Recently, male reproductive health has attracted extensive attention, with the adverse effects of circadian disruption on male fertility gradually gaining recognition. However, the mechanism by which circadian disruption leads to damage to male reproductive system remains unclear. In this review, we first summarized the dual regulatory roles of circadian clock genes on the male reproductive system: (1) circadian regulation of testosterone synthesis via the hypothalamic-pituitary-testicular (HPT) and hypothalamic-pituitary-adrenal (HPA) axes; (2) non-circadian regulation of spermatogenesis. Next, we further listed the possible mechanisms by which circadian disruption impairs male fertility, including interference with the oscillatory function of the reproductive system, i.e., synchronization of the HPT axis, crosstalk between the HPT axis and the HPA axis, as well as direct damage to germ cells by disturbing the non-oscillatory function of the reproductive system. Future research using spatiotemporal omics, epigenomic assays, and neural circuit mapping in studying the male reproductive system may provide new clues to systematically unravel the mechanisms by which circadian disruption affects male reproductive system through circadian clock genes.
Male ; Humans ; Animals ; Circadian Clocks/physiology* ; Hypothalamo-Hypophyseal System/physiology* ; Circadian Rhythm/genetics* ; Spermatogenesis/physiology* ; Pituitary-Adrenal System/physiology* ; Testis/physiology* ; Testosterone/biosynthesis* ; CLOCK Proteins ; Infertility, Male/physiopathology*

Most of the life forms on Earth have gradually evolved an endogenous biological clock under the long-term influence of periodic daily light-dark cycles. This biological clock system plays a crucial role in the orderly progression of life activities. In mammals, central circadian clock is located in the suprachiasmatic nucleus of the hypothalamus and the function of the biological clock relies on a transcription-translation negative feedback loop. As a negative regulator in this loop, the function of CHRONO is less known. To deeply explore the role of the Chrono gene in rhythm entrainment and physiology, we constructed a Chrono gene knockout mouse strain using the CRISPR/Cas9 technology and analyzed its entrainment ability under different T cycles. Running wheel tests and glucose tolerance tests were also performed. The results showed that the period of the endogenous biological clock of Chrono knockout mice was prolonged, and the entrainment rate under the T21 cycle was decreased. In addition, metabolic abnormalities, including weight gain and impaired glucose tolerance, were observed in the non-entrained mice. Overall, this study reveals a crucial role of the Chrono gene in maintaining circadian rhythms and metabolic balance, providing a new perspective for understanding the relationship between the biological clock and metabolism. Further research is needed to fully understand the underlying molecular mechanisms.
Animals ; Mice, Knockout ; Mice ; Circadian Rhythm/genetics* ; Metabolic Diseases/physiopathology* ; Photoperiod ; Male ; Period Circadian Proteins/physiology* ; Light ; Circadian Clocks/physiology*

ObjectiveTemporal heterogeneity in lung cancer presents as fluctuations in the biological characteristics, genomic mutations, proliferation rates, and chemotherapeutic responses of tumor cells over time, posing a significant barrier to effective treatment. The complexity of this temporal variance, coupled with the spatial diversity of lung cancer, presents formidable challenges for research. This article will pave the way for new avenues in lung cancer research, aiding in a deeper understanding of the temporal heterogeneity of lung cancer, thereby enhancing the cure rate for lung cancer. MethodsRaman spectroscopy emerges as a powerful tool for real-time surveillance of biomolecular composition changes in lung cancer at the cellular scale, thus shedding light on the disease’s temporal heterogeneity. In our investigation, we harnessed Raman spectroscopic microscopy alongside multivariate statistical analysis to scrutinize the biomolecular alterations in human lung epithelial cells across various timeframes after benzo(a)pyrene exposure. ResultsOur findings indicated a temporal reduction in nucleic acids, lipids, proteins, and carotenoids, coinciding with a rise in glucose concentration. These patterns suggest that benzo(a)pyrene induces structural damage to the genetic material, accelerates lipid peroxidation, disrupts protein metabolism, curtails carotenoid production, and alters glucose metabolic pathways. Employing Raman spectroscopy enabled us to monitor the biomolecular dynamics within lung cancer cells in a real-time, non-invasive, and non-destructive manner, facilitating the elucidation of pivotal molecular features. ConclusionThis research enhances the comprehension of lung cancer progression and supports the development of personalized therapeutic approaches, which may improve the clinical outcomes for patients.

Ichthyosis is a hereditary dyskeratotic skin disease with systemic skin dryness and roughness,mainly manifested by scaly skin,which may be accompanied by ocular abnormalities.At present,there are many studies on skin fungal infection caused by ichthyosis,but only few reports on cases with combined ocular fungal infection.This paper reports a case of X-linked recessive hereditary ichthyosis with recurrent fungal keratitis(FK),which is expec-ted to provide reference for clinical early diagnosis and treatment of this disease.

Objective To study the risk factors and prognostic characteristics of pediatric silent lupus nephritis(SLN)with class Ⅲ to V.Methods A retrospective study was conducted to collect clinical data from 30 children diagnosed with SLN at the Department of Pediatrics,Second Xiangya Hospital,Central South University,from May 2007 to April 2023.Based on renal pathological classification,the patients were divided into a class Ⅱ group(12 cases)and a class Ⅲ to Ⅴ group(18 cases).The risk factors for the occurrence of class Ⅲ to Ⅴ SLN were analyzed,and the prognostic characteristics were summarized.Results Among the 30 SLN patients,the median follow-up time was 61.50 months.There were no statistically significant differences in the proportions of patients who discontinued glucocorticoids or achieved low disease activity status,nor in the annual decline rate of estimated glomerular filtration rate(eGFR)between the class Ⅱ and class Ⅲ to V groups(P>0.05).However,three patients in the class Ⅱ group progressed to stage 1 chronic kidney disease(CKD),while eight patients in the class Ⅲ to Ⅴ group reached stage 1 CKD,and four patients reached stage 2 CKD.Among the 26 female SLN patients,serum complement C3 levels in the class Ⅲ to Ⅴ group were lower than those in the class Ⅱ group(P<0.05).Serum C3 levels in SLN patients,as well as in female SLN patients,were negatively correlated with the fluorescence intensity of IgA,IgG,and C3 immune complexes in the kidneys(P<0.05).Additionally,serum C3 levels in female SLN patients were negatively correlated with the renal pathological activity index(P<0.05).Binary logistic regression analysis indicated that being female and having low serum complement C3 levels were risk factors for the occurrence of class Ⅲ to Ⅴ SLN in children(P<0.05).Conclusions Class Ⅲ to Ⅴ SLN is not uncommon among SLN children,and there remains a risk of long-term renal function progression.Being female and having low serum complement C3 levels are identified as risk factors for class Ⅲ to Ⅴ SLN in children.

Trib. Lorantheae used as traditional Chinese materia medica has a long history. There are 41 genera of Trib. Lorantheae， of which 6 belong to China， all have medicinal value， mainly distributed in Southwest， Southern， and Central and Southern China， with abundant resources. Twenty-two species of Trib. Lorantheae are used as medicinal materials or herbs in China. It mainly includes Taxillus. chinensis， T. sutchuenensis， Scurrula parasitica， Loranthus tanakae， Dendrophthoe pentandra， S. ferruginea， etc.， of which T. chinensis is the most widely used. The main chemical components of Trib. Lorantheae include flavonoids， terpenoids， sterols， phenylpropanoids， curcumins， phenolic acids， violate oils， sugars， and other compounds. Modern studies show that the extracts and monomer compounds of Trib. Lorantheae have various pharmacological effects such as anti-inflammation， anti-tumor， anti-oxidation， anti-osteoporosis， bacteriostasis， anti-virus， and lowering blood sugar， blood pressure， and lipid. It is believe that most active components related to their pharmacological effects are flavonoids， most of which are the main pharmacodynamic substances of the parasitic plants of Trib. Lorantheae， playing an important role in anti-inflammation， anti-tumor， anti-oxidation， anti-osteoporosis， and other pharmacological effect. This paper systematically summarized the literature and data on plants of Trib. Lorantheae and reviewed their chemical components and pharmacological effects， which provided references for the research， development， and utilization of Trib. Lorantheae.

AIM: To investigate the difference, correlation, and consistency of corneal thickness and the thinnest point position detected by Pentacam HR corneal topography map and RTVue optical coherence tomography(OCT)in patients with keratoconus.METHODS: Cross-sectional comparative study. The corneal curvature map, corneal thickness map, thinnest point position, and thinnest point thickness were detected by Pentacam HR and RTVue OCT. Paired sample t-test was used for data consistent with normal distribution, and paired sample rank sum test was used for data inconsistent with normal distribution. Spearman correlation analysis and Bland-Altman analysis were used for the correlation and consistency of the two measurement methods.RESULTS: A total of 63 patients(105 eyes)with keratoconus were included in this study, including 49 males(77.8%)and 14 females(22.2%), aged 22.24±6.19 years; among them, relevant data of Pentacam HR topographic map: Km was 47.85±4.73D and Kmax was 55.43±8.72D. In measuring central corneal thickness and the thinnest point thickness of keratoconus, the Pentacam HR was 4.70μm and 19.46μm thicker than the mean value measured by RTVue OCT(P<0.05). There was no significant difference between the horizontal and vertical coordinates of the thinnest points measured by the two devices(P>0.05). The central corneal thickness and the thinnest point thickness measured by the two devices were highly correlated, the horizontal coordinate of the thinnest point was moderately correlated, and the vertical coordinate of the thinnest point was weakly correlated. Bland-Altman analysis showed that the central corneal thickness, the thinnest point thickness, the horizontal coordinate of the thinnest point, and the vertical coordinate of the thinnest point were 95.2%(100/105)and 93.3%(98/105), 95.2%(100/105), 95.2%(100/105)respectively, which were within the 95% consistency limit, while the consistency ranges were -36.00～+26.62μm, -42.27～+3.36μm, -0.80～+0.84mm, and -1.95～+1.06mm, respectively.CONCLUSION: In keratoconus, the central corneal thickness and the thinnest point thickness measured by Pentacam HR were higher than those measured by RTVue OCT. It is not recommended that the central corneal thickness and the thinnest point thickness measured by the two instruments be interchangeable in clinical use because of the wide range of consistency between the two instruments' results. The position of the thinnest corneal point measured by the two instruments is similar and consistent, so it could be considered to replace the measured values of the two instruments in clinical use.

Objective: This cross-sectional investigation aimed to determine the incidence, clinical characteristics, prognosis, and related risk factors of olfactory and gustatory dysfunctions related to infection with the SARS-CoV-2 Omicron strain in mainland China. Methods: Data of patients with SARS-CoV-2 from December 28, 2022, to February 21, 2023, were collected through online and offline questionnaires from 45 tertiary hospitals and one center for disease control and prevention in mainland China. The questionnaire included demographic information, previous health history, smoking and alcohol drinking, SARS-CoV-2 vaccination, olfactory and gustatory function before and after infection, other symptoms after infection, as well as the duration and improvement of olfactory and gustatory dysfunction. The self-reported olfactory and gustatory functions of patients were evaluated using the Olfactory VAS scale and Gustatory VAS scale. Results: A total of 35 566 valid questionnaires were obtained, revealing a high incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain (67.75%). Females(χ2=367.013, P<0.001) and young people(χ2=120.210, P<0.001) were more likely to develop these dysfunctions. Gender(OR=1.564, 95%CI: 1.487-1.645), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), oral health status (OR=0.881, 95%CI: 0.839-0.926), smoking history (OR=1.152, 95%CI=1.080-1.229), and drinking history (OR=0.854, 95%CI: 0.785-0.928) were correlated with the occurrence of olfactory and taste dysfunctions related to SARS-CoV-2(above P<0.001). 44.62% (4 391/9 840) of the patients who had not recovered their sense of smell and taste also suffered from nasal congestion, runny nose, and 32.62% (3 210/9 840) suffered from dry mouth and sore throat. The improvement of olfactory and taste functions was correlated with the persistence of accompanying symptoms(χ2=10.873, P=0.001). The average score of olfactory and taste VAS scale was 8.41 and 8.51 respectively before SARS-CoV-2 infection, but decreased to3.69 and 4.29 respectively after SARS-CoV-2 infection, and recovered to 5.83and 6.55 respectively at the time of the survey. The median duration of olfactory and gustatory dysfunctions was 15 days and 12 days, respectively, with 0.5% (121/24 096) of patients experiencing these dysfunctions for more than 28 days. The overall self-reported improvement rate of smell and taste dysfunctions was 59.16% (14 256/24 096). Gender(OR=0.893, 95%CI: 0.839-0.951), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), history of head and facial trauma(OR=1.180, 95%CI: 1.036-1.344, P=0.013), nose (OR=1.104, 95%CI: 1.042-1.171, P=0.001) and oral (OR=1.162, 95%CI: 1.096-1.233) health status, smoking history(OR=0.765, 95%CI: 0.709-0.825), and the persistence of accompanying symptoms (OR=0.359, 95%CI: 0.332-0.388) were correlated with the recovery of olfactory and taste dysfunctions related to SARS-CoV-2 (above P<0.001 except for the indicated values). Conclusion: The incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain is high in mainland China, with females and young people more likely to develop these dysfunctions. Active and effective intervention measures may be required for cases that persist for a long time. The recovery of olfactory and taste functions is influenced by several factors, including gender, SARS-CoV-2 vaccination status, history of head and facial trauma, nasal and oral health status, smoking history, and persistence of accompanying symptoms.
Female ; Humans ; Adolescent ; SARS-CoV-2 ; Smell ; COVID-19/complications* ; Cross-Sectional Studies ; COVID-19 Vaccines ; Incidence ; Olfaction Disorders/etiology* ; Taste Disorders/etiology* ; Prognosis

OBJECTIVE: To investigate autophagy-related mechanisms of electroacupuncture (EA) action in improving gastrointestinal motility in mice with functional constipation (FC). METHODS: According to a random number table, the Kunming mice were divided into the normal control, FC and EA groups in Experiment I. The autophagy inhibitor 3-methyladenine (3-MA) was used to observe whether it antagonized the effects of EA in Experiment II. An FC model was established by diphenoxylate gavage. Then the mice were treated with EA stimulation at Tianshu (ST 25) and Shangjuxu (ST 37) acupoints. The first black stool defecation time, the number, weight, and water content of 8-h feces, and intestinal transit rate were used to assess intestinal transit. Colonic tissues underwent histopathological assessment, and the expressions of autophagy markers microtubule-associated protein 1 light chain 3 (LC3) and Beclin-1 were detected by immunohistochemical staining. The expressions of phosphoinositide 3-kinases (PI3K)-protein kinase B (AKT)-mammalian target of rapamycin (mTOR) signaling pathway members were investigated by Western blot and quantitative reverse transcription-polymerase chain reaction, respectively. The relationship between enteric glial cells (EGCs) and autophagy was observed by confocal immunofluorescence microscopy, localization analysis, and electron microscopy. RESULTS: EA treatment shortened the first black stool defecation time, increased the number, weight, and water content of 8-h feces, and improved the intestinal transit rate in FC mice (P<0.01). In terms of a putative autophagy mechanism, EA treatment promoted the expressions of LC3 and Beclin-1 proteins in the colonic tissue of FC mice (P<0.05), with glial fibrillary acidic protein (GFAP) and LC3 significantly colocalized. Furthermore, EA promoted colonic autophagy in FC mice by inhibiting PI3K/AKT/mTOR signaling (P<0.05 or P<0.01). The positive effect of EA on intestinal motility in FC mice was blocked by 3-MA. CONCLUSION EA treatment can inhibit PI3K/AKT/mTOR signaling in the colonic tissues of FC mice, thereby promoting EGCs autophagy to improve intestinal motility.
Mice ; Animals ; Proto-Oncogene Proteins c-akt/metabolism* ; Phosphatidylinositol 3-Kinases/metabolism* ; Electroacupuncture ; Beclin-1 ; Signal Transduction ; Constipation/therapy* ; TOR Serine-Threonine Kinases/metabolism* ; Autophagy ; Neuroglia/metabolism* ; Mammals/metabolism*

Objective:Partial stereotactic ablative boost radiotherapy(P-SABR)is a method to deliver SABR boost to the gross tumor boost volume(GTVb), followed by conventionally fractionated radiotherapy to the whole tumor area(GTV). GTVb is the max volume receiving SABR while ensuring the critical organ-at-risk(OAR)falloff to 3 GyE/f. We investigated the potential advantage of proton therapy in treating bulky non-small cell lung cancer(the tumor length greater than 8 cm).Methods:Nine patients with bulky NSCLC treated with photon P-SABR in our institute were selected. For the treatment planning of proton therapy, the GTVb target area was gradually outwardly expanded based on the photon GTVb target area until the dose to critical OARs reached 3 GyE/f. The GTV and CTV areas remained the same as photon plan. A proton intensity-modulated radiation treatment plan(proton-IMPT), a photon intensity-modulated radiation treatment plan(photon-IMRT)and a photon volumetric modulated arc therapy(photon-VMAT)were created for each patient, respectively. The dosimetric parameters of different treatment plans were compared.Results:The volume ratio of GTVb-photon and GTVb-proton to GTV was(25.4±13.4)% and(69.7±30.0)%,respectively( P<0.001). In photon-IMRT, photon-VMAT, and proton-IMPT plan groups, the mean dose of CTV was(76.1±4.9)Gy, (78.2±3.6)Gy, and(84.7±4.9)Gy, respectively; the ratio of tumor volume with Biologic Effective Dose(BED)≥ 90 Gy to GTV volume was(70.7±21.7)%, (76.8±22.1)%,and(97.9±4.0)%,respectively. The actual dose and BED to the tumor area of the proton-IMPT plan group were significantly higher than those of the photon plan group(both P<0.05). Besides, the OARs dose was significantly decreased in the proton-IMPT group, with(49.2±22.0)%, (56.8±19.0)% and(16.1±6.3)% of the whole lung V5 for photon-IMRT, photon-VMAT and proton-IMPT, respectively(all P<0.001). Conclusions:Larger GTV boost target volume, higher BED and reduced OARs dose can be achieved in proton plans compared with photon plans. Proton P-SABR is expected to further improve the local control rate of bulky NSCLC with fewer adverse effects.