Neuraxial opioids, widely used in obstetric and perioperative pain management, often lead to unwanted itch, reducing patient satisfaction. While the μ-opioid receptor has been implicated in opioid-induced itch, the genetic basis for variable itch incidence remains unknown. This study examined 3616 patients receiving epidural opioids, revealing an itch occurrence of 26.55%, with variations among opioid types and gender. Analysis of the OPRM1 gene identified six single-nucleotide polymorphisms, notably rs1799971 (A118G), that correlated with opioid-induced itch. Mouse models with an equivalent A112G mutation showed reduced neuraxial opioid-induced itch and light touch-evoked itch, mirroring human findings. The 118G allele demonstrated an anti-itch effect without impacting analgesia, addiction, or tolerance, offering insights for risk stratification and potential anti-itch pretreatment strategies.
Receptors, Opioid, mu/genetics* ; Pruritus/chemically induced* ; Humans ; Analgesics, Opioid/administration & dosage* ; Female ; Male ; Animals ; Polymorphism, Single Nucleotide/genetics* ; Adult ; Mice ; Middle Aged

Objective:To explore the impact of female body mass index (BMI) on pregnancy outcomes in artificial insemination with donor sperm (AID).Methods:A retrospective cohort study was conducted on 4 484 couples with 9 852 AID treatment cycles treated at Reproductive Center of Guangdong Institute of Reproductive Science from January 2011 to September 2024. Participants were divided into four groups based on BMI: low BMI group (BMI<18.5 kg/m 2), normal BMI group (18.5 kg/m 2≤BMI<24.0 kg/m 2), overweight group (24.0 kg/m 2≤BMI<28.0 kg/m 2), and obese group (BMI≥28.0 kg/m 2). General characteristics and pregnancy outcomes were compared across groups. Kaplan-Meier survival analysis was used to calculate cumulative pregnancy rates from one to six cycles. Generalized estimating equations (GEE), univariate and multivariate logistic and Cox regression analysis were performed, adjusting for age, basal follicle-stimulating hormone, basal luteinizing hormone, endometrial thickness, clinical diagnosis, and treatment protocol, to explore correlations between female BMI and clinical pregnancy rate, spontaneous abortion rate, and cumulative pregnancy rate. Results:1) There were no statistically significant differences in clinical pregnancy rate and spontaneous abortion rate among the low BMI group, the normal BMI group, the overweight group, and the obesity group (all P>0.05). 2) Cumulative pregnancy rates for AID cycles 1-6 were 17.60%, 31.60%, 43.08%, 54.37%, 61.83% and 73.68%, respectively. 3) Multivariate GEE analysis revealed that female age ( OR=0.962, 95% CI: 0.950-0.974, P<0.001), endometrial thickness ( OR=1.040, 95% CI:1.011-1.069, P=0.006), and natural cycles ( OR=1.171, 95% CI: 1.060-1.294, P=0.002) influenced clinical pregnancy rates. Compared with the normal BMI group, there were no statistically significant differences in clinical pregnancy rates of low BMI group, overweight group, and obese group (all P>0.05). Multivariate logistic analysis showed that female age ( OR=1.051, 95% CI: 1.012-1.091, P=0.010), endometrial thickness ( OR=0.920 , 95% CI: 0.847-1.000, P=0.049) and polycystic ovary syndrome ( OR=1.927, 95% CI: 1.044-3.556, P=0.036) influenced spontaneous abortion rates. Compared with the normal BMI group, there were no statistically significant differences in spontaneous abortion rates of low BMI group, overweight group and obese group (all P>0.05). 4) Cox regression analysis indicated that female age ( HR=0.939, 95% CI: 0.928-0.950, P<0.001), endometrial thickness ( HR=1.039, 95% CI: 1.013-1.066, P=0.003) and natural cycles ( HR=1.957, 95% CI: 1.785-2.146, P<0.001) influenced cumulative pregnancy rates. Compared with the normal BMI group, there were no statistically significant differences in cumulative pregnancy rates of low BMI group, overweight group and obese group (all P>0.05). Conclusion:Female BMI does not significantly affect clinical pregnancy rates, spontaneous abortion rates and cumulative pregnancy rates in AID.

Objective:To explore the impact of female body mass index (BMI) on pregnancy outcomes in artificial insemination with donor sperm (AID).Methods:A retrospective cohort study was conducted on 4 484 couples with 9 852 AID treatment cycles treated at Reproductive Center of Guangdong Institute of Reproductive Science from January 2011 to September 2024. Participants were divided into four groups based on BMI: low BMI group (BMI<18.5 kg/m 2), normal BMI group (18.5 kg/m 2≤BMI<24.0 kg/m 2), overweight group (24.0 kg/m 2≤BMI<28.0 kg/m 2), and obese group (BMI≥28.0 kg/m 2). General characteristics and pregnancy outcomes were compared across groups. Kaplan-Meier survival analysis was used to calculate cumulative pregnancy rates from one to six cycles. Generalized estimating equations (GEE), univariate and multivariate logistic and Cox regression analysis were performed, adjusting for age, basal follicle-stimulating hormone, basal luteinizing hormone, endometrial thickness, clinical diagnosis, and treatment protocol, to explore correlations between female BMI and clinical pregnancy rate, spontaneous abortion rate, and cumulative pregnancy rate. Results:1) There were no statistically significant differences in clinical pregnancy rate and spontaneous abortion rate among the low BMI group, the normal BMI group, the overweight group, and the obesity group (all P>0.05). 2) Cumulative pregnancy rates for AID cycles 1-6 were 17.60%, 31.60%, 43.08%, 54.37%, 61.83% and 73.68%, respectively. 3) Multivariate GEE analysis revealed that female age ( OR=0.962, 95% CI: 0.950-0.974, P<0.001), endometrial thickness ( OR=1.040, 95% CI:1.011-1.069, P=0.006), and natural cycles ( OR=1.171, 95% CI: 1.060-1.294, P=0.002) influenced clinical pregnancy rates. Compared with the normal BMI group, there were no statistically significant differences in clinical pregnancy rates of low BMI group, overweight group, and obese group (all P>0.05). Multivariate logistic analysis showed that female age ( OR=1.051, 95% CI: 1.012-1.091, P=0.010), endometrial thickness ( OR=0.920 , 95% CI: 0.847-1.000, P=0.049) and polycystic ovary syndrome ( OR=1.927, 95% CI: 1.044-3.556, P=0.036) influenced spontaneous abortion rates. Compared with the normal BMI group, there were no statistically significant differences in spontaneous abortion rates of low BMI group, overweight group and obese group (all P>0.05). 4) Cox regression analysis indicated that female age ( HR=0.939, 95% CI: 0.928-0.950, P<0.001), endometrial thickness ( HR=1.039, 95% CI: 1.013-1.066, P=0.003) and natural cycles ( HR=1.957, 95% CI: 1.785-2.146, P<0.001) influenced cumulative pregnancy rates. Compared with the normal BMI group, there were no statistically significant differences in cumulative pregnancy rates of low BMI group, overweight group and obese group (all P>0.05). Conclusion:Female BMI does not significantly affect clinical pregnancy rates, spontaneous abortion rates and cumulative pregnancy rates in AID.

Objective:To investigate the preventive and therapeutic effects of compound wild chrysanthemum eye pad on blue light-induced alteration of meibomian gland function in mice and its mechanism.Methods:Sixty-four 15-week-old male C57BL/6J mice were divided into two groups of 32 mice each according to random numbers for the prevention test and the treatment test.The respective 32 mice in the prevention and treatment experiments were randomly divided into normal group, blue light group, solvent group and eye pad group according to random numbers, with eight mice in each group, respectively.In the prevention experiments, mice in each group were exposed to blue light at a wavelength of 460 nm and a light intensity of 2 000 lx for 6 hours per day for 15 consecutive days to establish a mouse model of meibomian gland function changes except for the normal group.The solvent group and the eye pad group were treated with the corresponding eye pad before and after the blue light exposure for 25 minutes daily for the 15 consecutive days.The blue light group was treated with blue light exposure only for 15 days, and the mice were photographed at the edge of the meibomian gland on day 15 to observe the function of the meibomian gland except for the normal group.In the treatment test, all groups of mice except the normal group were induced the altered function of the mouse meibomian gland by the above method.The solvent and eye pad groups were treated with corresponding eye pads for 25 minutes in the morning and afternoon of each day for 15 consecutive days after blue light exposure.The blue light group was kept in a standard environment for 15 days and the changes in meibomian gland function of mice were detected by meibomian gland photographs on day 15.Photography of the eyelid margin in vitro, oil red O staining, and hematoxylin-eosin staining were performed to observe the histologic changes in the meibomian glands of mice after the preventive and experimental treatment.The relative expression of interleukin-1β (IL-1β), IL-6, tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ) mRNA in mouse meibomian gland tissues was detected by real-time fluorescence quantitative PCR.The expression of nuclear factor-κB (NF-κB) and phosphorylation of NF-κB (p-NF-κB) proteins in mice meibomian gland tissues was detected by Western blot to assess the degree of amelioration of blue light-induced inflammation in mouse meibomian glands by the compound wild chrysanthemum eye pad.This study was conducted in accordance with the Statement of the Association for Research in Vision and Ophthalmology on the Use of Animals in Ophthalmology and Vision Research, and was approved by the Animal Ethics Committee of Xiamen University (No.XMULAC20220258). Results:Compared with the normal group, a gradually increased number of blocked meibomian gland openings, and a gradually decreased remaining area of lower meibomian gland, were observed in the mice after 15 days of blue light group, and all the differences were statistically different (all at P<0.05). In the prevention test, the number of obstructed opening in the eye pad group was 1.833±0.753, which was significantly less than 3.667±1.033 in the solvent group ( P<0.05). The relative remaining area of the lower lid meibomian gland in the eye pad group was 0.718±0.091, which was significantly greater than 0.624±0.130 in the solvent group ( P<0.05). Hematoxylin-eosin staining showed inflammatory cell infiltration in mouse meibomian gland in the blue light and solvent groups.There was no inflammatory cell infiltration in eye pad group, and the morphology of the acini was similar to that of the normal group.Oil red O staining showed that there was no significant lipid deposition in the groups.The relative expressions of IL-1β, IL-6, TNF-α, and IFN-γ mRNA were significantly lower, and the relative expressions of NF-κB and p-NF-κB proteins were significantly lower in the eye pad group than in the solvent group, showing statistically significant differences (all at P<0.05). In the treatment test, the number of obstructed openings in the eye pad group and solvent group was 4.333±1.211 and 4.833±1.722, respectively, and the relative remaining area of the lower meibomian gland was 0.572±0.151 and 0.588±0.154, respectively, showing no statistically significant differences (both at P>0.05). Hematoxylin-eosin staining showed inflammatory cell infiltration in mouse meibomian glands in the blue light and solvent groups, with a similar morphology of acini as in the normal group.There was no inflammatory cell infiltration in eye pad group.Oil red O staining showed that there was no significant lipid deposition in the groups.The relative expressions of IL-1β, IL-6, and IFN-γ mRNA were significantly lower and the relative expressions of NF-κB and p-NF-κB proteins were significantly lower in the eye pad group than in the solvent group (all at P<0.05). Conclusions:Compound wild chrysanthemum eye pad may have preventive and therapeutic effects on blue light-induced changes in meibomian gland function by reducing the inflammatory response of meibomian gland tissue through the inhibition of the NF-κB signaling pathway.

Objective To observe the functional recovery situation after prostate cancer radical opera-tion with maximal preservation of the periprostatic structures (MS-RARP).Methods Sixty-seven patients with localized prostatic cancer undergoing MS-RARP in the Second Affiliated Hospital of Army Military Med-ical University from June 2019 to June 2022 were selected as the study subjects.The changes of urinary con-trol function,erection function,quality of life and total prostate specific antigen (t-PSA) were compared at the time between before operation and postoperative 6 weeks,3 months,6 months,12 months.The expanded pros-tate cancer index composite index (EPIC-50) was used to evaluate the urinary control function,the interna-tional index of erectile function (IIEF-5) questionnaire was used to evaluate the erection function of the pa-tients,and EPIC-50 and the american urological associated symptom score rating scale (AUA-SS) were used to evaluate the life satisfaction of the patients.Results The urinary control function recovery rate,erection function recovery rate and life quality satisfaction rate in postoperative 6 weeks,3 months,6 months,12 months were 71.8％,95.5％,97.3％ and 98.1％;31.7％,38.1％,41.3％ and 44.4％;38.9％,83.6％,88.1％ and 97.0％,respectively.The median t-PSA was gradually decreased,which were 0.026(0.010,0.410),0.009 (0.003,0.060),0.006(0.001,0.050)and 0.004(0.001,0.006)ng/mL,respectively.The life quality satisfac-tion rates at various postoperative time points were significantly increased when compared with before opera-tion (P<0.05).t-PSA was significantly decreased compared with before operation (P<0.05).Conclusion RARP could protect the postoperative urinary function and sexual function,and increase the postoperative life quality of the patients.

Human induced pluripotent stem cells (hiPSCs) are promising in regenerative medicine. However, the pluripotent stem cells (PSCs) may form clumps of cancerous tissue, which is a major safety concern in PSCs therapies. Rapamycin is a safe and widely used immunosuppressive pharmaceutical that acts through heterodimerization of the FKBP12 and FRB fragment. Here, we aimed to insert a rapamycin inducible caspase 9 (riC9) gene in a safe harbor AAVS1 site to safeguard hiPSCs therapy by drug induced homodimerization. The donor vector containing an EF1α promoter, a FRB-FKBP-Caspase 9 (CARD domain) fusion protein and a puromycin resistant gene was constructed and co-transfected with sgRNA/Cas9 vector into hiPSCs. After one to two weeks screening with puromycin, single clones were collected for genotype and phenotype analysis. Finally, rapamycin was used to induce the homodimerization of caspase 9 to activate the apoptosis of the engineered cells. After transfection of hiPSCs followed by puromycin screening, five cell clones were collected. Genome amplification and sequencing showed that the donor DNA has been precisely knocked out at the endogenous AAVS1 site. The engineered hiPSCs showed normal pluripotency and proliferative capacity. Rapamycin induced caspase 9 activation, which led to the apoptosis of all engineered hiPSCs and its differentiated cells with different sensitivity to drugs. In conclusion, we generated a rapamycin-controllable hiPSCs survival by homodimerization of caspase 9 to turn on cell apoptosis. It provides a new strategy to guarantee the safety of the hiPSCs therapy.
Humans ; Induced Pluripotent Stem Cells ; Sirolimus/metabolism* ; Caspase 9/metabolism* ; RNA, Guide, CRISPR-Cas Systems ; Pluripotent Stem Cells/metabolism* ; Cell Differentiation ; Puromycin/metabolism*

Objectives:To compare the efficiacy of retro-auricular single-site endoscopic thyroidectomy (RASSET) and that of transoral endoscopic thyroidectomy vestibular approach (TOETVA).Methods:In Department of Head and Neck Surgery, Sun Yat-sen University Cancer Center, 10 patients underwent RASSET from June 2021 to August 2021, and 21 patients underwent TOETVA from January 2016 to August 2021. All the 21 patients′ clinical data was analyzed retrospectively. There were 2 males and 8 females in the RASSET group, aging (48.2±13.9) years (range: 28 to 67 years). There were 5 males and 16 females in the TOETVA group, aging (31.3±8.2) years (range: 21 to 49 years). All patients underwent thyroid lobectomy. A 3 cm in length incision was cut on single auricula posterior sulci to creat the approach in the RASSET group. Then a Trocar made with of a glove was inserted. Retaining the omohyoid, the sternocleidomastoid muscle and anterior cervical muscle were pulled apart, exposing a single lobe of the thyroid gland and lymphatic tissue of zone Ⅵ, for en-bloc resection. The clinical data of the two groups were collected and analyzed by t test, Mann-Whitney U test, Fisher exact test or χ 2 test. Clinical data and postoperative efficacy indexes such as operation time, postoperative C reactive protein level, and postoperative complications were recorded. Results:Compared with the TOETVA group, the operation time was longer in the RASSET group ((256.8±77.0) minutes vs. (201.2±54.9) minutes, t=2.31, P=0.028), and increase of postoperative C reaction protein (24 hours postoperative vs. preoperative) was lower in the RASSET group (8.58(13.24) mg/L vs. 46.24(48.88) mg/L, Z=-4.311, P<0.01). But there was no significant difference between the RASSET group and TOETVA group in the number of lymph nodes dissection (2(5) vs. 2(3), Z=-0.326, P=0.759). Besides, there were no complications in the RASSET group. Conclusion:Retro-auricular single-site endoscopic thyroid loectomy is easy to achieve the en-bloc resection of tumors with a well-concealed scar and less traumatic dissection.

Objectives:To compare the efficiacy of retro-auricular single-site endoscopic thyroidectomy (RASSET) and that of transoral endoscopic thyroidectomy vestibular approach (TOETVA).Methods:In Department of Head and Neck Surgery, Sun Yat-sen University Cancer Center, 10 patients underwent RASSET from June 2021 to August 2021, and 21 patients underwent TOETVA from January 2016 to August 2021. All the 21 patients′ clinical data was analyzed retrospectively. There were 2 males and 8 females in the RASSET group, aging (48.2±13.9) years (range: 28 to 67 years). There were 5 males and 16 females in the TOETVA group, aging (31.3±8.2) years (range: 21 to 49 years). All patients underwent thyroid lobectomy. A 3 cm in length incision was cut on single auricula posterior sulci to creat the approach in the RASSET group. Then a Trocar made with of a glove was inserted. Retaining the omohyoid, the sternocleidomastoid muscle and anterior cervical muscle were pulled apart, exposing a single lobe of the thyroid gland and lymphatic tissue of zone Ⅵ, for en-bloc resection. The clinical data of the two groups were collected and analyzed by t test, Mann-Whitney U test, Fisher exact test or χ 2 test. Clinical data and postoperative efficacy indexes such as operation time, postoperative C reactive protein level, and postoperative complications were recorded. Results:Compared with the TOETVA group, the operation time was longer in the RASSET group ((256.8±77.0) minutes vs. (201.2±54.9) minutes, t=2.31, P=0.028), and increase of postoperative C reaction protein (24 hours postoperative vs. preoperative) was lower in the RASSET group (8.58(13.24) mg/L vs. 46.24(48.88) mg/L, Z=-4.311, P<0.01). But there was no significant difference between the RASSET group and TOETVA group in the number of lymph nodes dissection (2(5) vs. 2(3), Z=-0.326, P=0.759). Besides, there were no complications in the RASSET group. Conclusion:Retro-auricular single-site endoscopic thyroid loectomy is easy to achieve the en-bloc resection of tumors with a well-concealed scar and less traumatic dissection.

Objective:To analyze the effects of various factors on the clinical outcome of artificial insemination with donor sperm (AID) under natural cycles.Methods:A total of 16 458 natural cycles with donor sperm were analyzed from January 2011 to December 2018 in Reproductive Center of Guangdong Province Family Planning Science and Technology Research Institute. The relationship between the clinical outcome and the factors such as the women's character, donor sperm quality and cycle related factors with χ 2 and multiple factor generalized estimating equation. Results:Many factors such as women's age ≤ 30 years ( OR=1.865, P<0.001), the woman's age from 31 to 35 years ( OR=1.215, P<0.001), duration of infertility≤5 ( OR=1.139, P=0.007), day 3 luteining hormone (LH) level>8.10 IU/L ( OR=1.309, P=0.022), day 3 estrogen level≤77.10 pmol/L ( OR=1.301, P=0.012), day 3 estrogen level from 77.11 pmol/L to 293.60 pmol/L ( OR=1.099, P=0.044), one dominant follicle per cycle ( OR=1.473, P=0.038), cervical mucus score ≥10 ( OR=1.256, P=0.026), A type endometrium ( OR=1.114, P=0.005), urinary LH strong positive ( OR=1.171, P=0.002), sperm activity ratio more than 54% after thawing ( OR=1.142, P=0.002), progressively motile sperm number ≥ 35×10 6 after thawing ( OR=1.217, P=0.001) and double inseminations per cycle ( OR=1.376, P=0.001) significantly affected the pregnancy rates of AID women under natural cycles. Conclusion:Many factors such as the woman's age, duration of infertility, day 3 LH level, day 3 estrogen level, dominant follicle number per cycle, cervical mucus score, endometrial type, sperm activity ratio after thawing, progressively motile sperm number and insemination times per cycle can affect the women’s pregnancy rate under AID natural cycles.

Objective:To analyze the effects of various factors on the clinical outcome of artificial insemination with donor sperm (AID) under natural cycles.Methods:A total of 16 458 natural cycles with donor sperm were analyzed from January 2011 to December 2018 in Reproductive Center of Guangdong Province Family Planning Science and Technology Research Institute. The relationship between the clinical outcome and the factors such as the women's character, donor sperm quality and cycle related factors with χ 2 and multiple factor generalized estimating equation. Results:Many factors such as women's age ≤ 30 years ( OR=1.865, P<0.001), the woman's age from 31 to 35 years ( OR=1.215, P<0.001), duration of infertility≤5 ( OR=1.139, P=0.007), day 3 luteining hormone (LH) level>8.10 IU/L ( OR=1.309, P=0.022), day 3 estrogen level≤77.10 pmol/L ( OR=1.301, P=0.012), day 3 estrogen level from 77.11 pmol/L to 293.60 pmol/L ( OR=1.099, P=0.044), one dominant follicle per cycle ( OR=1.473, P=0.038), cervical mucus score ≥10 ( OR=1.256, P=0.026), A type endometrium ( OR=1.114, P=0.005), urinary LH strong positive ( OR=1.171, P=0.002), sperm activity ratio more than 54% after thawing ( OR=1.142, P=0.002), progressively motile sperm number ≥ 35×10 6 after thawing ( OR=1.217, P=0.001) and double inseminations per cycle ( OR=1.376, P=0.001) significantly affected the pregnancy rates of AID women under natural cycles. Conclusion:Many factors such as the woman's age, duration of infertility, day 3 LH level, day 3 estrogen level, dominant follicle number per cycle, cervical mucus score, endometrial type, sperm activity ratio after thawing, progressively motile sperm number and insemination times per cycle can affect the women’s pregnancy rate under AID natural cycles.