A major obstacle in type 2 diabetes mellitus (T2DM) is sleep fragmentation (SF), which negatively affects testicular function. However, the underlying mechanisms remain to be elucidated. In this study, we demonstrate that SF induces testicular damage through a mechanism involving lipid metabolism, specifically mediated by melatonin (MEL) receptor 1a (MT1). T2DM mice with SF intervention displayed several deleterious phenotypes such as apoptosis, deregulated lipid metabolism, and impaired testicular function. Unexpectedly, sleep recovery (SR) for 2 consecutive weeks could not completely abrogate SF's detrimental effects on lipid deposition and testicular function. Interestingly, MEL and MT1 agonist 2-iodomelatonin (2IM) effectively improved lipid homeostasis, highlighting MEL/2IM as a promising therapeutic drug for SF-trigged testicular damage. Mechanistically, MEL and 2IM activated FGFR1 and sequentially restrained the crosstalk and physical interaction between TAB1 and TAK1, which ultimately suppressed the phosphorylation of TAK1 to block lipid deposition and cell apoptosis caused by SF. The ameliorating effect of MEL/2IM was overtly nullified in Fgfr1 knockout (Fgfr1-KO ^+/- ) diabetic mice. Meanwhile, testicular-specific overexpression of Tak1 abolished the protective effect of FGF1^mut on diabetic mouse testis. Our findings offer valuable insights into the molecular mechanisms underlying the testicular pathogenesis associated with SF and propose a novel therapeutic approach for addressing male infertility in T2DM.

Magnetic stimulation has made significant strides in the treatment of psychiatric disorders. Nonetheless, current magnetic stimulation techniques lack the precision to accurately modulate specific nuclei and cannot realize deep brain magnetic stimulation. To address this, we utilized superparamagnetic iron oxide nanoparticles as mediators to achieve precise targeting and penetration. We investigated the effects of magnetic fields with varying frequencies on neuronal activity and compared the activation effects on neurons using a 10-Hz precise magneto-stimulation system (pMSS) with repetitive transcranial magnetic stimulation in mice. Oxytocin levels, dendritic morphology and density, and mouse behavior were measured before and after pMSS intervention. Our findings suggest that pMSS can activate oxytocinergic neurons, leading to upregulation of oxytocin secretion and neurite outgrowth. As a result, sociability was rapidly improved after a one-week pMSS treatment regimen. These results demonstrate a promising magneto-stimulation method for regulating neuronal activity in deep brain nuclei and provide a promising therapeutic approach for autism spectrum disorder.
Animals ; Autism Spectrum Disorder/physiopathology* ; Paraventricular Hypothalamic Nucleus/physiology* ; Disease Models, Animal ; Transcranial Magnetic Stimulation/methods* ; Male ; Social Behavior ; Mice ; Oxytocin/metabolism* ; Mice, Inbred C57BL ; Neurons/physiology*

Objective:To analyze the incidence and clinical phenotype of the concomitant extragenital malformations in the patients with female reproductive tract anomalies.Methods:A retrospective study was conducted using clinical data of hospitalized patients diagnosed with uterine, cervical, or vaginal malformations from January 2003 to December 2022 in Peking Union Medical College Hospital. The malformations were classified according to American Society for Reproductive Medicine müllerian anomalies classification 2021, and in each type, the incidence and specific manifestations of concomitant extragnital malformations were analyzed.Results:A total of 444 patients were included. The overall incidence of concomitant extragenital malformations was 43.5% (193/444), including urinary system, skeletal system, and other system malformations. Renal malformations on the obstructed side were present in all patients with oblique vaginal septum syndrome (100.0%, 78/78). The total incidence of concomitant extragnital malformations was as high as 8/11 in uterus didelphys, 43.5% (10/23) in unicornuate uterus, 33.6% (79/235) in Mayer-Rokitansky-Küster-Hauser syndrome, 18.8% (6/32) in septate uterus and 18.5% (12/65) in cervical agenesis. Urinary system malformations (30.6%, 136/444) and skeletal system malformations (13.5%, 60/444) were the most common concomitant malformations in all types, in which, unilateral renal agenesis and scoliosis were the most common.Conclusions:Urinary and skeletal system malformations are important features of female reproductive tract anomalies. Urologic ultrasonography and spinal roentgenogram are recommended for all patients with female reproductive tract anomalies.

Objective To investigate the effect of acupuncture on the morphology of the dry eye rabbit's cornea and the nuclear factor κB(NF-κB)signaling pathway of the corneal tissue to analyze the mechanism of acupuncture on dry eyes.Methods Twenty-four healthy New Zealand rabbits,without restriction on sex,were randomly divided into four groups,including a blank group,a model group,an acupuncture group,and a sham acupuncture group,with 6 in each group.Rabbits in the blank group were not treated;rabbits in the other three groups were treated with scopolamine hydro-bromide 2.0 mg·kg-1 by subcutaneous injection at 8:00,11:00,14:00 and 18:00 each day for 35 consecutive days un-til the end of the experiment.Rabbits in the sham acupuncture group were treated with sham acupuncture on the 22nd day after successful modeling by quickly pricking acupoints(Jingming BL1,Cuanzhu BL2,Sizhukong SJ23,Taiyang EX-HN5 and Tongziliao GB1)with a blunt acupuncture needle,once a day,for a total of 14 days.Rabbits in the acupuncture group were treated with acupuncture at the same acupoints as the sham acupuncture group after successful modeling.The corneal fluorescence staining was conducted on Days 0,21,28 and 35 after modeling.On Day 35,corneal confocal microscope ex-aminations were conducted.Then,the rabbits were sacrificed,the corneal morphological changes were observed by light microscope and transmission electron microscope,and the expression of corneal NF-κB protein was detected by Western blot.Results Compared with the model group,the score of rabbit corneal fluorescein staining in the acupuncture group and blank group decreased on the 28th and 35th days after modeling,and the differences were statistically significant(all P＜0.05).The results of the confocal microscope examination on Day 35 after modeling showed that,compared with other groups,there were a large number of globular immune cells and activated stromal cells with unclear boundaries and irregu-lar sizes in the stromal layer and inflammation in the area with irregular intercellular space in the model group and the sham acupuncture group.In the acupuncture group,the morphology of stromal layer cells improved,the cells were slightly acti-vated,and there were no obvious abnormalities in the corneal nerve morphology.On the 35th day after modeling,the re-sults of the light microscope showed that,the surface of the corneal tissue in the model group and the sham acupuncture group showed hyperkeratinized flat epithelial cells,lymphocyte infiltration,increased number of focal epithelial cell layers,and epithelial cell detachment.In the acupuncture group,there were 4-6 layers of epithelial cells in the corneal epitheli-um,and epithelial shedding decreased.In addition,the lymphocyte infiltration decreased compared with the model group.On the 35th day after modeling,the results of the transmission electron microscope showed that abnormal microvilli oc-curred and epithelial cells were absent in the corneal epithelial cells of rabbits in the model group and the sham acupuncture group,the cell space was widened,the rough endoplasmic reticulum was severely expanded,and desmosomes were dis-banded with mitochondrial swelling.In the acupuncture group,the microvilli structure of epithelial cells was sparse and short,local deletion was still observed,the rough endoplasmic reticulum was slightly expanded,and no obvious swelling of mitochondria was observed.On the 35th day after modeling,the Western blot examination results showed that,compared with the blank group,the expression of p-NF-κB p65 was up-regulated in both the model group and sham acupuncture group(both P＜0.05);compared with the model group and sham acupuncture group,the expression of p-NF-κB p65 in the acupuncture group was down-regulated(both P＜0.05).Conclusion Acupuncture can inhibit the NF-κB signaling path-way to play an anti-inflammatory role and relieve corneal inflammation and injury of dry eye rabbit models.

Objective:To analyze the epidemic characteristics of brucellosis in China from 2004 to 2018, in order to understand the development trend of brucellosis.Methods:The surveillance data of brucellosis in China from 2004 to 2018 were collected from National Public Health Science Data Center. Joinpoint regression was used to analyze the trend of brucellosis incidence in China and various provinces. Overall trends were estimated by the average annual percentage change (AAPC). Seasonal and trend decomposition using loess (STL) was used to analyze the seasonal characteristics of brucellosis in China and various provinces. The age-related thermodynamic diagram of incidence rate was used to analyze the characteristics of age-onset changes.Results:From 2004 to 2018, a total of 524 980 brucellosis cases and 16 deaths were reported nationwide, with a incidence rate of 2.61/100 000 and a case fatality rate of (3.05 × 10 -3)%. The incidence of brucellosis in China was on the rise (AAPC = 11.58%, 95% CI: 7.91% - 15.25%, P < 0.001). There was no significant trend of change in Inner Mongolia Autonomous Region, Shanxi and Shaanxi provinces ( P > 0.05). Tibet Autonomous Region showed a downward trend (AAPC = - 55.19%, P < 0.001). All other provinces were showing an upward trend (AAPC > 0, P < 0.05). The peak incidence in China occurred from April to June. In terms of provinces, the peak incidence in Hainan, Sichuan, Guizhou, Fujian and Anhui provinces occurred from April to August, the peak incidence in Chongqing and Shanghai cities occurred from June to August, and the peak incidence in other provinces was generally from April to June. There were reports of brucellosis cases in all age groups nationwide, and the age distribution showed an inverted "V" shape. The peak incidence occurred in the 50 - 54 years old (5.43/100 000), followed by the 60 - 64 years old (4.94/100 000). From 2004 to 2018, the top 3 age groups of incidence rate changed from 40 - 44, 50 - 54 and 35 - 39 years old in 2004 to 50 - 54, 60 - 64 and 55 - 59 years old in 2018. Conclusions:The incidence of brucellosis is on the rise nationwide and in most provinces from 2004 to 2018. The high incidence age is gradually changing to the elderly population.

Objective To understand the current status of emergency vaccination of hemorrhagic fever with renal syndrome (HFRS) vaccine in Jingzhou, serological monitoring and the incidence of vaccinated population, and to evaluate the protective effect of emergency vaccination of HFRS vaccine on the control of HFRS epidemic in the city. Methods From 2018 to 2020, HFRS vaccination was carried out in Jianli City, Honghu City, Jiangling County, Gongan County and some townships in Shashi City, Jingzhou City, focusing on people aged 30-59 years old. The incidence of HFRS, vaccination history of cases and HFRS vaccination data of Jingzhou City were collected and analyzed by descriptive epidemiological methods. The sera of those who had not been vaccinated with HFRS vaccine (non-vaccinated group) and those who had been vaccinated with HFRS vaccine (vaccinated group) were collected for IgG antibody detection, and the serum IgG was detected by ELISA method. The correlation between the change in the number of cases in townships where people were vaccinated (comparison between 2017-2018 and 2020) and the vaccination rate before 2019 was analyzed. Results A total of 446 900 doses of HFRS vaccine were vaccinated from 2018 to 2020, covering 22 townships in 5 counties and cities, accounting for 17.19% (22/128) of the total number of townships in the city. A total of 120 953 people completed 3 doses of vaccination, accounting for 11.30% of the total population and 23.77% of the population aged 30-59 in the vaccinated township. The positive rate of IgG in the unvaccinated group in Jingzhou was 9.91% (85/858). The positive rate of IgG in the vaccination group was 40.96% (34/83). The positive rates of IgG in the 1-dose group, 2- dose group, and 3-dose group were 0 (0/2), 18.18% (6/33), and 58.33% (28/48), respectively. From 2017 to 2020, a total of 16 cases had been vaccinated with HFRS before the onset of the disease, and 81.25% (13/16) received 2 doses or less of HFRS vaccine. The changes in the number of cases was negatively correlated with the vaccination rate of the whole population in townships where people were vaccinated (r_s=-0.58, P=0.011). The changes in the number of cases was negatively correlated with the vaccination rate of people aged 30-59 years in townships where people were vaccinated (r_s=-0.46, P=0.055). Conclusion The HFRS vaccination before 2019 has played a certain protective effect on the vaccinated population. However, the inoculation rate of HFRS vaccine in Jingzhou City is still low, and the protective effect on the whole population has not yet appeared.

The declining fertility has emerged as a significant concern impacting national welfare, with obesity identified as a major contributing factor. In the hypothalamus, gonadotropin-releasing hormone(GnRH) neurons release GnRH, which regulates the secretion of estrogen and testosterone via the hypothalamic-pituitary-gonadal(HPG) axis, thereby influencing sexual development and fertility. The proper function of GnRH neurons is crucial for maintaining normal sexual development and fertility. Research indicates that obesity can impact GnRH neuron function through several pathways, such as disrupting pulsatile secretion core kisspeptin neurons, causing imbalance in energy sensing and metabolic factor secretion, and triggering hypothalamic inflammation. These pathways directly or indirectly influence GnRH neuron function in the hypothalamus, which ultimately affects sexual development and impairs fertility. Therefore, this review consolidates recent advancements in understanding the mechanisms by which obesity induces dysfunction in hypothalamic GnRH neurons, offering new perspectives for early clinical interventions aimed at enhancing fertility outcomes in obese individuals.

Objective:To document any effect of a pulsed electromagnetic field (PEMF) on the regulation of neuropeptide Y (NPY) in nucleus pulposus (NP) tissue, NP cell apoptosis and matrix degradation using rats with intervertebral disc degeneration (IDD).Methods:Eighteen Sprague-Dawley rats were randomly divided into a control group, an IDD model group (the model group), and a PEMF group. IDD was induced in both the model and PEMF groups. Right after the modeling, the PEMF group received 14 days of PEMF treatment, while the control group and model group were given no special treatment. Meanwhile, the primary rat nucleus pulposus cells (NPCs) were cultured using Dulbecco′s Modified Eagle Medium at 37℃ and 5% CO 2. When the fusion rate reached 90% after passage, the NPCs were divided into a control group, a TNF-α model group (referred to as model group) and TNF-α + PEMF group (referred to as PEMF group) and treated accordingly. Eight weeks after the modeling, safranin-o/fast green staining was used to assess any pathological morphology changes. The expression of NPY, neuropeptide Y receptor Y2 (NPY2R), bcl-2-associated X protein (Bax), B-cell lymphoma 2 (Bcl-2), collagen type II (Col-II) and matrix metalloproteinase-3 (MMP3) in the intervertebral disc and the cultivated nucleus pulposus cells of the 3 groups were determined. Results:The intervertebral disc cells in the model group were ruptured and folded, with significantly increased polysaccharide and protein components, and significantly increased bone fibers. In the PEMF group the cell boundaries were clearer, with less fibrin fracture and increased cartilage tissue. NPY was expressed in the fibrous annulus and the nucleus pulposus of the intervertebral disc in the model group. The average expression levels of NPY and NPY2R were significantly higher than in the control group and the model group. Compared with the control group, there was a significant increase in the level of Bax and a significant decrease in the expression of Bcl-2 in the model group, and there was a significant decrease in the level of Bax in the PEMF group. Compared with the control group, there was a significant decrease in the Col-II level but a significant increase in the MMP3 protein expression in the model group. The average Col-II mRNA expression was significantly higher in the PEMF group compared with the model group, but the average MMP3 protein expression was significantly less. Those results are consistent with observations in vivo.Conclusion:PEMF may reverse the imbalance of ECM metabolism and delay IDD degeneration by up-regulating the expression of NPY and Bcl-2, as well as blocking the Bax/Bcl-2 signaling pathway to inhibit apoptosis of nucleus pulposus cells.

Objective:To analyze the epidemic characteristics and periodicity of hemorrhagic fever with renal syndrome (HFRS) in Jingzhou City, Hubei Province, and provide a basis for scientific prevention and control of HFRS in Jingzhou City.Methods:Retrospective analysis was used to collect HFRS case data and population data of Jingzhou City and 8 counties (cities, districts) within its jurisdiction, including Shashi District, Jingzhou District, Gongan County, Jianli City, Jiangling County, Shishou City, Honghu City, and Songzi City from 1962 to 2020, from the Archives of the Jingzhou Center for Disease Control and Prevention and the Infectious Disease Report Information Management System of the China Disease Control and Prevention Information System; and the epidemic characteristics of HFRS was analyzed in Jingzhou City and 8 counties (cities, districts) within its jurisdiction. The periodicity of HFRS onset was determined using wavelet analysis.Results:From 1962 to 2020, 18 936 HFRS cases were reported in Jingzhou City, with an average incidence rate of 5.95/100 000. There were a total of three epidemic peaks, namely from 1972 to 1973 (24.82/100 000, 24.84/100 000), 1983 (60.08/100 000), and 1995 (14.57/100 000). According to different regions, the high incidence areas of HFRS showed a phased transfer trend: from the 1960s to the 1970s, the Jiangbei area (Honghu City, Jianli City) was the highest incidence area; in the 1980s and 1990s, the high incidence areas were transferred to Jiangnan area (Songzi City, Shishou City, and Gongan County); after 2005, high incidence areas were relocated to Jiangbei area (Honghu City, Jianli City, Jiangling County). The wavelet analysis results showed that there were 12.30 and 21.77 years of HFRS epidemic cycles in Jingzhou City before 2000 ( P < 0.05); among them, the periodicity of Shashi District, Gongan County, Jiangling County, Shishou City, and Honghu City was relatively consistent with that of Jingzhou City, with epidemic cycles of about 12 or 22 years ( P < 0.05). Conclusions:Jingzhou City is currently at the peak of a 22-year epidemic cycle of HFRS, with Jiangbei area as the high incidence areas. The 12-year epidemic cycle in Jingzhou City has ended after 2000.

Objectives:To explore the clinical efficacy of applying the accurate foraminoplasty technique with visualized chisel under full-visualized spinal endoscopy(FVSE)in the treatment of lumbar disc herniation(LDH).Methods:The clinical data of 143 patients with single-segment LDH undergone operative treatment under FVSE in our hospital between July 2020 and December 2022 were retrospectively analyzed.63 cases were treated with the accurate framinoplasty technique with visualized chisel(Chisel group),consisting of 37 males and 26 females,aged 45.3±15.1 years(range,19-68 years),and body mass index(BMI)was 22.3± 1.8kg/m2(range,19.2-25.6kg/m2);Operative segment:L2/3 in 8 cases,L3/4 in 15 cases,L4/5 in 25 cases,L5/S1 in 15 cases;LDH anatomical classification:20 cases of bulging type,22 cases of protruding type,12 cases of prolapsing type,and 9 cases of free type;LDH location classification:10 cases of central type,21 cases of paracentral type,24 cases of foraminal type,and 8 cases of extreme lateral type.The other 80 cases were treated with trepan technique(Trephine group),consisting of 46 males and 34 females,aged 43.8±14.1 years(range,19-68 years),BMI was 21.5±1.6kg/m2(range,19.2-24.1kg/m2);Operative segment:L2/3 in 9 cases,L3/4 in 17 cases,L4/5 in 30 cases,and L5/S1 in 24 cases;LDH anatomical classification:23 cases of bulging type,31 cases of protruding type,19 cases of prolapsing type,7 cases of free type;LDH location classification:13 cases of central type,27 cases of paracentral type,29 cases of foraminal type,and 11 cases of extreme lateral type.The operative time,total intraoperative bleeding,number of fluoroscopies,and hospitalization time were recorded and compared between the two groups.The intervertebral foraminal area before operation,at 3d after operation and final follow-up,visual analogue scale(VAS)score,Oswestry disability index(ODI),and Japanese Orthopedic Association(JOA)score before operation,at postoperative 3d,1 month,6 months,and final follow-up were recorded and compared between the two groups.The clinical efficacy was assessed by MacNab criteria at the final follow-up.Results:The operative time,total intraoperative bleeding and number of fluoroscopies were 84.6±14.3min,23.1±8.3mL and 2.9±1.6 times in the chisel group and 86.6±15.1min,32.2±6.4mL and 5.6±1.0 times in the trephine group,and the intraoperative bleeding and number of fluoroscopies in the chisel group were less than those in the trephine group(P＜0.05),while no significant difference was there in the operative time between the two groups(P＞0.05).143 patients were followed up for 9-20 months.The VAS scores,JOA scores and ODI at 3d,1 month,6 months and the final follow-up of both groups showed significant improvements compared with the preoperative data,respectively(P＜0.05),and there was no statistical difference between the two groups at the same time points(P＞0.05).The intervertebral foramina area at 3d postoperatively and at the final follow-up in both groups increased than that before surgery(P＜0.05),and the rate of change in the intervertebral foramina area at 3d postoperatively and at the final follow-up in the trephine group was greater than that in the chisel group(P＜0.05).At the final follow-up,according to the MacNab standard,chisel group was excellent in 43 cases,good in 18 cases,moderate in 2 cases,and poor in 0 case,with an excellence and good rate of 96.8％,while the trephine group was excellent in 57 cases,good in 20 cases,moderate in 3 cases,and poor in 0 case,with an excellence and good rate of 96.3％.There was no statistical difference between the two groups in terms of excellent and good rate according to MacNab criteria(P＞0.05).Conclusions:The clinical efficacy of accurate foraminoplasty technique with visualized chisel is similar to foraminalplasty with trephine under FVSE,but foraminoplasty technique with visualized chisel reduces the number of fluoroscopies and bleeding volume.