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 evaluate the effect and safety of Chinese medicine (CM) Fuzheng Huazhuo Decoction (FHD) in treating patients with coronavirus disease 2019 (COVID-19) who persistently tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: This retrospective cohort study was conducted at Shanghai New International Expo Center shelter hospital in China between April 1 and May 30, 2022. Patients diagnosed as COVID-19 with persistently positive SARS-CoV-2 reverse transcription-polymerase chain reaction (RT-PCR) test results for ⩾8 days after diagnosis were enrolled. Patients in the control group received conventional Western medicine (WM) treatment, while those in the FHD group received conventional WM plus FHD for at least 3 days. The primary outcome was viral clearance time. Secondary outcomes included negative conversion rate within 14 days, length of hospital stay, cycle threshold (Ct) values of the open reading frame 1ab (ORF1ab) and nucleocapsid protein (N) genes, and incidence of new-onset symptoms during hospitalization. Adverse events (AEs) that occurred during the study period were recorded. RESULTS: A total of 1,765 eligible patients were enrolled in this study (546 in the FHD group and 1,219 in the control group). Compared with the control group, patients receiving FHD treatment showed shorter viral clearance time for nucleic acids [hazard ratio (HR): 1.500, 95% confidence interval (CI): 1.353-1.664, P<0.001] and hospital stays (HR: 1.371, 95% CI: 1.238-1.519, P<0.001), and a higher negative conversion rate within 14 days (96.2% vs. 82.6%, P<0.001). The incidence of new-onset symptoms was 59.5% in the FHD group, similar to 57.8% in the control group (P>0.05). The Ct values of ORF1ab and N genes increased more rapidly over time in the FHD group than those in the control group post-randomization (ORF1ab gene: β =0.436±0.053, P<0.001; N gene: β =0.415 ±0.053, P<0.001). The incidence of AEs in the FHD group was lower than that in the control group (24.2% vs. 35.4%, P<0.001). No serious AEs were observed. CONCLUSION FHD was effective and safe for patients with persistently positive SARS-CoV-2 PCR tests. (Registration No. ChiCTR2200063956).
Humans ; Drugs, Chinese Herbal/adverse effects* ; Retrospective Studies ; Male ; Female ; Middle Aged ; COVID-19 Drug Treatment ; SARS-CoV-2/drug effects* ; COVID-19/virology* ; Adult ; Aged ; Treatment Outcome

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

Intracranial atherosclerotic stenosis (ICAS) is one of the most common causes of ischemic stroke. Stenting is a treatment option for symptomatic ICAS, but it also has problems such as procedure-related complications and in-stent restenosis. This article reviews the application of stenting, particularly different stent systems, in patients with symptomatic ICAS.

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.

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 utilized ultra-performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry(UPLC-Q-TOF-MS) to rapidly analyze and identify the chemical constituents in five processed products of Strychni Semen(raw, sand-roasted, fried, urine-soaked, and vinegar-processed products). Using PeakView software to extract compound information, 50 chemical components were identified based on retention time, accurate molecular ion peaks, secondary mass spectrometry data, and comparison with reference standards and relevant literature. Specifically, 41 components were identified in raw Strychni Semen, 48 in sand-roasted, 43 in fried, 41 in urine-soaked, and 40 in vinegar-processed products. Principal component analysis(PCA) and orthogonal partial least squares discriminant analysis(OPLS-DA) were employed to identify differential components among the processed products, with variable importance in projection(VIP) values>1 and a t-test with P<0.05 as criteria. PCA revealed significant differences among the five processed products, demonstrating good clustering and separation. OPLS-DA identified 13 differential components, including brucine, strychnine, loganic acid, and chlorogenic acid. The results indicated that S. nux-vomica primarily contained alkaloids, organic acids, and glycosides, with significant compositional differences among the various processed products. Notably, the content of key components such as brucine and strychnine decreased after processing, with the most significant reduction observed in vinegar-processed Strychni Semen. In conclusion, this study provides a comprehensive comparison of the effects of different processing methods on the chemical composition of Strychni Semen, exploring the differences in the material basis of the processed products and offering data to support the scientific rationale behind the processing of Strychni Semen.
Chromatography, High Pressure Liquid/methods* ; Drugs, Chinese Herbal/analysis* ; Mass Spectrometry/methods* ; Strychnos/chemistry* ; Principal Component Analysis

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

OBJECTIVE: To retrospectively analyze efficacy of single structure internal fixation and double structure internal fixation in the treatment of ipsilateral femoral shaft and neck fracture, and analyze their indications. METHODS: From June 2015 to December 2020, 21 patients with ipsilateral femoral shaft and femoral neck fracture were treated, including 14 males and 7 females, aged 23 to 69 years old with an average of(38.1±12.9) years old. According to different femoral shaft fracture sites, some patients were fixed with cephalomedullary implant for both femoral neck and the femoral shaft(single structure, InterTan or PFNA Ⅱ), some patients were fixed with cannulated screws for the femoral neck and a retrograde locking nail for the femoral shaft (dual structure), and postoperative function and complications were recorded during follow-up. In 10 cases of single-structure fixation, the femoral necks were all basicervical fractures, and the femoral shaft fractures were located in the proximal isthmus;11 cases were double-structure fixation, 9 cases in 11 were basal type of femoral neck, 2 cases in 11 were neck type, and the femoral shaft fractures were located in the isthmus and the distal isthmus. RESULTS: All patients were followed up for 12 to 27 months. No femoral head necrosis, deformity, delay or nonunion occurred in the patients with single-structure fixation, and no delayed union or nonunion occurred in femoral shaft fractures;At the final follow-up, Harris score of patients with single-structure fixation was 91.8±4.1, with 8 cases were excellent and 2 cases were good. The fractures of patients with dual-structure fixation achieved good union without femoral head necrosis, except 1 case of femoral shaft fracture had delayed union;At the final follow-up, Harris score of patients with dual-structure fixation was 92.4±5.9, 7 cases were excellent, 3 cases were good, and 1 case was fair. CONCLUSION Good reduction and fixation is the key to the treatment of such fractures. Both the single-structure fixation and the dual-structure fixation are good methods, and it should be selected according to the locations of femoral shaft and femoral neck fractures. Single-structure fixation is a good choice for femoral shaft fractures located at the proximal isthmus and basal femoral neck fractures. For isthmus and distal femoral shaft fractures combined with ipsilateral femoral neck fractures, dual-structure fixation is recommended.
Male ; Female ; Humans ; Young Adult ; Adult ; Middle Aged ; Aged ; Femur Neck ; Retrospective Studies ; Femoral Neck Fractures/complications* ; Femoral Fractures/complications* ; Fracture Fixation, Internal/methods* ; Femoral Fractures, Distal ; Treatment Outcome ; Fracture Fixation, Intramedullary/methods*