Objective To analyze the rules and characteristics of cross-allergy cases related to drug-related medical disputes,and to provide reference for the formulation of cross-allergy prescription review strategy.Methods The judgments of cross-allergy related medical damage liability disputes recorded in the legal document database of Beijing Yingke Law Firm and the Chinese Judgment Document Network database from August 2010 to June 2023 were analyzed,the causes of relevant disputes were summarized and analyzed,and more comprehensive response measures were formulated.Results A total of 65 judgments were retrieved,and seven judgments were included.The main drugs causing cross allergy were antibiotics(penicillins,cephalosporins and sulfonamides).Seven cases of medical disputes,all of which were ruled by the court that the medical party had medical errors due to cross-allergies,and had to bear 30％to 80％of the compensation liability.The main reasons for the punishment were that the doctor did not pay enough attention to the patient's past history of allergy and chose unreasonable drugs.Conclusion Medical institutions can reduce the risk of cross-allergy by means of information technology,and play the role of pharmacists in prescription review and pharmaceutical care.Physicians should pay attention to the patient's past history,earnly inquire,strengthen medication education and monitoring,reduce the threat of adverse reactions to the patient's life safety and related drug disputes,and protect the legitimate rights and interests of both doctors and patients.

Objective:To analyze the clinical phenotype, sperm morphological characteristics and assisted reproductive therapy efficiency in patients with total globozoospermia.Methods:Four male patients with total globozoospermia were collected during November 2019 to May 2022 from Reproductive Medical and Genetic Center, the People's Hospital of Guangxi Zhuang Autonomous Region. Peripheral blood samples were collected for genetic detection and the whole exome sequencing to explore the pathogenic genes. Semen characteristics, sperm morphology and ultrastructure were analyzed. Four patients were treated with intracytoplasmic sperm injection (ICSI) combined with artificial oocyte activation (AOA). Conventional ICSI cycles ( n=9) were selected as control group, and the development dynamic parameters were monitored by Time-lapse. The fertilization and embryo development parameters, developmental dynamic parameters and clinical outcomes were analyzed between the two groups. Results:Four patients were complicated with low sperm motility and increased sperm DNA fragmentation. Sperm morphology analysis and acrosome fluorescence staining represented that all the spermatozoas were with a small round head lacked of acrosome. By the transmission electron microscope, it was observed that round-headed spermatozoas were lacked of acrosome completely, loose chromatin structure, vacuolation and other abnormal changes in the head, mitochondrial sheath in neck were reduced arranged in disorder, and the structure of "9+2" of the flagellar axial filament was incomplete. Of the 4 patients, 1 was homozygous deletion of DPY19L2 gene and 1 was homozygous frameshift mutation of DPY19L2 gene. There were no significance differences in fertilization rate, two pronuclei fertilization rate, day 3 high-quality embryo rate, day 6 blastocyst formation rate and day 6 high-quality blastocyst formation rate between total globozoospermia group and control group (all P>0.05). The developmental dynamic parameters as the time at which the second polar body is extruded, the time when both (or the last) PN disappear, two to six discrete cells in the total globozoospermia group were significantly earlier than those in control group, and the difference was statistically significant (all P<0.05). There was no significant difference in the embryo cleavage patterns between the two groups ( P>0.05). Among the 4 patients with total globozoospermia, 2 live births with signal healthy male baby were achieved by fresh embryo transfer, and 2 live births with one signal healthy male baby and one healthy female baby were achieved by frozen-thawed embryo transfer respectively. Conclusion:Abnormal morphology characteristics of spermatozoas from patients with total globozoospermia are obvious, patients with total globozoospermia could have favorable clinical outcomes following ICSI combined with AOA.

Objective:To analyze the clinical phenotype, sperm morphological characteristics and assisted reproductive therapy efficiency in patients with total globozoospermia.Methods:Four male patients with total globozoospermia were collected during November 2019 to May 2022 from Reproductive Medical and Genetic Center, the People's Hospital of Guangxi Zhuang Autonomous Region. Peripheral blood samples were collected for genetic detection and the whole exome sequencing to explore the pathogenic genes. Semen characteristics, sperm morphology and ultrastructure were analyzed. Four patients were treated with intracytoplasmic sperm injection (ICSI) combined with artificial oocyte activation (AOA). Conventional ICSI cycles ( n=9) were selected as control group, and the development dynamic parameters were monitored by Time-lapse. The fertilization and embryo development parameters, developmental dynamic parameters and clinical outcomes were analyzed between the two groups. Results:Four patients were complicated with low sperm motility and increased sperm DNA fragmentation. Sperm morphology analysis and acrosome fluorescence staining represented that all the spermatozoas were with a small round head lacked of acrosome. By the transmission electron microscope, it was observed that round-headed spermatozoas were lacked of acrosome completely, loose chromatin structure, vacuolation and other abnormal changes in the head, mitochondrial sheath in neck were reduced arranged in disorder, and the structure of "9+2" of the flagellar axial filament was incomplete. Of the 4 patients, 1 was homozygous deletion of DPY19L2 gene and 1 was homozygous frameshift mutation of DPY19L2 gene. There were no significance differences in fertilization rate, two pronuclei fertilization rate, day 3 high-quality embryo rate, day 6 blastocyst formation rate and day 6 high-quality blastocyst formation rate between total globozoospermia group and control group (all P>0.05). The developmental dynamic parameters as the time at which the second polar body is extruded, the time when both (or the last) PN disappear, two to six discrete cells in the total globozoospermia group were significantly earlier than those in control group, and the difference was statistically significant (all P<0.05). There was no significant difference in the embryo cleavage patterns between the two groups ( P>0.05). Among the 4 patients with total globozoospermia, 2 live births with signal healthy male baby were achieved by fresh embryo transfer, and 2 live births with one signal healthy male baby and one healthy female baby were achieved by frozen-thawed embryo transfer respectively. Conclusion:Abnormal morphology characteristics of spermatozoas from patients with total globozoospermia are obvious, patients with total globozoospermia could have favorable clinical outcomes following ICSI combined with AOA.

Emerging SARS-CoV-2 variants have made COVID-19 convalescents susceptible to re-infection and have raised concern about the efficacy of inactivated vaccination in neutralization against emerging variants and antigen-specific B cell response. To this end, a study on a long-term cohort of 208 participants who have recovered from COVID-19 was conducted, and the participants were followed up at 3.3 (Visit 1), 9.2 (Visit 2), and 18.5 (Visit 3) months after SARS-CoV-2 infection. They were classified into three groups (no-vaccination (n = 54), one-dose (n = 62), and two-dose (n = 92) groups) on the basis of the administration of inactivated vaccination. The neutralizing antibody (NAb) titers against the wild-type virus continued to decrease in the no-vaccination group, but they rose significantly in the one-dose and two-dose groups, with the highest NAb titers being observed in the two-dose group at Visit 3. The NAb titers against the Delta variant for the no-vaccination, one-dose, and two-dose groups decreased by 3.3, 1.9, and 2.3 folds relative to the wild-type virus, respectively, and those against the Omicron variant decreased by 7.0, 4.0, and 3.8 folds, respectively. Similarly, the responses of SARS-CoV-2 RBD-specific B cells and memory B cells were boosted by the second vaccine dose. Results showed that the convalescents benefited from the administration of the inactivated vaccine (one or two doses), which enhanced neutralization against highly mutated SARS-CoV-2 variants and memory B cell responses. Two doses of inactivated vaccine among COVID-19 convalescents are therefore recommended for the prevention of the COVID-19 pandemic, and vaccination guidelines and policies need to be updated.

Objective:To establish a technical system for early judgment and rescue artificial oocyte activation of oocytes after fertilization failed, intracytoplasmic sperm injection (ICSI) and to explore the activation efficiency and application value.Methods:Firstly, a retrospective analysis was performed in 150 ICSI cycles cultured by Time-lapse system during January 2017 to March 2018 from Reproductive Medical and Genetic Center, the People's Hospital of Guangxi Zhuang Autonomous Region, the time distribution of the second polar body (Pb2) exclusion and its relationship with fertilization and embryo development outcomes, the feasibility of Pb2 exclusion as an early indicator of fertilization failure in ICSI was discussed. Secondly, 225 fertilization failed oocytes from 93 ICSI cycles during March 2018 to June 2019 were collected for randomized controlled trials according to different artificial activation modes. They were divided into three groups including non-activation group (NAOA group), rescue activation group (RAOA group) and late activation group (LAOA group). At the same time, the rest of injected oocytes from ICSI cycles include in this study were used as control group. Fertilization and embryo development parameters were used to explore the efficiency and application value of rescue artificial activation for after fertilization failure oocytes ICSI.Results:Time-lapse monitoring showed that the fertilization rate and 2PN fertilization rate were 99.91% and 97.76% in the Pb2-exclusion group, 0.03% and 0% in the without Pb2-exclusion group after ICSI, with significant differences between the two groups ( P<0.001); the exclusion time of Pb2 after ICSI was (3.04±1.45) h, and the distribution and proportion of Pb2 exclusion time were 0-3 h (58.00%), 3-5 h (36.29%), 5-8 h (3.92%) and >8 h (1.21%). The Pb2 exclusion rate, the fertilization rate and the 2PN fertilization rate in NAOA group were all 0%, and the 2PN fertilization rate (36.00%), day 3 (D3) high-quality embryo rate (8.00%), day 5 (D5) blastocyst formation rate (0%) and D5 high-quality blastocyst formation rate (0%) in LAOA group were significantly lower than those in RAOA group (60.00%, 44.19%, 51.16%, 25.58%) ( P=0.005, P=0.002, P<0.001, P=0.005), and also in control group (97.63%, 48.62%, 63.23%, 37.94%) ( P<0.001); the Pb2 exclusion rate (84.00%), the fertilization rate (81.33%), the 2PN fertilization rate (60.00%) and the 2PN cleavage rate (95.56%) in RAOA group were significantly lower than those in control group (100.00%, 99.68%, 97.63%, 99.51%) ( P<0.001, P<0.001, P<0.001, P=0.04). However, there was no significant difference in D3 high-quality embryo rate, D5 blastocyst formation rate and D5 high-quality blastocyst formation rate between the two groups ( P>0.05). Conclusion:Time-lapse monitoring of the Pb2 exclusion can be used as an early judgment indicator of fertilization failure in ICSI cycles. Rescue artificial activation of fertilization failed oocytes in 5 h after ICSI can achieve normal fertilization and acceptable embryo development outcomes.

Objective:To establish a technical system for early judgment and rescue artificial oocyte activation of oocytes after fertilization failed, intracytoplasmic sperm injection (ICSI) and to explore the activation efficiency and application value.Methods:Firstly, a retrospective analysis was performed in 150 ICSI cycles cultured by Time-lapse system during January 2017 to March 2018 from Reproductive Medical and Genetic Center, the People's Hospital of Guangxi Zhuang Autonomous Region, the time distribution of the second polar body (Pb2) exclusion and its relationship with fertilization and embryo development outcomes, the feasibility of Pb2 exclusion as an early indicator of fertilization failure in ICSI was discussed. Secondly, 225 fertilization failed oocytes from 93 ICSI cycles during March 2018 to June 2019 were collected for randomized controlled trials according to different artificial activation modes. They were divided into three groups including non-activation group (NAOA group), rescue activation group (RAOA group) and late activation group (LAOA group). At the same time, the rest of injected oocytes from ICSI cycles include in this study were used as control group. Fertilization and embryo development parameters were used to explore the efficiency and application value of rescue artificial activation for after fertilization failure oocytes ICSI.Results:Time-lapse monitoring showed that the fertilization rate and 2PN fertilization rate were 99.91% and 97.76% in the Pb2-exclusion group, 0.03% and 0% in the without Pb2-exclusion group after ICSI, with significant differences between the two groups ( P<0.001); the exclusion time of Pb2 after ICSI was (3.04±1.45) h, and the distribution and proportion of Pb2 exclusion time were 0-3 h (58.00%), 3-5 h (36.29%), 5-8 h (3.92%) and >8 h (1.21%). The Pb2 exclusion rate, the fertilization rate and the 2PN fertilization rate in NAOA group were all 0%, and the 2PN fertilization rate (36.00%), day 3 (D3) high-quality embryo rate (8.00%), day 5 (D5) blastocyst formation rate (0%) and D5 high-quality blastocyst formation rate (0%) in LAOA group were significantly lower than those in RAOA group (60.00%, 44.19%, 51.16%, 25.58%) ( P=0.005, P=0.002, P<0.001, P=0.005), and also in control group (97.63%, 48.62%, 63.23%, 37.94%) ( P<0.001); the Pb2 exclusion rate (84.00%), the fertilization rate (81.33%), the 2PN fertilization rate (60.00%) and the 2PN cleavage rate (95.56%) in RAOA group were significantly lower than those in control group (100.00%, 99.68%, 97.63%, 99.51%) ( P<0.001, P<0.001, P<0.001, P=0.04). However, there was no significant difference in D3 high-quality embryo rate, D5 blastocyst formation rate and D5 high-quality blastocyst formation rate between the two groups ( P>0.05). Conclusion:Time-lapse monitoring of the Pb2 exclusion can be used as an early judgment indicator of fertilization failure in ICSI cycles. Rescue artificial activation of fertilization failed oocytes in 5 h after ICSI can achieve normal fertilization and acceptable embryo development outcomes.

The harm of tobacco is one of the most serious public health issues nowadays, and the social cost produced by smoking is increasing year by year. There are about 6 million people dying from smoking-related diseases each year, and the number of death will surpass 8 million by 2030. Helping smokers quit is the most direct and effective method to reduce the burden of disease caused by tobacco. M-health based on smartphone shows huge potential in prompting health behavior. Progress of studies on smartphone applications (APP), a new way of tobacco control, is reviewed to provide reference for future tobacco control practice and exploration.