Efficacy Analysis of Bortezomib Combined with Lenalidomide in Newly Diagnosed Multiple Myeloma with 1q21 Gain/Amp.

OBJECTIVE: 1q21 gain/Amp is one of the most common cytogenetic abnormalities. There are controversies about its effects on prognosis and may be associated with inferior outcomes in patients with newly diagnosed multiple myeloma (NDMM). To explore the optimal induction treatment, we analyzed and compared the efficacy of combinations of bortezomib-lenalidomide-dexamethasone (VRD) and only bortezomib-based triplet regimens without lenalidomide (only bortezomib-based) as induction therapy in patients with NDMM with 1q21 gain/Amp. METHODS: Seventy-six NDMM patients with 1q21 gain/Amp who were admitted to our center from 2016 to 2022 were retrospectively analyzed in this study. The progression and efficacy of the patients were observed. RESULTS: Within our study group, the overall survival rate stood at 75.0%, and the progression-free survival (PFS) rate reached 40.8% in NDMM patients with 1q21 gain/Amp. The best outcome assessment was that 17.1% achieved complete response (CR) and 44.7% achieved very good partial response (VGPR). Patients in the VRD group had a deeper response (VGPR: 63.6% vs 37.0%, P = 0.034), lower disease progression rate (31.8% vs 70.3%, P = 0.002), longer sustained remission (median 49.7 months vs 18.3 months, P = 0.030), and longer PFS (median 61.9 months vs 22.9 months, P = 0.032) than those treated with only bortezomib-based induction therapy. No significant differences were found among patients with partial response or better (86.4% vs 77.8%, P = 0.532) or CR (27.3% vs 13.0%, P = 0.180). Multivariate analysis showed that only bortezomib-based induction therapy (P = 0.003, HR 0.246, 95% CI 0.097-0.620), International Staging System stage III (P = 0.003, HR 3.844, 95% CI 1.588-9.308) and LMR <3.6 (P = 0.032, HR 0.491, 95% CI 0.257-0.940) were significantly associated with adverse PFS. CONCLUSIONS: When compared with the sequential administration of bortezomib and lenalidomide or only bortezomib-based protocols, NDMM patients with 1q21 gain/Amp may benefit more from VRD as initial treatments.

The multifaceted mechanisms of Dihydrotanshinone I in the treatment of tumors.

The morbidity and mortality of malignant tumors are progressively rising on an annual basis. Traditional Chinese Medicine (TCM) holds promise as a possible therapeutic agent for the avoidance or therapy of malignant tumors. Salvia miltiorrhiza Bunge (Danshen), a traditional Asian functional food, has therapeutic characteristics in application for the treatment of malignant tumors. Dihydrotanshinone I (DHTS) is the principal lipophilic phenanthraquinone compound found in Salvia miltiorrhiza Bunge, whose anti-tumor effect has attracted widespread attention. The anti-tumor effects include inhibiting cancer cell proliferation, triggering apoptosis of tumor cells, inducing ferroptosis in tumor cells, inhibiting tumor cell invasion and metastasis, and improving drug resistance of tumor cells. In this paper, we summarized and analyzed the mechanisms and targets of anti-tumor effect of DHTS, providing new ideas and establishing a solid theoretical basis for the future advancement and clinical treatment of DHTS.

Research progress of traditional Chinese medicine in the treatment of allergic rhinitis.

Allergic rhinitis, one of the common diseases in otolaryngology, has shown an increasing incidence under the influence of various geographical, cultural and economic factors, making it a common and serious global public health problem. Modern medicine uses medication as the primary therapy for allergic rhinitis, but poor symptom control and easy relapse are the disadvantages of this treatment. However, Traditional Chinese medicine, with its long history, has treated allergic rhinitis by symptomatic treatment according to pattern differentiation with its unique insights and methods, which are effective and safe in numerous clinical studies. Therefore, this paper describes TCM decoction, acupuncture, moxibustion, acupoint application, catgut-embedding therapy and ear acupuncture in the treatment of AR. This study aims to provide more personalized and precise treatment for allergic rhinitis patients by investigating the mechanism of action, clinical research and development of traditional Chinese medicine treatments.

Knowledge, Attitude, and Practice About Antibiotic Use and Antimicrobial Resistance Among Nursing Students in China: A Cross Sectional Study.

Purpose: The knowledge, attitude, and practices (KAP) concerning antibiotics by healthcare students have the potential impact on controlling antibiotic abuse and antimicrobial resistance (AMR) growth. This study aims to evaluate the levels and explore the associated factors with KAP on antibiotic use and AMR in Chinese nursing students. Methods: A cross-sectional survey using a self-administered questionnaire consisting of demographics and selected features and KAP on antibiotic use and AMR was conducted to measure KAP levels among nursing students at various universities in Hubei Province, China. The logistic regression analyses were performed to analyze the potential factors associated with the KAP. Results: The survey eventually included a total of 1959 nursing students. The mean scores for KAP were 57.89 ±26.32, 55.00 ±12.50, and 71.88 ±15.63, respectively. Regarding knowledge, 54.3% of participants were unaware that antibiotic was ineffective against viral infections. Regarding attitude, 36% of participants agreed that current antibiotic abuse existed; 96.2% of participants thought it necessary to set up a special course on antibiotics. Regarding practice, only 48.4% of participants usually purchased antibiotics with a prescription. Multivariable analyses indicated that lack of discussion on AMR in school courses was an independent risk factor against KAP, respectively. The main knowledge sources of antibiotic being outside the classroom was an independent risk factor related to knowledge and practice. The average score >80 points was an independent protective factor related to knowledge and practice. Conclusion: The KAP level on antibiotic use and AMR among Hubei nursing students was general and required further strengthening. Nursing students with risk factors should be prioritized in educational interventions. The findings of our study pointed out some directions for tailored interventions to improve the training on antibiotics.

Activation of ERß hijacks the splicing machinery to trigger R-loop formation in triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is a subtype of breast cancer with aggressive behavior and poor prognosis. Current therapeutic options available for TNBC patients are primarily chemotherapy. With our evolving understanding of this disease, novel targeted therapies, including poly ADP-ribose polymerase (PARP) inhibitors, antibody-drug conjugates, and immune-checkpoint inhibitors, have been developed for clinical use. Previous reports have demonstrated the essential role of estrogen receptor ß (ERß) in TNBC, but the detailed molecular mechanisms downstream ERß activation in TNBC are still far from elucidated. In this study, we demonstrated that a specific ERß agonist, LY500307, potently induces R-loop formation and DNA damage in TNBC cells. Subsequent interactome experiments indicated that the residues 151 to 165 of U2 small nuclear RNA auxiliary factor 1 (U2AF1) and the Trp439 and Lys443 of ERß were critical for the binding between U2AF1 and ERß. Combined RNA sequencing and ribosome sequencing analysis demonstrated that U2AF1-regulated downstream RNA splicing of 5-oxoprolinase (OPLAH) could affect its enzymatic activity and is essential for ERß-induced R-loop formation and DNA damage. In clinical samples including 115 patients from The Cancer Genome Atlas (TCGA) and 32 patients from an in-house cohort, we found a close correlation in the expression of ESR2 and U2AF1 in TNBC patients. Collectively, our study has unraveled the molecular mechanisms that explain the therapeutic effects of ERß activation in TNBC, which provides rationale for ERß activation-based single or combined therapy for patients with TNBC.

N6-methyladenosine (m6A) modification in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the deadliest cancers of human, the tumor-related death of which ranks third among the common malignances. N6-methyladenosine (m6A) methylation, the most abundant internal modification of RNA in mammals, participates in the metabolism of mRNA and interrelates with ncRNAs. In this paper, we overviewed the complex function of m6A regulators in HCC, including regulating the tumorigenesis, progression, prognosis, stemness, metabolic reprogramming, autophagy, ferroptosis, drug resistance and tumor immune microenvironment (TIME). Furthermore, we elucidated the interplay between m6A modification and non-coding RNAs (ncRNAs), including microRNAs (miRNAs), long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs). Finally, we summarized the potential of m6A regulators as diagnostic biomarkers. What's more, we reviewed the inhibitors targeting m6A enzymes as promising therapeutic targets of HCC. We aimed to help understand the function of m6A methylation in HCC systematically and comprehensively so that more effective strategies for HCC treatment will be developed.

Establishment of self-reported hearing cut-off value on the Chinese version of short form of speech, spatial and qualities of hearing scale (SSQ12).

OBJECTIVE: The aim of this study was to evaluate the efficacy of the Chinese version of Speech, Spatial and Qualities of Hearing Scale (C-SSQ12) in the Chinese Mandarin-speaking population and to determine its screening cut-off value by comparing measured pure-tone average (PTA), the Hearing Handicap Inventory for the Elderly-Screening Version (HHIE-S) scores and C-SSQ12 scores. DESIGN: All participants completed the C-SSQ12 questionnaire and underwent the pure-tone audiometry. Older subjects aged ≧ 60 years completed the HHIE-S questionnaire. The optimal cut-off value for the C-SSQ12 as a hearing screening tool was calculated by comparing different cut-offs and hearing thresholds. STUDY SAMPLE: A total of 300 subjects were recruited. RESULTS: There was a negative correlation between C-SSQ12 scores and HHIE-S scores (r = -0.749). C-SSQ12 scores were negatively correlated with PTA (r = -0.507; r = -0.542). The best cut-off value for the C-SSQ12 was 6.0, with a sensitivity of 78.2%, specificity of 80.3%, positive predictive value of 63.7% and negative predictive value of 97.0% (PTA > 40dBHL for bilateral ears). CONCLUSIONS: Compared to mild hearing loss, the C-SSQ12 is a reliable and validated hearing screening tool with increased sensitivity for detecting moderate-to-severe hearing loss.

Recurrent miscarriage and low-titer antiphospholipid antibodies.

OBJECTIVE: To evaluate the clinical features and pregnancy outcomes in patients experiencing recurrent miscarriage (RM) with either low-titer or medium-high titer positivity of antiphospholipid antibodies (aPL). METHODS: A retrospective review of medical records was conducted for patients with aPL positivity and recurrent miscarriage between 2018 and 2022. The clinical features, treatment strategies, outcomes were compared between the patients with low (n = 92) and medium (n = 32) titer of aPL. RESULTS: A total of 118 patients, resulting in 124 obstetric episodes (pregnancies), with a mean age of 33. 15 ± 4.56 and 31.47 ± 4.41 years between the two groups. The low-titer group exhibited a higher frequency of anti-cardiolipin antibodies IgM (P < 0.001), whereas the medium-high titer group demonstrated a higher frequency of anti-ß2-glycoprotein 1 antibodies IgG (P < 0.001) and IgM (P = 0.032). Moreover, the medium-high titer group displayed a significantly elevated erythrocyte sedimentation rate compared to the low-titer group (P < 0.05). In the low-titer group, 71 patients (77.2%) received appropriate treatment, resulting in 48 live births (67.6%) and 23 repeat abortions (32.4%). In the medium-high titer group, 29 patients (90.6%) received relevant treatment, leading to 23 live births (79.3%) and 6 repeat abortions (20.7%). No significant differences were observed in live births or maternal-fetal complications between the two groups (all P > 0.05). CONCLUSION: Noteworthy distinctions in laboratory parameters were identified between the low-titer and medium-high titer groups. However, when appropriately treated, the fetal-maternal outcomes were comparable in both groups. Timely intervention by clinicians is imperative to enhance pregnancy outcomes in patients experiencing recurrent miscarriage with low levels of aPL. Key Points • This study challenges the conventional belief that only the higher antiphospholipid antibodies (aPL) titers directly correlated with worse pregnancy outcomes, which emphasized the importance of patients with low titer positive aPL-positive RM. • The results underscore the need for timely intervention in women with low titer aPL-positive RM, as it leads to favorable maternal-fetal outcomes.

Knowledge, attitudes and practices towards the diagnosis and management of paediatric sepsis among paediatric physicians and nurses: a cross-sectional study of 21 hospitals in Hubei Province, China.

OBJECTIVES: To evaluate the knowledge, attitudes and practices towards diagnosing and managing paediatric sepsis among paediatric physicians and nurses. DESIGN: A cross-sectional, questionnaire-based study. SETTING: 21 hospitals in Hubei Province between February 2023 and March 2023. PARTICIPANTS: Paediatric physicians and nurses. INTERVENTIONS: None. PRIMARY AND SECONDARY OUTCOME MEASURES: The questionnaire contained 35 items across four dimensions (demographic information, knowledge, attitude and practice). RESULTS: The study included 295 participants (173 women). The average knowledge, attitude and practice scores were 10.93±2.61 points (possible range, 0-20 points), 32.22±2.65 points (possible range, 7-35 points) and 36.54±5.24 points (possible range, 9-45 points), respectively. Knowledge had a direct influence on both attitude (ß=0.240, 95% CI 0.136 to 0.365, p=0.009) and practice (ß=0.278, 95% CI 0.084 to 0.513, p=0.010), which also indirectly influenced practice through attitude (ß=0.162, 95% CI 0.078 to 0.290, p=0.007). Attitude directly influenced practice (ß=0.677, 95% CI 0.384 to 0.902, p=0.025). A higher attitude score was associated with good practice (OR=1.392; 95% CI 1.231 to 1.576; p<0.001), while not working in a tertiary hospital reduced the odds of good practice (OR=0.443; 95% CI 0.2390.821; p=0.010). CONCLUSIONS: The knowledge regarding paediatric sepsis, especially knowledge about sepsis management, is poor among paediatric physicians and nurses in Hubei Province. The findings of this study may facilitate the development and implementation of training programmes to improve the diagnosis and management of paediatric sepsis.

Association between alcohol consumption and sleep traits: observational and mendelian randomization studies in the UK biobank.

Previous studies have shown that excessive alcohol consumption is associated with poor sleep. However, the health risks of light-to-moderate alcohol consumption in relation to sleep traits (e.g., insomnia, snoring, sleep duration and chronotype) remain undefined, and their causality is still unclear in the general population. To identify the association between alcohol consumption and multiple sleep traits using an observational and Mendelian randomization (MR) design. Observational analyses and one-sample MR (linear and nonlinear) were performed using clinical and individual-level genetic data from the UK Biobank (UKB). Two-sample MR was assessed using summary data from genome-wide association studies from the UKB and other external consortia. Phenotype analyses were externally validated using data from the National Health and Nutrition Examination Survey (2017-2018). Data analysis was conducted from January 2022 to October 2022. The association between alcohol consumption and six self-reported sleep traits (short sleep duration, long sleep duration, chronotype, snoring, waking up in the morning, and insomnia) were analysed. This study included 383,357 UKB participants (mean [SD] age, 57.0 [8.0] years; 46% male) who consumed a mean (SD) of 9.0 (10.0) standard drinks (one standard drink equivalent to 14 g of alcohol) per week. In the observational analyses, alcohol consumption was significantly associated with all sleep traits. Light-moderate-heavy alcohol consumption was linearly linked to snoring and the evening chronotype but nonlinearly associated with insomnia, sleep duration, and napping. In linear MR analyses, a 1-SD (14 g) increase in genetically predicted alcohol consumption was associated with a 1.14-fold (95% CI, 1.07-1.22) higher risk of snoring (P < 0.001), a 1.28-fold (95% CI, 1.20-1.37) higher risk of evening chronotype (P < 0.001) and a 1.24-fold (95% CI, 1.13-1.36) higher risk of difficulty waking up in the morning (P < 0.001). Nonlinear MR analyses did not reveal significant results after Bonferroni adjustment. The results of the two-sample MR analyses were consistent with those of the one-sample MR analyses, but with a slightly attenuated overall estimate. Our findings suggest that even low levels of alcohol consumption may affect sleep health, particularly by increasing the risk of snoring and evening chronotypes. The negative effects of alcohol consumption on sleep should be made clear to the public in order to promote public health.

PROTECTIVE ROLE OF MELATONIN FOR ACUTE KIDNEY INJURY: A SYSTEMATIC REVIEW AND META-ANALYSIS.

ABSTRACT: Introduction : Acute kidney injury (AKI) is an important clinical issue that arouses global concerns, which puzzles clinicians and lacks effective drug treatment for AKI until the present. Melatonin has been well recognized to modulate the sleep-wake cycle and had the renal protective effect. However, there are still few clinical trials investigating the relationship between melatonin and AKI. The conclusions drawn in existing clinical studies are still inconsistent. The study systematically reviewed and assessed the efficacy of melatonin in preventing AKI. Methods : A systematic literature search was conducted in the PubMed, Embase, and Cochranelibrary on May 19, 2023. Eligible records were screened according to the inclusion and exclusion criteria. The risk ratio and the corresponding 95% confidence intervals were selected to evaluate the effects of melatonin on AKI. We pooled extracted data using a fixed- or random effects model based on a heterogeneity test. Results : Six randomized controlled trials regarding the use of melatonin in preventing kidney injury met our inclusion criteria. The pooled results showed that melatonin increased the estimated glomerular filtration rate, and effectively inhibited the occurrence of AKI. Melatonin tended to reduce the serum creatinine and urea nitrogen levels, but there was no statistical significance. Conclusions : Melatonin can increase the estimated glomerular filtration rate and effectively inhibit the occurrence of AKI. More well-designed randomized controlled trials are needed to verify the protective effect of melatonin in the future.

miR-148a and miR-551b-5p regulate inflammatory responses via regulating autophagy in acute pancreatitis.

Acute pancreatitis (AP) is a common inflammatory response that occurs in the pancreas with mortality rates as high as 30 %. However, there is still no consistent and effective treatment for AP now. MicroRNA-148 was reported to be involved in AP through IL-6 signaling pathway. Therefore, we aimed to further explore the detailed mechanisms of AP, to develop more therapeutic approach for AP. Exosomes were isolated from peripheral blood mononuclear cells of 20 AP patients and 20 healthy volunteers to evaluate the abnormally expressed miRNA. Then pancreatic acinar cells (PACs) were transfected with retrovirus to overexpress miR-148a/miR-551b-5p to evaluate their function. Both miR-148a and miR-551b-5p were highly expressed in AP patients than these in healthy cases. Then overexpressing miR-551b-5p in PACs could regulate autophagy through directly binding to Baculoviral IAP Repeat Containing 6, leading to the increased secretions of interleukin-1ß (IL-1ß) and interleukin-18 (IL-18) through interleukin-1 (IL-1) signaling pathway. Moreover, overexpressing miR-148a in PACs could decrease the secretions of IL-1ß and IL-18 to modulate autophagy. The exosomal miRNA-148a and miRNA-551b-5p derived from peripheral blood mononuclear cells of AP patients may two-way mediate autophagy damage through IL-6/STAT3 signaling pathway, which participated in the AP pathogenesis. Our findings may provide new targets for the diagnosis and treatment of AP.

Dual-mode tunable absorber based on quasi-bound states in the continuum.

In this Letter, we propose a novel, to the best of our knowledge, dual-mode tunable absorber that utilizes quasi-bound states in the continuum (q-BIC) based on the periodically arranged silicon cylinders tetramer. By introducing asymmetry perturbation through manipulating the diameters of diagonal cylinders in the all-dielectric structure, the symmetry-protected BIC (SP-BIC) transforms into q-BIC, leading to the emergence of one transmission and one reflection Fano-like resonant mode. The relationship between the quality factor of each mode and the asymmetry parameter α is analyzed, revealing an exponential dependence with an exponent of -1.75, i.e., Q ∝ α-1.75. To explain the underlying physics, multipole decomposition analysis and Aleksandra's theory are applied. Subsequently, a monolayer graphene is introduced to the all-dielectric structure to demonstrate the application of the dual-mode tunable absorber. When the critical coupling condition is satisfied, each mode can achieve the theoretical maximum absorption, demonstrating the distinctive capability of our proposed absorber for tuning and efficient light absorption. This research provides valuable insights into light-matter interactions and opens up possibilities for optical modulation and the development of graphene-based devices.

Effect of individualized nutrition interventions on clinical outcomes of pregnant women with gestational diabetes mellitus.

BACKGROUND: Gestational diabetes mellitus (GDM) can lead to excessive pregnancy weight gain (PWG), abnormal glucolipid metabolism, and delayed lactation. Therefore, it is necessary to provide appropriate and effective interventions for pregnant women with GDM. AIM: To clarify the effects of individualized nutrition interventions on PWG, glucolipid metabolism, and lactation in pregnant women with GDM. METHODS: The study population consisted of 410 pregnant women with GDM who received treatment at the Northern Jiangsu People's Hospital of Jiangsu Province and Yangzhou Maternal and Child Health Hospital between December 2020 and December 2022, including 200 who received routine in-terventions [control (Con) group] and 210 who received individualized nutrition interventions [research (Res) group]. Data on PWG, glucolipid metabolism [total cholesterol, (TC); triglycerides (TGs); fasting blood glucose (FPG); glycosylated hemoglobin (HbA1c)], lactation time, perinatal complications (cesarean section, premature rupture of membranes, postpartum hemorrhage, and pregnancy-induced hypertension), and neonatal adverse events (premature infants, fetal macrosomia, hypo-glycemia, and respiratory distress syndrome) were collected for comparative analysis. RESULTS: The data revealed markedly lower PWG in the Res group vs the Con group, as well as markedly reduced TG, TC, FPG and HbA1c levels after the intervention that were lower than those in the Con group. In addition, obviously earlier lactation and statistically lower incidences of perinatal complications and neonatal adverse events were observed in the Res group. CONCLUSION: Individualized nutrition interventions can reduce PWG in pregnant women with GDM, improve their glucolipid metabolism, and promote early lactation, which deserves clinical promotion.

Current knowledge on the role of extracellular vesicles in endometrial receptivity.

Endometrial receptivity has been widely understood as the capacity of the endometrium to receive implantable embryos. The establishment of endometrial receptivity involves multiple biological processes including decidualization, tissue remodeling, angiogenesis, immune regulation, and oxidative metabolism. Extracellular vesicles (EVs) are lipid-bilayer-membrane nanosized vesicles mediating cell-to-cell communication. Recently, EVs and their cargo have been proven as functional factors in the establishment of endometrial receptivity. In this review, we comprehensively summarized the alteration of endometrium/embryo-derived EVs during the receptive phase and retrospected the current findings which revealed the pivotal role and potential mechanism of EVs to promote successful implantation. Furthermore, we highlight the potentiality and limitations of EVs being translated into clinical applications such as biomarkers of endometrial receptivity or reproductive therapeutic mediators, and point out the direction for further research.

The Effect of Latent Tuberculosis Infection on Ovarian Reserve and Pregnancy Outcomes among Infertile Women Undergoing Intrauterine Insemination: A Retrospective Cohort Study with Propensity Score Matching.

Latent tuberculosis infection (LTBI) widely exists in patients with unexplained infertility, and whether LTBI would affect the ovarian reserve and pregnancy outcome of infertile women undergoing intrauterine insemination (IUI) is still unknown. A single-center, retrospective, cohort study was designed that included infertile women undergoing IUI at the Department of Reproductive Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology in Wuhan, China, from January 2018 to December 2020. The primary outcomes of this study were ovarian reserve and live birth rate. Secondary outcomes included pregnancy outcomes and maternal and neonatal complications. As a result, 3066 IUI cycles were eventually enrolled in this study. Of these women, 9.6% (295/3066) had LTBI evidence. After propensity score matching (PSM), there was no significant difference in the baseline between the LTBI and non-LTBI groups. The data showed that women who had LTBI had trends toward lower biochemical pregnancy rates (12.9% vs. 17.7%, p-value 0.068), lower clinical pregnancy rates (10.8% vs. 15.1%, p-value 0.082) and lower live birth rates (8.1% vs. 12.1%, p-value 0.076), with no significant differences. There were also no significant differences in ovarian reserve and other secondary outcomes between the two groups. In conclusion, there were no significant differences in ovarian reserve, perinatal or neonatal complications between women with and without LTBI. Women with LTBI tended to have worse pregnancy outcomes after receiving IUI, but the difference was not significant.

Laparoscopic cholecystectomy for giant gallbladder: A case report.

RATIONALE: An overdistended gallbladder is usually observed in cases of distal bile obstruction due to malignancy. The gallbladder may also become enlarged and distended during cystic duct or gallbladder neck obstruction due to gallstones. However, a grossly distended gallbladder ( > 14 cm in length) without any pathology is rare. We present the case of a 46-year-old female patient who suffered from acute right lower quadrant pain for 4 days. Initially, a liver cyst and a choledochal cyst were diagnosed by the local hospital. Then, the diagnosis of giant gallbladder (measuring approximately 20.0 cm × 7.0 cm and containing more than 30 gallbladder stones) was made by magnetic resonance cholangiopancreatography at our hospital. Finally, we successfully performed a laparoscopic cholecystectomy and the patient had an uneventful recovery. PATIENT CONCERNS: A 46-year-old female patient presented with acute right lower quadrant pain lasting 4 days. At first, the abdominal pain was severe and paroxysmal, and then it subsided spontaneously. Computed tomography of the abdomen at another hospital revealed a hepatic cyst and a choledochal cyst. Come to our hospital for surgical treatment. DIAGNOSES: giant gallbladder with gallstones. INTERVENTIONS: Laparoscopic cholecystectomy was successfully performed in this patient after decompressing the gallbladder. OUTCOMES: On the third postoperative day, the patient recovered well, and the abdominal pain resolved following the operation. At the 3-year postoperative follow-up, the patient was symptom-free, with no obvious abnormalities seen in liver function and hepatobiliary color Doppler ultrasound. LESSONS: The patient was successfully treated using laparoscopic cholecystectomy. This rare case may contribute to the development of mechanisms for treating giant gallbladders.

Impact of growth hormone on IVF/ICSI outcomes and endometrial receptivity of patients undergoing GnRH antagonist protocol with fresh embryo transfer: a pilot study.

Introduction: Gonadotropin-releasing hormone antagonist (GnRH-ant) protocol is widely used in the world for controlled ovarian hyperstimulation (COH). However, previous studies have shown that pregnancy outcomes of fresh embryo transfer with GnRH-ant protocol are not ideal. Current studies have demonstrated the value of growth hormone (GH) in improving the pregnancy outcome of elderly women and patients with diminished ovarian reserve, but no prospective studies have confirmed the efficacy of GH in fresh embryo transfer with GnRH-ant protocol, and its potential mechanism is still unclear. This study intends to evaluate the impact of GH on IVF/ICSI outcomes and endometrial receptivity of patients undergoing GnRH-ant protocol with fresh embryo transfer, and preliminarily explore the possible mechanism. Methods: We designed a randomized controlled trial of 120 infertile patients with normal ovarian response (NOR) who will undergo IVF/ICSI from April 2023 to April 2025, at Department of Reproductive Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology. The patients will be divided into the depot gonadotropin-releasing hormone agonist (GnRH-a) protocol group, GnRH-ant protocol control group, and GnRH-ant protocol plus GH intervention group at a ratio of 1:1:1 by block randomization design. Patients will be followed on enrollment day, trigger day, embryo transfer day, 7 days after oocytes pick-up, 15 days after embryo transfer, 28 days after embryo transfer, and 12 weeks of gestation. The primary outcome is the ongoing pregnancy rate. Secondary outcomes include the gonadotropin dosage, duration of COH, endometrial thickness and pattern, luteinizing hormone, estradiol, progesterone level on trigger day, numbers of retrieved oocytes, high-quality embryo rate, biochemical pregnancy rate, clinical pregnancy rate, implantation rate, ectopic pregnancy rate, early miscarriage rate, multiple pregnancy rate and incidence of moderate and severe ovarian hyperstimulation syndrome. The endometrium of certain patients will be collected and tested for endometrial receptivity. Ethics and dissemination: The study was approved by the Ethics Committee of Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology [approval number: TJ-IRB20230236; approval date: February 10, 2023]. The research results will be presented at scientific/medical conferences and published in academic journals. Clinical trial registration: Chinese Clinical Trial Registry; identifier: ChiCTR2300069397.

Comparison of Cumulative Live Birth Rates between Flexible and Conventional Progestin-Primed Ovarian Stimulation Protocol in Poor Ovarian Response Patients According to POSEIDON Criteria: A Cohort Study.

RESEARCH QUESTION: To compare the cumulative live birth rate (CLBR) per oocyte retrieval cycle of a conventional progestin-primed ovarian stimulation (cPPOS) regimen with a flexible progestin-primed ovarian stimulation (fPPOS) regimen in poor ovarian response patients, according to POSEIDON criteria. DESIGN: Poor ovarian response women, according to POSEIDON criteria, who underwent the first PPOS protocol for in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) between January 2018 and December 2020 were included. The fPPOS group involved 113 participants, and the cPPOS group included 1119 participants. In the cPPOS group, medroxyprogesterone acetate (MPA) (10 mg/d) was administrated on the gonadotropin injection the same day as gonadotropin injections in the cPPOS group, while MPA was started either on the day when the leading follicle with mean diameter > 12mm was present and/or serum E2 was >300 pg/mL in the fPPOS protocol group. The primary outcome was CLBR. RESULTS: The fPPOS protocol had higher CLBR per oocyte retrieval cycle compared to the cPPOS group, even without a statistically significant difference (29.6% vs. 24.9%, p = 0.365). The fPPOS group had fewer numbers of retrieved oocytes (2.87 ± 2.03 vs. 3.76 ± 2.32, p < 0.001) but a higher MII oocyte rate (89.8% vs. 84.7%, p = 0.016). In addition, the number of available embryos in the two groups was comparable (1.37 ± 1.24 vs. 1.63 ± 1.38, p = 0.095). There were five women in the fPPOS group, and 86 women in the cPPOS group had a premature LH surge (4.2% vs. 6.8%, p = 0.261). In the fPPOS group, there was one instance of premature ovulation, while in the cPPOS group, there were six occurrences of premature ovulation (0.8 vs. 0.5%, p = 1.000). CONCLUSION(S): The novel fPPOS protocol appears to achieve higher CLBR even without significant differences and with MPA consumption compared with cPPOS protocol in low-prognosis patients.

Biomechanical evaluation of a novel individualized zero-profile cage for anterior cervical discectomy and fusion: a finite element analysis.

Introduction: Anterior cervical discectomy and fusion (ACDF) is a standard procedure for treating symptomatic cervical degenerative disease. The cage and plate constructs (CPCs) are widely employed in ACDF to maintain spinal stability and to provide immediate support. However, several instrument-related complications such as dysphagia, cage subsidence, and adjacent segment degeneration have been reported in the previous literature. This study aimed to design a novel individualized zero-profile (NIZP) cage and evaluate its potential to enhance the biomechanical performance between the instrument and the cervical spine. Methods: The intact finite element models of C3-C7 were constructed and validated. A NIZP cage was designed based on the anatomical parameters of the subject's C5/6. The ACDF procedure was simulated and the CPCs and NIZP cage were implanted separately. The range of motion (ROM), intradiscal pressure (IDP), and peak von Mises stresses of annulus fibrosus were compared between the two surgical models after ACDF under four motion conditions. Additionally, the biomechanical performance of the CPCs and NIZP cage were evaluated. Results: Compared with the intact model, the ROM of the surgical segment was significantly decreased for both surgical models under four motion conditions. Additionally, there was an increase in IDP and peak von Mises stress of annulus fibrosus in the adjacent segment. The NIZP cage had a more subtle impact on postoperative IDP and peak von Mises stress of annulus fibrosus in adjacent segments compared to CPCs. Meanwhile, the peak von Mises stresses of the NIZP cage were reduced by 90.0-120.0 MPa, and the average von Mises stresses were reduced by 12.61-17.56 MPa under different motion conditions. Regarding the fixation screws, the peak von Mises stresses in the screws of the NIZP cage increased by 10.0-40.0 MPa and the average von Mises stresses increased by 2.37-10.10 MPa. Conclusion: The NIZP cage could effectively reconstruct spinal stability in ACDF procedure by finite element study. Compared with the CPCs, the NIZP cage had better biomechanical performance, with a lower stress distribution on the cage and a more moderate effect on the adjacent segmental discs. Therefore, the NIZP cage could prevent postoperative dysphagia as well as decrease the risk of subsidence and adjacent disc degeneration following ACDF. In addition, this study could serve as a valuable reference for the development of personalized instruments.