Circadian rhythms are core regulatory mechanisms that evolved to align biological functions with the Earth's rotation. These rhythms are conserved across organisms from unicellular life to multicellular species and play essential roles in metabolism, immune responses, and sleep-wake cycle. Circadian disruptions are strongly associated with various diseases. Over the past decades, genetic studies in Drosophila and mice have identified key conserved clock genes and uncovered transcription-translation feedback loops governing circadian regulation. Additionally, rhythmic neurons in the brain integrate complex neural circuits to precisely regulate physiological and behavioral rhythms. This review highlights recent advances in understanding the neuronal circuit mechanisms of rhythmic neurons in the Drosophila brain and discusses future directions for translating circadian rhythm research into chronomedicine and precision therapies.
Animals ; Circadian Rhythm/genetics* ; Neurons/physiology* ; Drosophila/physiology* ; Brain/physiology* ; Nerve Net/physiology*

OBJECTIVE: To compare the lipid metabolites in the seminal plasma of normal fertile men from those of the patients with oligoasthenoteratozoospermia (OAT), and perform a pathway enrichment analysis on the differentially expressed lipids. METHODS: According to strict inclusion and exclusion criteria, we recruited 30 males seeking medical attention in our Center of Reproductive Medicine and equally divided them into an OAT and a normal fertile control group. Employing the untargeted metabolomics approach, we screened the differential lipids in the seminal plasma of the OAT patients and subjected them to pathway enrichment analysis using the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway database. RESULTS: In the OAT patients, the expressions of 22 lipids were significantly upregulated and those of 32 downregulated in the positive ion mode, and the expressions of 2 lipids upregulated and those of 12 downregulated in the negative ion mode. And 5 of the significantly downregulated lipids, namely anandamide(20:4,n-6), adrenic acid, cis-gondoic acid, (3'-sulfo)galbeta-cer(d18:1/24:1(15Z)) and palmitoylcarnitine, were associated with 4 branches and 8 sub-branches of the KEGG metabolic pathways, among which the differential lipid anandamide (20:4,n-6) was involved in the regeneration of the biological system in the KEGG sub-pathway and considered to be a significantly differentially enriched pathway. CONCLUSION Lipid metabolites in the seminal plasma of OAT patients are significantly different from those in normal fertile males, and the differential lipid anandamide (20:4,n-6) may be involved in the regulation of sperm function and play an important role in male fertility.
Humans ; Male ; Semen/metabolism* ; Adult ; Lipids/analysis* ; Case-Control Studies ; Asthenozoospermia/metabolism* ; Oligospermia/metabolism* ; Lipid Metabolism ; Mass Spectrometry

OBJECTIVE: To assess the independent and combined effects of air pollutants, meteorological factors, and greenspace exposure on new tuberculosis (TB) cases. METHODS: TB case data from Shanghai (2013-2018) were obtained from the Shanghai Center for Disease Control and Prevention. Environmental data on air pollutants, meteorological variables, and greenspace exposure were obtained from the National Tibetan Plateau Data Center. We employed a distributed-lag nonlinear model to assess the effects of these environmental factors on TB cases. RESULTS: Increased TB risk was linked to PM _2.5, PM ₁₀, and rainfall, whereas NO ₂, SO ₂, and air pressure were associated with a reduced risk. Specifically, the strongest cumulative effects occurred at various lags: PM _2.5 ( RR = 1.166, 95% CI: 1.026-1.325) at 0-19 weeks; PM ₁₀ ( RR = 1.167, 95% CI: 1.028-1.324) at 0-18 weeks; NO ₂ ( RR = 0.968, 95% CI: 0.938-0.999) at 0-1 weeks; SO ₂ ( RR = 0.945, 95% CI: 0.894-0.999) at 0-2 weeks; air pressure ( RR = 0.604, 95% CI: 0.447-0.816) at 0-8 weeks; and rainfall ( RR = 1.404, 95% CI: 1.076-1.833) at 0-22 weeks. Green space exposure did not significantly impact TB cases. Additionally, low temperatures amplified the effect of PM _2.5 on TB. CONCLUSION Exposure to PM _2.5, PM ₁₀, and rainfall increased the risk of TB, highlighting the need to address air pollutants for the prevention of TB in Shanghai.
China/epidemiology* ; Humans ; Air Pollutants/analysis* ; Tuberculosis/epidemiology* ; Incidence ; Meteorological Concepts ; Particulate Matter/adverse effects* ; Environmental Exposure ; Male ; Female ; Adult ; Air Pollution ; Middle Aged

For the past 30 years,percutaneous balloon mitral valve dilatation has been performed under the guidance of X-rays and bedside ultrasound.However,there are still some cases of mitral valve stenosis in the large atrium where balloon dilation failed.Intraperitoneal ultrasound-guided percutaneous balloon mitral valve plasty is accurate and feasible,which can reduce the occurrence of complications and improve the success rate of such elderly complex cases.Two patients with severe mitral stenosis underwent percutaneous balloon mitral valve plasty guided by intracardiac ultrasound.The operations were successful without any complications,which can provide reference for clinical treatment of mitral stenosis.

This study was designed to investigate the effects of wheat grain moxibustion on the immune function of mice immunosuppressed by cyclophosphamide,and to delve into the potential mechanisms by analyzing factors related to NF-κB signaling pathway.Sixty SPF-grade ICR mice were randomly allocated into four groups:blank group,model group,traditional Chinese medicine group and wheat grain moxibustion group,with 15 mice in each group.Immunosuppression was induced in mice of the model,traditional Chinese medicine and wheat grain moxibustion groups by intraperitoneal injection of cyclophosphamide at 80 mg/kg daily for three days,while mice of the blank group received an equivalent volume of saline.The traditional Chinese medicine group was treated with oral administration of Zhēn Qí Fú Zhèng granules,and the wheat grain moxibustion group was treated with wheat grain moxibustion at"Da Zhui,"bilateral"Zu San Li,"and bilateral"San Yin Jiao"once a day for seven consecutive days.After corresponding treatment,spleens were harvested from the mice of different groups for pathological examination,and enzyme-linked immunosorbent assay(ELISA)was utilized to measure the serum levels of IL-2,IL-4,TNF-α and IFN-γ.Additionally,Western blot analysis was conducted to assess the protein expression levels of IκBα and P-IκBα in spleen tissue.Compared with the blank group,mice in the model group exhibited poorer general conditions,significantly reduced white blood cell(WBC)count(P＜0.01),extensive damage in spleen tissue,significant decreases in serum IL-4 and IL-2 concentrations,increases in TNF-α and IFN-γ levels(P＜0.01),lower level of P-IκBα protein in spleen tissue(P＜0.01),and higher level of IκBα protein(P＜0.01).These changes mentioned above were reversed in mice of both the wheat grain moxibustion group and the traditional Chinese medicine group(P＜0.01).Compared to the traditional Chinese medicine group,on the last day of treatment,the wheat grain moxibustion group showed slightly higher WBC counts(P＜0.05),better tissue repair,and lower levels of IFN-γ(P＜0.01).In conclusion,wheat grain moxibustion can affect the activity of NF-κB signaling pathway by regulating the relative expression of IκBα and P-IκBα,and then regulate the immune response of the body,thus play a role in alleviating the immunosuppression caused by cyclophosphamide.

OBJECTIVE: To assess the effect and safety of Reyanning Mixture (RYN) in treating asymptomatic or mild severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children and adolescents. METHODS: This is a prospective, open-label, randomized controlled trial. Patients aged 1-17 years and diagnosed with asymptomatic or mild coronavirus disease-2019 (COVID-19) were assigned to an intervention group (RYN plus standard care) and a control group (standard care) according to a randomization list. The primary outcomes were SARS-CoV-2 negative conversion time. Secondary outcomes included negative conversion rate on days 3 and 7, hospital length of stay, symptom relief rate, new-onset symptoms of asymptomatic infected patients, and progressive disease rate. The cycle threshold (Ct) values of ORF1ab or N genes were also tested. RESULTS: A total of 214 patients in the intervention group and 217 in the control group were analyzed. The SARS-CoV-2 negative conversion time was significantly shortened in the intervention group [5 days (interquartile range (IQR): 5-6) vs. 7 days (IQR: 6-7), P<0.01]. By days 3 and 7, the negative conversion rates were significantly higher in the intervention group (day 3: 32.7% vs. 21.2%, P=0.007; day 7: 75.2% vs. 60.8%, P=0.001). Ct values significantly increase on day 2 [ORF1ab gene: 35.62 (IQR: 29.17-45.00) vs. 34.22 (IQR: 28.41-39.41), P=0.03; N gene: 34.97 (IQR: 28.50-45.00) vs. 33.51 (IQR: 27.70-38.25), P=0.024] and day 3 [ORF1ab gene: 38.00 (IQR: 32.72-45.00) vs. 35.81 (IQR: 29.96-45.00), P=0.003; N gene: 37.16 (IQR: 32.01-45.00) vs. 35.26 (IQR: 29.09-45.00), P=0.01]. No significant difference was found in hospital length of stay between the two groups (P>0.05). Symptoms of cough were significantly improved (82.2% vs. 70.0%, P=0.02) and wheezing was significantly reduced (0.7% vs. 12.9%, P<0.01) in the intervention group compared with the control group. During the trial, no disease progression or serious adverse events were reported. CONCLUSION Adding RYN to standard care may be a safe and effective treatment for children with asymptomatic and mild SARS-CoV-2 infection. (Registration No. ChiCTR2200060292).

Objective:To study the safety and feasibility of early enteral feeding during therapeutic hypothermia guided by intestinal ultrasound in neonates with hypoxic-ischemic encephalopathy (HIE).Methods:From January 2019 to December 2021, neonates with HIE who received therapeutic hypothermia in the neonatology department of our hospital were retrospectively selected. They were assigned into the ultrasound-guided observation group (admitted from May 2020 to December 2021) and the control group (admitted from January 2019 to April 2020). In the ultrasound-guided observation group, intestinal ultrasound was performed during therapeutic hypothermia. Based on clinical manifestations and ultrasound results, a small amount of enteral feeding [20 ml/(kg·d)] was initiated and gradually increased to total enteral feeding after rewarming. In the control group, 5 ml (once every 3 h) of glucose and sodium chloride solution was given during 72 h of therapeutic hypothermia. After rewarming, enteral feeding was started and gradually increased to total enteral feeding without intestinal ultrasound. The time to start enteral feeding, the time to achieve total enteral feeding, the incidences of feeding intolerance, necrotizing enterocolitis (NEC) and late-onset sepsis were compared between the two groups.Results:A total of 17 cases were in the ultrasound-guided observation group and 18 cases in the control group. The median time to start enteral feeding and to achieve total enteral feeding in the ultrasound-guided observation group were earlier than the control group [36.0 (33.5, 39.0) h vs. 77.0 (74.0, 79.3) h, 6.0 (5.5, 6.5) d vs. 8.0 (7.0, 9.0) d, P<0.001]. No significant difference existed in the incidence of feeding intolerance between the two groups. Neither groups had NEC or late-onset sepsis. Conclusions:Early enteral feeding during therapeutic hypothermia in neonates with HIE is safe and feasible. Intestinal ultrasound helps implementing feeding plan and achieving early total enteral feeding.

OBJECTIVE: To observe the effects of auricular thumbtack needle on breast feeding and lactation function in primiparous women with cesarean section, and to explore its mechanism of action from the perspective of lactation-related gene expression. METHODS: One hundred cases of primiparous women with cesarean section were randomly divided into an observation group (50 cases, 3 cases dropped off) and a control group (50 cases, 2 cases were eliminated). The patients in the control group were treated with routine obstetric care. Based on the treatment of the control group, the patients in the observation group were treated with auricular thumbtack needle at Neifenmi (CO₁₈), Xiong (AH₁₀), Xiongzhui (AH₁₁), Shenmen (TF₄), and Jiaogan (AH_6a), etc., with one side of auricular point selected, only once for a total of 3 d. The lactation initiation time, lactation adequacy rate at postpartum 72 h, exclusive breastfeeding rate at postpartum 42 d, and breastfeeding score after treatment were compared between the two groups. Real-time quantitative PCR and Western blot method were used to detect the mRNA and protein expression levels of TDP-43, Btn1A1 and XDH. RESULTS: After treatment, the lactation initiation time in the observation group was earlier than that in the control group (P<0.01), and breastfeeding score in the observation group was higher than that in the control group (P<0.01). The lactation adequacy rate at postpartum 72 h was 63.8% (30/47) in the observation group, which was higher than 41.7% (20/48) in the control group (P<0.05). The exclusive breastfeeding rate at postpartum 42 d was 72.3% (34/47) in the observation group, which was higher than 47.9% (23/48) in the control group (P<0.05). The mRNA and protein expression levels of TDP-43 and Btn1A1 in breast milk in the observation group were higher than those in the control group (P<0.01), while there was no statistically significant difference in mRNA and protein expression of XDH in breast milk between the two groups (P>0.05). CONCLUSION The auricular thumbtack needle in addition to routine care could promote lactation initiation, improve lactation adequacy rate and exclusive breastfeeding rate in primiparous women with cesarean section, and the action mechanism may be related to up-regulation of TDP-43 and Btn1A1 expression.
Pregnancy ; Humans ; Female ; Breast Feeding ; Cesarean Section ; Lactation ; Milk, Human ; DNA-Binding Proteins

Coronavirus disease 2019 (COVID-19) has yet to be proven to alter male reproductive function, particularly in the majority of mild/asymptomatic patients. The purpose of this study was to explore whether mild/asymptomatic COVID-19 affects semen quality and sex-related hormone levels. To find suitable comparative studies, a systematic review and meta-analysis was done up to January 22, 2022, by using multiple databases (Web of Science, PubMed, and Embase). Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were used to identify and choose the studies. Meta-analysis was used to examine the semen parameters and sex-related hormones of mild/asymptomatic COVID-19 patients before and after infection. The effects of semen collection time, fever, and intensity of verification on semen following infection were also investigated. A total of 13 studies (n = 770) were included in the analysis, including three case-control studies, six pre-post studies, and four single-arm studies. A meta-analysis of five pre-post studies showed that after infection with COVID-19, sperm concentration (I² = 0; P = 0.003), total sperm count (I² = 46.3%; P = 0.043), progressive motility (I² = 50.0%; P < 0.001), total sperm motility (I² = 76.1%; P = 0.047), and normal sperm morphology (I² = 0; P = 0.001) decreased. Simultaneously, a systematic review of 13 studies found a significant relationship between semen collection time after infection, inflammation severity, and semen parameter values, with fever having only bearing on semen concentration. Furthermore, there was no significant difference in sex-related hormone levels before and after infection in mild/asymptomatic patients. Mild/asymptomatic COVID-19 infection had a significant effect on semen quality in the short term. It is recommended to avoid initiating a pregnancy during this period of time.
Pregnancy ; Female ; Humans ; Male ; Semen Analysis ; Semen ; Infertility, Male ; Sperm Motility ; COVID-19 ; Sperm Count ; Spermatozoa ; Testosterone ; Gonadal Steroid Hormones

The plateau zokor (Myospalax baileyi) and plateau pika (Ochotona curzoniae) are native species unique to the Qinghai-Tibetan Plateau with successful adaptation to the hypoxic environment. In this study, the number of red blood cells, hemoglobin concentration, mean hematocrit and mean volume of red blood cells were measured in plateau zokors and plateau pikas at different altitudes. Hemoglobin subtypes of two plateau animals were identified by mass spectrometry sequencing. The forward selection sites in two animals' hemoglobin subunits were analyzed by PAML4.8 program. Homologous modeling was used to analyze the effect of forward selection sites on the affinity of hemoglobin to oxygen. The adapting strategies of plateau zokors and plateau pikas to hypoxia at different altitudes were analyzed through comparing blood parameters between the two species. The results indicated that, with increasing altitudes, plateau zokors responded to hypoxia by increasing red blood cell count and decreasing red blood cell volume, while plateau pikas took the opposite strategies to plateau zokors. In erythrocytes of plateau pikas, both adult α₂β₂ and fetal α₂ε₂ hemoglobins were identified, while erythrocytes of plateau zokors only had adult α₂β₂ hemoglobin, however the affinities and the allosteric effects of the hemoglobin of plateau zokors were significantly higher than those of plateau pikas. Mechanistically, in the α and β subunits of hemoglobin of plateau zokors and pikas, the numbers and the sites of the positively selected amino acids as well as the side chain groups polarities and orientations of the amino acids differed significantly, which may result in the difference of the affinities to oxygen of hemoglobin between plateau zokors and pikas. In conclusion, the adaptive mechanisms to respond to hypoxia in blood properties of plateau zokors and plateau pikas are species-specific.
Animals ; Altitude ; Amino Acids ; Hemoglobins ; Hypoxia ; Lagomorpha