Acephalic spermatozoa syndrome is a rare type of teratozoospermia that severely impairs the reproductive ability of male patients, and genetic defects have been recognized as the main cause of acephalic spermatozoa syndrome. Spermatogenesis and centriole-associated 1 like (SPATC1L) is indispensable for maintaining the integrity of sperm head-to-tail connections in mice, but its roles in human sperm and early embryonic development remain largely unknown. Herein, we conducted whole-exome sequencing (WES) of 22 infertile men with acephalic spermatozoa syndrome. An in silico analysis of the candidate variants was conducted, and WES data analysis was performed using another cohort consisting of 34 patients with acephalic spermatozoa syndrome and 25 control subjects with proven fertility. We identified biallelic mutations in SPATC1L (c.910C>T:p.Arg304Cys and c.994G>T:p.Glu332X) from a patient whose sperm displayed complete acephalia. Both SPATC1L variants are rare and deleterious. SPATC1L is mainly expressed at the head-tail junction of elongating spermatids. Plasmids containing pathogenic variants decreased the level of SPATC1L in vitro. Moreover, none of the patient's four attempts at intracytoplasmic sperm injection (ICSI) resulted in a transplantable embryo, which suggests that SPATC1L defects might affect early embryonic development. In conclusion, this study provides the first identification of SPATC1L as a novel gene for human acephalic spermatozoa syndrome. Furthermore, WES might be applied for patients with acephalic spermatozoa syndrome who exhibit reiterative ICSI failures.
Centrioles/genetics* ; Homozygote ; Humans ; Infertility, Male/genetics* ; Male ; Mutation ; Spermatogenesis/genetics* ; Spermatozoa

Objective:To explore the effect of self-made dynamic cardiovascular three-dimensional model combined with CBL (case-based learning) teaching method in the clerkship of valvular heart disease for medical students.Methods:Sixty five-year clinical medical undergraduates from Nanjing Medical University (Batch 2016) were randomly divided into experimental group and control group. The experimental group received dynamic cardiovascular 3D model combined with CBL teaching method, while the control group received traditional model combined with CBL teaching method. After the course, the teaching effect was evaluated by examination and questionnaire. SPSS 19.0 was used for independent sample t test and chi-square test. Results:Compared with the control group, the students in experimental group had higher scores of basic theoretical knowledge [(43.10±3.51) vs. (40.87±3.19)] and clinical thinking ability [(42.20±3.15) vs. (40.20±3.81)], with significant differences ( P<0.05). Furthermore, they showed higher evaluation and satisfaction to learning initiative and enthusiasm, mastery of theoretical knowledge, clinical thinking ability, classroom learning interest, classroom activity and clarity of knowledge teaching, with significant differences ( P<0.05). Conclusion:In the teaching of valvular heart disease clerkship, the application of self-made dynamic cardiovascular three-dimensional model combined with CBL teaching method, can cultivate students' clinical diagnostic thinking ability and improve teaching quality.

Chemical constituents were isolated and purified from fruiting bodies of Ganoderma calidophilum by various column chromatographic techniques, and their chemical structures were identified through combined analysis of physicochemical properties and spectral data. As a result, 11 compounds were isolated and identified as(24E)-lanosta-8,24-dien-3,11-dione-26-al(1), ganoderone A(2), 3-oxo-15α-acetoxy-lanosta-7,9(11), 24-trien-26-oleic acid(3),(23E)-27-nor-lanosta-8,23-diene-3,7,25-trione(4), ganodecanone B(5), ganoderic aldehyde A(6), 11β-hydroxy-lucidadiol(7), 3,4-dihydroxyacetophenone(8), methyl gentiate(9), ganoleucin C(10), ganotheaecolumol H(11). Among them, compound 1 is a new triterpenoid. The cytotoxic activities of all of the compounds against tumor cell lines were evaluated. The results showed that compounds 1, 3, 4 and 6 showed cytotoxic activity against BEL-7402, with IC_(50) values of 26.55, 11.35, 23.23, 18.66 μmol·L~(-1); compounds 1 and 3-6 showed cytotoxic activity against K562, with IC_(50) values of 5.79, 22.16, 12.16, 35.32, and 5.59 μmol·L~(-1), and compound 4 showed cytotoxic activity against A549, with IC_(50) value of 42.50 μmol·L~(-1).
Cell Line, Tumor ; Fruiting Bodies, Fungal ; Ganoderma ; Molecular Structure ; Triterpenes/pharmacology*

Objective: To analyze the current adherence to imatinib in patients with gastrointestinal stromal tumors (GIST) in China and its influencing factors. Methods: A cross-sectional survey was conducted. Study period: from October 1, 2020 to November 31, 2020. Study subjects: GIST patients taking imatinib who were diagnosed and treated in public tertiary level A general hospitals or oncology hospitals; those who had not been pathologically diagnosed, those who never received imatinib, or those who had taken imatinib in the past but stopped afterwards were excluded. The Questionnaire Star online surgery platform was used to design a questionnaire about the adherence to adjuvant imatinib therapy of Chinese GIST patients. The link of questionnaire was sent through WeChat. The questionnaire contained basic information of patients, medication status and Morisky Medication Adherence Scale. Results: A total of 2162 questionnaires from 31 provinces, autonomous regions, and municipalities were collected, of which 2005 were valid questionnaires, with an effective rate of 92.7%. The survey subjects included 1104 males and 901 females, with a median age of 56 (22-91) years old. Working status: 609 cases (30.4%) in the work unit, 729 cases (36.4%) of retirement, 667 cases of flexible employment or unemployment (33.3%). Education level: 477 cases (23.8%) with bachelor degree or above, 658 cases (32.8%) of high school, 782 cases (39.0%) of elementary or junior high school, 88 cases (4.4%) without education. Marital status: 1789 cases (89.2%) were married, 179 cases (8.9%) divorced or widowed, 37 cases (1.8%) unmarried. Two hundred and ninety-four patients (14.7%) had metastasis when they were first diagnosed, including 203 liver metastases, 52 peritoneal metastases, and 39 other metastases. One thousand eight hundred and sixty-nine patients underwent surgical treatment, of whom 1642 (81.9%) achieved complete resection. The median time of taking imatinib was 25 (1-200) months. Common adverse reactions of imatinib included 1701 cases (84.8%) of periorbital edema, 1031 cases (51.4%) of leukopenia, 948 cases (47.3%) of fatigue, 781 cases (39.0%) of nausea and vomiting, 709 cases (35.4%) of rash, and 670 cases (33.4%) of lower extremity edema. The score of the Morisky Medication Adherence Scale showed that 392 cases (19.6%) had poor adherence, 1023 cases (51.0%) had moderate adherence, and 590 cases (29.4%) had good adherence. Univariate analysis showed that gender, age, work status, economic income, residence, education level, marriage, the duration of taking medication and adverse reactions were associated with adherence to adjuvant imatinib therapy (all P<0.05). Multivariate analysis showed that female (OR=1.264, P=0.009), non-retirement (OR=1.454, P=0.001), monthly income ≤4000 yuan (OR=1.280, P=0.036), township residents (OR=1.332, P=0.005), unmarried or divorced or widowed (OR=1.362, P=0.026), the duration of imatinib medication >36 months (OR=1.478, P<0.001) and adverse reactions (OR=1.719, P=0.048) were independent risk factors for poor adherence to adjuvant imatinib. Among patients undergoing complete resection, 324 (19.7%) had poor adherence, 836 (50.9%) had moderate adherence, and 482 (29.4%) had good adherence. Meanwhile, 55 patients with good adherence (11.4%) developed recurrence after surgery, 121 patients with moderate adherence (14.5%) developed recurrence, 61 patients with poor adherence (18.8%) developed recurrence, and the difference was statistically significant (P=0.017). Conclusions: The adherence to adjuvant therapy with imatinib in Chinese GIST patients is relatively poor. Females, non-retirement, monthly income ≤4000 yuan, township residents, unmarried or divorced or widowed, the duration of imatinib medication >36 months, and adverse reactions are independently associated with poor adherence of GIST patients. Those with poor adherence have a higher risk of recurrence after surgery. Positive interventions based on the above risk factors are advocated to improve the prognosis of patients with GIST.
Aged ; Aged, 80 and over ; Antineoplastic Agents/therapeutic use* ; Chemotherapy, Adjuvant ; Cross-Sectional Studies ; Female ; Gastrointestinal Stromal Tumors/drug therapy* ; Humans ; Imatinib Mesylate/therapeutic use* ; Male ; Middle Aged ; Neoplasm Recurrence, Local/drug therapy*

Gastrectomy ; Humans ; Lymph Node Excision ; Lymph Nodes ; Lymphatic Metastasis ; Retrospective Studies ; Stomach Neoplasms/surgery*

OBJECTIVE: Meta-analysis was used to compare the clinical efficacy of high tibial osteotomy(HTO) and unicondylar arthroplasty (UKA) in the treatment of medial compartment osteoarthritis (MIOA) and provide a better surgical choice for patients with MIOA. METHODS: The Cochrane Library (Issue 6, 2017), PubMed, Ovid, ELSIVE, CNKI and Wanfang databases were searched by a computer. Literatures on HTO and UKA for MIOA from January 1, 1970 to June 30, 2017, including complications, knee joint score, knee mobility, revision rate and excellent and good rate, were searched and screened out according to the inclusion criteria, and strict quality evaluation was carried out. RevMan 5.0 software provided by Cochrane collaboration network was used to conduct the meta-analysis of the included research results and to test the heterogeneity of the data. RESULTS: Total 13 articles met the inclusion criteria, and the total sample size was 1 043. Among them, 462 were HTO treatment group and 581 were UKA treatment group. By comparison between HTO treatment group and UKA treatment group, there were significant differences in the contralateral deterioration rate[WMD=3.21, 95%CI(1.13, 9.10)], pre-operative knee range of motion[WMD=6.55, 95%CI(1.44, 11.66)], Lysholm knee score[WMD=-3.15, 95%CI(-4.77, -1.53)], complications[WMD=2.78, 95%CI(1.52, 5.11], revision rate[WMD=1.81, 95%CI(1.17, 2.80)], the rate of excellent and good[WMD=0.49, 95%CI(0.30, 0.80)], and femorotibial angle changes[WMD=-2.37, 95%CI, (-3.63, -1.11)](<0.05). There were no significant differences between the HTO treatment group and the UKA treatment group in patellofemoral deterioration rate[WMD=1.59, 95%CI(0.65, 3.84)] and the free walking speed[WMD=-0.02, 95%CI(-0.09, 0.04)](>0.05). CONCLUSIONS Based on the limited data, high tibial osteotomy is a better choice for the treatment of medial compartment osteoarthritis in the comparison of short and medium-term clinical outcomes, and long-term clinical outcomes may need further study.
Arthroplasty, Replacement, Knee ; Humans ; Knee Joint ; Osteoarthritis, Knee ; Osteotomy ; Tibia ; surgery ; Treatment Outcome

OBJECTIVETo discuss the advantages and disadvantages of two different surgical approaches combined fixation with lumbar interbody fusion in treating single segmental lumbar vertebra diseases.

METHODSThe clinical data of 86 patients with single segmental lumbar vertebra diseases treated from June 2011 to June 2013 was retrospectively analyzed. There were 33 males and 53 females, aged from 28 to 76 years old with an average of 53.0 years. Among them, there were 39 cases of lumbar disc degeneration, 22 cases of lumbar disc herniation complicated with spinal canal stenosis, 9 cases of huge lumbar disc herniation and 16 cases of lumbar degenerative spondylolisthesis (Meyerding degree I ). Lesion sites contained L3, 4 in 5 cases, L4, 5 in 70 cases and L5S1 in 11 cases. All the patients were treated with internal fixation and lumbar interbody fusion with 45 cases by midline incision approach (median incision group) and the other 41 cases by channel-assisted by muscle-splitting approach(channel group). Incision length, operation time, intraoperative bleeding and postoperative drainage were recorded in two groups. Visual analogue scale(VAS) was used to assess lumbar incision pain 72 h after operation. Depended on imaging results to compare the changes of the disc space height in lesion in preoperative, postoperative and final follow-up, the coronal and sagittal Cobb angle in preoperative and final follow-up, the area of multifidus and the degree of multifidus fat deposition before and after operation between two groups. Loosening or fragmentation of internal fixation, displacement of intervertebral cage and interbody fusion were observed in each group. Japanese Orthopedic Association (JOA) scoring system was used to evaluate the function before operation and at the final follow-up.

RESULTSThe channel group was superior to the median incision group in incision length and postoperative drainage while the median incision group was less than the channel group in the operation time and intraoperative bleeding. The average VAS score of lumbar incision 72 h after operation was 1.50 points in median incision group and 0.97 points in channel group, and there was significant difference between two groups(<0.05). No incision infection was found, but there were 4 cases of incisional epidermal necrosis, 1 case of incision healed badness, and 3 cases of nerve injury in channel group. The incidence of cacothesis of pedicle screw were 5.0% and 3.6% in median incision group and channel group respectively, and there was no significant difference between two groups(>0.05). The incidence of cacothesis of translaminar facet screw were 6.6% and 12.2% in median incision group and channel group respectively, and there was significant difference between two groups(<0.05). All the patients were followed up for 12 to 36 months with a mean of 22.8 months. The changes of disc space height had statistical difference between preoperative and postoperative(<0.05) in all patients, but there was no significant difference between postoperative and final follow-up(>0.05), however, there was no significant difference 3 days after operation and final follow-up between two groups(>0.05). At final follow-up, coronal and sagittal Cobb angle were obviously improved in all patients(<0.05), but there was no significant difference between two groups(>0.05). One year after operation, the area of multifidus in median incision group was (789.00±143.15) mm² less than preoperative(1 066.00±173.55) mm² (<0.05), and in channel group, was(992.00±156.75) mm² at 1 year after operation and(1 063.00±172.13) mm² preoperatively, there was no significant difference between them(>0.05), however, there was significant difference one year after operation between two groups (<0.05) . About the degree of multifidus fat deposition, there was significant difference between one year after operation and preoperation in median incision group (<0.05), but there was no significant difference between one year after operation and preoperation in channel group (>0.05), and there was significant difference at one year after operation between two groups(<0.05). During the follow-up period, neither pedicle screw and/or translaminar facet screw loosening, displacement or fragmentation nor displacement of intervertebral cage were found. The lumbar interbody fusion rate was 95.6% in median incision group and was 95.1% in channel group, and there was no significant difference between two groups(>0.05). No obvious adjacent segmental degeneration was observed in fixed position. JOA score in median incision group was significantly increased from 8-16 points (average: 12.77±2.56) preoperative to 21-29 points (average: 25.20±2.43) at final follow-up(<0.05); and in channel group was significantly increased from 8-16 points (average: 12.64±2.37) preoperative to 23-29 points(average: 26.7±1.82) at final follow-up(<0.05); there was also significant difference between two groups at final follow-up.

CONCLUSIONSCompared to the median incision approach, unilateral pedicle screw combined with contralateral translaminar facet screw fixation using channel-assisted by muscle-splitting approach has advantages of small incision, less trauma, fast recovery and so on. However, it also has shortages such as high surgical complications incidence, especially in cases that.

IG-105, N-(2,6-dimethoxypyridine-3-yl)-9-methylcarbazole-3-sulfonamide, a novel antimicrotubule agent, showed potent anticancer activity in a variety of human tumor cells in vitro and in vivo. In order to characterize the metabolism and the possible drug-drug interaction of IG-105, we carried out a series of experiments. Drug metabolizing enzymes involved in IG-105 metabolism were investigated by using pooled human liver microsomes (HLMs) and recombinant cytochrome P450 isoforms (rP450s) respectively. The possible metabolites were analyzed by liquid chromatography-orbitrap-mass spectrometry (LC-Orbitrap-MS). The inhibitory effect of IG-105 on main P450 enzymes was also evaluated. The results showed that IG-105 can be metabolized by a series of rP450s, including CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, CYP3A4 and CYP3A5, with the major contribution enzymes being CYP1A2, CYP2B6, CYP2C19, and CYP3A. Three metabolites (M1-M3) were identified and demethylation was the major phase I metabolic reaction for IG-105. IG-105 moderately inhibited CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A enzyme activities with IC₅₀ values of 6.42, 23.64, 0.39, 1.4, and 3.14 μmol·L^-1, respectively. Since the biotransformation of IG-105 involves multiple enzymatic pathways, the compound is less likely to be a victim of a concomitantly used medicine which inhibits activity of one of the CYPs. However, as IG-105 showed medium to strong inhibition on CYP1A2, CYP2D6, CYP3A, and CYP2C19, caution is particularly needed when IG-105 is co-administrated with other anticancer drugs which are mainly metabolized by the above enzymes.

OBJECTIVETo compare the advantages and disadvantages of unilateral pedicle screw fixation plus lumbar interbody fusion and unilateral pedicle screw fixation combined with contralateral translaminar facet screw fixation plus lumbar interbody fusion in treating single segmental lower lumbar vertebra diseases.

METHODSSixty-two patients with single segmental lower lumbar vertebra disease who received treatment between January 2008 and June 2009. These patients were consisted of 16 males and 46 females, ranging in age from 27 to 72 years old, with a mean age of 51.6 years old. Among these patients, lumbar degenerative disease had in 22 patients, recurrence of lumbar intervertebral disc protrusion in 13 patients, lumbar intervertebral disc protrusion accompany with spinal canal stenosis in 12 patients, massive lumbar intervertebral disc protrusion in 5 patients and lumbar degenerative spondylolisthesis with degree I in 10 patients. The lesions occurred at L3,4 segment in 5 patients, at L4,5 segment in 42 patients, and at L5S1 segment in 15 patients. Thirty patients underwent unilateral pedicle screw fixation (unilateral screw fixation group, group A) and thirty-two patients received unilateral pedicle screw fixation combined with contralateral translaminar facet screw fixation (bilateral screw fixation group, group B). Lumbar interbody fusion with intervertebral cages was also performed in all patients. Incision length, operation time, intraoperative blood loss and postoperative wound drainage were compared between two groups. Loosening or breakage of internal fixations, displacement of intervertebral cages and interbody fusion conditions were observed in each group. Preoperative and postoperative intervertebral height, coronal and sagittal Cobb angle and wound pain at 72 h after operation were compared between two groups. The Japanese Orthopedic Association (JOA) scoring system was used to evaluate the cinical effects.

RESULTSNeither wound infection, skin necrosis, nerve root or cauda equia injury, nor worsened neurological dysfunction in the lower limb occurred in each group. There were no significant differences in incision length, intraoperative blood loss and postoperative wound drainage between two groups. The operation time in group A was significantly shorter than that of group B (P < 0.05). There were no significant differences in visual analogue scale value of the wound pain at postoperative 72 h between two groups (P > 0.05). All patients were followed up for 12-48 months,with a mean of 27.5 months. The intervertebral height of all patients had obviously recovered at 5 days after operation, furthermore, at the final follow-up, it still had well maintained. During follow-up, no pedicle screw and/or translaminar facet screw loosening, displacement or breakage and displacement of intervertebral cages were found. The lumbar interbody fusion rate was 96.7% and 96.9% in group A and group B, respectively, and there was no significant difference between two groups (P > 0.05). JOA score of all patients got obviously improved after operation (P < 0.05) and there was no significant difference between two groups (P > 0.05).

CONCLUSIONBoth unilateral pedicle screw fixation plus lumbar interbody fusion and unilateral pedicle screw fixation combined with contralateral translaminar facet screw fixation plus lumbar interbody fusion have advantages of small incision, minimal invasion, simple operation, reliable stability, high interbody fusion rate,rapid recovery, encouraging clinical effects and less complications. Compared with unilateral pedicle screw fixation combined with contralateral translaminar facet screw fixation, the operation of unilateral pedicle screw fixation is simpler and can avoid using special equipments. Therefore, unilateral pedicle screw fixation plus lumbar interbody fusion can be used in treating single-segmental lower lumbar vertebra diseases under the precondition of strictly grasping indications for surgery and improving surgical skills.

Adult ; Aged ; Bone Screws ; Female ; Humans ; Lumbar Vertebrae ; surgery ; Male ; Middle Aged ; Spinal Diseases ; surgery ; Spinal Fusion ; methods

OBJECTIVETo investigate the advantages and disadvantages of unilateral pedicle screw fixation combined with contralateral translaminar facet screw fixation and interbody fusion with cages in the treatment of two-level lumbar vertebra diseases, by comparing bilateral pedicle screw fixation and interbody fusion with cages.

METHODSForty-nine patients with two-level lumbar diseases who received treatments from June 2009 to December 2011 were included in this study. Among these patients, 23 patients received unilateral pedicle screw fixation combined with contralateral translaminar facet screw fixation and interbody fusion with cages (combined fixation group) and the remaining 26 patients underwent bilateral pedicle screw fixation and interbody fusion with cages (bilateral fixation group). These patients consisted of 17 males and 32 females, ranging in age from 29 to 68 years old. Among these patients, lumbar intervertebral disc herniation accompanied by the spinal canal stenosis was found in 29 patients, degenerative lumbar disc diseases in 17 patients and lumbar degenerative spondylolisthesis (degree I) in 3 patients. The lesions occurred at L2,3 and L3,4 segments in 1 patient, at L3,4 and L4,5 segments in 30 patients, and at L4,5 segment and L5S1 segment in 18 patients. Wound length, operation time, intraoperative blood loss and postoperative wound drainage were compared between two groups. Intervertebral space height in the lesioned segment before and during surgery and at the latest follow up was also compared between two groups. Before surgery and at the latest follow-up, the Cobb angle of the coronal plane and sagittal plane of the lumbar spine, loosening or breakage of internal fixations, the dislocation of intervertebral cages, and interbody fusion were all evaluated in each group. The visual analogue scale (VAS) was used to measure lumbar incision pain. The Japanese Orthopedic Association (JOA) scoring system was used to evaluate the function before surgery and at the latest follow-up.

RESULTSNo wound infection or skin necrosis was observed after surgery in all patients. No cerebrospinal fluid leakage, nerve root injury, cauda equia injury or worsened neural function in the lower limb occurred in all patients during and after surgery. Wound length, operation time, intraoperative blood loss and postoperative wound drainage in the combined fixation group were superior to those in the bilateral fixation group. At postoperative 72 hours, the VAS score in the combined fixation group (1 to 4 points, mean 2.35±1.20) was significantly lower than that in the bilateral fixation group (2 to 5 points, mean 3.11±1.00; P<0.05). All the patients were followed up for 12 to 48 months, with a mean of 29 months. After surgery, intervertebral space height was well recovered in each patient and it was well maintained at the latest follow-up, and there was no significant difference between two groups (P>0.05). During follow-up, pedicle screw and translaminar facet screw loosening, dislocation or breakage and dislocation of intervertebral cages were all not found. At the latest follow-up, the Cobb angle of the coronal plane and sagittal plane of the lumbar spine was obviously improved and was not significantly different between two groups (P>0.05). The lumbar interbody fusion rate was 93.5% and 96.2% in the combined fixation group and bilateral fixation group, respectively, and there was no significant difference between them (P>0.05). There was a significant difference in JOA score between before surgery and at the latest follow-up in each patient (P<0.05), and at the latest follow-up, significant difference in JOA score was found between two groups (P<0.05).

CONCLUSIONCompared to bilateral pedicle screw fixation and lumbar interbody fusion with cages, unilateral pedicle screw fixation combined with contralateral translaminar facet screw fixation and lumbar interbody fusion with cages shows advantages including small skin incision, minimal invasion, ease of operation, highly reliable stability, high interbody fusion rate, rapid recovery in the treatment of two-level lumbar vertebra diseases and therefore can be preferred as a treatment method of this disease.

Adult ; Aged ; Female ; Humans ; Intervertebral Disc Degeneration ; surgery ; Lumbar Vertebrae ; surgery ; Male ; Middle Aged ; Pedicle Screws ; Spinal Fusion ; methods ; Spinal Stenosis ; surgery ; Spondylolisthesis ; surgery