Olfactory receptors (ORs) form the largest superfamily of G protein-coupled receptors (GPCRs). Traditionally recognized for their role in the nasal olfactory epithelium, where they mediate the sense of smell, accumulating evidence has firmly established their ectopic expression in non-olfactory tissues, including the intestine, lungs, and kidneys. The intestine, as the primary site for nutrient digestion and absorption, harbors a highly complex chemical environment. To adapt to this environment, the gut employs a sophisticated network of “chemosensors” to monitor luminal contents and maintain homeostasis. Among these sensors, intestinal ORs have emerged as crucial functional components, serving as a molecular bridge that connects environmental chemical signals—such as food-derived odorants—to specific physiological responses. This discovery has significantly deepened our understanding of how dietary flavors and compounds influence intestinal physiology at the molecular level. This review systematically summarizes the expression profiles, ligand classification, and biological functions of ORs within the gastrointestinal tract. Studies indicate that intestinal ORs exhibit distinct spatial distribution patterns across different gut segments and display cell-type specificity, particularly within enterocytes and enteroendocrine cells. These receptors function as versatile sensors capable of recognizing a wide variety of ligands, including exogenous dietary components, gut microbiota metabolites such as short-chain fatty acids, and endogenous small molecules like azelaic acid. Upon activation by specific ligands, intestinal ORs trigger intracellular signaling cascades, primarily involving the AC-cAMP-PKA pathway or calcium influx channels. A major focus of this review is to elucidate the molecular mechanisms by which these receptors regulate the secretion of gut hormones. Activation of specific ORs in enteroendocrine cells has been shown to stimulate the release of hormones such as glucagon-like peptide-1 (GLP-1), peptide YY (PYY), and serotonin (5-HT), thereby modulating systemic energy metabolism, glucose homeostasis, and gastrointestinal motility. Furthermore, the review addresses the critical roles of ORs in immune regulation and pathology. Evidence suggests that specific ORs contribute to the maintenance of intestinal immune homeostasis and may offer protection against inflammation. Beyond their involvement in inflammatory responses, ORs such as Olfr78 have been shown to regulate the differentiation and function of intestinal endocrine cells. Similarly, Olfr544 has been demonstrated to alleviate intestinal inflammation by remodeling the gut microbiome and metabolome. These findings collectively suggest that specific ORs hold promise as therapeutic targets for mitigating intestinal inflammation and maintaining gut homeostasis. Additionally, the review explores the emerging role of ORs in cancer. Although OR expression is often downregulated in tumor tissues compared to normal mucosa, activation of specific ORs by certain ligands can inhibit tumor cell proliferation and migration and induce apoptosis via pathways such as MEK/ERK and p38 MAPK. Conversely, other receptors, such as OR7C1, may serve as biomarkers for cancer-initiating cells. In conclusion, intestinal ORs represent a vital component of the gut’s sensory network. The review also discusses the translational potential of these findings. By elucidating the precise pairing relationships between dietary components and specific ORs, novel therapeutic strategies could be developed. Intestinal ORs may thus emerge as promising targets for nutritional and pharmacological interventions in metabolic diseases, inflammatory bowel diseases, and malignancies.

Sensorineural hearing loss is one of the most common sensory disorders. In recent years, auditory neuropathy spectrum disorders caused by mutations in the OTOF gene have garnered significant attention worldwide, marking it as the first deafness gene with breakthroughs in gene therapy. Most patients with OTOF gene mutations present with stable, congenital, or prelingual onset of hearing loss, which can range from severe to profound and even complete hearing loss. However, a minority of patients may exhibit mild to moderate progressive hearing loss or temperature-sensitive hearing loss. This review further explores the genotype-phenotype relationship of the OTOF gene based on reported cases in China and abroad. Additionally, we analyze the characteristics of the natural history of OTOF gene mutations within the Chinese population. This study aims to provide a reference for the clinical diagnosis, evaluation, and treatment of hearing loss associated with OTOF gene mutations.
Humans ; Mutation ; Phenotype ; Genotype ; Hearing Loss, Sensorineural/genetics* ; Membrane Proteins/genetics*

Objective:To compare the treatment time stability, inter- and intra-fraction errors, and clinical target volume (CTV) to planning target volume (PTV) margin expansions under different gated window settings in deep inspiration breath hold (DIBH) radiotherapy for breast cancer, and to analyze the correlation between organ at risk (OAR) dose optimization and changes in lung volume.Methods:A retrospective analysis was conducted on 65 patients with left-sided breast cancer who received DIBH radiotherapy after modified radical mastectomy. CT simulation positioning was performed using 2 mm or 3 mm gated window for DIBH, followed by target delineation, treatment planning, and dose verification. During treatment, setup errors guided by cone beam CT (CBCT), intra-fraction monitoring errors, and treatment times were recorded. The coefficient of variation (CV) of treatment time was calculated for both gated window settings. Based on inter- and intra-fraction error distributions, the expansion distance of the CTV were determined using the van Herk formula. Dosimetric differences between DIBH and free-breathing (FB) plans for the left lung, heart, and left anterior descending coronary artery (LAD) were compared. Spearman correlation analysis was performed between the relative increase in left lung volume and the relative reduction in OAR dose. Paired t-tests were used for inter-group comparisons. Results:The mean CV of the 3 mm gated window group was 0.08±0.03, which was lower than that of the 2 mm group (0.10±0.04; t=-3.91, P<0.001). The setup errors of the 2 mm group in the X, Y, and Z directions were (1.27±1.03), (1.68±0.94), (1.90±1.25) mm, respectively-significantly smaller than those of the 3 mm group [(1.81±1.41), (2.07±1.69), (2.93±1.90) mm; t=-5.80, -2.33, -5.33; P<0.001,=0.014,<0.001). Setup errors for both groups were within the 25%-75% range and all below 5 mm. The intra-fraction deviations of the 2 mm group in the X, Y, and Z directions were (0.54±0.33), (0.79±0.44), (0.70±0.53) mm, respectively, significantly smaller than those of the 3 mm group [(0.62±0.43), (0.93±0.66), (0.87±0.67) mm; t=-3.87, -3.46, -2.71,all P<0.001). The mean intra-fraction errors of both groups were within 1 mm, with greater deviations in the Y and Z directions than those in the X direction. The CTV expansion margins for the 2 mm group in the X, Y, and Z directions were 4.21, 5.35, 5.99 mm, respectively, while those for the 3 mm group were 5.81, 6.89, 9.06 mm. Compared with FB, DIBH significantly reduced the doses to the left lung, heart, and LAD (all P<0.01). The increase in left lung volume was moderately negatively correlated with the reduction in left lung D mean ( r=-0.43, P=0.028), and highly negatively correlated with the dose reductions to the heart and LAD (both P<0.001). Conclusions:The variability in respiratory gated window settings can lead to differences in treatment time stability as well as inter- and intra-fraction errors, consequently affecting CTV-to-PTV margins. The DIBH technique demonstrates significant dosimetric benefits in reducing radiation exposure to the left lung, heart, and LAD. Volumetric expansion of the left lung is strongly and inversely correlated with the reduction in radiation dose to both the heart and LAD.

Objective:To compare the treatment time stability, inter- and intra-fraction errors, and clinical target volume (CTV) to planning target volume (PTV) margin expansions under different gated window settings in deep inspiration breath hold (DIBH) radiotherapy for breast cancer, and to analyze the correlation between organ at risk (OAR) dose optimization and changes in lung volume.Methods:A retrospective analysis was conducted on 65 patients with left-sided breast cancer who received DIBH radiotherapy after modified radical mastectomy. CT simulation positioning was performed using 2 mm or 3 mm gated window for DIBH, followed by target delineation, treatment planning, and dose verification. During treatment, setup errors guided by cone beam CT (CBCT), intra-fraction monitoring errors, and treatment times were recorded. The coefficient of variation (CV) of treatment time was calculated for both gated window settings. Based on inter- and intra-fraction error distributions, the expansion distance of the CTV were determined using the van Herk formula. Dosimetric differences between DIBH and free-breathing (FB) plans for the left lung, heart, and left anterior descending coronary artery (LAD) were compared. Spearman correlation analysis was performed between the relative increase in left lung volume and the relative reduction in OAR dose. Paired t-tests were used for inter-group comparisons. Results:The mean CV of the 3 mm gated window group was 0.08±0.03, which was lower than that of the 2 mm group (0.10±0.04; t=-3.91, P<0.001). The setup errors of the 2 mm group in the X, Y, and Z directions were (1.27±1.03), (1.68±0.94), (1.90±1.25) mm, respectively-significantly smaller than those of the 3 mm group [(1.81±1.41), (2.07±1.69), (2.93±1.90) mm; t=-5.80, -2.33, -5.33; P<0.001,=0.014,<0.001). Setup errors for both groups were within the 25%-75% range and all below 5 mm. The intra-fraction deviations of the 2 mm group in the X, Y, and Z directions were (0.54±0.33), (0.79±0.44), (0.70±0.53) mm, respectively, significantly smaller than those of the 3 mm group [(0.62±0.43), (0.93±0.66), (0.87±0.67) mm; t=-3.87, -3.46, -2.71,all P<0.001). The mean intra-fraction errors of both groups were within 1 mm, with greater deviations in the Y and Z directions than those in the X direction. The CTV expansion margins for the 2 mm group in the X, Y, and Z directions were 4.21, 5.35, 5.99 mm, respectively, while those for the 3 mm group were 5.81, 6.89, 9.06 mm. Compared with FB, DIBH significantly reduced the doses to the left lung, heart, and LAD (all P<0.01). The increase in left lung volume was moderately negatively correlated with the reduction in left lung D mean ( r=-0.43, P=0.028), and highly negatively correlated with the dose reductions to the heart and LAD (both P<0.001). Conclusions:The variability in respiratory gated window settings can lead to differences in treatment time stability as well as inter- and intra-fraction errors, consequently affecting CTV-to-PTV margins. The DIBH technique demonstrates significant dosimetric benefits in reducing radiation exposure to the left lung, heart, and LAD. Volumetric expansion of the left lung is strongly and inversely correlated with the reduction in radiation dose to both the heart and LAD.

Objective To explore the birthdate circuit qi endowment of the five circuit phases and six climatic factors in the female patients with benign and malignant breast tumors,and to analyze the benign and malignant tendency of breast tumors.Methods The birth date information of 723 patients with breast malignant tumor(breast cancer)and 1 595 patients with benign breast tumor were collected from the electronic medical record system of the First Affiliated Hospital of Guangzhou University of Chinese Medicine.SPSS 25.0 statistical software was used to analyze the circuit qi information of the two groups of patients.Results(1)The analysis of suiyun(yearly evolutive phase)showed that the patients born in the years of excessive wood phase,excessive fire phase,and deficiency earth phase tended to suffer from breast cancer,while the patients born in the years of deficiency gold phase,deficiency wood phase,and excessive water phase tended to suffer from benign breast tumors.(2)The analysis of dominant qi(regular yearly circuit qi)showed that the patients born at the time of shaoyin monarch fire were more likely to suffer from breast cancer,while patients born at the time of jueyin wind-wood and taiyin damp-earth were more likely to suffer from benign breast tumors.(3)The analysis of guest qi(alterable yearly circuit qi)showed that the patients born at the time of jueyin wind-wood and yangming dry-gold were more likely to suffer from breast cancer,and the patients born at the time of shaoyang ministerial fire and taiyang cold-water were more likely to suffer from benign breast tumors.(4)The analysis of birth season showed that the patients born in spring were more likely to suffer from breast cancer.(5)The analysis of the combination of circuit and qi(circuit phases and climatic factors)showed that the patients born in the year of xiaoni(circuit phases generating climatic factors),buhe(circuit phases restricting climatic factors),and tianxing(sitian climatic factors restricting the predominant circuit phases)tended to suffer from breast cancer,and patients born in the year of suihui(yearly heavenly-stem circuit phase accorded with the yearly earthly-branch circuit qi)and tongsuihui(deficiency yearly circuit phase in accordance with the second half of the alterable yearly circuit qi)tended to suffer from benign breast tumors.(6)The analysis of celestial control-terrestrial effect showed that the combination of celestial control-terrestrial had no significant effect on the incidence of breast cancer or benign breast tumors(P＞0.05).Conclusion(1)Certain differences and tendencies of birthdate circuit qi endowment exist between benign breast tumors and breast cancer.(2)The birthdate circuit qi endowment of breast cancer is characterized by wind and heat,and mainly involves liver,spleen,heart and kidney.Compared with patients with benign breast tumors,patients with breast cancer usually have the excess and heat biased constitution endowment.

Objective To investigate the effect of reducing the image-guided X-ray field area on the accuracy of Cyberknife radiotherapy,in order to provide a feasible method for achieving patient protection optimization.Methods Firstly,the spine-tracking,fiducial tracking and lung-tracking radiotherapy plans were formulated for the simulation phantom,and then image-guided full-field localization and position pre-setting were carried out for the simulation phantom,and the spine-tracking,fiducial tracking and lung-tracking radiotherapy plans were executed for the simulation phantom using a reduced lead block field area,respectively.Secondly,the radiotherapy accuracy of different radiotherapy plans was verified by end-to-end(E2E)software using new EBT films of the same batch as the base film.Finally,the changes of the simulation phantom were compared in terms of position pre-presetting error,radiotherapy accuracy and lead block field area.Results The spine-tracking and fiducial tracking radiotherapy plans had the translation errors not higher than 0.1 mm and the rotation errors not higher than 0.1°,which were comparable to the fluctuated conventional Cyberknife image-guided locating;the spine-tracking,fiducial tracking and lung-tracking radiotherapy plans had the lead block field radiotherapy accu-racies being 0.71,0.18 and 1.06 mm,respectively,which met the clinical requirements for Cyberknife radiotherapy;the lead block field areas of the spine-tracking,fiducial tracking and lung-tracking radiotherapy plans were reduced to 19.75％,29.28％and 12.71％of the full field area,respectively,and the efficacy for field area optimization was significant.Conclusion It's feasible to involve a reduced image-guided X-ray field area in Cyberknife radiotherapy,which contributes to optimizing radiation protection for the patients.[Chinese Medical Equipment Journal,2024,45(11):49-53]

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

OBJECTIVE: To explore application value and effectiveness of virtual reality technology combined with isokinetic muscle strength training in the rehabilitation of patients after anterior cruciate ligament (ACL) reconstruction surgery. METHODS: Forty patients who underwent ACL reconstruction surgery from December 2021 to January 2023 were selected and divided into control group and observation group according to treatment methods, 20 patients in each group. Control group was received routine rehabilitation training combined with isokinetic muscle strength training, including 15 males and 5 females, aged from 17 to 44 years old, with an average of (29.10±8.60) years old. Observation group was performed virtual reality technology combined with isokinetic muscle strength training, including 16 males and 4 females, aged from 17 to 45 years old with an average of (30.95±9.11) years old. Lysholm knee joint score, knee extension peak torque, and knee flexion peak torque between two groups at 12 (before training) and 16 weeks (after training) after surgery were compared. RESULTS: All patients were followed up for 1 to 6 months with an average of (3.30±1.42) months. There were no statistically significant difference in Lysholm knee joint score, peak knee extension peak torque, and peak knee flexion peak torque between two groups (P>0.05) before training. After training, Lysholm knee joint score, knee extension peak torque, and knee flexion peak torque of both groups were improved compared to before training (P<0.05);there were significant difference in Lysholm knee joint score, knee extension peak torque, and knee flexion peak torque between two groups(P<0.05). CONCLUSION The application of virtual reality technology combined with isokinetic muscle strength training could promote recovery of knee joint function and enhance muscle strength in patients after ACL reconstruction surgery in further.
Male ; Female ; Humans ; Adolescent ; Young Adult ; Adult ; Middle Aged ; Anterior Cruciate Ligament Injuries/surgery* ; Resistance Training ; Knee Joint/surgery* ; Anterior Cruciate Ligament Reconstruction/methods* ; Knee Injuries/surgery* ; Muscle Strength/physiology*

Objective:To evaluate the effect of intrathecal exosomes derived from human amniotic fluid (hAF exo) on neuropathic pain induced by spared nerve injury (SNI) in mice.Methods:Eighteen clean-grade healthy male Kunming mice, aged 7-8 weeks, weighing 30-35 g, were divided into 3 groups ( n=6 each) using a random number table method: sham operation group (Sham group), SNI group, and SNI+ hAF exo group. Spared nerve injury was produced by exposing the sciatic nerve and its branches and ligation and transection of tibial nerve and common fibular nerve in anesthetized mice. Another three mice were selected to develop the model of neuropathic pain after anesthesia. PKH-26 labeled hAF exo 7 μl was intrathecally injected on days 1, 2 and 3 after developing the model. The mice were sacrificed at 10 h after the end of administration, and the uptake of hAF exo by the dorsal horn of the injured lumbar enlargement of the spinal cord was observed with the fluorescence microscope. On 1, 2 and 3 days after developing the model, 1 μg/μl hAF exo 7 μl was intrathecally injected in SNI+ hAF exo group, and PBS 7 μl was intrathecally injected in Sham group and SNI group. The mechanical paw withdrawal threshold (MPWT) was measured at 1 day before and 1, 3, 5 and 7 days after operation. And then the mice were sacrificed after measurement of the pain threshold at 7 days after developing the model, and the ipsilateral lumbar enlargement of the spinal cord was taken for determination of the expression of CD11b, interleukin-1beta (IL-1β) and IL-10 by Western blot. Results:The dorsal horn of the lumbar enlargement of the spinal cord on the injured side could absorb hAF exo with the fluorescence microscope. Compared with Sham group, the MPWT was significantly decreased at 3-7 days after developing the model, the expression of CD11b and IL-1β was up-regulated ( P<0.05), and no significant change was found in the expression of IL-10 in SNI group ( P>0.05). Compared with SNI group, the MPWT was significantly increased at 3-7 days after developing the model, the expression of CD11b and IL-1β was down-regulated, and the expression of IL-10 was up-regulated in SNI+ hAF exo group ( P<0.05). Conclusions:Intrathecal exosomes derived from human amniotic fluid can alleviate neuropathic pain in mice, and the mechanism may be related to mediation of the polarization of microglia from M1 type to M2 type and attenuation of neuroinflammation.

Objective:To observe the effect of combined acupuncture and medication on hyperarousal state and serum copeptin(CPT)in patients with chronic insomnia(CI),and to explore its possible mechanism of action.Methods:A total of 70 CI patients meeting the inclusion criteria were divided into an observation group and a control group by the random number table method,with 35 cases in each group.The control group was given estazolam tablets before bedtime,1 mg/time,once a day.The observation group was treated with additional Yi Nao An Shen acupuncture therapy(acupuncture for benefiting the brain and tranquillization)on the basis of the medication treatment,4 times a week.After 4 weeks of treatment,the Pittsburgh sleep quality index(PSQI)score,insomnia severity index(ISI)score,pre-sleep arousal scale(PSAS)score,hyperarousal scale(HAS)score,and the change in serum CPT level were compared between the two groups.Results:During the study,there were 2 dropout cases in the observation group and 1 dropout case in the control group.After treatment,the PSQI,ISI,PSAS,and HAS scores and the serum CPT level in both groups decreased compared with the same group before treatment,and the intra-group differences were statistically significant(P<0.05).After treatment,changes in each above scale score and the serum CPT level in the observation group were much more significant and were statistically different from those in the control group(P<0.05).Conclusion:Acupuncture plus medication can improve sleep quality,reduce the degree of insomnia,and regulate hyperarousal state in patients with CI,and its mechanism of action may be related to the down-regulation of serum CPT level.