BACKGROUND:Establishing an objective and standard animal model of bone nonunion is essential for experimental studies and treatment of nonunion. OBJECTIVE:To establish an objective animal model for experimental studies of nonunion. METHODS:Specific pathogen-free male Wistar rats were selected and prepared by cutting off a 5 mm bone defect in the middle femur,peeling off a large periosteum and removing bone marrow.Animal models were fixed with a 1.2 mm Kirschner wire.At 1,4 and 8 weeks,bone nonunion was observed by gross specimen observation,X-ray examination and histopathological examination. RESULTS AND CONCLUSION:The gross specimen,X-ray film and histopathological examination showed that there was no callus formation in the bone defect area,the broken end was filled with fiber tissue,and the bone callus was rare or even invisible.To conclude,the rat model of nonunion can be successfully established by osteotomy of the middle femur,large periosteum peeling and bone marrow removal.This modeling method is simple,reliable and effective.

The relationship between the duration of type 2 diabetes mellitus (T2DM) and the risk of female reproductive malignancies is complex and multifaceted. Large population cohort studies revealed a negative association between the duration of T2DM and the incidence of breast cancer and endometrial cancer. Furthermore, the risk of breast and endometrial cancer is the highest within a short time after T2DM diagnosis and remains remarkably higher in patients with longer diabetes duration than in the nondiabetic population. This phenomenon suggests causal reverse bias and potential detection bias. Nevertheless, T2DM remains an important risk factor for breast and endometrial cancer. Research on the association between diabetes with cervical and ovarian cancer is limited, and results vary by region. Future epidemiological studies should focus on large prospective studies with long follow-up to further investigate this association. Research into the biological mechanisms linking diabetes and female reproductive cancers is also necessary to develop effective cancer prevention and early intervention strategies.

Liver cancer is a significant global disease burden with a major impact on population health,and it is one of the important concerns in terms of public health worldwide.Cancer risk prediction models can estimate an individual's absolute risk of developing cancer.Individual risk assessment allows targeted screening of high-risk populations,which is essential for primary and secondary cancer prevention.In this review,we examine existing epidemiological studies to explore key issues in the design,predictive variables,and performance of risk prediction models for liver cancer in the general population.The aim is to provide an important reference for the future development of highly comprehensive liver cancer risk prediction models.

Gynecological cancer significantly affect the health of women.This review aimed to describe the global patterns and trends in the survival of patients with gynecological cancers.We searched PubMed,Embase,Web of Science,SinoMed,and SEER for survival analyses of cancer registration data of cervical,endometrial,and ovarian cancers published between 1980 and 2022.Globally,the highest 5-year observed survival rate for cervical cancer was 76.5%in Anshan,Liaoning,China(2008-2017).The 5-year observed survival rates of endometrial and ovarian cancers were higher in Finland(1995-1999,82.5%)and Singapore(1988-1992,62.0%).The 5-year relative survival rate of cervical cancer patients was higher in Haining,Zhejiang,China(2011-2014,85.8%).Korea ranked first at 89.0%and 64.5%for endometrial and ovarian cancers,respectively.Survival rates have improved for cervical,endometrial,and ovarian cancers.Patients aged≥75 years and those with advanced-stage disease had the worst 5-year survival rates.Survival rates were better for squamous cell carcinoma in cervical cancer,for endometrial carcinoma and mucinous adenocarcinoma in endometrial cancer,and for germ cell and sex-cord stromal tumors in ovarian cancer.Over the past four decades,the survival rates of gynecological cancers have increased globally,with notable increases in cervical and endometrial cancers.Survival rates are higher in developed countries,with a slow-growing trend.Future studies should focus on improving survival,especially in ovarian cancer patients.

Objective:To evaluate the clinical efficacy of Xiaoqinglong Decoction Granules in the treatment of chronic persistent cold syndrome of bronchial asthma; To explore its treatment mechanism.Methods:A randomized double-blind controlled study was performed. Totally 60 patients from the Respiratory Department of Guang'anmen Hospital, Chinese Academy of Traditional Chinese Medicine from January 2021 to January 2022 were selected as the observation subjects. They were divided into two groups using a random number table method, with 30 cases in each group. The control group was given conventional treatment plus placebo, and the experimental group was given conventional treatment plus Xiaoqinglong Decoction Granules. The treatment for both group lasted for 14d. TCM syndromes and clinical symptoms before and after treatment were scored. Asthma Control Test Questionnaire (ACT) was used to evaluate asthma control status, and the Asthma Quality of Life Questionnaire (Mini AQLQ) was used to evaluate the physiological and psychological effects of asthma on patients; FEV1 was detected using a German Jaeger lung function instrument FEV1/FVC. A exhaled nitric oxide (FeNO) detection instrument was used to observe the changes in FeNO at a flow rate of 50 ml/s, and non-targeted metabolomics analysis was performed using liquid chromatography-mass spectrometry (LC-MS); adverse reactions were observed during treatment and drug safety was evaluated.Results:Eventually 47 cases were included, 24 cases of test group and of 23 cases of control group. Xiaoqinglong Decoction Granules could reduce the TCM syndrome score of patients with chronic duration cold syndrome of asthma ( P<0.05). 2 weeks after treatment, follow up for 4 weeks experimental group clinical symptom score [3.00(1.00,4.00),3.00(0.00,4.00) vs. 3.5(3.00,5.00), Z=8.62], breathing symptom scores [1.00(0.00,1.00),1.00(0.00,1.00) vs. 1.00(0.75,2.00), Z=6.80], cough symptom score [0.50(0.00,1.00),1.00(0.00,1.00) vs. 1.00(0.00,1.25), Z=6.12] were lower than those in the experimental group before treatment in the same group ( P<0.01 or P<0.05). The ACT score of the experimental group at 4 weeks of follow-up was [22.50 (21.00, 24.00) vs. 9.00 (15.00, 21.50), Z=-4.87], Mini AQLQ score (78.5 ± 12.46 vs. 71.27 ± 9.70, t=-2.46) and the control group had an ACT score of [24.00 (19.00, 25.00) vs. 21.5 (8.00, 23.00) Z=-3.18] at 4 weeks of follow-up was higher than before treatment in the same group ( P<0.01 or P<0.05). The experimental group was followed up for 4 weeks with a FEV1 of [2.96 (2.27, 3.49) L vs. 2.60 (2.32, 3.49) L, Z=-3.72], FEV1/FVC [(80.83 ± 6.84)% vs. (77.46 ± 8.15)%, t=-2.32] and FeNO [24.00 (12.50, 31.00) ppb vs. 30.00 (17.00, 91.00) ppb, Z=-3.72] was higher than before treatment in the same group ( P<0.01 or P<0.05). Through LC-MS technique analysis, there were 75 kinds of different metabolites between the experimental group before and after treatment, and 295 kinds of different metabolites between the control group and the experimental group after treatment. Further intersection of differential metabolites showed that they were mainly concentrated in histidine metabolic pathway, phosphonate metabolic pathway and phosphate metabolic pathway. Related metabolites 2-aminoethyl phosphonate and thiomalonic acid were involved. Conclusions:Xiaoqinglong Decoction Granules can effectively improve the TCM syndrome and clinical symptoms of patients with chronic persistent cold syndrome of asthma, especially for wheezing, cough and chest tightness, which can improve the levels of FEV1 and FEV1/FVC in patients and effectively reduce FeNO. Through metabolomics studies, it is speculated that Xiaoqinglong Decoction Granules may play a role in the treatment of asthma by regulating histidine metabolism pathway through thiomalonic acid.

Objective:To observe the clinical features and disease outcomes of patients with fundus lesions associated with novel coronavirus infection (COVID-19).Methods:A case series observational study was conducted.Eighteen eyes of 10 patients with COVID-19 related fundus lesions diagnosed in the First Affiliated Hospital of Zhengzhou University from December 2022 to February 2023 were included.The affected eyes were examined by best corrected visual acuity (BCVA), intraocular pressure, slit lamp microscopy, scanning laser fundus photography (SLO), infrared fundus photography, optical coherence tomography (OCT), visual field and microperimetry.After the diagnosis was confirmed, according to the patients' willingness, 6 patients were treated with mecobalamin, vinblastine, and Aescuven forte orally.The other 4 patients were treated with glucocorticoid and methylprednisolone tablets orally with an initial dose of 32 mg/d, and the dose was reduced by 4 mg every 5 days, and potassium chloride tablets, calcium carbonate tablets, and omeprazole enteric-coated capsules were taken orally.According to the diagnosis and treatment of acute macular neuroretinopathy (AMN), the patients were divided into glucocorticoid treatment group (4 cases, 7 eyes) and non-glucocorticoid treatment group (4 cases, 8 eyes).The patients were followed up for 4 weeks.The BCVA, retinal morphology and structure, retinal sensitivity and fixation stability were compared before and after treatment.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of the First Affiliated Hospital of Zhengzhou University (No.2022-KY-1482-002).Written informed consent was obtained from each subject.Results:Among the enrolled 10 cases (18 eyes), there were 9 cases (17 eyes) of AMN, including 1 eye with Purtscher-like retinopathy (PLR), 1 eye with acute para-central medial maculopathy (PAMM), and 1 eye with multiple transient white dot syndrome (MEWDS).The SLO images of AMN patients showed redbrown irregular lesions in the fovea or parafovea of the macular area.The OCT images showed patchy strong reflection between the OPL and ONL in the fovea or parafovea of the macular area, and the adjacent EZ/IZ had different degrees of local fracture, and the reflection signal was disordered.The BCVA of the eyes after 4 weeks of treatment was higher than that before treatment, and the difference was statistically significant ( Z=-2.823, P<0.05).After 4 weeks of treatment, the retinal sensitivity of the eyes was (26.57±2.24)dB, which was significantly higher than that before treatment (24.17±2.73)dB ( t=-11.329, P<0.001).There was no statistically significant difference in LogMAR BCVA and retinal sensitivity between the AMN glucocorticoid treatment group and the AMN non-glucocorticoid treatment group before and after 4 weeks of treatment ( Z=-0.986, P>0.05; t=-1.656, P>0.05). Conclusions:The main manifestations of COVID-19 related fundus lesions are AMN, PAMM, PLR, MEWDS, etc.OCT, microperimetry and other auxiliary examinations can help to diagnose the disease.The visual impairment and fundus structural changes caused by COVID-19 gradually improve after 4 weeks of treatment.

Colorectal cancer (CRC) is a type of malignant tumor that seriously threatens human health and life, and its treatment has always been a difficulty and hotspot in research. Herein, this study for the first time reports that antipsychotic aripiprazole (Ari) against the proliferation of CRC cells both in vitro and in vivo, but with less damage in normal colon cells. Mechanistically, the results showed that 5-hydroxytryptamine 2B receptor (HTR2B) and its coupling protein G protein subunit alpha q (Gαq) were highly distributed in CRC cells. Ari had a strong affinity with HTR2B and inhibited HTR2B downstream signaling. Blockade of HTR2B signaling suppressed the growth of CRC cells, but HTR2B was not found to have independent anticancer activity. Interestingly, the binding of Gαq to HTR2B was decreased after Ari treatment. Knockdown of Gαq not only restricted CRC cell growth, but also directly affected the anti-CRC efficacy of Ari. Moreover, an interaction between Ari and Gαq was found in that the mutation at amino acid 190 of Gαq reduced the efficacy of Ari. Thus, these results confirm that Gαq coupled to HTR2B was a potential target of Ari in mediating CRC proliferation. Collectively, this study provides a novel effective strategy for CRC therapy and favorable evidence for promoting Ari as an anticancer agent.

Objective:To observe and analyze the changes and correlation of macular mean sensitivity (MS) and the thickness of ganglionic plexiform layer (GCIPL) in patients with non-arteriotic anterior ischemic optic neuropathy (NAION).Methods:A cross-sectional clinical study. From March to August 2023, 37 patients with 38 eyes of NAION (NAION group) diagnosed by ophthalmic examination in the First Affiliated Hospital of Zhengzhou University were included in the study. In the NAION group, 29 patients with contralateral healthy eyes were selected as the contralateral healthy eye group. A total of 31 eyes of 16 healthy subjects matching gender and age were selected as the normal control group. NAION group was divided into acute stage group (disease course ≤3 weeks), subacute stage group (disease course 4-12 weeks) and chronic stage group (disease course>12 weeks), with 16, 10 and 12 eyes, respectively. Best corrected visual acuity (BCVA), optical coherence tomography (OCT), perimetry, and microperimetry were performed. BCVA statistics are converted to logarithm of the minimum angle of resolution (logMAR). The macular region was scanned by Cirrus HD-OCT macular volume 512×128 scanning program. The mean (GCIPLav), minimum (GCIPLmin), and the GCIPL thickness at supranasal, superior, subnasal, supratemporal, inferior, and inferotemporal quadrants were detected. The Humphrey 24-2 automated visual field test was utilized to measure the mean defect (MD) of the visual field. MP-3 microperimetry was used to measure MS (total MS) in the 10° macular region and MS in the supranasal, superior, subnasal, supratemporal, inferior, and inferotemporal quadrants. MS> 21 dB was defined as normal. One-way analysis of variance was used to compare among groups. t test was used to compare GCIPL thickness between MS≤21 dB and> 21 dB regions. Spearman correlation analysis was used to analyze the correlation between GCIPL thickness and MS in corresponding areas. Results:There were statistically significant differences in logMAR BCVA and MS in the NAION group, contralateral healthy eye group, and normal control group ( F=13.595, 83.741; P<0.05). GCIPL thickness in the MS≤21 dB region was significantly lower than that in the> 21 dB region in the NAION group ( t=2.634, P=0.009). The thickness of GCIPL in the inferotemporal quadrant decreased in the NAION group compared with the contralateral healthy eye group and normal control group, but the difference was not statistically significant ( P=0.092, 0.192). The thickness differences of GCIPLav and GCIPLmin and GCIPL in other quadrants were statistically significant ( P<0.05). Compared with the contralateral healthy eye group and normal control group, the thickness of GCIPLmin, superior and supratemporal of GCIPL in the acute stage group were significantly decreased ( P<0.05). The thickness of GCIPLav, GCIPLmin, GCIPL in upranasal, superior and supratemporal quadrants were significantly decreased in the subacute stage group ( P<0.05). The thickness of GCIPLav, GCIPLmin and GCIPL in all quadrants were significantly decreased in the chronic stage group ( P<0.05). Correlation analysis showed that total MS were significantly correlated with logMAR BCVA ( r=0.779, -0.596, P<0.001) in NAION group. The inferior GCIPL thickness was significantly correlated with MS in the corresponding region ( r=0.410, P=0.046), while no correlation was found in the other quadrants ( r=0.220, 0.148, -0.131, 0.296, 0.321; P>0.05) in NAION group. GCIPL thickness in acute and subacute groups was significantly correlated with MS ( r=0.329, 0.400; P=0.007, 0.028). There was no correlation in the chronic phase group ( r=0.238, P=0.103). Conclusions:GCIPL atrophy and thinning and MS decrease in the macular area of NAION. The thickness of GCIPL in the MS decreasing region is significantly lower than that in the MS normal region. GCIPL atrophy and thinning in acute and subacute stages are correlated with MS.

Objective To investigate the clinical effect of pars plana vitrectomy combined with segmental scleral buckling(PPV-SSB)in the treatment of inferior rhegmatogenous retinal detachment(RRD).Methods Totally 87 eyes of 87 patients with inferior RRD who attended the Ophthalmology Department Ⅱ,the First Affiliated Hospital of Zhengzhou University from October 2020 to April 2022 were retrospectively included.Among them,45 patients(45 eyes)were treated with PPV-SSB(PPV-SSB group),and 42 patients(42 eyes)were treated with PPV(PPV group).The retinal reattachment rate,best corrected visual acuity(BCVA)and complications of patients who underwent single surgery in the two groups were compared.Results After a single surgery,the retinal reattachment rate was 95.56％(43/45)in the PPV-SSB group and 80.95％(34/42)in the PPV group,with a statistically significant difference(P=0.033).At 3 months and 6 months af-ter surgery,there were significant differences in BCVA between the PPV-SSB group and the PPV group(P=0.010,0.004).The incidence of postoperative phacoscotasmus in the PPV-SSB group and the PPV group was 28.89(13/45)and 54.76％(23/42),respectively,with a significant difference(P=0.018),while there were no significant differences in the inci-dence of the remaining few complications(all P＞0.05).Conclusion PPV-SSB has a higher retinal reattachment rate,better visual effect and fewer complications in the treatment of inferior RRD.

Objective:To explore the curative effect of wide pedicled with double-vessel flap of posterior lateral calf in repair of soft tissue defect in hind foot.Methods:From January 2018 to June 2021, 12 patients with soft tissue defects on hind foot were reconstructed with double-vessel flaps pedicled perforator of peroneal artery and sural nerve nutrient vessels in the Department of Trauma Orthopaedics, No.940 Hospital of Chinese People's Liberation Army Joint Service Support Force. The patients were 8 males and 4 females, aged 9-45(27.17±12.14) years old. Time after injury to admission was 6-24(10.17±4.80) hours. Six patients were with simple soft tissue defects, 2 with tendon defects, 3 with bone defects and 1 with postoperative infection due to an open fracture. The sizes of soft tissue defect ranged from 4 cm×5 cm-8 cm×12 cm. Soft tissue defects were reconstructed by transfer of posterolateral calf flaps, and the bone defects were repaired by phase I or phase II bone grafts or antibiotic cement and membrane induction according to the wound surface. For larger bone defects, stage-II bone transport was carried out to restore the length of the hind foot. Defects of Achilles tendon were reconstructed by direct suture or tendon transposition. Foot functions were evaluated by American Orthopaedic Foot and Ankle Surgery(AOFAS) ankle-posterior sufficient scale, visual analogue scale(VSA) score and flap healing. All patients were included in postoperative follow-up regularly through outpatient clinic or via WeChat.Results:All 12 patients had postoperative follow-up that lasted for 6-24(12.92±6.22) months. One flap developed dark purple colour with swelling at the distal end of the flap 3 days after surgery. It eventually healed after removed some sutures from the pedicle together with blood-letting on the flap surface. Three flaps developed local infection, and they were cured after debridement, dressing change and the use of sensitive antibiotics. The remaining 8 patients had achieved good appearance of flaps and normal ankle function. According to AOFAS, scores of ankle-posterior sufficiency scale increased from 14-45(25.25±5.42) before surgery up to 65-96(75.92±7.73) at the final follow-up. Of the 12 patients, 8 were in excellent, 2 in good and 2 in fair. The VAS scores decreased from 5-8(6.55±1.13) before surgery down to 0-4(1.55±1.37) at the final follow-up. The difference had statistics significance( P<0.01). All patients had satisfactory recovery of ankle function, with the extension at 15-20 degrees and plantar flexion of 30-40 degrees. The donor site healed well and all skin grafts survived. Conclusion:The double-vessel flap pedicled with perforating branch of peroneal artery and nutrient vessels of sural nerve can be used for reconstruction of soft tissue defect of hind foot. It achieved good surgical effects with reliable blood supply, smooth venous return, strong anti-infection ability, satisfactory appearance at donor site and flap itself, as well as a good recovery of foot function.