Objective To explore the efficacy and safety of recombinant human anti-severe acute respiratory syn-drome coronavirus 2(anti-SARS-CoV-2)monoclonal antibody injection(F61 injection)in the treatment of patients with coronavirus disease 2019(COVID-19)combined with renal damage.Methods Patients with COVID-19 and renal damage who visited the PLA General Hospital from January to February 2023 were selected.Subjects were randomly divided into two groups.Control group was treated with conventional anti-COVID-19 therapy,while trial group was treated with conventional anti-COVID-19 therapy combined with F61 injection.A 15-day follow-up was conducted after drug administration.Clinical symptoms,laboratory tests,electrocardiogram,and chest CT of pa-tients were performed to analyze the efficacy and safety of F61 injection.Results Twelve subjects(7 in trial group and 5 in control group)were included in study.Neither group had any clinical progression or death cases.The ave-rage time for negative conversion of nucleic acid of SARS-CoV-2 in control group and trial group were 3.2 days and 1.57 days(P=0.046),respectively.The scores of COVID-19 related target symptom in the trial group on the 3rd and 5th day after medication were both lower than those of the control group(both P＜0.05).According to the clinical staging and World Health Organization 10-point graded disease progression scale,both groups of subjects improved but didn't show statistical differences(P＞0.05).For safety,trial group didn't present any infusion-re-lated adverse event.Subjects in both groups demonstrated varying degrees of elevated blood glucose,elevated urine glucose,elevated urobilinogen,positive urine casts,and cardiac arrhythmia,but the differences were not statistica-lly significant(all P＞0.05).Conclusion F61 injection has initially demonstrated safety and clinical benefit in trea-ting patients with COVID-19 combined with renal damage.As the domestically produced drug,it has good clinical accessibility and may provide more options for clinical practice.

Aim To investigate the changes in the proliferation and apoptosis of Siha cells after knocking down Rho GTPase-activating protein 30(ARHGAP30).Methods After designing specific shARHGAP30 primers and connecting them to the pLKO.1 vector,we transformed them into Escherichia coli competent cells,then co-transfecting them with lentiviral helper plasmids into HEK-293T cells.We collected and filtered cell supernatant to obtain the vi-rus to infect Siha cells.RT-qPCR and Western blot were used to detect knockdown efficiency,as well as changes in the expression of Bax and Bcl-2 after trans-fection.The CCK-8 method was employed to measure the proliferation level of cells after knockdown.Results After successful construction of a lentiviral plasmid with knockdown of the ARHGAP30 gene and establish-ment of stably transfected Siha cells,ARHGAP30 tran-scription and translation(P＜0.01)in Siha cells de-creased,Bax/Bcl-2 significantly decreased(P＜0.01),indicating decreased apoptosis and increased cell proliferation(P＜0.01).Conclusions This study suggests the involvement of ARHGAP30 in the proliferation and apoptosis of Siha cells,and regulating the ARHGAP30 gene may interfere with the occurrence and development of cervical cancer.

This study aimed to investigate the therapeutic effect of Yunkang Oral Solution on the improvement of spleen deficiency and pregnancy outcomes in pregnant mice with spleen deficiency syndrome induced by irregular diet and over consumption of cold and bitter foods. To simulate human irregular diet and over consumption of cold and bitter foods leading to spleen deficiency, the pregnant mice with spleen deficiency syndrome were prepared using an alternate-day fasting and high-fat diet combined with oral administration of Sennae Folium. During the experiment, spleen deficiency-related indicators and diarrhea-related parameters were measured. Gastric and intestinal motility(gastric emptying rate and intestinal propulsion rate) were evaluated. The levels of serum ghrelin, growth hormone(GH), gastrin(Gas), total cholesterol(TC), low-density lipoprotein cholesterol(LDL-c), chorionic gonadotropin β(β-CG), progesterone(P), and estradiol(E_2) were measured. Intestinal barrier function in pregnant mice with spleen deficiency syndrome was assessed. Conception rate, ovarian coefficient, litter-bearing uterine coefficient, number of live fetuses, average fetal weight, and fetal length were calculated. The results showed that Yunkang Oral Solution significantly improved spleen deficiency-related indicators and diarrhea in pregnant mice with spleen deficiency syndrome, increased gastric emptying rate and intestinal propulsion rate, elevated the levels of gastrointestinal hormones(ghrelin, GH, and Gas) in the serum, and reduced lipid levels(TC and LDL-c), thereby improving lipid metabolism disorders. It also improved colonic tissue morphology, increased the number of goblet cells, and promoted the mRNA and protein expression of occludin and claudin-1 in colonic tissues, thereby alleviating intestinal barrier damage. Yunkang Oral Solution also regulated the levels of pregnancy hormones(β-CG, P, and E_2) in the serum of pregnant mice with spleen deficiency syndrome. Moreover, it increased the conception rate, ovarian coefficient, litter-bearing uterine coefficient, number of live fetuses, average fetal weight, and fetal length. These findings suggest that Yunkang Oral Solution can improve spleen deficiency-related symptoms in pregnant mice before and during pregnancy, regulate pregnancy-related hormones, and improve pregnancy outcomes.
Pregnancy ; Female ; Mice ; Humans ; Animals ; Spleen ; Ghrelin ; Fetal Weight ; Cholesterol, LDL ; Diarrhea

Objective: To analyze the clinical and molecular diagnostic status of Fanconi anemia (FA) in China. Methods: The General situation, clinical manifestations and chromosome breakage test and genetic test results of 107 pediatric FA cases registered in the Chinese Blood and Marrow Transplantation Registry Group (CBMTRG) and the Chinese Children Blood and Marrow Transplantation Registry Group (CCBMTRG) from August 2009 to January 2022 were analyzed retrospectively. Children with FANCA gene variants were divided into mild and severe groups based on the type of variant, and Wilcoxon-test was used to compare the phenotypic differences between groups. Results: Of the 176 registered FA patients, 69 (39.2%) cases were excluded due to lack of definitive genetic diagnosis results, and the remaining 107 children from 15 hospitals were included in the study, including 70 males and 37 females. The age at transplantation treatment were 6 (4, 9) years. The enrolled children were involved in 10 pathogenic genes, including 89 cases of FANCA gene, 7 cases of FANCG gene, 3 cases of FANCB gene, 2 cases of FANCE gene and 1 case each of FANCC, FANCD1, FANCD2, FANCF, FANCJ, and FANCN gene. Compound heterozygous or homozygous of loss-of-function variants account for 69.2% (72/104). Loss-of-function variants account for 79.2% (141/178) in FANCA gene variants, and 20.8% (37/178) were large exon deletions. Fifty-five children (51.4%) had chromosome breakage test records, with a positive rate of 81.8% (45/55). There were 172 congenital malformations in 80 children.Café-au-Lait spots (16.3%, 28/172), thumb deformities (16.3%,28/172), polydactyly (13.9%, 24/172), and short stature (12.2%, 21/172) were the most common congenital malformations in Chinese children with FA. No significant difference was found in the number of congenital malformations between children with severe (50 cases) and mild FANCA variants (26 cases) (Z=-1.33, P=0.185). Conclusions: FANCA gene is the main pathogenic gene in children with FA, where the detection of its exon deletion should be strengthened clinically. There were no phenotypic differences among children with different types of FANCA variants. Chromosome break test is helpful to determine the pathogenicity of variants, but its accuracy needs to be improved.
Male ; Female ; Humans ; Child ; Fanconi Anemia/genetics* ; Chromosome Breakage ; Retrospective Studies ; Exons ; China/epidemiology*

Objective: To assess the risk of foodborne diseases caused by Cronobacter sakazakii in infant formula powder from retail to feeding and provide formulate suggestions for safe feeding of infants at home. Methods: This study used the special monitoring and risk monitoring data of infant formula powder in Heilongjiang Province and combined data at home and abroad. The @RISK software was used to evaluate the disease risk caused by Cronobacter sakazakii in the process of infant formula powder from retail to feeding. Results: According to the results of this quantitative risk assessment, the risk of foodborne diseases caused by Cronobacter sakazakii at the current consumption pattern in Heilongjiang Province was 5.158×10^-5 persons/million (40.0 ℃ and 50.0 ℃), 1.072×10^-7 persons/million (60.0 ℃), 5.544×10^-14 persons/million (70.0 ℃). When the feeding time of infant formula powder was adjusted to 0-2 h and 2-3 h respectively, the above prediction results did not change. When it was adjusted to 3-4 h, the risk increased. If it was adjusted to 4-24 h, the number of Cronobacter sakazakii increased by 14-24 orders of magnitude at room temperature. If the initial pollution concentration (after flushing) was adjusted to 1 MPN/ml, the average disease risk per meal was 805.7 persons/million (40.0 ℃ and 50.0 ℃), 1.7 persons/million (60.0 ℃) and 9.1 × 10^-7 persons/million (70.0 ℃). The results of sensitivity analysis showed that the water temperature (70.0 ℃), initial pollution concentration, room storage time and temperature were important factors of risk. Conclusion: Controlling the contamination level of Cronobacter sakazakii in infant formula powder, controlling the feeding time within 3 h, storing in refrigerator and mixing with water with temperature not lower than 70.0 ℃ are effective measures to prevent infants from eating infant formula powder infected by Cronobacter sakazakii.
Infant ; Humans ; Cronobacter sakazakii ; Infant Formula ; Food Microbiology ; Powders ; Risk Assessment ; Foodborne Diseases

ObjectiveTo explore the correlation between the content of 4 functional components in Codonopsis pilosula roots from different areas and soil factors， and thereby to lay a theoretical basis for soil ecological regulation and improvement of quality of C. pilosula roots. MethodThe content of lobetyolin， atractylenolide Ⅲ， alcohol extract， and polysaccharides， as well as soil fertility and 16 soil factors in 24 batches of samples from different producing areas were determined. Principal component analysis （PCA） and Pearson's correlation analysis were used to explore the key soil factors leading to the variation of chemical component content in C. pilosula roots. ResultThe content of lobetyolin and atractylenolide Ⅲ in samples from Longxi was the highest， and the content of polysaccharides peaked in samples from Huguan. The content of lobetyolin was in positive correlation with soil total nitrogen， total phosphorus， total potassium， alkali-hydrolyzable nitrogen， and available potassium （P<0.01）， as well as soil organic matter， pH， available manganese， and available zinc （P<0.05）. There was a positive correlation between pH and atractylenolide Ⅲ content （P<0.05）. Soil total potassium was in positive correlation with alcohol extract and polysaccharide content （P<0.01）. Soil available zinc was positively correlated with alcohol extract and the polysaccharide content （P<0.05）. Sample sites with higher PCA scores were Pingshun， Huguan， and Longxi， which were significantly positively correlated with the content of polysaccharides in C. pilosula roots in different habitats. ConclusionThe content of functional components in C. pilosula roots can be improved by raising soil organic matter content and applying specific fertilizers.

Objective:To analyze the clinical characteristics and prognosis of pregnant women with hemorrhagic fever with renal syndrome (HFRS).Methods:A total of 11 pregnant women with HFRS admitted to The Second Affiliated Hospital of Xi′an Jiaotong University (four cases), The Second Affiliated Hospital of Air Force Medical University (four cases), The First Affiliated Hospital of Xi′an Jiaotong University (one case) and Central Hospital of Xianyang City (two cases) between November 2009 and February 2019 were included as the study group, and 24 age-matched non-pregnant women with HFRS were selected as the control group. The age, complications, clinical classification and laboratory indexes of the two groups were analyzed retrospectively, and the clinical outcomes of pregnant women and their fetuses in the study group were followed up. The data between two groups were compared using Mann-Whitney U test or chi-square test. Results:Patients in the study and control groups were 29 (22, 33) and 32 (24, 37) years old, respectively. Seven of 11 patients in study group were severe and critical cases, which was significantly higher than that in the control group (16.7%(4/24), χ2=7.722, P=0.015). In the study group, 10 patients had hypervolemic syndrome, 10 patients had pulmonary edema and six patients had overlapping hypotension shock phase and oliguria phase, which were all higher than those in the control group ((2/24, 8.3%), (2/24, 8.3%) and (2/24, 8.3%), respectively; χ2=22.828, 22.828 and 9.135, respectively, all P<0.01). Compared with the control group, the pregnant patients in study group had a higher urea nitrogen maximum and serum creatinine maximum, and the differences were both statistically significant ( Z=-2.453 and -2.336, respectively, both P<0.05), while they had a lower serum albumin minimum, hemoglobin maximum and hemoglobin minimum, and the differences were all statistically significant ( Z=-3.742, -3.350 and -4.034, respectively, all P<0.01). All pregnant women with HFRS recovered. Nine pregnant women gave birth to nine healthy infants. All of them received breastfeeding and the feeding duration were more than six months. No abnormal growth and development were found during an average follow-up of three years. Conclusions:Pregnancy can aggravate the severity of HFRS, and pregnant women have higher risk of the multiple stages overlap and the complications such as hypervolemic syndrome and acute pulmonary edema. After recovery from HFRS, mother may carry to full-term pregnancy.

BACKGROUND: Heterotopic ossification (HO) is a known complication of hip arthroscopy. We investigated incidence of HO after hip arthroscopy and determined whether revision for HO improved outcome. METHODS: A retrospective study was conducted on 242 patients (140 men and 102 women, mean age: 36.2 ± 9.5 years) who underwent hip arthroscopy for femoroacetabular impingement (FAI) between January 2016 and January 2018. The average follow-up period was 22.88 ± 11.74 months (range: 11-34 months). Thirteen (5.37%) cases of HO (six men and seven women, five left hips and eight right hips; mean age: 37.5 ± 4.7 years) were observed. Among them, four cases with HO with obvious pain symptoms and persistent non-remission underwent revision surgery to remove HO. Monthly follow-up was conducted. Visual analog scale (VAS), modified Harris Hip Score (mHHS), and non-Arthritis Hip Score (NAHS) were evaluated and compared between HO and non-HO patients. Independent sample t test, Mann-Whitney U test and the Chi-square test were used for inter-group comparisons. HO degree was evaluated using Brooker classification. Symptoms and function were evaluated before and after revision. RESULTS: A total of 242 patients were involved in this study. Thirteen cases (5.4%) had imaging evidence of HO. Nine (9/13) were classified as Brooker stage I, three (3/13) Brooker stage II, and one (1/13) Brooker stage III. HO was detected by ultrasonography as early as 3 weeks after operation. After primary surgery, the mHHS of the HO group and non-HO group increased by 13.00 (8.50, 25.50) and 24.00 (14.00, 34.50) points (Z = -1.80, P = 0.08), NAHS increased by 18.00 (9.50, 31.50) and 26.00 (13.50, 36.00) points (Z = -1.34, P = 0.18), and VAS decreased by 3.00 (2.00, 4.00) and 4.00 (3.00, 4.50) points (Z = -1.55, P = 0.12). Average follow-up time after revision was 9.00 ± 2.94 months; mHHS increased by 34.75 points (t = -55.23, P < 0.01) and NAHS by 28.75 points (t = -6.03, P < 0.01), and VAS decreased by 4 points (t = 9.80, P < 0.01). HO and non-HO patients were similar for demographic and surgical data, and clinical and functional scores. CONCLUSION HO incidence after arthroscopic treatment of FAI is similar to that found in previous studies. Most HO have no effect on clinical symptoms. Patients who undergo revision HO resection show improvement in pain and joint function.
Adult ; Arthroscopy ; adverse effects ; Female ; Femoracetabular Impingement ; surgery ; Hip Joint ; pathology ; surgery ; Humans ; Male ; Middle Aged ; Ossification, Heterotopic ; diagnosis ; etiology ; Retrospective Studies ; Treatment Outcome

OBJECTIVE: To observe the effect of Bruton's tyrosine kinase (BTK) on the proliferation and differentiation of osteoclasts and to explore the mechanism of BTK on bone destruction in periapical periodontitis. METHODS: After RAW264.7 cells induced with 100 ng·L⁻¹ receptor activator for nuclear factor-κB ligand (RANKL) for 5 days, osteoclast induction was confirmed by light microscopy, tartrate-resistant acid phosphatase (TRAP) staining, and quantitative real-time PCR (RT-qPCR). Then, BTK-small interfering RNA (BTK-siRNA) was transfected into cells induced for 5 days. After 24 h, the expression of TRAP mRNA was measured using RT-qPCR, and the proliferation and differentiation of osteoclasts were detected using CCK-8 and TRAP activity assay. Statistical analysis was performed. RESULTS: After RAW264.7 was induced with RANKL for 5 days, a large number of round, ellipse, irregularly protuberant, and TRAP-positive macrophages were observed under light microscopy. The expression of TRAP mRNA significantly reduced after 24 h of BTK-siRNA transfection (P<0.05). The detection of CCK-8 and TRAP activities showed that the proliferation and differentiation of osteoclasts significantly decreased (P<0.05). CONCLUSIONS Silencing of BTK can inhibit the proliferation and differentiation of osteoclasts. BTK can be used as a new target for the inhibition of osteoclasts.
Agammaglobulinaemia Tyrosine Kinase ; Cell Differentiation ; Cell Proliferation ; Macrophages ; Osteoclasts ; RANK Ligand

Objective: To investigate the influence of subchronic exposure to low-dose subchronic nano-nickel oxide (NNO) on the reproductive function of male rats and embryonic development of the pregnant rats. METHODS: Fifty normal healthy male SD rats weighing 180－220 g were randomly divided into five groups of equal number, negative control, 4 mg/ml micro-nickel oxide (MNO), and 0.16, 0.8 and 4 mg/ml NNO, those of the latter four groups exposed to MNO or NNO by non-contact intratracheal instillation once every 3 days for 60 days, and then all mated with normal adult female rats in the ratio of 1∶2. After the female animals were confirmed to be pregnant, the males were sacrificed and the weights of the body, testis and epididymis obtained, followed by calculation of the visceral coefficients, determination of epididymal sperm concentration and viability and the nickel contents in the blood and semen by atomic fluorescence spectrometry. The female rats were killed on the 20th day of gestation for counting of the implanted fertilized eggs and live, dead and resorbed fetuses. RESULTS: After 60 days of exposure, the rats of the NNO groups showed no statistically significant differences from those of the negative control and MNO groups in the weights of the body, testis and epididymis or visceral coefficients. Compared with the negative control group, the animals of the 0.8 and 4 mg/ml NNO groups exhibited markedly decreased sperm concentration (［9.36 ± 0.98］ vs ［7.49 ± 1.46］ and ［6.30 ± 1.36］ ×10⁶/ml, P < 0.05) and viable sperm (［85.35 ± 9.16］% vs ［68.26 ± 16.63］% and ［65.88 ± 14.68］ %, P < 0.05), increased morphologically abnormal sperm (［8.30 ± 2.47］% vs ［13.99 ± 4.87］% and ［15.38 ± 8.86］ %, P < 0.05), and elevated rate of dead and resorbed fetuses (1.18% vs 6.89% and 7.37%, P < 0.05), blood nickel content (［0.13 ± 0.16］ vs ［0.52 ± 0.34］ and ［0.82 ± 0.44］ mg/L, P < 0.05) and semen nickel content (［0.08 ± 0.13］ vs ［0.35 ± 0.23］ and ［0.63 ± 0.61］ mg/L, P < 0.05). The nickel level in the semen was correlated significantly with that in the blood (r = 0.912, P <0.01), negatively with the rate of viable sperm (r = －0.879, P <0.01) and positively with the percentage of morphologically abnormal sperm (r = －0.898, P <0.01). CONCLUSIONS Sixty-day exposure to nano-nickel oxide at 0.8 and 4 mg/ml can produce reproductive toxicity in male rats and result in fetal abnormality in the females, while that at 0.16 mg/ml has no significant toxic effect on the reproductive function of the males.