Objective To provide valuable insights for improving China’s special drug approval system by conducting an in-depth analysis of the practices of the U.S. Food and Drug Administration （FDA） in granting Emergency Use Authorizations （EUAs） for drugs. Methods A retrospective analysis was conducted on the FDA’s EUA decision-making process for COVID-19 therapeutics between January 2020 and June 2023. Results During the COVID-19 pandemic, the FDA adopted a series of regulatory science approaches to facilitate rapid approval of COVID-19 therapeutic drugs. The FDA granted EUA for a total of 15 COVID-19 therapeutic drugs and 4 COVID-19 vaccines, including expanded indications for marketed drugs, EUA for investigational drugs, revocation of EUA, and marketing after EUA. The main mechods for the rapid approval of EUA drugs by the FDA included the use of existing clinical trial data, omission of animal efficacy testing, merging of phase 1 and phase 2 clinical trials, and the use of clinical outcomes as surrogate endpoints, among other regulatory science methods. Conclusion The practices of the FDA in Emergency Use Authorization (EUA) of drugs, particularly its incorporation of regulatory scientific methods into the EUA process and the establishment of proactive monitoring mechanisms for drugs granted EUA, are worthy of emulation by China. It is suggested that China consider the experience of the FDA in the EUA system for drugs to further optimize and improve its special approval system for drugs.

Malocclusion,identified by the World Health Organization(WHO)as one of three major oral diseases,profoundly impacts the dental-maxillofacial functions,facial esthetics,and long-term development of～260 million children in China.Beyond its physical manifestations,malocclusion also significantly influences the psycho-social well-being of these children.Timely intervention in malocclusion can foster an environment conducive to dental-maxillofacial development and substantially decrease the incidence of malocclusion or reduce the severity and complexity of malocclusion in the permanent dentition,by mitigating the negative impact of abnormal environmental influences on the growth.Early orthodontic treatment encompasses accurate identification and treatment of dental and maxillofacial morphological and functional abnormalities during various stages of dental-maxillofacial development,ranging from fetal stages to the early permanent dentition phase.From an economic and societal standpoint,the urgency for effective early orthodontic treatments for malocclusions in childhood cannot be overstated,underlining its profound practical and social importance.This consensus paper discusses the characteristics and the detrimental effects of malocclusion in children,emphasizing critical need for early treatment.It elaborates on corresponding core principles and fundamental approaches in early orthodontics,proposing comprehensive guidance for preventive and interceptive orthodontic treatment,serving as a reference for clinicians engaged in early orthodontic treatment.

Objective: Retrospective analysis of the efficacy and influencing factors of bladder preservation integrated therapy for unresectable invasive bladder cancer confined to the pelvis was done, also including the bladder function preservation and adverse effects analysis. Methods: Sixty-nine patients with unresectable locally invasive bladder cancer who received radiotherapy-based combination therapy from March 1999 to December 2021 at our hospital were selected. Among them, 42 patients received concurrent chemoradiotherapy, 32 underwent neoadjuvant chemotherapyand 43 with transurethral resection of bladder tumors (TURBT) prior to radiotherapy. The late adverse effect of radiotherapy, preservation of bladder function, replase and metastasis and survival were followed-up. Cox proportional hazards models were applied for the multifactorial analysis. Results: The median age was 69 years. There were 63 cases (91.3%) of uroepithelial carcinoma, 64 of stage Ⅲ and 4 of stage Ⅳ. The median duration of follow-up was 76 months. There were 7 grade 2 late genito urinary toxicities, 2 grade 2 gastrointestinal toxicities, no grade 3 or higher adverse events occurred. All patients maintained normal bladder function, except for 8 cases who lost bladder function due to uncontrolled tumor in the bladder. Seventeen cases recurred locally. There were 11 cases in the concurrent chemoradiotherapy group with a local recurrence rate of 26.2% (11/42) and 6 cases in the non-concurrent chemoradiotherapy group with a local recurrence rate of 22.2% (6/27), and the difference in local recurrence rate between the two groups was not statistically significant (P=0.709). There were 23 cases of distant metastasis (including 2 cases of local recurrence with distant metastasis), including 10 cases in the concurrent chemoradiotherapy group with a distant metastasis rate of 23.8% (10/42) and 13 cases in the non-concurrent chemoradiotherapy group with a distant metastasis rate of 48.1% (13/27), and the distant metastasis rate in the non-concurrent chemoradiotherapy group was higher than that in the concurrent chemoradiotherapy group (P=0.036). The median 5-year overall survival (OS) time was 59 months and the OS rate was 47.8%. The 5-year progression-free survival (PFS) time was 20 months and the PFS rate was 34.4%. The 5-year OS rates of concurrent and non-concurrent chemoradiotherapy group were 62.9% and 27.6% (P<0.001), and 5-year PFS rates were 45.4% and 20.0%, respectively (P=0.022). The 5-year OS rates of with or without neoadjuvant chemotherapy were 78.4% and 30.1% (P=0.002), and the 5-year PFS rates were 49.1% and 25.1% (P=0.087), respectively. The 5-year OS rates with or without TURBT before radiotherapy were 45.5% and 51.9% (P=0.233) and the 5-year PFS rates were 30.8% and 39.9% (P=0.198), respectively. Multivariate Cox regression analysis results showed that the clinical stage (HR=0.422, 95% CI: 0.205-0.869) was independent prognostic factor for PFS of invasive bladder cancer. The multivariate analysis showed that clinical stages (HR=0.278, 95% CI: 0.114-0.678), concurrent chemoradiotherapy (HR=0.391, 95% CI: 0.165-0.930), neoadjuvant chemotherapy (HR=0.188, 95% CI: 0.058-0.611), and recurrences (HR=10.855, 95% CI: 3.655-32.638) were independent prognostic factors for OS of invasive bladder cancer. Conclusion: Unresectable localized invasive bladder cancer can achieve satisfactory long-term outcomes with bladder-preserving combination therapy based on radiotherapy, most patients can retain normal bladder function with acceptable late adverse effects and improved survival particularly evident in patients with early, concurrent chemoradiotherapy and neoadjuvant chemotherapy.
Humans ; Aged ; Treatment Outcome ; Retrospective Studies ; Combined Modality Therapy ; Chemoradiotherapy/methods* ; Urinary Bladder Neoplasms/radiotherapy* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Neoplasm Staging

To explore the changes and the reaction mechanisms between soil microecological environment and the content of secon-dary metabolites of plants under water deficit, this study carried out a pot experiment on the 3-leaf stage seedlings of Rheum officinale to analyze their response mechanism under different drought gradients(normal water supply, mild, moderate, and severe drought). The results indicated that the content of flavonoids, phenols, terpenoids, and alkaloids in the root of R. officinale varied greatly under drought stresses. Under mild drought stress, the content of substances mentioned above was comparatively high, and the content of rutin, emodin, gallic acid, and(+)-catechin hydrate in the root significantly increased. The content of rutin, emodin, and gallic acid under severe drought stress was significantly lower than that under normal water supply. The number of species, Shannon diversity index, richness index, and Simpson index of bacteria in the rhizosphere soil were significantly higher than those in blank soil, and the number of microbial species and richness index decreased significantly with the aggravation of drought stresses. In the context of water deficit, Cyanophyta, Firmicutes, Actinobacteria, Chloroflexi, Gemmatimonadetes, Streptomyces, and Actinomyces were the dominant bacteria in the rhizosphere of R. officinale. The relative content of rutin and emodin in the root of R. officinale was positively correlated with the relative abundance of Cyanophyta and Firmicutes, and the relative content of(+)-catechin hydrate and(-)-epicatechin gallate was positively correlated with the relative abundance of Bacteroidetes and Firmicutes. In conclusion, appropriate drought stress can increase the content of secondary metabolites of R. officinale from physiological induction and the increase in the association with beneficial microbe.
Rhizosphere ; Rheum ; Droughts ; Soil ; Catechin ; Emodin ; Bacteria/metabolism* ; Water/metabolism* ; Firmicutes ; Soil Microbiology

Objective: To investigate the role of Keap1/Nrf2/HO-1 signaling pathway in liver injury induced by neodymium oxide (Nd(2)O(3)) in mice. Methods: In March 2021, forty-eight SPF grade healthy male C57BL/6J mice were randomly divided into control group (0.9% NaCl), low dose group (62.5 mg/ml Nd(2)O(3)), medium dose group (125.0 mg/ml Nd(2)O(3)), and high dose group (250.0 mg/ml Nd(2)O(3)), each group consisted of 12 animals. The infected groups were treated with Nd(2)O(3) suspension by non-exposed tracheal drip and were killed 35 days after dust exposure. The liver weight of each group was weighed and the organ coefficient was calculated. The content of Nd(3+) in liver tissue was detected by inductively coupled plasma mass spectrometry (ICP-MS). HE staining and immunofluorescence was used to observe the changes of inflammation and nuclear entry. The mRNA expression levels of Keap1, Nrf2 and HO-1 in mice liver tissue were detected by qRT-PCR. Western blotting was used to detect the protein expression levels of Keap1 and HO-1. The contents of catalase (CAT), glutathione peroxidase (GSH-Px) and total superoxide dismutase (T-SOD) were detected by colorimetric method. The contents of interleukin 1β (IL-1β), interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α) were determined by ELISA. The data was expressed in Mean±SD. Two-independent sample t-test was used for inter-group comparison, and one-way analysis of variance was used for multi-group comparison. Results: Compared with the control group, the liver organ coefficient of mice in medium and high dose groups were increased, and the Nd(3+) accumulation in liver of mice in all dose groups were significantly increased (P<0.05). Pathology showed that the structure of liver lobules in the high dose group was slightly disordered, the liver cells showed balloon-like lesions, the arrangement of liver cell cords was disordered, and the inflammatory exudation was obvious. Compared with the control group, the levels of IL-1β and IL-6 in liver tissue of mice in all dose groups were increased, and the levels of TNF-α in liver tissue of mice in high dose group were increased (P<0.05). Compared with the control group, the mRNA and protein expression levels of Keap1 in high dose group were significantly decreased, while the mRNA expression level of Nrf2, the mRNA and protein expression levels of HO-1 were significantly increased (P<0.05), and Nrf2 was successfully activated into the nucleus. Compared with the control group, the activities of CAT, GSH-Px and T-SOD in high dose group were significantly decreased (P<0.05) . Conclusion: A large amount of Nd(2)O(3) accumulates in the liver of male mice, which may lead to oxidative stress and inflammatory response through activation of Keap1/Nrf2/HO-1 signal pathway. It is suggested that Keap1/Nrf2/HO-1 signal pathway may be one of the mechanisms of Nd(2)O(3) expose-induced liver injury in mice.
Mice ; Male ; Animals ; NF-E2-Related Factor 2/metabolism* ; Tumor Necrosis Factor-alpha/metabolism* ; Kelch-Like ECH-Associated Protein 1/metabolism* ; Interleukin-6/metabolism* ; Mice, Inbred C57BL ; Oxidative Stress ; Liver/metabolism* ; Metals, Rare Earth ; Signal Transduction ; Superoxide Dismutase/metabolism* ; RNA, Messenger/metabolism*

Objective:To study the clinical manifestations and treatment of neonatal testicular torsion (NTT) and to summarize the experience of diagnosis and treatment.Methods:The clinical data of the patients with NTT admitted to the Department of Pediatric Urology in Guangzhou Women and Children's Medical Center from January 2015 to January 2021 were analyzed retrospectively. The data included demographic information, testicular torsion duration, clinical presentation, ultrasonography findings, surgical procedures, pathological results, follow-ups, and prognosis.Results:A total of 17 cases were enrolled in this study, and the median age was 5.2 d, ranging from 1 d to 17 d; the weight ranging from 2 800 g to 4 000 g. 11 cases of left testicular torsion and 6 cases of right testicular torsion. The median time from onset to medical attention was 3.8 d, ranging from 10 h to 15 d. The first manifestations being reported were scrotal swelling, color change, or painless mass. Emergency ultrasound revealed that the blood flow signal in the testis was significantly reduced or disappeared, and heterogeneous mass echoes were detected in the scrotum. Surgical exploration was performed in all 17 cases and confirmed to be testicular torsion. There were 15 cases of extravaginal torsion and 2 cases of intravaginal torsion. There were 6 cases of clockwise torsion and 11 cases of anticlockwise torsion. The average degree of twisted testis was 450.8°, ranging from 270° to 720°. The rate of orchiectomy was 88.2% (15/17). All patients were followed up for a minimum of 1 year postoperatively. None of the patients experienced postoperative bleeding or infection at the scrotal incision site. There were no instances of recurrent testicular torsion, and the contralateral testicles showed no abnormalities. In 2 cases where the affected testicle was preserved, ultrasound reevaluation at 6 months postoperatively revealed atrophy of the affected testicle.Conclusions:NTT is rare in clinics and lacks specificity, with a high rate of testis loss. When the newborns exhibit scrotal swelling, color change, or other abnormalities, testicular torsion cannot be ruled out, and early surgical exploration is required.

Objective:To test and evaluate the reliability and clinical effectiveness of osteoporotic thoracolumbar fracture (OTLF) scoring and classification system.Methods:A multicenter retrospective case series study was conducted to analyze the clinical data of 530 OTLF patients admitted to 8 hospitals including Honghui Hospital Affiliated to Xi'an Jiaotong University from January 2021 to June 2022. There were 212 males and 318 females, aged 55-90 years [(72.6±10.8)years]. There were 4 patients with grade C and 18 with grade D according to American Spinal Injury Association (ASIA) classification. According to the osteoporotic thoracolumbar injury classification and severity (OTLICS) score, all patients had an OTLICS score over 4 points and required surgical treatment. Among them, 410 patients had acute symptomatic OTLF (ASOTLF), including 24 patients with type I, 159 type IIA, 47 type IIB, 31 type IIC, 136 type IIIA, 8 type IIIB, 2 type IV (absence of neurological symptoms) and 3 type IV (presence of neurological symptoms), and 120 patients had chronic symptomatic OTLF (CSOTLF), including 62 patients with type I, 21 type II, 17 type III, 3 type IV (reducible under general anesthesia), 9 type IV (not reducible under general anesthesia), 1 type V (reducible under general anesthesia), 5 type V (presence of neurological symptoms), and 2 type V (not reducible under general anesthesia). Surgical procedures included percutaneous vertebroplasty (PVP), positional repositioning plus PVP, percutaneous kyphoplasty (PKP), posterior open reduction combined with bone graft fusion and bone cement augmented screw internal fixation, posterior open reduction combined with decompression, bone graft fusion and bone cement augmented screw internal fixation, and posterior open reduction combined with osteotomy and orthopedics, bone graft fusion and bone cement augmented screw internal fixation. A weighted Kappa was used to test the interobserver and intraobserver reliability of the OTLICS score, the ASOTLF classification, and the CSOTLF classification. The visual analog scale (VAS), Oswestry disability index (ODI), ASIA classification were compared before, at 1 month after surgery and at the last follow-up. Incidence of postoperative complications was observed.Results:The percentage of mean interobserver agreement for OTLICS staging was 93.4%, with a mean confidence Kappa value of 0.86, and the percentage of mean intraobserver agreement was 93.0%, with a mean confidence kappa value of 0.86. The percentage of mean interobserver agreement for ASOTLF staging was 94.2%, with a mean confidence Kappa value of 0.84, and the percentage of mean intraobserver agreement was 92.5%, with a mean confidence Kappa value of 0.83. The percentage of mean interobserver agreement for CSOTLF subtyping was 91.9%, with a mean confidence Kappa value of 0.80, and the percentage of mean intraobserver agreement was 91.3%, with a mean confidence Kappa value of 0.81. All the patients were followed up for 6-12 months [(9.0±2.1)months]. The VAS and ODI scores were significantly lower in patients with ASOTLF and CSOTLF classifications at 1 month after surgery and at the last follow-up than those before surgery (all P<0.05). The VAS scores in patients with ASOTLF types IIA, IIB, IIC, IIIA, and IV were significantly lower at the last follow-up than that at 1 month after surgery; the ODI scores in patients with ASOTLF types I, IIA, IIB, IIIA, IIIB and IV were significantly lower at the last follow-up than those at 1 month after surgery. The VAS scores in patients with CSOTLF types II, III, IV, and V were significantly lower at the last follow-up than those at 1 month after surgery, and the ODI scores in patients with all CSOTLF types were significantly lower at the last follow-up than those at 1 month after surgery (all P<0.05). Two patients with ASIA grade C recovered to grade D, and the rest recovered to grade E at the last follow-up ( P<0.01). No major vessel or nerve injury or internal fixation failure was found during follow-up. There were 18 patients with cement leakage, none of whom showed relevant clinical symptoms. There were 35 patients with new vertebral fractures, all of whom recovered well after symptomatic treatment. Conclusions:The OTLICS score, ASOTLF classification and CSOTLF classification have a high degree of reliability. Application of stepwise treatment for patients with different levels of injury according to the scoring and classification system can reduce pain, promote recovery of the spinal function, and reduce complications, which is of some significance in guiding the selection of clinical treatment.

Objective: To summarize the management and short-term outcomes of neonates delivered by mothers infected with SARS-CoV-2 Omicron variant. Methods: A retrospective study was performed on 158 neonates born to mothers infected with SARS-CoV-2 Omicron variant admitted to the isolation ward of Children's Hospital of Fudan University from March 15^th, 2022 to May 30^th, 2022. The postnatal infection control measures for these neonates, and their clinical characteristics and short-term outcomes were analyzed. They were divided into maternal symptomatic group and maternal asymptomatic group according to whether their mothers had SARS-CoV-2 symptoms. The clinical outcomes were compared between the 2 groups using Rank sum test and Chi-square test. Results: All neonates were under strict infection control measures at birth and after birth. Of the 158 neonates, 75 (47.5%) were male. The gestational age was (38⁺³±1⁺³) weeks and the birth weight was (3 201±463)g. Of the neonates included, ten were preterm (6.3%) and the minimum gestational age was 30⁺¹ weeks. Six neonates (3.8%) had respiratory difficulty and 4 of them were premature and required mechanical ventilation. All 158 neonates were tested negative for SARS-COV-2 nucleic acid by daily nasal swabs for the first 7 days. A total of 156 mothers (2 cases of twin pregnancy) infected with SARS-CoV-2 Omicron variant, the time from confirmed SARS-CoV-2 infection to delivery was 7 (3, 12) days. Among them, 88 cases (56.4%) showed clinical symptoms, but none needed intensive care treatment. The peripheral white blood cell count of the neonates in maternal symptomatic group was significantly higher than that in maternal symptomatic group (23.0 (18.7, 28.0) × 10⁹ vs. 19.6 (15.4, 36.6) × 10⁹/L, Z=2.44, P<0.05). Conclusions: Neonates of mothers infected with SARS-CoV-2 Omicron variant during third trimester have benign short-term outcomes, without intrauterine infection through vertical transmission. Strict infection control measures at birth and after birth can effectively protect these neonates from SARS-CoV-2 infection.
Female ; Humans ; Infant ; Infant, Newborn ; Male ; Pregnancy ; COVID-19 ; Mothers ; Pregnancy Complications, Infectious/prevention & control* ; Retrospective Studies ; SARS-CoV-2

OBJECTIVES: To investigate the incidence of extrauterine growth retardation (EUGR) and its risk factors in very preterm infants (VPIs) during hospitalization in China. METHODS: A prospective multicenter study was performed on the medical data of 2 514 VPIs who were hospitalized in the department of neonatology in 28 hospitals from 7 areas of China between September 2019 and December 2020. According to the presence or absence of EUGR based on the evaluation of body weight at the corrected gestational age of 36 weeks or at discharge, the VPIs were classified to two groups: EUGR group (n=1 189) and non-EUGR (n=1 325). The clinical features were compared between the two groups, and the incidence of EUGR and risk factors for EUGR were examined. RESULTS: The incidence of EUGR was 47.30% (1 189/2 514) evaluated by weight. The multivariate logistic regression analysis showed that higher weight growth velocity after regaining birth weight and higher cumulative calorie intake during the first week of hospitalization were protective factors against EUGR (P<0.05), while small-for-gestational-age birth, prolonged time to the initiation of total enteral feeding, prolonged cumulative fasting time, lower breast milk intake before starting human milk fortifiers, prolonged time to the initiation of full fortified feeding, and moderate-to-severe bronchopulmonary dysplasia were risk factors for EUGR (P<0.05). CONCLUSIONS It is crucial to reduce the incidence of EUGR by achieving total enteral feeding as early as possible, strengthening breastfeeding, increasing calorie intake in the first week after birth, improving the velocity of weight gain, and preventing moderate-severe bronchopulmonary dysplasia in VPIs.
Female ; Fetal Growth Retardation ; Gestational Age ; Hospitalization ; Humans ; Incidence ; Infant ; Infant, Newborn ; Infant, Premature ; Infant, Very Low Birth Weight ; Prospective Studies ; Risk Factors

OBJECTIVES: To explore the optimal maintenance dose of caffeine citrate for preterm infants requiring assisted ventilation and caffeine citrate treatment. METHODS: A retrospective analysis was performed on the medical data of 566 preterm infants (gestational age ≤34 weeks) who were treated and required assisted ventilation and caffeine citrate treatment in the neonatal intensive care unit of 30 tertiary hospitals in Jiangsu Province of China between January 1 and December 31, 2019. The 405 preterm infants receiving high-dose (10 mg/kg per day) caffeine citrate after a loading dose of 20 mg/kg within 24 hours after birth were enrolled as the high-dose group. The 161 preterm infants receiving low-dose (5 mg/kg per day) caffeine citrate were enrolled as the low-dose group. RESULTS: Compared with the low-dose group, the high-dose group had significant reductions in the need for high-concentration oxygen during assisted ventilation (P=0.044), the duration of oxygen inhalation after weaning from noninvasive ventilation (P<0.01), total oxygen inhalation time during hospitalization (P<0.01), the proportion of preterm infants requiring noninvasive ventilation again (P<0.01), the rate of use of pulmonary surfactant and budesonide (P<0.05), and the incidence rates of apnea and bronchopulmonary dysplasia (P<0.01), but the high-dose group had a significantly increased incidence rate of feeding intolerance (P=0.032). There were no significant differences between the two groups in the body weight change, the incidence rates of retinopathy of prematurity, intraventricular hemorrhage or necrotizing enterocolitis, the mortality rate, and the duration of caffeine use (P>0.05). CONCLUSIONS This pilot multicenter study shows that the high maintenance dose (10 mg/kg per day) is generally beneficial to preterm infants in China and does not increase the incidence rate of common adverse reactions. For the risk of feeding intolerance, further research is needed to eliminate the interference of confounding factors as far as possible.
Caffeine/therapeutic use* ; Citrates ; Humans ; Infant ; Infant, Newborn ; Infant, Premature ; Respiration, Artificial ; Retrospective Studies