Objective:To investigate the drug resistance of newly diagnosed HIV-1 infected patients in Shanghai and to provide reference value for clinical antiretroviral therapy (ART).Methods:The peripheral venous blood plasma of 196 newly diagnosed HIV-1 infected patients screened according to the inclusion and exclusion criteria at the Shanghai Public Health Clinical Center from April to June 2023 was collected, HIV-1 RNA was extracted, the pol region was amplified by reverse transcription-polymerase chain reaction (RT-PCR) for sequencing, the mutation sites and ART drug resistance were analyzed.Results:The plasma of 196 newly diagnosed HIV-1 infected patients was amplified successfully in 162 cases (amplification success rate was 82.65%). The subtypes consisted of CRF07_BC(51.23%), CRF01_AE (27.78%), and others (6.79%), CRF55_01B (5.56%), B (3.70%), CRF01_AE/B (3.70%) and CRF08_BC (1.23%). The overall transmitted drug resistance rate was 7.41%, the protease inhibitors (PIs), non-nucleoside/nucleotide reverse transcriptase inhibitors (NNRTIs), nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs), integrase inhibitors (INSTIs) resistance rates were 3.09%, 3.70%, 0.00% and 0.62%, respectively. The proportion of NNRTIs-related mutation sites in B (66.67%) and CRF55_01B (88.89%) was higher than that in CRF07_BC (13.25%); the proportion of NNRTIs-related mutation sites in CRF55_01B (88.89%) was higher than that in CRF01_AE (22.22%) and other subtypes (18.18%), the difference was statistically significant (all P<0.05). Multivariate logistic regression analysis showed that the probability of PIs-related mutation sites in CRF01_AE/B was 21.71 times that of CRF07_BC[odds ratio ( OR)=21.71, 95% confidence interval ( CI): 3.36-140.27, P=0.001]. Conclusions:The transmitted drug resistance among newly diagnosed HIV-1 infected patients in Shanghai is at the moderate epidemic level, mainly NNRTIs and PIs-related drug resistance, and the INSTIs resistance rate is low, the use of INSTIs in ART regimens should be considered.

Respiratory viral infections such as influenza and respiratory syncytial virus infections continue to rapidly increase in patients worldwide.Host immune responses to respiratory viruses play a key role in the pathogenesis and clinical manifestations of the disease.Respiratory viruses not only activate antiviral immune responses,but also may lead to uncontrolled inflammatory re-sponses,characterized by significant release of pro-inflammatory cytokines in severely infected patients,resulting in lymphopenia,lymphocyte dysfunction,and abnormalities in immune cells such as neutrophils and macrophages.These respiratory virus-induced im-mune abnormalities may lead to microbial infection,septic shock,and severe multiorgan dysfunction.Therefore,clarifying the immu-nopathogenic mechanisms of patients with respiratory viral infections can guide clinical treatment and patient prognosis;in addition,rational regulation of the immune response of respiratory viruses in the host,including enhancing antiviral immunity while suppressing systemic inflammation,may be the key to successful treatment.This review mainly discusses the immunomodulation and related clini-cal treatment strategies for respiratory viral infections to help develop new therapeutic strategies for respiratory viral infections and pa-tient prognosis.

Respiratory viral infections such as influenza and respiratory syncytial virus infections continue to rapidly increase in patients worldwide.Host immune responses to respiratory viruses play a key role in the pathogenesis and clinical manifestations of the disease.Respiratory viruses not only activate antiviral immune responses,but also may lead to uncontrolled inflammatory re-sponses,characterized by significant release of pro-inflammatory cytokines in severely infected patients,resulting in lymphopenia,lymphocyte dysfunction,and abnormalities in immune cells such as neutrophils and macrophages.These respiratory virus-induced im-mune abnormalities may lead to microbial infection,septic shock,and severe multiorgan dysfunction.Therefore,clarifying the immu-nopathogenic mechanisms of patients with respiratory viral infections can guide clinical treatment and patient prognosis;in addition,rational regulation of the immune response of respiratory viruses in the host,including enhancing antiviral immunity while suppressing systemic inflammation,may be the key to successful treatment.This review mainly discusses the immunomodulation and related clini-cal treatment strategies for respiratory viral infections to help develop new therapeutic strategies for respiratory viral infections and pa-tient prognosis.

Objective:To investigate the drug resistance of newly diagnosed HIV-1 infected patients in Shanghai and to provide reference value for clinical antiretroviral therapy (ART).Methods:The peripheral venous blood plasma of 196 newly diagnosed HIV-1 infected patients screened according to the inclusion and exclusion criteria at the Shanghai Public Health Clinical Center from April to June 2023 was collected, HIV-1 RNA was extracted, the pol region was amplified by reverse transcription-polymerase chain reaction (RT-PCR) for sequencing, the mutation sites and ART drug resistance were analyzed.Results:The plasma of 196 newly diagnosed HIV-1 infected patients was amplified successfully in 162 cases (amplification success rate was 82.65%). The subtypes consisted of CRF07_BC(51.23%), CRF01_AE (27.78%), and others (6.79%), CRF55_01B (5.56%), B (3.70%), CRF01_AE/B (3.70%) and CRF08_BC (1.23%). The overall transmitted drug resistance rate was 7.41%, the protease inhibitors (PIs), non-nucleoside/nucleotide reverse transcriptase inhibitors (NNRTIs), nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs), integrase inhibitors (INSTIs) resistance rates were 3.09%, 3.70%, 0.00% and 0.62%, respectively. The proportion of NNRTIs-related mutation sites in B (66.67%) and CRF55_01B (88.89%) was higher than that in CRF07_BC (13.25%); the proportion of NNRTIs-related mutation sites in CRF55_01B (88.89%) was higher than that in CRF01_AE (22.22%) and other subtypes (18.18%), the difference was statistically significant (all P<0.05). Multivariate logistic regression analysis showed that the probability of PIs-related mutation sites in CRF01_AE/B was 21.71 times that of CRF07_BC[odds ratio ( OR)=21.71, 95% confidence interval ( CI): 3.36-140.27, P=0.001]. Conclusions:The transmitted drug resistance among newly diagnosed HIV-1 infected patients in Shanghai is at the moderate epidemic level, mainly NNRTIs and PIs-related drug resistance, and the INSTIs resistance rate is low, the use of INSTIs in ART regimens should be considered.

Objective:To study the influence of periventricular-intraventricular hemorrhage (PVH-IVH) on cerebral blood flow (CBF) of preterm infants in the late postnatal period using arterial spin labeling (ASL) magnetic resonance imaging (MRI).Methods:From January 2023 to June 2023, 65 preterm infants (gestational age <32 weeks, birth weight <1 500 g) who were born in the Department of Obstetrics, Third Affiliated Hospital of Zhengzhou University and transferred to the Neonatal Intensive Care Unit were included in the prospective study.They were examined by the brain MRI and ASL at the corrected gestational age of 35-40 weeks.According to the results of the brain ultrasound within 1 week after birth, they were divided into the mild IVH group (25 cases) and the non-IVH group (40 cases). The CBF values in regions of interest (frontal lobe, temporal lobe, parietal lobe, occipital lobe, thalamus, and basal ganglia) on ASL images were compared.Multiple linear regression analysis was used to analyze the effect of PVH-IVH on CBF values in different ASL regions of interest, including frontal cortex, temporal cortex, parietal cortex, occipital cortex, thalamus, and basal ganglia.Results:Compared with those of non-IVH group, infants in the mild IVH group presented significantly older gestational age [29.0 (28.5, 30.4) weeks vs.28.2 (27.0, 31.0) weeks, Z=-2.398, P=0.016], higher hematocrit (HCT) in the latest examination prior to the brain MRI [29.6(26.4, 32.3)% vs.27.8 (25.6, 30.5)%, Z=-2.155, P=0.031], and larger body weight at the time of examination [2 015.0 (1 930.0, 2 127.5) g vs.1 950.0 (1 900.0, 1 997.5) g, Z=-3.314, P=0.001]. After adjustment for confounding factors of gestational age at birth, latest HCT and weight at the time of examination, the multivariable linear regression analysis showed that CBF values in the frontal lobe (95% CI: -8.367--4.042; P<0.001), temporal lobe (95% CI: -19.077--2.854; P=0.008), parietal lobe (95% CI: -8.344--3.502; P<0.001), occipital lobe (95% CI: -9.446--3.645; P<0.001), basal ganglia (95% CI: -7.543--1.963; P=0.001) and thalamus (95% CI: -8.051--2.372; P<0.001) were significantly lower in infants of the mild IVH group than those of non-IVH group. Conclusions:At the same corrected gestational age, mild IVH is correlated with low CBF values in local cerebral cortex and subcortical gray matter in premature infants.However, the predictive potential of CBF values in long-term neurological prognosis requires further explorations.

As a retrovirus with high recombination and mutation rate， HIV targets CD4⁺ T lymphocytes， causing damage to the body's immune system and eventually leading to severe immune function defects. Different subtypes of the HIV virus exhibit significant sequence differences in their structural and regulatory genes， and this diversity is closely related to etiology， transmission， diagnosis， drug therapy， disease progression， and vaccine development. As a country with the largest number of HIV subtypes， rapid and accurate typing of the HIV virus holds great significance for China's efforts in disease prevention and control. This study provides a comprehensive reveiw of domestic and international HIV genotyping methods， and summarizes the clinical significance of different subtypes in order to provide reference for further research.

Delayed endolymphatic hydrops （DEH） is a rare disease that causes vertigo and is often misdiagnosed as other vertigo diseases. This article reports on a patient with vertigo who was easily misdiagnosed. The patient was a middle ear cholesteatoma complicated by labyrinthine fistula （LF）; however, his vertigo was episodic vertigo, which could not be explained solely by LF causing labyrinthitis. The possibility of endolymphatic hydrops was suspected, which was confirmed by inner ear magnetic resonance gadolinium imaging. This is the first reported case of middle ear cholesteatoma complicated by LF and DEH. The patient underwent surgical resection of the cholesteatoma and three semicircular canal obstructions at the same time. During two years postoperative follow-up, the patient did not experience a recurrence of vertigo. When diagnosing vertigo diseases, a careful history of vertigo is of utmost importance.
Humans ; Endolymphatic Hydrops/diagnosis* ; Cholesteatoma, Middle Ear/complications* ; Vertigo/complications* ; Labyrinth Diseases/complications* ; Magnetic Resonance Imaging/adverse effects* ; Semicircular Canals

The clinical, imaging, genetic, therapeutic and prognostic features of a case of pediatric stroke who was finally diagnosed with Aicardi-Goutières syndrome (AGS) in Xi′an International Medical Center Hospital on October 24, 2021 were reported. A 10-year-old boy was admitted to the hospital due to weakness of the right limb for more than 10 hours. The pre-hospital CT showed multiple patchy calcifications in the bilateral frontal lobe and the right parietal lobe cortex-medullary junction. The physical examination on admission had chilblains on the hands, feet and face. National Institutes of Health Stroke Scale Score was 4 points. Brain magnetic resonance imaging showed acute brainstem infarction, no abnormality in magnetic resonance angiography, ultrasound and electrocardiogram of heart and neck vessels were normal, cerebrospinal fluid biochemistry and routine examination were normal, blood routine, biochemistry, coagulation, autoantibody series, thyroid function, tumor markers, human immunodeficiency virus and syphilis examinations were normal. After oral administration of aspirin anti-platelet aggregation and rehabilitation exercises, the muscle strength returned to normal and the patient was discharged. One month later, the result of genetic testing was reported as AGS caused by TREX1 gene mutation, and the mutation site is c.58G>A. AGS is a rare autoimmune hereditary encephalopathy with a large heterogeneity of clinical manifestations. When a hereditary disease was suspected, genetic testing should be done.

Objective:To investigate the clinical effects and influence factors of intravitreal injection of anti-vascular endothelial growth factor (VEGF) drugs in the treatment of idiopathic choroidal neovascularization (ICNV).Methods:This retrospective study involved 27 patients (27 eyes) with ICNV from July 2012 to July 2015. Patients received intravitreal bevacizumab (1.25 mg), ranibizumab (0.05 mg), additional injection was provided if it was needed. The average follow-up time was 168 weeks. The recovery of best corrected visual acuity (BCVA) and central foveal retinal thickness (CRT) of the affected eye was observed. Follow up once a month after the initial treatment until the lesion was completely absorbed or scarred (the first follow-up period). Follow up every 12 weeks was performed to observe the recurrence of the lesions (the second stage of long-term follow-up). One month after the last injection of the first follow-up period, according to the regression of choroidal neovascularization (CNV), the affected eyes were divided into a significant improvement group (significant improvement group) and an insignificant improvement group (non-significant improvement group)), to analyze the effects of age, course of disease, type of drugs, number of injections, baseline BCVA and CRT on the regression of CNV lesions. According to the results of long-term follow-up, the eyes were divided into recurrence group and non-recurrence group, and the factors affecting the recurrence of CNV lesions were analyzed. Measurement data between groups was compared by using independent sample t test or non-parametric test; count data was compared by using χ2 test. Logistic regression analysis was used to analyze the factors affecting the regression and recurrence of the lesion. Results:At baseline and 1 month after the last injection in the first stage, the average BCVA of the eyes were 55.70±15.21 and 73.59±12.08 letters; CRT was 338.3±89.32 and 264.5±47.47 μm, respectively. The BCVA and CRT of the affected eyes were compared at the two time points, and the differences were statistically significant ( Z= -3.886, -4.061; P<0.001). The BCVA of the eyes in the significant improvement group and the insignificant improvement group were 65.38±17.27 and 51.63±12.61 letters, respectively; the difference between the two groups of BCVA was statistically significant ( t=-2.316, P=0.029). The results of long-term follow-up showed that of the 27 eyes, 6 eyes had recurrence; the average recurrence time was 90.83±49.02 weeks. After another intravitreal injection of anti-VEGF drugs, the CNV lesions was resolved. The average injection times of the relapsed group and the non-relapsed group were 3.67±0.816 and 2.24±0.768, respectively. The average injection times of the relapsed group was significantly higher than that of the non-relapsed group, and the difference was statistically significant ( Z=-3.253, P<0.001). There was no statistically significant difference between the two groups of eyes at baseline and CRT at the last follow-up ( Z=-1.342,-1.313; P=0.195, 0.195). Conclusion:Intravitreal injection of anti-VEGF drugs can effectively increase the regression rate of BCVA and CNV lesions in ICNV eyes; high baseline visual acuity indicates better CNV lesion regression after treatment. Relapsed patients can be effectively improved after re-treatment with anti-VEGF drugs, and CNV recurrence has no significant effect on the final prognosis.

Objective:To develop a biomimetic nanoparticle probe of hematoporphyrin monomethyl ether (HMME) coated with breast cancer cell membrane, to observe its ability to target homologous breast cancer cells in vitro, and to investigate its effect of enhanced photoacoustic imaging and sonodynamic therapy (SDT) for breast cancer in vitro.Methods:The cell membrane of breast cancer 4T1 was extracted by chemical cleavage and repeated freezing and thawing. Then the HMME-coated polylactic acid-glycolic acid copolymer biomimetic nanoparticle was prepared by double emulsification and extrusion. The basic characteristics of nanoparticles were detected. The target ability of nanoparticles to homologous breast cancer cells and the enhancement of photoacoustic imaging were observed in vitro. Singlet oxygen sensor green (SOSG) was used to verify the reactive oxygen species (ROS) production of nanoparticles, and its SDT effect on breast cancer cells was evaluated by CCK8 cytotoxicity assay.Results:The size of the prepared CHP-NPs was uniform, the morphology was spherical "core-shell structure" , the particle size was (275.23±8.25)nm, and the surface potential was (-18.43±0.45)mV. It was observed that CHP-NPs could target homologous 4T1 cells under laser confocal microscopy. In vitro photoacoustic imaging experiments show that the photoacoustic signal of nanoparticles increases with the increase of its concentration. According to SOSG probe detection, CHP-NPs could produce ROS under ultrasonic irradiation.When CHP-NPs was incubated with 4T1 cells alone and no ultrasonic irradiation was used, the cell survival rate was not significantly affected. When the concentration was 0.6 mg/ml, the cell survival rate was still 95%. After ultrasonic irradiation, CCK8 experiment showed that the CHP-NPs had a significant SDT effect on breast cancer cells.Conclusions:The biomimetic nanomolecular probe of breast cancer cell membrane is successfully prepared. The probe has good ability to target homologous tumor, and can significantly enhance tumor photoacoustic imaging and SDT effect.