d. The pathological features were blurred residual contour of the seminiferous tubule (9 cases) or the disappearance of the seminiferous tubule structure (3 cases). After 3 to 24 months of follow-up, no contralateral testicular torsion or atrophy was found. Conclusion The rate of testicular necrosis in children with torsion of testes is high. The newborn with scrotal swelling should be diagnosed promptly with color Doppler ultrasound. If necessary, surgical exploration should be performed in time.