[Prognosis of different hemodynamic classifications in patients with pulmonary hypertension due to left heart disease].

Objective: To compare the prognostic values of different classification by using transpulmonary pressure gradient (TPG), diastolic pressure gradient (DPG) and pulmonary vascular resistance (PVR) in patients with pulmonary hypertension due to left heart disease (PH-LHD), and investigated hemodynamic and clinical factors associated with mortality in patients with PH-LHD. Methods: This was a single-center prospective cohort study. In-hospital patients diagnosed with PH-LHD via right heart catheterization at the Department of Cardiology, the First Affiliated Hospital of Nanjing Medical University, from September 2013 to December 2019 were enrolled. Patients were divided according to TPG (cutoff value 12 mmHg; 1 mmHg=0.133 kPa), DPG (cutoff value 7 mmHg), PVR (cutoff value 3 Wood Units), and the combination of TPG and PVR. Baseline characteristic was recorded. All patients were followed up until the occurrence of endpoint event, defined as all-cause death that occurred during the follow-up period, or until April 18, 2022. Receiver operating characteristic curves were used to compare the predictive value of 3 classification methods for all-cause death in PH-LHD patients. The optimal cutoff values were calculated using Jorden index. Survival analysis was performed using Kaplan-Meier analysis, and log-rank test was used to compare the predictive efficacy of classification methods based on optimal cutoff values or guidance-recommended thresholds for the survival of PH-LHD patients. Variables showing statistical significance in the univariate analysis were incorporated into multivariate Cox regression model to analyze the independent risk factors for all-cause mortality. Results: A total of 243 patients were enrolled, aged (54.9±12.7) years old, including 169 (69.5%) males. During a median follow-up of 57 months, there were 101 (41.6%) deaths occurred. Grouping results were as follows: (1) TPG: TPG≤12 mmHg group 115 patients, TPG>12 mmHg group 128 patients; (2) DPG: DPG<7 mmHg group 193 patients, DPG≥7 mmHg group 50 patients; (3) PVR: PVR≤3 Wood Units group 108 patients, PVR>3 Wood Units group 135 patients; (4) TPG and PVR: TPG≤12 mmHg and PVR≤3 Wood Units group 89 patients, TPG>12 mmHg and PVR>3 Wood Units group 109 patients. PVR (AUC=0. 698,95%CI:0.631-0.766) had better predictive value for all-cause mortality than TPG (AUC=0.596, 95%CI: 0.523-0.669) and DPG (AUC=0.526, 95%CI: 0.452-0.601) (all P<0.05). The optimal cutoff values for TPG, DPG, and PVR were13.9 mmHg, 2.8 mmHg, and 3.8 Wood Units, respectively. Kaplan-Meier analysis based on the optimal cutoff values or guidance-recommended thresholds showed that PVR and TPG were the predictors of survival (P<0.05), while DPG did not showed significance (P>0.05). Multivariate Cox regression analysis showed that age, PVR and log2N-terminal pro-B-type natriuretic peptide were independent risk factors for all-cause mortality in PH-LHD patients (all P<0.05). Conclusion: Classification according to PVR was most valuable in predicting all-cause death in PH-LHD patients, while TPG showed moderate predictive ability and DPG had no predictive value.

[Application of IgG antibody combination of wild strain and epidemic strain of COVID-19 in identifying epidemic Omicron BA.5 strain infection].

Objective: To explore the application of COVID-19-specific IgG antibody in identifying epidemic Omicron BA.5 strain infection. Method: Omicron BF.7/BA.5 naturally infected population, healthy population vaccinated with the COVID-19 vaccine, and Omicron BF.7/BA.5 breakthrough cases were enrolled into this study. The serum WT-S-IgG and BA.5-S-IgG were detected by indirect ELISA, and the serum-specific IgG antibody levels of different populations were compared. The application value of the two antibody titers and the ratio of the two antibodies in identifying Omicron BA.5 epidemic strain infection were explored by the ROC curve, aiming to provide technical support for pathogen diagnosis. Results: The antibody titers of WT-S-IgG and BA.5-S-IgG in the breakthrough cases were higher than those in the naturally infected population and the healthy population (P<0.05). The area under the curve (AUC) of WT-S-IgG and BA.5-S-IgG in identifying epidemic Omicron BA.5 strain infection was 0.947 and 0.961, respectively. The AUC of BA.5-S-IgG and WT-S-IgG antibody titer ratio was 0.873. When the antibody titer ratio was 0.855, the sensitivity and specificity were 80.00% and 90.00%, respectively. According to the interval since the last infection, the AUC of the ratio of BA.5-S-IgG to WT-S-IgG antibody titer to identify the infection of epidemic strains less than 30 days and more than 30 days was 0.887 and 0.863, respectively, and the sensitivity and specificity were both above 80%. Conclusion: Both BA.5-S-IgG and WT-S-IgG, as well as the combination of these two antibodies, are of high value in the identification of epidemic strains.

Epidemiological characteristics and strategies for prevention and elimination of malaria in Qingdao, Shandong Province, China from 1949 to 2021.

Malaria is an insect-borne disease transmitted by Anopheles mosquitoes or the importation of Plasmodium-infected blood, posing a serious threat to human health and life safety. This study aims to analyze the incidence of malaria in Qingdao at various stages from 1949 to 2021, to collate the control measures taken at different epidemic stages to assess the effectiveness of malaria control, and to identify a set of malaria control strategies suitable for Qingdao, while providing Chinese experience for other countries or cities in their malaria elimination efforts. A retrospective survey was used to collect information on malaria cases, control measures and prevention and control effects in Qingdao from 1949 to 2021, and to evaluate malaria control strategies and measures in Qingdao. 704 155 cases have been reported from 1949 to 2021, with three epidemic peaks: the incidence rate was 1715.9/100 000 in 1961, 1409.7/100 000 in 1965, and the most severe case occurred in 1972, with an incidence rate of 1635.6/100 000 and a case count exceeding 90 000. Throughout the various stages of malaria epidemics, Qingdao has effectively eliminated indigenous malaria by implementing diverse preventive and control measures. Since the last indigenous case of Plasmodium vivax was reported in 2002, all locally reported cases have been imported, mainly by returning migrant workers from Africa. This study examines a range of malaria prevention and control strategies and interventions that are appropriate for Qingdao. These measures have enabled Qingdao to successfully eliminate malaria and maintain malaria-free status for more than 20 years. These measures can also serve as a reference for similarly situated cities in Africa and Southeast Asia.

[Clinical efficacy and safety of blinatumomab bridging CAR-T cell therapy in the treatment of patients with adult acute B-cell lymphoblastic leukemia].

Objective: Exploring the efficacy and safety of bridging blinatumomab (BiTE) in combination with chimeric antigen receptor T (CAR-T) cell therapy for the treatment of adult patients with acute B-cell lymphoblastic leukemia (B-ALL) . Methods: Clinical data from 36 adult B-ALL patients treated at the First Affiliated Hospital of Suzhou University from August 2018 to May 2023 were retrospectively analyzed. A total of 36 cases were included: 18 men and 18 women. The median age was 43.5 years (21-72 years). Moreover, 21 cases of Philadelphia chromosome-positive acute lymphoblastic leukemia were reported, and 16 of these cases were relapsed or refractory. Eighteen patients underwent blinatumomab bridging followed by CAR-T cell therapy, and 18 patients received CAR-T cell therapy. This study analyzed the efficacy and safety of treatment in two groups of patients. Results: In the BiTE bridge-to-CAR-T group, 16 patients achieved complete remission (CR) after BiTE immunotherapy, with a CR rate of 88.9%. One month after bridging CAR-T therapy, bone marrow examination showed a CR rate of 100.0%, and the minimal residual disease (MRD) negativity rate was higher than the nonbridging therapy group (94.4% vs. 61.1%, Fisher, P=0.041). The incidence of cytokine release syndrome and other adverse reactions in the BiTE bridge-to-CAR-T group was lower than that in the nonbridging therapy group (11.1% vs. 50.0%, Fisher, P=0.027). The follow-up reveals that 13 patients continued to maintain MRD negativity, and five patients experienced relapse 8.40 months (2.57-10.20 months) after treatment. Two of five patients with relapse achieved CR after receiving the second CAR-T cell therapy. In the nonbridging therapy group, 10 patients maintained continuous MRD negativity, 7 experienced relapse, and 6 died. The 1 year overall survival rate in the BiTE bridge-to-CAR-T group was higher than that in the nonbridging therapy group, with a statistically significant difference at the 0.1 level (88.9%±10.5% vs. 66.7%±10.9%, P=0.091) . Conclusion: BiTE bridging CAR-T cell therapy demonstrates excellent efficacy in adult B-ALL treatment, with a low recent recurrence rate and ongoing assessment of long-term efficacy during follow-up.

[The application value of whole exome sequencing technology in diagnosis of hereditary renal cysts].

The data of 57 renal cyst patients who visited the First Affiliated Hospital of Zhengzhou University from January 2023 to March 2024 were retrospectively analyzed. The age of patients ranged from three months to 60 years old, with 31 males and 26 females. The whole exome sequencing (WES) detected pathogenic or suspected pathogenic (P/LP) variants in 48 renal cystic probands, with a detection rate of 84.2% (48/57), including PKD1, PKD2, PKHD1, LRP5, COL4A4 and ALG8 gene variants as well as copy number variations (CNV). In addition, four PKD1 gene variants of uncertain significance (VUS) were detected. In five WES negative families, one PKD1 nonsense variation was detected through long-range PCR (LR-PCR)+Oxford nanopore technologies, and one heterozygous deletion in exon 22 of PKD1 gene was detected through multiplex ligation-dependent probe amplification (MLPA). In summary, WES can detect multiple types of variations, which is helpful for early diagnosis and prognosis prediction of renal cyst patients. However, there is still a risk of failing to detect PKD1 gene by WES, therefore, healthcare practitioners should beware of the negative results of WES.

[Genotype-phenotype relationship and genetics study of 115 cases with Wilson's disease].

Objective: To explore the genotype-phenotype relationship of Wilson's disease (WD) and further study the mutation spectrum in the ATP7B gene. Methods: The clinical data and genetic test results of 115 cases with WD diagnosed in the First Affiliated Hospital of Zhengzhou University from 2015 to 2022 were retrospectively analyzed. The rank sum test was used for quantitative data comparison, and χ(2) test was used for count data comparison. Multivariate logistic regression was used to analyze the relationship between patients' genotype and phenotype. Results: The onset of liver manifestations (hepatic type) accounted for 60.9%, neurological symptoms (cerebral type) for 13.0%, and mixed hepato-cerebral symptoms for 26.1%. Presymptomatic individuals (hepatic types) accounted for 62.9%. Next-generation sequencing- diagnosed WD cases accounted for 87.8%. Combined multiplex ligation-dependent probe amplification assay-diagnosed WD cases accounted for 89.6%. A single case with a detected pathogenic locus accounted for 10.4%. The diagnostic rate of WD by genetic testing combined with clinical data was 100%. A total of 76 ATP7B mutations were detected, and the top three mutation frequencies were c.2333G>T (p.Arg778Leu) (30.7%), c.2975C>T (p.Pro992Leu) (7.3%), and c.2621C>T (p.Ala874Val) (6.4%). The mutations were mainly distributed in exons 8, 11-13, and 15-18, accounting for more than 90% of the total mutations. Eight new mutations were found, including c.3724G>A (p.Glu1242Lys), c.3703G>C (p.Gly1235Arg), c.3593T>C (p.Val1198Ala), c.2494A>C (p.Lys832Gln), c.1517T>A (p.Ile506Lys), c.484G>T (p.Glu162Ter), c.1870-49A>G, and the missing of exons 10-21. Liver histopathology showed cellular edema, degeneration, inflammation, and necrosis, as well as a 42.8% copper staining positive rate. Genotype-phenotype analysis showed that the p.Arg778Leu mutation had higher alanine aminotransferase (ALT) levels than those carrying other mutations (P=0.024), while the homozygous mutation of p.Arg778Leu was associated with cerebral-type patients (P=0.027). Conclusion: Genetic testing plays an important role in the diagnosis of WD. p.Arg778Leu is the first high-frequency mutation in the Chinese population, and patients carrying it have higher ALT levels. The p.Arg778Leu homozygous mutation is prone to causing cerebral-type WD. This study expands the ATP7B gene mutation spectrum.

[Comparison of the efficacy of gasless robotic surgery through transaxillary apporach and open surgery for papillary thyroid carcinoma].

Objective: To compare the efficacy of gasless robotic surgery through transaxillary approach and open surgery for papillary thyroid carcinoma (PTC). Methods: The data of patient undergoing robotic surgery through transaxillary approach and traditional open surgery for PTC at the Sun Yat-sen Memorial Hospital, Sun Yat-sen University, from November 2016 to June 2023 were retrospectively analyzed. A 1∶1 propensity score matching (PSM) was performed to balance age, sex, extent of surgery, tumor size, capsule invasion, and multifocality. Surgical data, postoperative pathological data, complications, postoperative 2-month visual analog scale (VAS) scores for aesthetics, and follow-up data were compared between the two groups. Results: A total of 728 PTC patients were included. There were 339 patients in the robotic group, among which 262 were female (77.3%) and 77 were male (22.7%), with the age of [M (Q1, Q3)] 39 (32, 46) years and a body mass index (BMI) of 22.8 (20.7, 25.0) kg/m². Meanwhile, 389 patients were in the open group, among which 290 were female (74.6%) and 99 were male (25.4%), with the age of 47 (38, 55) years and a BMI of 23.2 (21.3, 25.5) kg/m2. Further analysis after PSM (there were 264 cases in both groups) showed that in the subtotal thyroidectomy and central neck dissection (LT+CCND) subgroup, the robotic group had longer operative time, higher blood loss, and greater drainage volume compared with the open group [100 (80, 130) min vs 60 (50, 80) min; 10 (10, 20) ml vs 10 (10, 20) ml; 103 (69, 145) ml vs 75 (57, 98) ml; all P<0.001], and the central lymph node metastasis rate was higher in the robotic group [45.6% (57/125) vs 31.8% (47/148), P=0.019]. In the total thyroidectomy and central neck dissection (TT+CCND) subgroup, the robotic group also had longer operative time, higher blood loss, and greater drainage volume compared with the open group [150 (110, 180) min vs 85 (75, 100) min; 20 (10, 20) ml vs 10 (10, 20) ml; 155 (107, 206) ml vs 90 (70, 120) ml; all P<0.001]. The incidence of chest skin numbness at 3 months postoperatively was higher in the robotic group compared with the open group (12.9% vs 0, P<0.001), while there were no statistically significant differences in other postoperative complications (all P>0.05). The VAS score at 2 months postoperatively was higher in the robotic group compared with the open group [9 (9, 9) vs 8 (7, 9), P<0.001]. Three cases of contralateral lobe recurrence occurred in the open group, while there were no case of recurrence in the robotic group. The 5-year overall survival rate was 100.0% in both the robotic and open groups, and there was no statistically significant difference in the 5-year disease-free survival rate between the robotic and open groups (100.0% vs 98.6%, P=0.068). Conclusion: Gasless robotic surgery through transaxillary approach for total thyroidectomy or lobectomy in the treatment of PTC is safe, feasible, and effective, with good cosmetic outcomes and comparable efficacy to traditional surgery.

[The impact of gallbladder cholesterolosis on the morphology of gallstones].

Objective: To investigate the impact of gallbladder cholesterolosis on the morphology of gallstones. Methods: The patients with gallstone who underwent cholecystectomy at the Gallstone Disease Center of East Hospital Affiliated to Tongjin University from December 2020 to October 2021 were retrospectively included. The patients were divided into the case group (sludge-like) and the control group (non-sludge-like stone), based on gallstone morphology. Clinical baseline characteristics between the two groups were compared. The related factors influencing gallstone morphology were analyzed using multivariate logistic regression analysis. Results: A total of 110 patients were included, with 30 cases in the case group (13 males, 17 females), aged 26-73 (54±14) years, 80 cases in the control group (24 males, 56 females), aged 18-75 (45±13) years. The age of the case group was higher than that of the control group (P=0.003). The occurrence rate of occult pancreaticobiliary reflux (OPBR) was higher in the case group compared to the control group [33.3% (10/30) vs 13.8% (11/80), P=0.020]; the occurrence rate of gallbladder cholesterolosis was lower in the case group compared to the control group [30.0% (9/30) vs 73.8% (59/80), P<0.001]. The results of multivariate logistic regression analysis showed that gallbladder cholesterolosis (OR=0.19, 95%CI: 0.07-0.49, P=0.001) was a significant factor associated with sludge-like stones. Conclusion: Gallbladder cholesterolosis can cause the formation of different forms of cholecystolithiasis, and promote the occurrence and development of "solid stones".

[Report on the application of endoscopic intermuscular dissection for diagnostic resection of early rectal cancer].

Objective: This report presents the initial outcomes of endoscopic intermuscular dissection (EID), a novel technique introduced by our team for the diagnostic resection of early rectal cancer, focusing on the postoperative status of the vertical margins. Methods: On January 26, 2024, a patient with early rectal cancer (cT1-2N0M0) underwent Endoscopic Intermuscular Dissection. The EID procedure consists of six steps: (1) mucosal incision; (2) submucosal dissection; (3) superficial muscular layer incision; (4) intermuscular dissection; (5) complete tumor removal; (6) wound management. Results: The patient was a 70-year-old male with rectal cancer (cT1-2N0M0). The tumor was located on the left anterior wall of the rectum, approximately 9 cm from the anal margin, and measured 20mm in size. The dissection rate was 2.68 mm²/minute, and the total duration of the surgery was 109 minutes. The patient was successfully discharged on the fifth day after surgery. Pathological examination of the post-endoscopic surgery specimen revealed pT1b, with negative vertical margins. Follow-up after more than one month showed good recovery with no complications such as bleeding, perforation, infection, or stricture occurring. Colonoscopy indicated the presence of a granulation tissue suggestive of inflammation. Conclusion: Endoscopic Intermuscular Dissection for the diagnostic resection of early rectal cancer is potentially safe and may achieve negative vertical margins.

[Preliminary outcomes of neoadjuvant chemoimmunotherapy combined with transoral robotic surgery for locally advanced oropharyngeal squamous cell carcinoma].

Objective: To evaluate the efficacy of neoadjuvant chemoimmunotherapy (NACI) combined with transoral robotic surgery (TORS) in the treatment of locally advanced oropharyngeal squamous cell carcinoma (OPSCC). Methods: This was a retrospective study of 15 patients with locally advanced OPSCC who underwent TORS after neoadjuvant therapy (NAT) at the Department of Otolaryngology-Head and Neck Surgery of Sun Yat-sen Memorial Hospital of Sun Yat-sen University from April 2019 to February 2023. There were 12 males and 3 females, aged 31 to 74 years. Twelve cases were tonsil cancer, and 3 cases were tongue base cancer. There were 11 cases in stage Ⅲ and 4 cases in stage Ⅳ. Two patients received neoadjuvant chemotherapy and 13 patients received NACI, with 2 to 3 cycles, and all patients underwent TORS after multidisciplinary team consultation. The clinicopathological characteristics, surgical outcomes, and oncological results were summarized. Results: All surgeries were successfully completed with negative surgical margins, and no case was required conversion surgery. All patients were fed via nasogastric tubes postoperatively, with a median gastric tube stay of 7 days (range: 2-60 days). No tracheotomy was applied. There were no major complications such as postoperative bleeding. Pathological complete response (pCR) was found in 10 cases (76.9%) among the 13 patients with NACI. The follow-up time was 21 months (range: 10-47 months), and there was no death or distant metastasis. One patient with rT0N3M0 tonsil cancer had local recurrence 5 months after surgery. The 2-year overall survival and 2-year disease-free survival were respectively 100.0% and 93.3% in the 15 patients. Conclusion: NACI combined with TORS provides a safe, effective and minimally invasive treatment for patients with locally advanced oropharyngeal squamous cell carcinoma.

[Safety and efficacy of acute stent implantation during endovascular treatment for patients with emergent large vessel occlusion due to intracranial atherosclerotic stenosis].

Objective: To investigate the efficacy and safety of acute stent implantation during endovascular treatment for patients with emergent large vessel occlusion due to intracranial atherosclerotic stenosis. Methods: A retrospective analysis was carried out on 46 patients with emergent large vessel occlusion due to intracranial atherosclerotic stenosis who received endovascular treatment at the Strategic Support Force Medical Center from January 2015 to August 2022. Twenty-seven patients underwent balloon angioplasty alone and 19 patients underwent acute stent implantation. The baseline characteristics, modified thrombolysis in cerebral infarction (mTICI) score of the responsible vessels, modified Rankin scale (mRS) score 90 days after operation, incidence of symptomatic intracranial hemorrhage and mortality of the two groups were evaluated. Results: The proportion of effective recanalization of the offending vessels (mTICI≥2b) in the acute stenting group was slightly higher than that in the balloon angioplasty group (16/19 vs. 81.5%), but the difference was not statistically significant (P>0.05). Besides, there was no significant difference in the median of mRS between the acute stenting group [3.0(0, 4.0)] and the balloon angioplasty group [4.0(1.0, 5.0)] 90 days after operation (P>0.05). In terms of safety, the incidence of symptomatic intracranial hemorrhage and mortality were comparable between the two groups (P>0.05). Conclusions: The effect of acute stent implantation during endovascular treatment for patients with emergent large vessel occlusion due to intracranial atherosclerotic stenosis is not inferior to that of balloon angioplasty, and it does not increase the risk of intracranial bleeding complications.

[Long-term outcomes of intravascular ultrasound-guided drug-eluting stents implantation in patients with acute coronary syndrome: ULTIMATE ACS subgroup].

Objective: To explore the long-term effects of intravascular ultrasound (IVUS) guidance on patients with acute coronary syndrome (ACS) undergoing drug-eluting stents (DES) implantation. Methods: Data used in this study derived from ULTIMATE trial, which was a prospective, multicenter, randomized study. A total of 1 448 all-comer patients were enrolled between 2014 August and 2017 May. Primary endpoint of this study was target vessel failure (TVF) at 3 years, including cardiac death, target-vessel-related myocardial infarction, and clinically-driven target vessel revascularization. Results: ACS was present in 1 136 (78.5%) patients, and 3-year clinical follow-up was available in 1 423 patients (98.3%). TVF in the ACS group was 9.6% (109/1 136), which was significantly higher than 4.5% (14/312) in the non-ACS group (log-rank P=0.005). There were 109 TVFs in the ACS patients, with 7.6% (43/569) TVFs in the IVUS group and 11.6% (66/567) TVFs in the angiography group (log-rank P=0.019). Moreover, patients with optimal IVUS guidance were associated with a lower risk of 3-year TVF compared to those with suboptimal IVUS results (5.4% (16/296) vs. 9.9% (27/273),log-rank P=0.041). Conclusions: This ULTIMATE-ACS subgroup analysis showed that ACS patients undergoing DES implantation were associated with a higher risk of 3-year TVF. More importantly, the risk of TVF could be significantly decreased through IVUS guidance in patients with ACS, especially in those who had an IVUS-defined optimal procedure.

[Clinical features and Y chromosome abnormalities in children with 45, X/46, XY mosaicism].

Objective: To investigate the clinical and genetic characteristics of children with 45, X/46, XY mosaicism. Methods: The retrospective study included 20 children diagnosed with 45, X/46, XY and 45, X/46, X,+mar mosaicism in the First Affiliated Hospital of Zhengzhou University from 2018 to 2022. The clinical features, gonadal pathology, treatment and follow-up were summarized. Genetic tests were performed by SRY gene test, azoospermia factor region (AZF) deletion test, copy number variation-sequencing (CNV-seq). Age at first diagnosis was compared between boys and girls using independent sample t-test. Results: The 20 patients included 3 boys and 17 girls, and the age at first diagnosis were (7.6±5.5) years, it is (2.1±1.9) years in boys, (8.7±5.4) years in girls, significantly younger for boys (t=-3.86, P=0.004). The chief complaint was external genitalia malformation for boys, and short stature (13 cases) and dysplastic external genital for girls (4 cases). Five girls presented with features of Turner syndrome. The gonadal phenotypes included mixed gonadal dysplasia (MGD, 6 cases), complete gonadal dysplasia (CGD, 10 cases), unilateral ovotestis (2 cases), possible ovaries (1 case) and undetermined gonad (1 case). One female with dysplastic genital was reassigned to male, and the gender of the remaining cases remained unchanged. Seven females were treated with recombinant human growth hormone. The height increased by (17±7) cm during the (2.9±1.2) years follow-up. No gonadal malignancy was observed. The karyotype was 45, X/46, XY in 16 cases, and 45, X/46, X,+mar in 4 cases. All of the 4 marker chromosomes were derived from Y chromosome confirmed by CNV-seq. SRY gene was detected in all 20 patients genome, and AZF deletion was found in 7 girls. Conclusions: 45, X/46, XY mosaicism presented with dysplastic external genital or female with remarkable short stature. Gonadal phenotypes included MGD, CGD and ovotestis. AZF microdeletions were found in the majority of female cases.

[Analysis of DMD gene variants in a single center].

Objective: To investigate the DMD genetic variants of the Chinese population with Duchenne (DMD) and Becker muscular dystrophies (BMD). Methods: A cross-sectional study was conducted on 2 690 unrelated patients with DMD and BMD aged 0-18 who visited the Genetic and Prenatal Diagnosis Center of the First Affiliated Hospital of Zhengzhou University from January 2005 to February 2022. The clinical data, such as gender, age, clinical manifestations, and address, were collected. Multiplex ligation-dependent probe amplification, next generation sequencing panel, Sanger sequencing, and PCR amplification were used to detect the variants of the DMD gene in the patients, whose clinical information and gene detection results were descriptively analyzed. Results: The 2 690 patients included 2 648 males and 42 females, with an age of 6.0 (4.0, 9.0) years. The serum creatine kinase increased in all patients. Pathogenic DMD gene variants were detected in the 2 618 patients, including 1 875 cases (71.6%) large deletions, 231 cases (8.8%) duplications, and 512 cases (19.6%) small variants. Among the deletion variants, the deletion of 3 exons was the most common, accounting for 15.4% (288/1 875); and hotspot deletion involved exons 45 to 50, accounting for 6.3% (119/1 875). Exon 2 was the most common type duplication region, accounting for 13.0% (30/231). Small variants were distributed in all 79 exons of the DMD gene, with no hotspots. In addition, the 46 small variants were previously unreported. Conclusion: Exon deletion is the most common type of DMD gene variant, followed by small variants and exon duplication.

[Overexpression of lncRNA HEM2M alleviates liver injury in mice with non-alcoholic fatty liver disease].

OBJECTIVE: To explore the effects of long non-coding RNA (lncRNA) HEM2M overexpression on liver injury in mice with non-alcoholic fatty liver disease (NAFLD). METHODS: Wild-type C57BL/6 (WT) mice and myeloid cell-specific HEM2M knock-in (MYKI) mice were fed normal (ND) or high-fat diet (HFD) for 12 weeks. After intraperitoneal glucose tolerance and insulin tolerance tests, the mice were euthanized for detection of liver function indicators in the serum and liver tissue. HE staining and F4/80 immunohistochemical staining were used to examine liver pathologies, and the levels of IL-6, IL-1ß, and TNF-α in the liver tissues were determined with ELISA. The mRNA expressions of HEM2M and the markers of M1 macrophages (TNF-α, iNOS, and IL-6) and M2 macrophages (Arg-1, YM-1, and IL-10) were detected using qRT-PCR, and the protein expressions of P-AKT, T-AKT, NLRC4, caspase-1 and GSDMD were assayed using immunoblotting. Caspase-1 activity in the liver tissues was determined with colorimetric measurement and immunofluorescence assay. RESULTS: Compared with HFD-fed WT mice, MYKI mice with HFD feeding showed milder liver function damage (P < 0.01), alleviated hepatic steatosis, and reduced liver macrophage infiltration, glucose tolerance impairment and insulin resistance (P < 0.01). The levels of IL-6, IL-1ß, and TNF-α and mRNA expressions of M1 type macrophage markers were significantly decreased (P < 0.01) and those of M2 type markers increased (P < 0.01) in the liver tissues of HFD-fed MYKI mice, which also showed reduced NLRC4 inflammasome activity, caspase-1 activation, and GSDMD-N protein expression compared with their WT counterparts (P < 0.05). CONCLUSION: Overexpression of HEM2M reduces the production of hepatic inflammatory factors, improves insulin resistance and inhibits hepatic NLRC4 inflammasome activation, which leads to reduced hepatic pyroptosis and liver injury in NAFLD mice.

[Clinical efficacy and safety of venetoclax combined with multidrug chemotherapy in the treatment of 15 patients with relapsed or refractory early T-cell precursor acute lymphoblastic leukemia].

Objective: To explore the efficacy and safety of Venetoclax combined with multidrug chemotherapy in patients with relapsed or refractory early T-cell precursor acute lymphoblastic leukemia (R/R ETP-ALL) . Methods: This study retrospectively analyzed 15 patients with R/R ETP-ALL who received Venetoclax combined with multidrug chemotherapy from December 2018 to February 2022. Among them, eight cases were combined with demethylated drugs, four cases were combined with demethylated drugs and HAAG chemotherapy regimen, two cases were combined with demethylated drugs and CAG regimen, and one case was combined with Cladribine. Specific usage and dosage of Venetoclax: 100 mg on day 1, 200 mg on day 2, 400 mg on day 3-28, orally; when combined with azole antifungal drugs, dosage was reduced to 100 mg/d. Results: Fifteen patients (10 males and 5 females) with R/R ETP-ALL were treated with Venetoclax and multidrug chemotherapy with a median age of 35 (12-42) years old. Of 4 refractory and 11 relapsed patients, the efficacy was evaluated on the 21th day following combined chemotherapy: the overall response rate, the complete response (CR) rate, and the CR with incomplete hematological recovery (CRi) rate were 67.7% (10/15), 60.0% (9/15), and 6.7% (1/15), respectively. For the overall study population, the 12-month overall survival (OS) rate was 60.0%, and the median OS was 17.7 months. The disease-free survival (DFS) rate of all CR patients at 12 months was 60.0%, and the median DFS did not reach. About 14 patients had Ⅲ-Ⅳ hematological toxicity, but these adverse reactions were all controllable. No adverse reaction in the nervous system and tumor lysis syndrome occurred in this study, and no adverse reaction of organs above grade Ⅲ occurred. Conclusion: Venetoclax combined with multidrug chemotherapy may be a safe and promising treatment option for patients with R/R ETP-ALL.

[Novel frameshift mutations in SALL4 in two Chinese families with Okihiro syndrome].

In the present study, clinical manifestations of two Chinese Okihiro syndrome families were analyzed, and genetic detections were performed on the two probands by exome sequencing and verified by Sanger sequencing for family members to determine the biological pathogenesis. Prenatal diagnoses were provided for three high-risk fetuses. The affected members exhibited a wildly spectrum of phenotypes, including ultrasound abnormalities of skeletal system (radius deformity and abnormal posture), and cardiac system (persistent common arterial trunk and ventricular septal defect) in the prenatal period of family 1, the severe phenotypes (grossly shortened and deformed forearm, Duane's anomaly and hearing loss), and the mild ones (usually only thenar dysplasia, or short radius styloid process). Two SALL4 variants, c.844delC p.(Q282Kfs*8) and c.2210delG p.(G737Vfs*23), have been identified respectively in two probands, and c.2210delG of SALL4 gene was unreported previously. The two variants were verified in all affected individuals, not in normal family members. Genotyping results of three fetuses indicated that one fetus was normal, and the two fetuses with heterozygous variation were affected. The two variants of SALL4 gene, c.844delC p.(Q282Kfs*8) and c.2210delG p.(G737Vfs*23), were the molecular pathological cause of Okihiro syndrome in the present study and enriched the spectrum of SALL4 variants. Our study provides accurate prenatal genetic diagnosis for the two families to avoid the birth of affected children.

[Hepatitis B virus down-regulates the expression of inhibin and promotes the proliferation and survival of hepatocellular carcinoma cells].

Objective: To investigate the effect and role of the hepatitis B virus (HBV) on the expression of inhibin (PHB) in the proliferation and survival of hepatocellular carcinoma (HCC) cells. Methods: The expression of PHB in 13 pairs of HBV-infected livers, normal livers and HepG2.2.15 and HepG2 cells was detected by real-time fluorescent quantitative PCR and Western blot. Liver tissues were collected from seven patients with chronic hepatitis B before and after antiviral (tenofovir) treatment, and the expression of PHB was detected by RT-PCR and Western blot. HepG2.2.15 cells were transfected with Pcmv6-AC-GFP-PHB, and control vectors were collected. DNA content was analyzed by flow cytometry. The proliferation level of each cell group was detected using the EdU cell proliferation assay. HepG2.2.15 cells transfected with Pcmv6-AC-GFP-PHB and the control vector were cultured in serum-free medium for 6 days. Apoptosis was measured at the indicated time points using fluorescence-activated cell sorting (FACS)-based Annexin-V/PI double staining. Results: Compared with normal liver tissue, the expression of PHB in HBV-infected liver tissue was down-regulated (P < 0.01). Compared with HepG2 cells, the expression of PHB in HepG2.2.15 cells was significantly decreased (P < 0.01). The expression level of PHB in liver tissue after antiviral treatment (tenofovir) was significantly higher than that before treatment (P < 0.01). Compared with the control vector, the proliferation rate of HepG2.2.15 cells transfected with Pcmv6-AC-GFP-PHB was significantly lower than that of the control vector, and the apoptosis rate of HepG2.2.15 cells transfected with the Pcmv6-AC-GFP-PHB vector was significantly higher than the control vector (P < 0.01). Conclusion: HBV down-regulates the expression of inhibin to promote the proliferation and survival of hepatocellular carcinoma cells.