A complex case study: coexistence of multi-drug-resistant pulmonary tuberculosis, HBV-related liver failure, and disseminated cryptococcal infection in an AIDS patient.

BACKGROUND: Hepatitis B virus (HBV) infection can cause liver failure, while individuals with Acquired Immunodeficiency Virus Disease (AIDS) are highly susceptible to various opportunistic infections, which can occur concurrently. The treatment process is further complicated by the potential occurrence of immune reconstitution inflammatory syndrome (IRIS), which presents significant challenges and contributes to elevated mortality rates. CASE PRESENTATION: The 50-year-old male with a history of chronic hepatitis B and untreated human immunodeficiency virus (HIV) infection presented to the hospital with a mild cough and expectoration, revealing multi-drug resistant pulmonary tuberculosis (MDR-PTB), which was confirmed by XpertMTB/RIF PCR testing and tuberculosis culture of bronchoalveolar lavage fluid (BALF). The patient was treated with a regimen consisting of linezolid, moxifloxacin, cycloserine, pyrazinamide, and ethambutol for tuberculosis, as well as a combination of bictegravir/tenofovir alafenamide/emtricitabine (BIC/TAF/FTC) for HBV and HIV viral suppression. After three months of treatment, the patient discontinued all medications, leading to hepatitis B virus reactivation and subsequent liver failure. During the subsequent treatment for AIDS, HBV, and drug-resistant tuberculosis, the patient developed disseminated cryptococcal disease. The patient's condition worsened during treatment with liposomal amphotericin B and fluconazole, which was ultimately attributed to IRIS. Fortunately, the patient achieved successful recovery after appropriate management. CONCLUSION: Enhancing medical compliance is crucial for AIDS patients, particularly those co-infected with HBV, to prevent HBV reactivation and subsequent liver failure. Furthermore, conducting a comprehensive assessment of potential infections in patients before resuming antiviral therapy is essential to prevent the occurrence of IRIS. Early intervention plays a pivotal role in improving survival rates.

The novel HLA-C*12:02:52 allele, identified by Sanger dideoxy nucleotide sequencing in a Chinese individual.

HLA-C*12:02:52 differs from HLA-C*12:02:02:01 by one nucleotide in exon 1.

A Case Series of Olfactory Dysfunction in Imported COVID-19 Patients: A 12-Month Follow-Up Study.

Objective: The scientific community knows little about the long-term influence of coronavirus disease 2019 (COVID-19) on olfactory dysfunction (OD). With the COVID-19 pandemic ongoing worldwide, the risk of imported cases remains high. In China, it is necessary to understand OD in imported cases. Methods: A prospective follow-up design was adopted. A total of 11 self-reported patients with COVID-19 and OD from Xi'an No. 8 Hospital were followed between August 19, 2021, and December 12, 2021. Demographics, clinical characteristics, laboratory and radiological findings, and treatment outcomes were analyzed at admission. We surveyed the patients via telephone for recurrence and sequelae at the 1-, 6-, and 12-month follow-up. Results: Eleven patients with OD were enrolled; of these, 54.5% (6/11) had hyposmia and 45.5% (5/11) had anosmia. 63.6% (7/11) reported OD before or on the day of admission as their initial symptom; of these, 42.9% (3/7) described OD as the only symptom. All patients in the study received combined treatment with traditional Chinese medicine and Western medicine, and 72.7% (8/11) had partially or fully recovered at discharge. In terms of OD recovery at the 12-month follow-up, 45.5% (5/11) reported at least one sequela, 81.8% (9/11) had recovered completely, 18.2% (2/11) had recovered partially, and there were no recurrent cases. Conclusions: Our data revealed that OD frequently presented as the initial or even the only symptom among imported cases. Most OD improvements occurred in the first 2 weeks after onset, and patients with COVID-19 and OD had favorable treatment outcomes during long-term follow-up. A better understanding of the pathogenesis and appropriate treatment of OD is needed to guide clinicians in the care of these patients.

3- to 24-month Follow-up on COVID-19 with Pulmonary Tuberculosis Survivors after Discharge: Results from a Prospective, Multicenter Study.

Objective: Coronavirus disease 2019 (COVID-19) and tuberculosis (TB) are major public health and social issues worldwide. The long-term follow-up of COVID-19 with pulmonary TB (PTB) survivors after discharge is unclear. This study aimed to comprehensively describe clinical outcomes, including sequela and recurrence at 3, 12, and 24 months after discharge, among COVID-19 with PTB survivors. Methods: From January 22, 2020 to May 6, 2022, with a follow-up by August 26, 2022, a prospective, multicenter follow-up study was conducted on COVID-19 with PTB survivors after discharge in 13 hospitals from four provinces in China. Clinical outcomes, including sequela, recurrence of COVID-19, and PTB survivors, were collected via telephone and face-to-face interviews at 3, 12, and 24 months after discharge. Results: Thirty-two COVID-19 with PTB survivors were included. The median age was 52 (45, 59) years, and 23 (71.9%) were men. Among them, nearly two-thirds (62.5%) of the survivors were moderate, three (9.4%) were severe, and more than half (59.4%) had at least one comorbidity (PTB excluded). The proportion of COVID-19 survivors with at least one sequela symptom decreased from 40.6% at 3 months to 15.8% at 24 months, with anxiety having a higher proportion over a follow-up. Cough and amnesia recovered at the 12-month follow-up, while anxiety, fatigue, and trouble sleeping remained after 24 months. Additionally, one (3.1%) case presented two recurrences of PTB and no re-positive COVID-19 during the follow-up period. Conclusion: The proportion of long symptoms in COVID-19 with PTB survivors decreased over time, while nearly one in six still experience persistent symptoms with a higher proportion of anxiety. The recurrence of PTB and the psychological support of COVID-19 with PTB after discharge require more attention.

A Case Series of Olfactory Dysfunction in Imported COVID-19 Patients: A 12-Month Follow-Up Study / 生物医学与环境科学（英文）

Objective@#The scientific community knows little about the long-term influence of coronavirus disease 2019 (COVID-19) on olfactory dysfunction (OD). With the COVID-19 pandemic ongoing worldwide, the risk of imported cases remains high. In China, it is necessary to understand OD in imported cases.@*Methods@#A prospective follow-up design was adopted. A total of 11 self-reported patients with COVID-19 and OD from Xi'an No. 8 Hospital were followed between August 19, 2021, and December 12, 2021. Demographics, clinical characteristics, laboratory and radiological findings, and treatment outcomes were analyzed at admission. We surveyed the patients via telephone for recurrence and sequelae at the 1-, 6-, and 12-month follow-up.@*Results@#Eleven patients with OD were enrolled; of these, 54.5% (6/11) had hyposmia and 45.5% (5/11) had anosmia. 63.6% (7/11) reported OD before or on the day of admission as their initial symptom; of these, 42.9% (3/7) described OD as the only symptom. All patients in the study received combined treatment with traditional Chinese medicine and Western medicine, and 72.7% (8/11) had partially or fully recovered at discharge. In terms of OD recovery at the 12-month follow-up, 45.5% (5/11) reported at least one sequela, 81.8% (9/11) had recovered completely, 18.2% (2/11) had recovered partially, and there were no recurrent cases.@*Conclusions@#Our data revealed that OD frequently presented as the initial or even the only symptom among imported cases. Most OD improvements occurred in the first 2 weeks after onset, and patients with COVID-19 and OD had favorable treatment outcomes during long-term follow-up. A better understanding of the pathogenesis and appropriate treatment of OD is needed to guide clinicians in the care of these patients.

Fabrication of Sub-Micron Polymer Waveguides through Two-Photon Polymerization in Polydimethylsiloxane.

Flexible ultra-compact low-loss optical waveguides play a vital role in the development of soft photonics. The search for suitable materials and innovative fabrication techniques to achieve low loss long polymer optical waveguides and interconnects has proven to be challenging. In this paper, we demonstrate the fabrication of submicron optical waveguides in polydimethylsiloxane (PDMS) using divinylbenzene (DVB) as the photopolymerizable monomer through two-photon polymerization (2PP). We show that the commercial oxime ester photoinitiator Irgacure OXE02 is suitable for triggering the DVB photopolymerization, resulting in a stable and controllable fabrication process for the fabrication of defect-free, 5-cm long waveguides. We further explore a multi-track fabrication strategy to enlarge the waveguide core size up to ~3 µm for better light confinement and reduced cross-talk. In these waveguides, we measured a refractive index contrast on the order of 0.005 and a transmission loss of 0.1 dB/cm at 710 nm wavelength.

Association of Overlapped and Un-overlapped Comorbidities with COVID-19 Severity and Treatment Outcomes: A Retrospective Cohort Study from Nine Provinces in China.

OBJECTIVE: Several COVID-19 patients have overlapping comorbidities. The independent role of each component contributing to the risk of COVID-19 is unknown, and how some non-cardiometabolic comorbidities affect the risk of COVID-19 remains unclear. METHODS: A retrospective follow-up design was adopted. A total of 1,160 laboratory-confirmed patients were enrolled from nine provinces in China. Data on comorbidities were obtained from the patients' medical records. Multivariable logistic regression models were used to estimate the odds ratio ( OR) and 95% confidence interval (95% CI) of the associations between comorbidities (cardiometabolic or non-cardiometabolic diseases), clinical severity, and treatment outcomes of COVID-19. RESULTS: Overall, 158 (13.6%) patients were diagnosed with severe illness and 32 (2.7%) had unfavorable outcomes. Hypertension (2.87, 1.30-6.32), type 2 diabetes (T2DM) (3.57, 2.32-5.49), cardiovascular disease (CVD) (3.78, 1.81-7.89), fatty liver disease (7.53, 1.96-28.96), hyperlipidemia (2.15, 1.26-3.67), other lung diseases (6.00, 3.01-11.96), and electrolyte imbalance (10.40, 3.00-26.10) were independently linked to increased odds of being severely ill. T2DM (6.07, 2.89-12.75), CVD (8.47, 6.03-11.89), and electrolyte imbalance (19.44, 11.47-32.96) were also strong predictors of unfavorable outcomes. Women with comorbidities were more likely to have severe disease on admission (5.46, 3.25-9.19), while men with comorbidities were more likely to have unfavorable treatment outcomes (6.58, 1.46-29.64) within two weeks. CONCLUSION: Besides hypertension, diabetes, and CVD, fatty liver disease, hyperlipidemia, other lung diseases, and electrolyte imbalance were independent risk factors for COVID-19 severity and poor treatment outcome. Women with comorbidities were more likely to have severe disease, while men with comorbidities were more likely to have unfavorable treatment outcomes.

Association of Overlapped and Un-overlapped Comorbidities with COVID-19 Severity and Treatment Outcomes: A Retrospective Cohort Study from Nine Provinces in China / 生物医学与环境科学（英文）

Objective@#Several COVID-19 patients have overlapping comorbidities. The independent role of each component contributing to the risk of COVID-19 is unknown, and how some non-cardiometabolic comorbidities affect the risk of COVID-19 remains unclear.@*Methods@#A retrospective follow-up design was adopted. A total of 1,160 laboratory-confirmed patients were enrolled from nine provinces in China. Data on comorbidities were obtained from the patients' medical records. Multivariable logistic regression models were used to estimate the odds ratio ( @*Results@#Overall, 158 (13.6%) patients were diagnosed with severe illness and 32 (2.7%) had unfavorable outcomes. Hypertension (2.87, 1.30-6.32), type 2 diabetes (T2DM) (3.57, 2.32-5.49), cardiovascular disease (CVD) (3.78, 1.81-7.89), fatty liver disease (7.53, 1.96-28.96), hyperlipidemia (2.15, 1.26-3.67), other lung diseases (6.00, 3.01-11.96), and electrolyte imbalance (10.40, 3.00-26.10) were independently linked to increased odds of being severely ill. T2DM (6.07, 2.89-12.75), CVD (8.47, 6.03-11.89), and electrolyte imbalance (19.44, 11.47-32.96) were also strong predictors of unfavorable outcomes. Women with comorbidities were more likely to have severe disease on admission (5.46, 3.25-9.19), while men with comorbidities were more likely to have unfavorable treatment outcomes (6.58, 1.46-29.64) within two weeks.@*Conclusion@#Besides hypertension, diabetes, and CVD, fatty liver disease, hyperlipidemia, other lung diseases, and electrolyte imbalance were independent risk factors for COVID-19 severity and poor treatment outcome. Women with comorbidities were more likely to have severe disease, while men with comorbidities were more likely to have unfavorable treatment outcomes.

Imaging hair cells through laser-ablated cochlear bone.

We report an innovative technique for the visualization of cells through an overlying scattering medium by combining femtosecond laser bone ablation and two-photon excitation fluorescence (TPEF) microscopy. We demonstrate the technique by imaging hair cells in an intact mouse cochlea ex vivo. Intracochlear imaging is important for the assessment of hearing disorders. However, the small size of the cochlea and its encasement in the densest bone in the body present challenging obstacles, preventing the visualization of the intracochlear microanatomy using standard clinical imaging modalities. The controlled laser ablation reduces the optical scattering of the cochlear bone while the TPEF allows visualization of individual cells behind the bone. We implemented optical coherence tomography (OCT) simultaneously with the laser ablation to enhance the precision of the ablation and prevent inadvertent damage to the cells behind the bone.

Hollow Mesoporous Plasmonic Nanoshells for Enhanced Solar Vapor Generation.

In the past decade, nanomaterials have made their way into a variety of technologies in solar energy, enhancing the performance by taking advantage of the phenomena inherent to the nanoscale. Recent examples exploit plasmonic core/shell nanoparticles to achieve efficient direct steam generation, showing great promise of such nanoparticles as a useful material for solar applications. In this paper, we demonstrate a novel technique for fabricating bimetallic hollow mesoporous plasmonic nanoshells that yield a higher solar vapor generation rate compared with their solid-core counterparts. On the basis of a combination of nanomasking and incomplete galvanic replacement, the hollow plasmonic nanoshells can be fabricated with tunable absorption and minimized scattering. When exposed to sun light, each hollow nanoshell generates vapor bubbles simultaneously from the interior and exterior. The vapor nucleating from the interior expands and diffuses through the pores and combines with the bubbles formed on the outer wall. The lack of a solid core significantly accelerates the initial vapor nucleation and the overall steam generation dynamics. More importantly, because the density of the hollow porous nanoshells is essentially equal to the surrounding host medium these particles are much less prone to sedimentation, a problem that greatly limits the performance and implementation of standard nanoparticle dispersions.

Clinical significance and prognostic value of Vav1 expression in Non-small cell lung cancer.

Vav1 has been reported to be involved in human cancers, however, the expression and clinical significance of Vav1 in NSCLC are not fully understood. In the present study, we examined the expression of Vav1 in 170 NSCLC patients who underwent radical resection by the immunohistochemical analyses. The association between the Vav1 expression and clinicopathological variables was analyzed. The multivariate Cox proportional hazards model was conducted to determine the prognostic value of Vav1 on the long-term survival. The results showed that the elevated Vav1 expression was correlated positively with lymph node metastasis (P<0.001), T stage (P<0.001) and poor histological differentiation (P<0.001). Patients with negative or low Vav1 expression had better prognoses than those with high Vav1 expression (P<0.001). Multivariate analysis indicated that Vav1 was independent prognostic factor for overall survival (OS) (HR 2.079, 95% CI 1.564 to 2.762, P<0.001) and disease-free survival (DFS) (HR 1.810, 95% CI 1.391 to 2.356, P<0.001). Our findings showed that overexpressed Vav1 was correlated with aggressive tumor behavior. Val1 was an independent factor for NSCLC prognosis, which may serve as a novel prognostic factor and potential target to improve the long-term outcome of NSCLC.

Imaging blood cells through scattering biological tissue using speckle scanning microscopy.

We demonstrate imaging of blood cells enclosed in chicken skin tissue using speckle scanning microscopy (SSM). Clear images of multiple cells were obtained with subcellular resolution and good image fidelity, provided that the object dimension was smaller than the maximum scanning range of the speckle pattern. These results point to the potential and the challenges of using SSM technique for biological imaging.

Seeing through turbidity with harmonic holography [Invited].

The ability to see inside the body noninvasively is indispensable in modern biology and medicine. Optical approaches to such abilities are of rapidly growing interest because of their nonionizing nature and low cost. However, the problem of opacity due to the optical turbidity of tissues must be addressed before optical means become practical. Harmonic holography amalgamates the capability of holographic phase conjugation with the contrast-forming mechanism of second-harmonic generation, which provides a unique opportunity for imaging through a turbid medium. In this review we give accounts of the effort of imaging through turbid media using harmonic holographic phase conjugation.

Two-photon microscopy of the mouse cochlea in situ for cellular diagnosis.

Sensorineural hearing loss is the most common type of hearing loss worldwide, yet the underlying cause is typically unknown because the inner ear cannot be biopsied today without destroying hearing, and intracochlear cells have not been imaged with resolution sufficient to establish diagnosis. Intracochlear imaging has been technologically challenging because of the cochlea's small size and encasement in bone. We report, for the first time, imaging of the mouse cochlea in situ without exogenous dyes, through a membranous round window, using a near-infrared femtosecond laser as the excitation and endogenous two-photon excitation fluorescence (TPEF) and second harmonic generation as the contrast mechanisms. We find that TPEF exhibits strong contrast allowing cellular, and even subcellular resolution, and detection of specific, noise-induced pathologic changes. Our results demonstrate that the round window provides a useful access to the cochlea through the middle ear, and they motivate future development of a new and efficient diagnostic tool based on two-photon micro-endoscopy.

Three-dimensional scanning microscopy through thin turbid media.

We demonstrate three-dimensional imaging through a thin turbid medium using digital phase conjugation of the second harmonic signal emitted from a beacon nanoparticle. The digitally phase-conjugated focus scans the volume in the vicinity of its initial position through numerically manipulated phase patterns projected onto the spatial light modulator. Accurate three dimensional images of a fluorescent sample placed behind a turbid medium are obtained.

Imaging with second-harmonic radiation probes in living tissue.

We demonstrate that second-harmonic radiation imaging probes are efficient biomarkers for imaging in living tissue. We show that 100 nm and 300 nm BaTiO(3) nanoparticles used as contrast markers could be detected through 50 µm and 120 µm of mouse tail tissue in vitro or in vivo. Experimental results and Monte-Carlo simulations are in good agreement.

Imaging through turbid layers by scanning the phase conjugated second harmonic radiation from a nanoparticle.

We demonstrate imaging through a turbid layer by using digital phase conjugation of the second harmonic field radiated from a beacon nanoparticle. We show that the phase-conjugated focus can be displaced from its initial position by illuminating the same region of the turbid layer with an angular offset. An image is obtained by scanning the phase-conjugated focus through the turbid layer in a region around the nanoparticle. We obtain a clear image of the target by measuring the light transmitted through it when scanning the focused beam.

Nonlinear optical properties of core-shell nanocavities for enhanced second-harmonic generation.

A nonlinear optical plasmonic core-shell nanocavity is demonstrated as an efficient, subwavelength coherent light source through second-harmonic generation. The nonlinear optical plasmonic nanocavity incorporates a noncentrosymmetric medium, which utilizes the entire mode volume for even-order nonlinear optical processes. In previous plasmonic nanocavities, enhancement of such processes was only possible at the interface but symmetry prohibited in the body. We measured an enhancement of over 500 times in the second-harmonic radiation power. Calculations show that an enhancement of over 3500 times is achievable.

Digital phase conjugation of second harmonic radiation emitted by nanoparticles in turbid media.

We demonstrate focusing coherent light on a nanoparticle through turbid media based on digital optical phase conjugation of second harmonic generation (SHG) field from the nanoparticle. A SHG active nanoparticle inside a turbid medium was excited at the fundamental frequency and emitted SHG field as a point source. The SHG emission was scattered by the turbid medium, and the scattered field was recorded by off-axis digital holography. A phase-conjugated beam was then generated by using a phase-only spatial light modulator and sent back through the turbid medium, which formed a nearly ideal focus on the nanoparticle.

Second harmonic generation from nanocrystals under linearly and circularly polarized excitations.

We study second harmonic generation (SHG) from non-centrosymmetric nanocrystals under linearly polarized (LP) and circularly polarized (CP) excitations. Theoretical models are developed for SHG from nanocrystals under both plane-wave and focused excitations. We find that the focused excitation reduces the polarization dependency of the SHG signal. We show that the SHG response under CP excitation is generally inferior to the average of LP excitations over all orientations. We verify the theory by measuring the SHG polar responses from BaTiO3 nanocrystals with a scanning confocal microscope. The experimental data agrees well with the theory.