High recallability of memory B cells requires ZFP318-dependent transcriptional regulation of mitochondrial function.

Expression of the transcriptional regulator ZFP318 is induced in germinal center (GC)-exiting memory B cell precursors and memory B cells (MBCs). Using a conditional ZFP318 fluorescence reporter that also enables ablation of ZFP318-expressing cells, we found that ZFP318-expressing MBCs were highly enriched with GC-derived cells. Although ZFP318-expressing MBCs constituted only a minority of the antigen-specific MBC compartment, their ablation severely impaired recall responses. Deletion of Zfp318 did not alter the magnitude of primary responses but markedly reduced MBC participation in recall. CD40 ligation promoted Zfp318 expression, whereas B cell receptor (BCR) signaling was inhibitory. Enforced ZFP318 expression enhanced recall performance of MBCs that otherwise responded poorly. ZFP318-deficient MBCs expressed less mitochondrial genes, had structurally compromised mitochondria, and were susceptible to reactivation-induced cell death. The abundance of ZFP318-expressing MBCs, instead of the number of antigen-specific MBCs, correlated with the potency of prime-boost vaccination. Therefore, ZFP318 controls the MBC recallability and represents a quality checkpoint of humoral immune memory.

Chang'E-4 initial spectroscopic identification of lunar far-side mantle-derived materials.

Over 60 years of spacecraft exploration has revealed that the Earth's Moon is characterized by a lunar crust1 dominated by the mineral plagioclase, overlying a more mafic (richer in iron and magnesium) mantle of uncertain composition. Both crust and mantle formed during the earliest stages of lunar evolution when late-stage accretional energy caused a molten rock (magma) ocean, flotation of the light plagioclase, sinking of the denser iron-rich minerals, such as olivine and pyroxene, and eventually solidification2. Very large impact craters can potentially penetrate through the crust and sample the lunar mantle. The largest of these craters is the approximately 2,500-kilometre-diameter South Pole-Aitken (SPA) basin3 on the lunar far side. Evidence obtained from orbiting spacecraft shows that the floor of the SPA basin is rich in mafic minerals4, but their mantle origin is controversial and their in situ geologic settings are poorly known. China's Chang'E-4 lunar far-side lander recently touched down in the Von Kármán crater5,6 to explore the floor of the huge SPA basin and deployed its rover, Yutu-2. Here we report on the initial spectral observations of the Visible and Near Infrared Spectrometer (VNIS)7 onboard Yutu-2, which we interpret to represent the presence of low-calcium (ortho)pyroxene and olivine, materials that may originate from the lunar mantle. Geological context6 suggests that these materials were excavated from below the SPA floor by the nearby 72-km-diameter Finsen impact crater event, and transported to the landing site. Continued exploration by Yutu-2 will target these materials on the floor of the Von Kármán crater to understand their geologic context, origin and abundance, and to assess the possibility of sample-return scenarios.

Research on fine co-focus adjustment method for segmented solar telescope.

For segmented telescopes, achieving fine co-focus adjustment is essential for realizing co-phase adjustment and maintenance, which involves adjusting the millimeter-scale piston between segments to fall within the capture range of the co-phase detection system. CGST proposes using a SHWFS for piston detection during the co-focus adjustment stage. However, the residual piston after adjustment exceeds the capture range of the broadband PSF phasing algorithm( ± 30µm), and the multi-wavelength PSF algorithm requires even higher precision in co-focus adjustment. To improve the co-focus adjustment accuracy of CGST, a fine co-focus adjustment based on cross-calibration is proposed. This method utilizes a high-precision detector to calibrate and fit the measurements from the SHWFS, thereby reducing the impact of atmospheric turbulence and systematic errors on piston measurement accuracy during co-focus adjustment. Simulation results using CGST demonstrate that the proposed method significantly enhances adjustment accuracy compared to the SHWFS detection method. Additionally, the residual piston after fine co-focus adjustment using this method falls within the capture range of the multi-wavelength PSF algorithm. To verify the feasibility of this method, experiments were conducted on an 800mm ring segmented mirror system, successfully achieving fine co-focus adjustment where the remaining piston of all segments fell within ±15µm.

Activation of Kv7 channels normalizes hyperactivity of the VTA-NAcLat circuit and attenuates methamphetamine-induced conditioned place preference and sensitization in mice.

The brain circuit projecting from the ventral tegmental area (VTA) to the nucleus accumbens lateral shell (NAcLat) has a key role in methamphetamine (MA) addiction. As different dopamine (DA) neuron subpopulations in the VTA participate in different neuronal circuits, it is a challenge to isolate these DA neuron subtypes. Using retrograde tracing and Patch-seq, we isolated DA neurons in the VTA-NAcLat circuit in MA-treated mice and performed gene expression profiling. Among the differentially expressed genes, KCNQ genes were dramatically downregulated. KCNQ genes encode Kv7 channel proteins, which modulate neuronal excitability. Injection of both the Kv7.2/3 agonist ICA069673 and the Kv7.4 agonist fasudil into the VTA attenuated MA-induced conditioned place preference and locomotor sensitization and decreased neuronal excitability. Increasing Kv7.2/3 activity decreased neural oscillations, synaptic plasticity and DA release in the VTA-NacLat circuit in MA-treated mice. Furthermore, overexpression of only Kv7.3 channels in the VTA-NacLat circuit was sufficient to attenuate MA-induced reward behavior and decrease VTA neuron excitability. Activation of Kv7 channels in the VTA may become a novel treatment strategy for MA abuse.

The curious case of TMEM120A: Mechanosensor, fat regulator, or antiviral defender?

Mechanical pain sensing, adipogenesis, and STING-dependent innate immunity seem three distinct biological processes without substantial relationships. Intriguingly, TMEM120A, a transmembrane protein, has been shown to detect mechanical pain stimuli as a mechanosensitive channel, contribute to adipocyte differentiation/function by regulating genome organization and promote STING trafficking to active cellular innate immune response. However, the role of TMEM120A as a mechanosensitive channel was challenged by recent studies which cannot reproduce data supporting its role in mechanosensing. Furthermore, the molecular mechanism by which TMEM120A contributes to adipocyte differentiation/function and promotes STING trafficking remains elusive. In this review, we discuss these multiple proposed functions of TMEM120A and hypothesize the molecular mechanism underlying TMEM120A's role in fatty acid metabolism and STING signaling.

Orthogonal genome-wide screens of bat cells identify MTHFD1 as a target of broad antiviral therapy.

Bats are responsible for the zoonotic transmission of several major viral diseases, including those leading to the 2003 SARS outbreak and likely the ongoing COVID-19 pandemic. While comparative genomics studies have revealed characteristic adaptations of the bat innate immune system, functional genomic studies are urgently needed to provide a foundation for the molecular dissection of the viral tolerance in bats. Here we report the establishment of genome-wide RNA interference (RNAi) and CRISPR libraries for the screening of the model megabat, Pteropus alecto. We used the complementary RNAi and CRISPR libraries to interrogate P. alecto cells for infection with two different viruses: mumps virus and influenza A virus, respectively. Independent screening results converged on the endocytosis pathway and the protein secretory pathway as required for both viral infections. Additionally, we revealed a general dependence of the C1-tetrahydrofolate synthase gene, MTHFD1, for viral replication in bat cells and human cells. The MTHFD1 inhibitor, carolacton, potently blocked replication of several RNA viruses, including SARS-CoV-2. We also discovered that bats have lower expression levels of MTHFD1 than humans. Our studies provide a resource for systematic inquiry into the genetic underpinnings of bat biology and a potential target for developing broad-spectrum antiviral therapy.

Chromosome-level genome assembly and functional characterization of terpene synthases provide insights into the volatile terpenoid biosynthesis of Wurfbainia villosa.

Wurfbainia villosa is a well-known medicinal and edible plant that is widely cultivated in the Lingnan region of China. Its dried fruits (called Fructus Amomi) are broadly used in traditional Chinese medicine for curing gastrointestinal diseases and are rich in volatile terpenoids. Here, we report a high-quality chromosome-level genome assembly of W. villosa with a total size of approximately 2.80 Gb, 42 588 protein-coding genes, and a very high percentage of repetitive sequences (87.23%). Genome analysis showed that W. villosa likely experienced a recent whole-genome duplication event prior to the W. villosa-Zingiber officinale divergence (approximately 11 million years ago), and a recent burst of long terminal repeat insertions afterward. The W. villosa genome enabled the identification of 17 genes involved in the terpenoid skeleton biosynthesis pathway and 66 terpene synthase (TPS) genes. We found that tandem duplication events have an important contribution to the expansion of WvTPSs, which likely drove the production of volatile terpenoids. In addition, functional characterization of 18 WvTPSs, focusing on the TPS-a and TPS-b subfamilies, showed that most of these WvTPSs are multi-product TPS and are predominantly expressed in seeds. The present study provides insights into the genome evolution and the molecular basis of the volatile terpenoids diversity in W. villosa. The genome sequence also represents valuable resources for the functional gene research and molecular breeding of W. villosa.

Dopamine D1 receptor in orbitofrontal cortex to dorsal striatum pathway modulates methamphetamine addiction.

The orbitofrontal cortex (OFC)-dorsal striatum (DS) is an important neural circuit that contributes to addictive behavior, including compulsive reinforcement, yet the specific types of neurons that play a major role still need to be further elucidated. Here, we used a place conditioning paradigm to measure the conditioned responses to methamphetamine (MA). The results demonstrated that MA increases the expression of c-Fos, synaptic plasticity in OFC and DS. Patch-clamp recording showed that MA activated projection neurons from the OFC to the DS, and chemogenetic manipulation of neuronal activity in OFC-DS projection neurons affects conditioned place preference (CPP) scores. And the combined patch-electrochemical technique was used to detect the DA release in OFC, the data indicated that the DA release was increased in MA group. Additionally, SCH23390, a D1R antagonist, was used to verify the function of D1R projection neurons, showing that SCH23390 reversed MA addiction-like behavior. Collectively, these findings provide evidence for the D1R neuron is sufficient to regulate MA addiction in the OFC-DS pathway, and the study provides new insight into the underlying mechanism of pathological changes in MA addiction.

Novel third-generation tyrosine kinase inhibitor for newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia: a case study.

Although Philadelphia chromosome-positive acute leukemia (Ph + -ALL) has been revolutionized with tyrosine kinase inhibitors (TKIs), resistance and mutation are universal events during treatment with first-generation and second-generation TKIs. The present third-generation TKI has a dose-dependent, increased risk of serious cardiovascular events and the sensitivity is poor for patients with ≥2 mutations accompanied by the T315I mutation. Thus, novel and well-tolerated TKIs should be explored. This study analyzes the efficacy and advert effects of olverembatinib, a novel third TKI, in the treatment of newly diagnosed adult Ph + -ALL in induction therapy. Four adult patients with newly diagnosed Ph + -ALL were treated with olverembatinib as the first-line treatment. For induction therapy, these patients received 40 mg of oral olverembatinib quaque omni die for 28 days, 1 mg/kg/d of prednisone for 14 days, then tapered and stopped at 28 days and vindesine 4 mg/d at days 1, 8 and 15. After induction therapy, these patients received median or high-dose of cytarabine and methotrexate combined with oral olverembatinib as consolidation therapy. Then the allogeneic hematopoietic stem cell transplantation (allo-HSCT) was performed. All patients reached complete remission with a complete cytogenetic response after induction therapy. Two patients reached major molecular remission and one with complete molecular remission. Before allo-HSCT, all the patients achieved complete molecular remission. All the patients have survived disease-free for 3-6 months. No severe advert effects were observed. It is well-tolerated and effective for olverembatinib in the treatment of newly diagnosed adult patients with Ph + -ALL. A prospective study should be performed to further testify the role.

Gene duplication and genetic innovation in cereal genomes.

Organisms continuously require genetic variation to adapt to fluctuating environments, yet major evolutionary events are episodic, making the relationship between genome evolution and organismal adaptation of considerable interest. Here, by genome-wide comparison of sorghum, maize, and rice SNPs, we investigated reservoirs of genetic variations with high precision. For sorghum and rice, which have not experienced whole-genome duplication in 96 million years or more, tandem duplicates accumulate relatively more SNPs than paralogous genes retained from genome duplication. However, maize, which experienced lineage-specific genome duplication and has a relatively larger supply of paralogous duplicates, shows SNP enrichment in paralogous genes. The proportion of genes showing signatures of recent positive selection is higher in small-scale (tandem and transposed) than genome-scale duplicates in sorghum, but the opposite is true in maize. A large proportion of recent duplications in rice are species-specific; however, most recent duplications in sorghum are derived from ancestral gene families. A new retrotransposon family was also a source of many recent sorghum duplications, illustrating a role in providing variation for genetic innovations. This study shows that diverse evolutionary mechanisms provide the raw genetic material for adaptation in taxa with divergent histories of genome evolution.

Microwave ablation versus radiofrequency ablation for subcapsular hepatocellular carcinoma: a propensity score-matched study.

OBJECTIVES: Thermal ablation is now accepted as one of the curative treatments for patients with early-stage hepatocellular carcinoma (HCC), but the efficacy of this treatment for subcapsular HCC is not well characterized. Therefore, we aimed to compare the outcomes of microwave ablation (MWA) and radiofrequency ablation (RFA) for patients with subcapsular HCC. METHODS: In total, 195 patients with subcapsular HCC who met the Milan criteria and underwent MWA or RFA were included. Local tumor progression (LTP), overall survival (OS), recurrence beyond the Milan criteria (RBM), and complications of these patients were compared. RESULTS: After propensity score matching, the 1-, 3-, and 5-year cumulative LTP rates were 6.7%, 9.6%, and 11.4% in the MWA group, and 13.4%, 24.6%, and 29.1% in the RFA group, respectively (p = 0.006). The cumulative rates of RBM were lower in patients treated with MWA than in those treated with RFA (4.4% versus 12% at 1 year; 14.5% versus 23.0% at 3 years; and 37.4% versus 53.9% at 5 years; p = 0.03). The OS rates at 1, 3, and 5 years were 97.1%, 85.9%, and 73.4% in the MWA group, and 95.6%, 80.4%, and 61.4% in the RFA group, respectively (p = 0.36). The rate of major complications showed no significant difference between the MWA group and the RFA group (17.4% vs. 11.6%, p = 0.33). CONCLUSION: Compared to RFA, MWA showed better tumor control for subcapsular HCC within the Milan criteria. There was no difference in the incidence of major complications between the two groups. KEY POINTS: •Compared to radiofrequency ablation, microwave ablation showed better local tumor control for patients with subcapsular hepatocellular carcinoma. •Microwave ablation showed similar major complication rates for patients with subcapsular hepatocellular carcinoma. •Microwave ablation may be preferred for patients with subcapsular hepatocellular carcinoma when they need to receive thermal ablation.

Functional Characterization of MdTAC1a Gene Related to Branch Angle in Apple (Malus x domestica Borkh.).

The Tiller Angle Control 1 (TAC1) gene belongs to the IGT family, which mainly controls plant branch angle, thereby affecting plant form. Two members of MdTAC1 are identified in apple; the regulation of apple branch angle by MdTAC1 is still unclear. In this study, a subcellular localization analysis detected MdTAC1a in the nucleus and cell membrane, but MdTAC1b was detected in the cell membrane. Transgenic tobacco by overexpression of MdTAC1a or MdTAC1b showed enlarged leaf angles, the upregulation of several genes, such as GA 2-oxidase (GA2ox), and a sensitive response to light and gravity. According to a qRT-PCR analysis, MdTAC1a and MdTAC1b were strongly expressed in shoot tips and vegetative buds of weeping cultivars but were weakly expressed in columnar cultivars. In the MdTAC1a promoter, there were losses of 2 bp in spur cultivars and 6 bp in weeping cultivar compared with standard and columnar cultivars. An InDel marker specific to the MdTAC1a promoter was developed to distinguish apple cultivars and F1 progeny. We identified a protein, MdSRC2, that interacts with MdTAC1a, whose encoding gene which was highly expressed in trees with large branch angles. Our results indicate that differences in the MdTAC1a promoter are major contributors to branch-angle variation in apple, and the MdTAC1a interacts with MdSRC2 to affect this trait.

Inactivation of the Lateral Hypothalamus Attenuates Methamphetamine-Induced Conditioned Place Preference through Regulation of Kcnq3 Expression.

Repeated administration of methylamphetamine (MA) induces MA addiction, which is featured by awfully unpleasant physical and emotional experiences after drug use is terminated. Neurophysiological studies show that the lateral hypothalamus (LH) is involved in reward development and addictive behaviors. Here, we show that repeated administration of MA activates the expression of c-Fos in LH neurons responding to conditioned place preference (CPP). Chemogenetic inhibition of the LH can disrupt the addiction behavior, demonstrating that the LH plays an important role in MA-induced reward processing. Critically, MA remodels the neurons of LH synaptic plasticity, increases intracellular calcium level, and enhances spontaneous current and evoked potentials of neurons compared to the saline group. Furthermore, overexpression of the potassium voltage-gated channel subfamily Q member 3 (Kcnq3) expression can reverse the CPP score and alleviate the occurrence of addictive behaviors. Together, these results unravel a new neurobiological mechanism underlying the MA-induced addiction in the lateral hypothalamus, which could pave the way toward new and effective interventions for this addiction disease.

Emoji use in China: popularity patterns and changes due to COVID-19.

Emojis are small pictograms that are frequently embedded within micro-texts to more directly express emotional meanings. To understand the changes in the emoji usage of internet users during the COVID-19 outbreak, we analysed a large dataset collected from Weibo, the most popular Twitter-like social media platform in China, from December 1, 2019, to March 20, 2020. The data contained 38,183,194 microblog posts published by 2,239,472 unique users in Wuhan. We calculated the basic statistics of users' usage of emojis, topics, and sentiments and analysed the temporal patterns of emoji occurrence. After examining the emoji co-occurrence structure, we finally explored other factors that may affect individual emoji usage. We found that the COVID-19 outbreak greatly changed the pattern of emoji usage; i.e., both the proportion of posts containing emojis and the ratio of users using emojis declined substantially, while the number of posts remained the same. The daily proportion of Happy emojis significantly declined to approximately 32%, but the proportions of Sad- and Encouraging-related emojis rose to 24% and 34%, respectively. Despite a significant decrease in the number of nodes and edges in the emoji co-occurrence network, the average degree of the network increased from 34 to 39.8, indicating that the diversity of emoji usage increased. Most interestingly, we found that male users were more inclined towards using regular textual language with fewer emojis after the pandemic, suggesting that during public crises, male groups appeared to control their emotional display. In summary, the COVID-19 pandemic remarkably impacted individual sentiments, and the normal pattern of emoji usage tends to change significantly following a public emergency. Supplementary Information: The online version contains supplementary material available at 10.1007/s10489-022-03195-y.

Liver resection versus radiofrequency ablation for recurrent hepatocellular carcinoma: a systematic review and meta-analysis.

BACKGROUND & AIMS: Liver resection (LR) and radiofrequency ablation (RFA) are commonly used for the treatment of recurrent hepatocellular carcinoma (HCC), but the optimal treatment modality remains unclear. We aimed to compare the efficacy and safety of LR vs RFA for recurrent HCC. METHODS: We searched PubMed, Embase, Web of Science, and the Cochrane Library for relevant studies. The primary outcomes were overall survival (OS) and disease-free survival (DFS). The secondary outcomes were major complications and hospital stay. RESULTS: Eighteen studies with 1991 patients with recurrent HCC were included. The pooled hazard ratio (HR) for OS demonstrated that LR had significantly better OS than RFA in recurrent HCC (HR, 0.81; 95% confidence interval [CI], 0.68-0.95). Specifically, LR was associated with higher 2-, 3- and 4-year OS rates compared with RFA. The pooled HR for DFS showed no significant difference between LR and RFA during the whole follow-up period (HR, 0.90; 95% CI, 0.76-1.07). However, LR was associated with significantly higher 2- to 5-year DFS rates compared to RFA. LR was also associated with more major complications (p < .001) and longer hospital stay (p < .001). Subgroup analyses demonstrated that LR and RFA had similar efficacy in patients with recurrent tumors less than 3 cm or patients presenting three or fewer recurrent nodules. CONCLUSION: LR could provide better long-term survival outcomes than RFA for recurrent HCC patients, while RFA has a higher safety profile. RFA can be a good alternative to LR for patients with small-sized recurrence or patients with a limited number of recurrent nodules. However, as tumor size increases, LR tends to be more efficacious.

Nicotinamide adenine dinucleotide promotes synaptic plasticity gene expression through regulation N-methyl-D-aspartate receptor/Ca2+/Erk1/2 pathway.

Nicotinamide adenine dinucleotide (NADH) has been reported to regulate synaptic plasticity recently, while its role in this process remains unclear. To explore the contribution and the underlying mechanisms of NADH regulating synaptic plasticity, here, we examined NADH's effect on immediate-early response genes (IEGs) expressions, including C-Fos and Arc in primary cultured cortical neurons and the frontal cortex of mouse brain. Our results showed that NADH promoted IEGs expression and that the C-Fos and Arc levels are increased in primary cultured cortical neurons, which is almost completely blocked by N-methyl-D-aspartate receptor (NMDAR) inhibitor, MK-801. Moreover, NADH significantly increased intracellular Ca2+ levels and the phosphorylation of Erk1/2, a downstream molecule of the NMDAR. Furthermore, NADH also significantly increased IEGs expression in vivo, accompanied by the changes of Ca2+ in neurons and activation of excitatory neurons in the mouse frontal cortex. In conclusion, this study indicates that NADH can promote the expression of synaptic plasticity-related IEGs through the NMDAR/Ca2+/Erk1/2 pathway, which provides a new way to understand the regulatory role of NADH in synaptic plasticity.

Recent advances in biocatalytic derivatization of L-tyrosine.

L-Tyrosine is an aromatic, polar, non-essential amino acid that contains a highly reactive α-amino, α-carboxyl, and phenolic hydroxyl group. Derivatization of these functional groups can produce chemicals, such as L-3,4-dihydroxyphenylalanine, tyramine, 4-hydroxyphenylpyruvic acid, and benzylisoquinoline alkaloids, which are widely employed in the pharmaceutical, food, and cosmetics industries. In this review, we summarize typical L-tyrosine derivatizations catalyzed by enzymatic biocatalysts, as well as the strategies and challenges associated with their production processes. Finally, we discuss future perspectives pertaining to the enzymatic production of L-tyrosine derivatives.Key points• Summary of recent advances in enzyme-catalyzed L-tyrosine derivatization.• Highlights of relevant strategies involved in L-tyrosine derivatives biosynthesis.• Future perspectives on industrial applications of L-tyrosine derivatization.

Kupffer Cells Regulate Natural Killer Cells Via the NK group 2, Member D (NKG2D)/Retinoic Acid Early Inducible-1 (RAE-1) Interaction and Cytokines in a Primary Biliary Cholangitis Mouse Model.

BACKGROUND Kupffer cells and natural killer (NK) cells has been identified as contributing factors in the pathogenesis of hepatitis, but the detailed mechanism of these cell types in the pathogenesis of primary biliary cholangitis (PBC) is poorly understood. MATERIAL AND METHODS In this study, polyinosinic: polycytidylic acid (poly I: C), 2-octynoic acid-bovine serum albumin (2OA-BSA) and Freund's adjuvant (FA) were injected to establish a murine PBC model, from which NK cells and Kupffer cells were extracted and isolated. The cells were then co-cultivated in a designed culture system, and then NK group 2, member D (NKG2D), retinoic acid early inducible-1 (RAE-1), F4/80, and cytokine expression levels were detected. RESULTS The results showed close crosstalk between Kupffer cells and NK cells. PBC mice showed increased surface RAE-1 protein expression and Kupffer cell cytokine secretion, which subsequently activated NK cell-mediated target cell killing via NKG2D/RAE-1 recognition, and increased inflammation. NK cell-derived interferon-γ (IFN-γ) and Kupffer cell-derived tumor necrosis factor alpha (TNF-alpha) were found to synergistically regulate inflammation. Moreover, interleukin (IL)-12 and IL-10 improved the crosstalk between NK cells and Kupffer cells. CONCLUSIONS Our findings in mice are the first to suggest the involvement of the NKG2D/RAE-1 interaction and cytokines in the synergistic effects of NK and Kupffer cells in PBC.

Viral Manipulations of the Cullin-RING Ubiquitin Ligases.

Cullin-RING ubiquitin ligases (CRLs) are efficient and diverse toolsets of the cells to regulate almost every biological process. However, these characteristics have also been usurped by many viruses to optimize for their replication. CRLs are often at the forefront of the arms races in the coevolution of viruses and hosts. Here we review the modes of actions and functional consequences of viral manipulations of host cell CRLs. We also discuss the therapeutic applications to target these viral manipulations for treating viral infections.

Successful treatment for bilateral femoral neck insufficiency fractures: a rare lesion case report and an updated review of the literature.

BACKGROUND: The incidence of insufficiency fracture (IF) at femoral neck is low, accounting for about 5% of all insufficiency fractures, and IF at bilateral femoral neck is less common with more occurrence in athlete or serviceman. With the aging of populations, more cases of bilateral femoral neck IF have occurred recently, while the standard clinical treatment still remains lacking due to the complexity of these patients. CASE PRESENTATION: A 55-year-old male patient complained pain in his bilateral hip, with no history of trauma, glucocorticoid hormone consumption or radiotherapy, and imaging examination revealed fracture nonunion and shortening in his left femoral neck, and double fracture line on the right femoral neck. The patient received a cementless THA for the left femoral neck fracture and conservative treatment for the right side, followed by Elcatonin injection and oral administration of Carbonate D3 Granules. After 4 months of fellow-up, the patient presented improved functional scorings in bilateral hip joints, with no signs of prothesis infection or loosening. CONCLUSION: We present a rare case of bilateral femoral neck IF in a middle-aged male and the treatment is successful. The timely CT and MRI examinations of bilateral hip joints for patients was necessary for orthopedists to select proper therapeutic regimen. In addition, the choice for therapeutic regimen of bilateral femoral IF should not only be based on the professional judgement of orthopedists, but also on the wishes of patients.